Comprehensive Medical Topics Overview

Carcinogenesis

Cancer develops through a multistage process involving genetic alterations in proto-oncogenes, cellular oncogenes, and tumor suppressor genes.

Carcinogenesis progresses through three distinct stages: initiation (irreversible genetic alterations including mutations, transversions, transitions, and small DNA deletions), promotion (reversible changes in genome expression without DNA structural changes), and progression (characterized by karyotypic instability and malignant growth) 1
Between four and seven mutations in key genes are typically necessary to produce most human cancers, as demonstrated by analysis of cancer frequency as a function of age 2
Cancer is fundamentally a genetic disease where tumor cells differ from normal progenitors through genetic alterations affecting growth-regulatory genes, specifically oncogenes (positive growth regulators) and tumor suppressor genes (negative growth regulators) 3
The mutator phenotype hypothesis suggests that normal mutation rates may be insufficient to account for multiple mutations found in tumors, indicating that during carcinogenesis, target cells may develop a mutator phenotype due to mutations affecting DNA replication fidelity, DNA repair, apoptosis pathways, or cell cycle checkpoint regulations 2
Most cancers harbor multiple genetic changes in both oncogenes and tumor suppressor genes, with these changes accumulating and increasing in number as tumors develop from benign to increasingly malignant 3

Endogenous vs. Exogenous Factors

Organ-specific cancer incidence varies dramatically between low- and high-incidence areas due to heritable susceptibility determinants, environmental/local living conditions (viruses, pollution), and personal lifestyle factors 4
For organs showing large differences between cancer registries, exogenous factors are most important, while organs showing small differences suggest endogenous and unavoidable factors predominate 4
Individual preventive measures taken by a nonsmoker can reduce cancer risk on average by only a factor of approximately 3, indicating a considerable fraction of cases appears hardly avoidable 4

Tumor Progression

Tumor progression represents the final irreversible stage of carcinogenesis characterized by accumulating genetic alterations and increasing malignancy.

Progression involves alterations in both alleles of tumor suppressor genes, found only in this final stage, distinguishing it from earlier stages of carcinogenesis 1
Genetic modeling demonstrates that 70% of statistically significant allelic losses occur early in low-grade intraurothelial dysplasia, with some involving morphologically normal mucosa preceding microscopically recognizable precursor lesions 5
The remaining 30% of markers develop allelic losses in later phases, implicating their involvement in progression to invasive disease 5
Whole organ histologic and genetic mapping reveals allelic losses cluster in 33 distinct chromosomal regions, indicating locations of putative tumor suppressor genes involved in development and progression 5
Tumor progression is not constant but increases in genetic changes as tumors develop from benign to more malignant, with both oncogenes (gain of function) and tumor suppressor genes (loss of function) working together 3

Phenylketonuria (PKU)

PKU is a genetic disorder requiring immediate dietary management to prevent intellectual disability and neurological complications.

PKU should be managed through careful control of phenylalanine intake before and during pregnancy, as it represents a known genetic disorder requiring specific management 6
Genetic screening and family history assessment should identify PKU risk based on family history, ethnic background, and age, with carrier screening offered as indicated 6
Management of known PKU before and during pregnancy is critical, as uncontrolled maternal PKU poses significant teratogenic risks to the developing fetus 6

Galactosemia

Galactosemia requires immediate dietary restriction of galactose-containing foods to prevent acute toxicity and long-term complications.

Galactosemia represents a metabolic disorder that should be identified through genetic screening based on family history and ethnic background 6
Carrier screening should be offered as indicated for galactosemia, particularly in high-risk populations 6
Management requires strict dietary modifications eliminating galactose-containing foods, particularly lactose from dairy products

Cystic Fibrosis

Cystic fibrosis requires multidisciplinary management addressing pulmonary, gastrointestinal, and nutritional complications.

Cystic fibrosis carrier screening should be offered based on family history and ethnic background during preconception care 6
Genetic screening and counseling should discuss family history of genetic disorders including cystic fibrosis 7
Management requires addressing exocrine pancreatic insufficiency, chronic pulmonary infections, and nutritional deficiencies through enzyme replacement, airway clearance, and supplementation

Sudden Infant Death Syndrome (SIDS)

SIDS prevention focuses on safe sleep practices, specifically placing infants on their backs to sleep.

Interconception care should promote placing infants on their backs to sleep to reduce SIDS risk 6
Safe sleep education must be provided to all parents, emphasizing supine positioning, firm sleep surfaces, and avoiding soft bedding or co-sleeping
Additional risk reduction includes avoiding maternal smoking, maintaining appropriate room temperature, and considering pacifier use

Exocrine Pancreas Function

The exocrine pancreas produces digestive enzymes (lipase, amylase, proteases) and bicarbonate essential for nutrient digestion and absorption.

Exocrine pancreatic function involves secretion of digestive enzymes into the duodenum via the pancreatic duct
Pancreatic insufficiency results in malabsorption of fats, proteins, and fat-soluble vitamins, manifesting as steatorrhea, weight loss, and nutritional deficiencies
Assessment includes fecal elastase testing, coefficient of fat absorption, and direct pancreatic function tests

Acute Pancreatitis

Acute pancreatitis presents with severe epigastric pain and elevated pancreatic enzymes, requiring aggressive fluid resuscitation and supportive care.

Common etiologies include gallstones (40-70% of cases) and alcohol (25-35% of cases), with less common causes including hypertriglyceridemia, hypercalcemia, medications, and trauma
Diagnosis requires two of three criteria: characteristic abdominal pain, serum lipase or amylase >3 times upper limit of normal, and characteristic imaging findings
Initial management prioritizes aggressive intravenous fluid resuscitation (250-500 mL/hour of lactated Ringer's solution), pain control, and nutritional support
Severity assessment using Ranson's criteria, APACHE II score, or CT severity index guides prognosis and management intensity
Complications include pancreatic necrosis (sterile or infected), pseudocyst formation, splenic vein thrombosis, and systemic complications (ARDS, acute kidney injury, shock)

Chronic Pancreatitis

Chronic pancreatitis results from irreversible pancreatic damage causing chronic pain, exocrine insufficiency, and diabetes.

Alcohol consumption accounts for 70-80% of chronic pancreatitis cases, with other causes including genetic mutations (PRSS1, SPINK1, CFTR), autoimmune pancreatitis, and idiopathic disease
Clinical manifestations include chronic or recurrent abdominal pain, steatorrhea from exocrine insufficiency, and diabetes from endocrine insufficiency
Diagnosis involves imaging (CT showing calcifications, ductal dilation, atrophy; MRI/MRCP; endoscopic ultrasound) and pancreatic function tests
Management includes pain control (analgesics, celiac plexus block), pancreatic enzyme replacement for exocrine insufficiency, diabetes management, and alcohol cessation
Surgical interventions (lateral pancreaticojejunostomy, pancreatic resection) may be considered for intractable pain or complications

Pancreatic Cancer

Pancreatic adenocarcinoma carries extremely poor prognosis, with surgical resection offering the only potential cure.

Pancreatic cancer typically presents late with nonspecific symptoms including painless jaundice (head tumors), weight loss, abdominal pain, and new-onset diabetes
Risk factors include smoking, chronic pancreatitis, family history, hereditary syndromes (BRCA2, Lynch syndrome, Peutz-Jeghers), obesity, and diabetes
Diagnosis requires high-quality pancreatic protocol CT or MRI, with tissue diagnosis via endoscopic ultrasound-guided fine needle aspiration
Only 15-20% of patients present with resectable disease; surgical options include pancreaticoduodenectomy (Whipple procedure) for head tumors or distal pancreatectomy for body/tail tumors
Adjuvant chemotherapy (FOLFIRINOX or gemcitabine-based regimens) improves survival in resected patients
For unresectable disease, systemic chemotherapy (FOLFIRINOX or gemcitabine plus nab-paclitaxel) provides modest survival benefit

Pancreatic Islet Cell Tumors

Islet cell tumors (pancreatic neuroendocrine tumors) present with hormone-specific syndromes or as incidental findings.

Functional tumors produce hormones causing specific syndromes: insulinoma (hypoglycemia), gastrinoma (Zollinger-Ellison syndrome), VIPoma (watery diarrhea), glucagonoma (necrolytic migratory erythema, diabetes)
Nonfunctional tumors present with mass effect symptoms or are discovered incidentally
Diagnosis requires biochemical testing (hormone levels, chromogranin A), imaging (CT, MRI, somatostatin receptor scintigraphy), and endoscopic ultrasound
Surgical resection is treatment of choice for localized disease; enucleation for small benign tumors or formal resection for larger/malignant tumors
Medical management includes somatostatin analogs (octreotide, lanreotide) for symptom control and tumor stabilization
Multiple endocrine neoplasia type 1 (MEN1) should be considered in patients with multiple pancreatic neuroendocrine tumors 6

Glomerulonephritis Principles

Glomerulonephritis encompasses immune-mediated kidney diseases causing hematuria, proteinuria, and progressive renal dysfunction.

Glomerulonephritis classification includes nephritic syndrome (hematuria, hypertension, edema, acute kidney injury) versus nephrotic syndrome (heavy proteinuria >3.5 g/day, hypoalbuminemia, edema, hyperlipidemia)
Pathophysiology involves immune complex deposition, anti-glomerular basement membrane antibodies, or pauci-immune mechanisms (ANCA-associated)
Diagnosis requires urinalysis (dysmorphic RBCs, RBC casts), quantification of proteinuria, serologic testing (complement levels, ANCA, anti-GBM antibodies), and often kidney biopsy
Treatment depends on specific etiology: immunosuppression (corticosteroids, cyclophosphamide, rituximab) for immune-mediated disease, supportive care for post-infectious glomerulonephritis

Membranoproliferative Glomerulonephritis (MPGN)

MPGN presents with combined nephritic and nephrotic features, requiring identification of underlying complement dysregulation or secondary causes.

MPGN classification includes immune complex-mediated MPGN (secondary to infections, autoimmune diseases, monoclonal gammopathies) and complement-mediated MPGN (C3 glomerulopathy)
Clinical presentation includes hematuria, proteinuria (often nephrotic range), hypertension, and progressive renal insufficiency
Diagnosis requires kidney biopsy showing mesangial proliferation, endocapillary proliferation, and double-contour ("tram-track") appearance of glomerular basement membrane
Complement studies (C3, C4, complement factor levels, anti-complement factor antibodies) help distinguish primary from secondary forms
Treatment addresses underlying causes (treat infections, control autoimmune disease, address monoclonal gammopathies) and may include immunosuppression or complement inhibition (eculizumab) for C3 glomerulopathy

Nephrotic Syndrome

Nephrotic syndrome is defined by heavy proteinuria (>3.5 g/day), hypoalbuminemia, edema, and hyperlipidemia.

Common causes include minimal change disease (most common in children), focal segmental glomerulosclerosis, membranous nephropathy, and diabetic nephropathy
Complications include thromboembolism (renal vein thrombosis), infections (due to immunoglobulin loss), hyperlipidemia, and acute kidney injury
Diagnosis requires 24-hour urine protein quantification or spot urine protein-to-creatinine ratio, serum albumin, lipid panel, and often kidney biopsy
General management includes dietary sodium restriction, diuretics (loop diuretics for edema), ACE inhibitors or ARBs for proteinuria reduction, and statin therapy for hyperlipidemia
Specific treatment depends on underlying cause: corticosteroids for minimal change disease, immunosuppression (corticosteroids, calcineurin inhibitors, rituximab) for FSGS or membranous nephropathy

Nephritic Syndrome

Nephritic syndrome presents with hematuria, hypertension, edema, and acute kidney injury from glomerular inflammation.

Classic presentation includes "tea-colored" or "cola-colored" urine from hematuria, periorbital and peripheral edema, hypertension, and oliguria
Common causes include post-infectious glomerulonephritis (post-streptococcal), IgA nephropathy, ANCA-associated vasculitis, anti-GBM disease, and lupus nephritis
Urinalysis shows dysmorphic RBCs, RBC casts (pathognomonic for glomerulonephritis), and variable proteinuria
Management includes sodium and fluid restriction, blood pressure control, diuretics for volume overload, and treatment of underlying cause
Post-streptococcal glomerulonephritis typically resolves spontaneously with supportive care; ANCA-associated vasculitis and anti-GBM disease require aggressive immunosuppression

Tubulointerstitial Disease

Tubulointerstitial disease involves inflammation and fibrosis of renal tubules and interstitium, causing tubular dysfunction and progressive renal failure.

Acute tubulointerstitial nephritis (AIN) commonly results from medications (NSAIDs, antibiotics, PPIs), infections, or autoimmune diseases
Chronic tubulointerstitial disease results from prolonged exposure to toxins, obstruction, reflux nephropathy, or chronic AIN
Clinical manifestations include acute kidney injury (AIN), tubular dysfunction (renal tubular acidosis, salt wasting, concentrating defects), and sterile pyuria
Diagnosis requires high clinical suspicion, urinalysis (WBCs, WBC casts, eosinophiluria), and often kidney biopsy showing interstitial inflammation and tubular injury
Treatment involves removing offending agent, corticosteroids for severe AIN, and addressing underlying causes

Urinary Tract Infection (UTI)

UTIs require prompt antibiotic treatment based on local resistance patterns, with special considerations in pregnancy.

Screening for asymptomatic bacteriuria is necessary in pregnancy, as untreated infection increases risk for pyelonephritis and adverse pregnancy outcomes 7
Urinalysis and urine culture should be performed at initial prenatal visit to screen for asymptomatic bacteriuria 7
Uncomplicated cystitis presents with dysuria, frequency, urgency, and suprapubic pain without systemic symptoms
Pyelonephritis presents with fever, flank pain, costovertebral angle tenderness, nausea, and vomiting, requiring hospitalization in pregnancy
Treatment for uncomplicated cystitis includes nitrofurantoin, trimethoprim-sulfamethoxazole (avoid in first trimester and near term), or fosfomycin
Pyelonephritis requires intravenous antibiotics (ceftriaxone, ampicillin-gentamicin) until afebrile for 24-48 hours, followed by oral antibiotics to complete 10-14 days

Acute Renal Failure (Acute Kidney Injury)

Acute kidney injury (AKI) is defined by rapid decline in kidney function, classified as prerenal, intrinsic, or postrenal.

AKI diagnosis requires serum creatinine increase ≥0.3 mg/dL within 48 hours, or ≥1.5 times baseline within 7 days, or urine output <0.5 mL/kg/hour for 6 hours
Prerenal AKI results from decreased renal perfusion (hypovolemia, heart failure, cirrhosis); characterized by BUN:Cr ratio >20:1, FENa <1%, and urine osmolality >500 mOsm/kg
Intrinsic AKI includes acute tubular necrosis (ischemic or nephrotoxic), acute interstitial nephritis, and glomerulonephritis
Postrenal AKI results from urinary tract obstruction (bilateral ureteral obstruction, bladder outlet obstruction, urethral obstruction)
Management includes identifying and treating underlying cause, avoiding nephrotoxins, adjusting medication doses, maintaining euvolemia, and providing renal replacement therapy if indicated

Chronic Renal Failure (Chronic Kidney Disease)

Chronic kidney disease (CKD) requires comprehensive management addressing progression, complications, and preparation for renal replacement therapy.

CKD is defined as kidney damage or GFR <60 mL/min/1.73m² for ≥3 months, staged from 1 (GFR ≥90) to 5 (GFR <15 or dialysis)
Common causes include diabetes (leading cause), hypertension, glomerulonephritis, polycystic kidney disease, and chronic tubulointerstitial disease
Complications include anemia (erythropoietin deficiency), mineral bone disease (secondary hyperparathyroidism), metabolic acidosis, hyperkalemia, and cardiovascular disease
Management focuses on slowing progression: blood pressure control (target <130/80 mmHg), ACE inhibitors or ARBs for proteinuria reduction, glycemic control in diabetes, and avoiding nephrotoxins
Complication management includes erythropoiesis-stimulating agents and iron for anemia, phosphate binders and vitamin D for mineral bone disease, and dietary modifications (protein restriction, potassium restriction)
Renal replacement therapy (hemodialysis, peritoneal dialysis, kidney transplantation) should be initiated when GFR <15 mL/min/1.73m² or earlier if uremic symptoms develop

Renal Function Tests & Acute Kidney Injury

Serum creatinine and urinary protein assessment should be evaluated to assess renal function, as protein excretion ≥190 mg/24h increases risk for hypertensive disorders in pregnancy. 7

Serum creatinine reflects GFR but is influenced by muscle mass, age, sex, and medications
Estimated GFR (eGFR) using CKD-EPI equation provides more accurate assessment of kidney function than creatinine alone
Urinalysis provides critical information: proteinuria, hematuria, pyuria, casts (RBC casts indicate glomerulonephritis, WBC casts indicate pyelonephritis or AIN, granular casts indicate ATN)
Fractional excretion of sodium (FENa) distinguishes prerenal AKI (FENa <1%) from ATN (FENa >2%)
Renal ultrasound assesses kidney size (small kidneys suggest CKD), hydronephrosis (obstruction), and structural abnormalities

Acute Tubular Necrosis (ATN)

ATN represents the most common cause of intrinsic AKI, resulting from ischemic or nephrotoxic injury to renal tubular epithelial cells.

Ischemic ATN results from prolonged renal hypoperfusion (shock, sepsis, major surgery, severe volume depletion)
Nephrotoxic ATN results from medications (aminoglycosides, amphotericin B, cisplatin, contrast agents), pigments (myoglobin, hemoglobin), or toxins
Clinical course includes initiation phase (hours to days), maintenance phase (1-2 weeks of oliguria or nonoliguric AKI), and recovery phase (gradual improvement in urine output and kidney function)
Urinalysis shows muddy brown granular casts and renal tubular epithelial cells; FENa typically >2%
Management is supportive: maintain euvolemia, avoid nephrotoxins, adjust medication doses, provide nutritional support, and initiate dialysis if indicated for volume overload, hyperkalemia, severe acidosis, or uremia
Prevention includes avoiding nephrotoxins, maintaining adequate hydration, and using N-acetylcysteine and isotonic saline for contrast-induced nephropathy prevention

Tubulointerstitial Nephritis

Acute interstitial nephritis (AIN) is an immune-mediated inflammatory process affecting renal tubules and interstitium, most commonly drug-induced.

Common causative medications include NSAIDs, antibiotics (beta-lactams, fluoroquinolones, sulfonamides), PPIs, and 5-ASA compounds
Classic triad (fever, rash, eosinophilia) occurs in <10% of cases; most present with nonspecific AKI
Urinalysis shows WBCs, WBC casts, and eosinophiluria (though eosinophiluria has low sensitivity and specificity)
Kidney biopsy confirms diagnosis showing interstitial inflammation with lymphocytes, eosinophils, and plasma cells, with tubulitis
Treatment requires immediate discontinuation of offending agent; corticosteroids (prednisone 1 mg/kg/day for 4-6 weeks with taper) may hasten recovery if started early

Chronic Kidney Disease (CKD) - Detailed Management

CKD management requires addressing multiple complications and preparing for eventual renal replacement therapy. 8

Blood pressure control targeting <130/80 mmHg using ACE inhibitors or ARBs as first-line agents reduces proteinuria and slows progression
Glycemic control (HbA1c <7%) in diabetic patients slows progression of diabetic nephropathy
Anemia management includes iron supplementation (target ferritin >100 ng/mL, transferrin saturation >20%) and erythropoiesis-stimulating agents when hemoglobin <10 g/dL
Mineral bone disease management includes dietary phosphate restriction, phosphate binders (calcium-based or non-calcium-based), vitamin D supplementation, and calcimimetics for secondary hyperparathyroidism
Metabolic acidosis correction with sodium bicarbonate when serum bicarbonate <22 mEq/L may slow CKD progression
Cardiovascular risk reduction through statin therapy, aspirin (if appropriate), and aggressive management of traditional cardiovascular risk factors
Dietary modifications include protein restriction (0.8 g/kg/day in CKD stages 3-5), sodium restriction (<2 g/day), potassium restriction (if hyperkalemic), and phosphate restriction

Nephrolithiasis (Kidney Stones)

Kidney stones present with acute flank pain radiating to groin, requiring imaging for diagnosis and management based on stone size and composition.

Clinical presentation includes sudden-onset severe flank pain (renal colic), hematuria, nausea, vomiting, and urinary urgency/frequency
Diagnosis requires non-contrast CT scan (gold standard, 95-98% sensitivity) showing stone location, size, and degree of obstruction
Initial management includes aggressive pain control (NSAIDs, opioids), antiemetics, hydration, and medical expulsive therapy (alpha-blockers like tamsulosin for stones 5-10 mm)
Stones <5 mm have 90% spontaneous passage rate; stones 5-10 mm have 50% passage rate; stones >10 mm rarely pass spontaneously
Indications for urgent intervention include infected obstructed kidney (urosepsis), bilateral obstruction, obstruction in solitary kidney, or intractable pain/vomiting
Intervention options include extracorporeal shock wave lithotripsy (ESWL) for stones <2 cm, ureteroscopy with laser lithotripsy, or percutaneous nephrolithotomy for large/complex stones

Calcium Oxalate & Calcium Phosphate Stones

Calcium-based stones account for 80% of kidney stones, requiring metabolic evaluation and targeted prevention strategies.

Risk factors include hypercalciuria (most common), hyperoxaluria, hypocitraturia, low urine volume, and hyperuricosuria
Metabolic evaluation includes 24-hour urine collection measuring volume, calcium, oxalate, citrate, uric acid, sodium, creatinine, and pH
Prevention strategies include increasing fluid intake (target urine output >2.5 L/day), dietary sodium restriction (<2 g/day), limiting animal protein intake, maintaining normal dietary calcium intake (1000-1200 mg/day)
Thiazide diuretics (hydrochlorothiazide, chlorthalidone) reduce urinary calcium excretion in hypercalciuric patients
Potassium citrate supplementation increases urinary citrate (stone inhibitor) and alkalinizes urine, beneficial for hypocitraturia and calcium oxalate stones
Dietary oxalate restriction for hyperoxaluria includes avoiding high-oxalate foods (spinach, rhubarb, nuts, chocolate, tea)

Magnesium Ammonium Phosphate (Struvite), Uric Acid, & Cystine Stones

Non-calcium stones require specific metabolic evaluations and targeted treatments based on stone composition.

Struvite (Magnesium Ammonium Phosphate) Stones

Struvite stones form in alkaline urine (pH >7.2) due to urease-producing bacteria (Proteus, Klebsiella, Pseudomonas)
Present as large staghorn calculi causing recurrent UTIs and progressive renal damage
Treatment requires complete stone removal (percutaneous nephrolithotomy) plus eradication of infection with culture-directed antibiotics
Urease inhibitors (acetohydroxamic acid) may prevent recurrence but have significant side effects

Uric Acid Stones

Form in acidic urine (pH <5.5) due to hyperuricosuria, low urine volume, or persistently acidic urine
Risk factors include gout, high purine diet, metabolic syndrome, chronic diarrhea, and ileostomy
Prevention includes urinary alkalinization with potassium citrate (target urine pH 6.0-6.5), increased fluid intake, and dietary purine restriction
Allopurinol or febuxostat reduces uric acid production in hyperuricosuria
Existing stones may dissolve with aggressive urinary alkalinization

Cystine Stones

Result from autosomal recessive disorder causing defective renal tubular reabsorption of cystine
Form in acidic urine; radiolucent on plain radiographs but visible on CT
Prevention requires very high fluid intake (>4 L/day), urinary alkalinization (target pH >7.0), and cystine-binding agents (tiopronin, penicillamine)

Renal Neoplasia

Renal cell carcinoma represents 90% of kidney malignancies, often discovered incidentally on imaging.

Classic triad (flank pain, hematuria, palpable mass) occurs in <10% of cases; most are asymptomatic incidental findings
Risk factors include smoking, obesity, hypertension, chronic kidney disease, acquired cystic kidney disease, and hereditary syndromes (von Hippel-Lindau, hereditary papillary RCC)
Diagnosis requires contrast-enhanced CT or MRI showing enhancing renal mass; biopsy rarely needed before treatment
Staging includes chest/abdomen/pelvis CT to assess for metastases; common metastatic sites include lungs, bones, liver, and brain
Treatment for localized disease includes partial nephrectomy (preferred for tumors <7 cm) or radical nephrectomy; ablative techniques (radiofrequency ablation, cryoablation) for small tumors in poor surgical candidates
Metastatic disease treatment includes targeted therapy (tyrosine kinase inhibitors: sunitinib, pazopanib; mTOR inhibitors: everolimus, temsirolimus) or immunotherapy (nivolumab, ipilimumab)

Nephroblastoma (Wilms Tumor)

Wilms tumor is the most common renal malignancy in children, typically presenting as asymptomatic abdominal mass.

Peak incidence occurs at age 3-4 years; associated with WAGR syndrome (Wilms tumor, Aniridia, Genitourinary abnormalities, mental Retardation), Denys-Drash syndrome, and Beckwith-Wiedemann syndrome
Mosaic variegated aneuploidy syndrome (MVA1 and MVA3) shows increased risk for Wilms tumor, requiring surveillance 6
Clinical presentation includes asymptomatic abdominal mass (most common), abdominal pain, hematuria, hypertension, and fever
Diagnosis requires abdominal ultrasound or CT showing intrarenal mass; chest CT assesses for pulmonary metastases
Treatment includes upfront nephrectomy followed by chemotherapy (vincristine, dactinomycin, doxorubicin) based on stage and histology
Prognosis is excellent with 5-year survival >90% for favorable histology; anaplastic histology has worse prognosis

Cystic Kidney Disease

Polycystic kidney disease includes autosomal dominant (ADPKD) and autosomal recessive (ARPKD) forms with distinct presentations and prognoses.

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Most common inherited kidney disease; caused by mutations in PKD1 (85%, more severe) or PKD2 (15%, milder)
Presents in adulthood with hypertension, flank pain, hematuria, nephrolithiasis, and progressive renal insufficiency
Extrarenal manifestations include hepatic cysts, intracranial aneurysms (screen with MRA if family history of aneurysms or hemorrhagic stroke), mitral valve prolapse, and colonic diverticulosis
Diagnosis by ultrasound criteria (age-dependent number of cysts) or genetic testing
Management includes blood pressure control (target <110/75 mmHg), tolvaptan (vasopressin V2 receptor antagonist) slows cyst growth and GFR decline in rapidly progressive disease, pain management, and treatment of complications

Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Rare disorder presenting in infancy with enlarged echogenic kidneys, pulmonary hypoplasia, and congenital hepatic fibrosis
Management is supportive; many require early dialysis and kidney transplantation

Hydronephrosis & Urinary Tract Obstruction

Urinary tract obstruction causes hydronephrosis and progressive renal damage if not promptly relieved.

Causes include nephrolithiasis, benign prostatic hyperplasia, malignancy (prostate, bladder, cervical, colorectal), retroperitoneal fibrosis, and ureteropelvic junction obstruction
Acute obstruction presents with flank pain, nausea, vomiting, and oliguria (if bilateral); chronic obstruction may be asymptomatic until advanced renal failure develops
Diagnosis requires renal ultrasound showing hydronephrosis; CT urography or retrograde pyelography defines level and cause of obstruction
Acute management includes urgent decompression via nephrostomy tube or ureteral stent for infected obstructed kidney, bilateral obstruction, or obstruction in solitary kidney
Definitive treatment addresses underlying cause: stone removal, prostate surgery, tumor resection, or pyeloplasty for UPJ obstruction

Renal Cell Carcinoma - Detailed Management

Surgical resection remains the only curative treatment for localized renal cell carcinoma.

Partial nephrectomy is preferred over radical nephrectomy for tumors <7 cm when technically feasible, preserving renal function with equivalent oncologic outcomes
Active surveillance is appropriate for small renal masses (<2 cm) in elderly or comorbid patients, with serial imaging every 3-6 months
Adjuvant therapy after nephrectomy is not routinely recommended; clinical trials investigating adjuvant targeted therapy and immunotherapy are ongoing
Metastatic disease treatment has evolved with immunotherapy combinations (nivolumab plus ipilimumab) showing superior outcomes compared to targeted therapy alone
Cytoreductive nephrectomy before systemic therapy may benefit select patients with good performance status and limited metastatic burden
Metastasectomy for oligometastatic disease (especially isolated lung metastases) may improve survival in select patients

Lower Urinary Tract Carcinoma (Bladder Cancer)

Bladder cancer typically presents with painless hematuria, requiring cystoscopy and transurethral resection for diagnosis and staging.

Risk factors include smoking (most important), occupational exposures (aromatic amines, benzene), chronic bladder inflammation, cyclophosphamide, and pelvic radiation
Genetic modeling demonstrates allelic losses occur early in low-grade intraurothelial dysplasia, with 70% of losses occurring in precursor lesions 5
Clinical presentation includes painless gross or microscopic hematuria, irritative voiding symptoms, and recurrent UTIs
Diagnosis requires cystoscopy with transurethral resection of bladder tumor (TURBT) for histologic diagnosis and staging
Non-muscle-invasive bladder cancer (Ta, T1, CIS) is treated with TURBT followed by intravesical therapy (BCG immunotherapy or mitomycin C chemotherapy) to reduce recurrence
Muscle-invasive bladder cancer (T2-T4) requires radical cystectomy with pelvic lymph node dissection and urinary diversion; neoadjuvant cisplatin-based chemotherapy improves survival
Metastatic disease is treated with platinum-based chemotherapy (gemcitabine-cisplatin or MVAC) or immunotherapy (pembrolizumab, atezolizumab) for platinum-ineligible or platinum-refractory disease

Testicular Tumors

Testicular cancer is the most common malignancy in men aged 15-35, with excellent cure rates even in metastatic disease.

Germ cell tumors account for 95% of testicular cancers, classified as seminoma (50-55%) or non-seminoma (embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma)
Risk factors include cryptorchidism, family history, contralateral testicular cancer, and Klinefelter syndrome
Presentation includes painless testicular mass, testicular swelling, or symptoms from metastases (back pain from retroperitoneal lymphadenopathy, dyspnea from pulmonary metastases)
Diagnosis requires scrotal ultrasound and serum tumor markers (AFP, beta-hCG, LDH) before orchiectomy; radical inguinal orchiectomy provides definitive diagnosis
Staging includes chest/abdomen/pelvis CT to assess for retroperitoneal and distant metastases
Stage I seminoma is treated with orchiectomy followed by surveillance, adjuvant carboplatin, or adjuvant radiotherapy
Advanced seminoma is treated with cisplatin-based chemotherapy (BEP or EP regimen) with excellent cure rates
Non-seminoma treatment depends on stage: surveillance or RPLND for stage I, chemotherapy for advanced disease, with post-chemotherapy RPLND for residual masses

Penile Disorders

Penile disorders range from benign conditions to malignancies requiring prompt diagnosis and treatment.

Phimosis (inability to retract foreskin) may be physiologic in young children or pathologic from scarring; treatment includes topical corticosteroids or circumcision
Paraphimosis (inability to reduce retracted foreskin) is a urologic emergency causing venous congestion and potential necrosis; requires manual reduction or emergency dorsal slit
Peyronie's disease causes penile curvature from fibrous plaque formation; treatment includes oral therapy (pentoxifylline, colchicine), intralesional injections (collagenase, verapamil), or surgery for severe cases
Priapism (prolonged painful erection >4 hours) requires emergency treatment to prevent permanent erectile dysfunction; ischemic priapism needs aspiration and intracavernosal phenylephrine
Penile cancer (squamous cell carcinoma) presents as ulcerative or exophytic lesion; risk factors include HPV infection, phimosis, poor hygiene, and smoking; treatment includes partial or total penectomy with inguinal lymph node dissection

Scrotal Disorders

Acute scrotal pain requires urgent evaluation to distinguish surgical emergencies from benign conditions.

Testicular torsion presents with sudden-onset severe testicular pain, nausea, vomiting, and absent cremasteric reflex; requires emergency surgical exploration and orchiopexy within 6 hours to salvage testis
Epididymitis presents with gradual-onset testicular pain, dysuria, and positive cremasteric reflex; treatment includes antibiotics (ceftriaxone plus doxycycline for STI-related, fluoroquinolone for enteric organisms)
Hydrocele (fluid collection in tunica vaginalis) presents as painless scrotal swelling that transilluminates; treatment is observation or surgical repair if symptomatic
Varicocele (dilated pampiniform plexus veins) presents as "bag of worms" on palpation, more common on left side; treatment indicated for pain, testicular atrophy, or infertility
Testicular cancer screening should be considered in patients with scrotal masses, as early detection improves outcomes 6

Testicular Cancer - Detailed Management

Testicular cancer treatment achieves cure rates >95% for early-stage disease and >80% for metastatic disease.

Tumor markers (AFP, beta-hCG, LDH) guide diagnosis, prognosis, and treatment monitoring; AFP elevation indicates non-seminoma; beta-hCG may be elevated in seminoma or non-seminoma
Good-risk metastatic disease (low markers, no non-pulmonary visceral metastases) receives 3 cycles of BEP (bleomycin, etoposide, cisplatin) or 4 cycles of EP
Intermediate/poor-risk disease receives 4 cycles of BEP
Post-chemotherapy residual masses in seminoma >3 cm require PET scan; if PET-positive, surgical resection or biopsy indicated
Post-chemotherapy residual masses in non-seminoma require retroperitoneal lymph node dissection (RPLND) regardless of size, as 40% contain viable tumor or teratoma
Salvage chemotherapy (TIP: paclitaxel, ifosfamide, cisplatin; or VeIP: vinblastine, ifosfamide, cisplatin) for relapsed disease achieves cure in 50-60%
High-dose chemotherapy with autologous stem cell transplant is considered for multiply relapsed disease

Benign Prostatic Hyperplasia (BPH)

BPH causes lower urinary tract symptoms in aging men, managed with lifestyle modifications, medications, or surgical intervention based on symptom severity.

BPH affects 50% of men by age 60 and 90% by age 85; results from proliferation of prostatic stromal and epithelial cells
Symptoms include obstructive (weak stream, hesitancy, incomplete emptying, straining) and irritative (frequency, urgency, nocturia) lower urinary tract symptoms
Assessment includes symptom scoring (IPSS questionnaire), digital rectal examination, urinalysis, PSA (to screen for prostate cancer), and post-void residual measurement
Mild symptoms are managed with watchful waiting and lifestyle modifications (limiting fluids before bedtime, avoiding caffeine/alcohol, timed voiding)
Moderate symptoms are treated with alpha-blockers (tamsulosin, alfuzosin) for rapid symptom relief or 5-alpha-reductase inhibitors (finasteride, dutasteride) to reduce prostate size over 6-12 months
Combination therapy (alpha-blocker plus 5-alpha-reductase inhibitor) is more effective than monotherapy for large prostates (>40 g)
Surgical intervention (TURP, laser prostatectomy, simple prostatectomy) is indicated for refractory symptoms, recurrent urinary retention, recurrent UTIs, bladder stones, or renal insufficiency from obstruction

Prostate Cancer

Prostate cancer screening remains controversial; treatment decisions depend on risk stratification and life expectancy.

Prostate cancer is the most common non-cutaneous malignancy in men; risk factors include age, African American race, and family history
Screening with PSA and digital rectal examination should be individualized based on patient preferences, life expectancy, and risk factors
Diagnosis requires transrectal ultrasound-guided prostate biopsy; Gleason score (sum of two most common patterns, range 6-10) predicts aggressiveness
Risk stratification uses PSA, Gleason score, and clinical stage to classify as low-risk (PSA <10, Gleason ≤6, stage T1c-T2a), intermediate-risk, or high-risk (PSA >20, Gleason 8-10, or stage ≥T2c)
Low-risk disease may be managed with active surveillance (PSA monitoring, repeat biopsies) in select patients
Localized disease treatment options include radical prostatectomy or radiation therapy (external beam or brachytherapy) with equivalent oncologic outcomes
High-risk localized disease benefits from multimodal therapy: radiation plus androgen deprivation therapy (ADT) for 2-3 years
Metastatic disease is treated with ADT (LHRH agonists/antagonists or bilateral orchiectomy); castration-resistant disease receives additional therapies (abiraterone, enzalutamide, docetaxel, radium-223)

Vaginal Cancer

Vaginal cancer is rare, accounting for 1-2% of gynecologic malignancies, with most cases being squamous cell carcinoma.

Risk factors include HPV infection (particularly HPV 16,18), prior cervical cancer or CIN, DES exposure in utero, chronic vaginal irritation, and smoking
HPV vaccination should be updated as needed during preconception care to prevent HPV-related malignancies 6
Presentation includes abnormal vaginal bleeding, vaginal discharge, pelvic pain, or dyspareunia; many cases are asymptomatic and detected on routine screening
Diagnosis requires biopsy of suspicious lesions; colposcopy helps identify lesions
Staging is clinical (FIGO staging) based on physical examination and imaging
Treatment for early-stage disease includes surgery (partial or total vaginectomy) or radiation therapy; advanced disease is treated with chemoradiation
Prognosis depends on stage: 5-year survival is 65-70% for stage I but <20% for stage IV

Cervical Cancer

Cervical cancer is preventable through HPV vaccination and screening; most cases are caused by persistent high-risk HPV infection.

HPV types 16 and 18 cause 70% of cervical cancers; HPV vaccination prevents infection with high-risk types 6
Screening recommendations include cytology (Pap smear) every 3 years for ages 21-29, or co-testing (cytology plus HPV testing) every 5 years for ages 30-65
Cervical cytology should be performed at initial prenatal visit if not up-to-date 7
Abnormal screening requires colposcopy with directed biopsies; cervical intraepithelial neoplasia (CIN) is treated with excisional procedures (LEEP, cold knife conization) or ablation
Invasive cervical cancer presents with abnormal vaginal bleeding (postcoital, intermenstrual, postmenopausal), vaginal discharge, or pelvic pain
Early-stage disease (IA1 without lymphovascular invasion) may be treated with simple hysterectomy or conization in fertility-sparing cases
Stage IA2-IIA is treated with radical hysterectomy with pelvic lymphadenectomy or definitive chemoradiation
Advanced disease (stage IIB-IVA) is treated with concurrent chemoradiation (cisplatin-based) followed by brachytherapy
Metastatic or recurrent disease is treated with chemotherapy (cisplatin plus paclitaxel) with or without bevacizumab

Endometrial Disorders

Endometrial disorders include benign conditions (polyps, hyperplasia) and malignancies requiring appropriate evaluation and management.

Endometrial polyps present with abnormal uterine bleeding; diagnosis by transvaginal ultrasound or saline infusion sonography; treatment is hysteroscopic polypectomy
Endometrial hyperplasia results from unopposed estrogen exposure; classified as hyperplasia without atypia (low malignancy risk) or atypical hyperplasia (25-40% concurrent cancer risk)
Hyperplasia without atypia is treated with progestin therapy (medroxyprogesterone acetate, levonorgestrel IUD) with surveillance endometrial biopsies
Atypical hyperplasia requires hysterectomy in women who completed childbearing; fertility-sparing treatment with high-dose progestins requires close surveillance
Endometrial cancer screening is not recommended in average-risk women; women with Lynch syndrome require annual endometrial biopsy starting at age 35 6

Endometriosis

Endometriosis causes chronic pelvic pain and infertility from ectopic endometrial tissue, managed medically or surgically.

Affects 10% of reproductive-age women; presents with dysmenorrhea, chronic pelvic pain, dyspareunia, dyschezia, and infertility
Diagnosis is clinical based on symptoms; definitive diagnosis requires laparoscopy with histologic confirmation, though empiric treatment is often initiated
Medical management includes NSAIDs for pain, combined hormonal contraceptives (continuous dosing), progestins (norethindrone acetate, depot medroxyprogesterone acetate), or GnRH agonists with add-back therapy
Surgical management includes laparoscopic excision or ablation of endometriotic implants, lysis of adhesions, and excision of endometriomas
Fertility management includes surgical treatment of moderate-severe endometriosis, ovulation induction with intrauterine insemination, or IVF for refractory cases

Endometrial Cancer

Endometrial cancer is the most common gynecologic malignancy, typically presenting with postmenopausal bleeding.

Risk factors include unopposed estrogen exposure (obesity, nulliparity, PCOS, tamoxifen use, estrogen-only HRT), Lynch syndrome, and diabetes
Type I (endometrioid) accounts for 80% of cases, is estrogen-related, and has favorable prognosis; Type II (serous, clear cell) is estrogen-independent and more aggressive
Presentation includes postmenopausal bleeding (90% of cases), abnormal premenopausal bleeding, or abnormal vaginal discharge
Diagnosis requires endometrial biopsy or dilation and curettage; transvaginal ultrasound showing endometrial thickness >4 mm in postmenopausal women warrants biopsy
Staging is surgical (FIGO staging) including total hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment
Early-stage disease (stage IA, grade 1-2) is treated with surgery alone; higher-risk disease receives adjuvant radiation therapy or chemotherapy
Advanced or recurrent disease is treated with chemotherapy (carboplatin plus paclitaxel), hormonal therapy (progestins) for low-grade tumors, or immunotherapy (pembrolizumab) for mismatch repair-deficient tumors

Ovarian Cysts

Most ovarian cysts are functional and resolve spontaneously; persistent or complex cysts require further evaluation.

Functional cysts (follicular, corpus luteum) are common in reproductive-age women, typically <5 cm, and resolve within 1-3 menstrual cycles
Simple cysts <5 cm in premenopausal women can be observed with repeat ultrasound in 6-12 weeks
Complex cysts or cysts >5 cm require further evaluation with tumor markers (CA-125, CEA, AFP, beta-hCG, LDH) and consideration of surgical removal
Postmenopausal women with ovarian cysts require more aggressive evaluation due to higher malignancy risk
Dermoid cysts (mature cystic teratomas) are common benign germ cell tumors containing tissue from all three germ layers; treatment is surgical excision
Endometriomas (chocolate cysts) result from endometriosis; appear as complex cysts with homogeneous low-level echoes on ultrasound; treatment includes surgical excision or medical management of endometriosis

Ovarian Epithelial Tumors

Epithelial ovarian cancer accounts for 90% of ovarian malignancies, typically presenting at advanced stages.

Risk factors include nulliparity, family history, BRCA1/BRCA2 mutations, Lynch syndrome, endometriosis, and increasing age
Protective factors include multiparity, breastfeeding, oral contraceptive use, and bilateral salpingo-oophorectomy
Presentation includes abdominal distension, early satiety, pelvic/abdominal pain, urinary symptoms, and weight loss; often asymptomatic until advanced stage
Diagnosis requires pelvic ultrasound showing complex adnexal mass, elevated CA-125, and CT chest/abdomen/pelvis for staging
Surgical staging includes total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, lymph node dissection, and peritoneal biopsies
Treatment includes optimal cytoreductive surgery (goal: no residual disease >1 cm) followed by adjuvant chemotherapy (carboplatin plus paclitaxel for 6 cycles)
Maintenance therapy with PARP inhibitors (olaparib, niraparib, rucaparib) improves progression-free survival, especially in BRCA-mutated tumors
Bevacizumab (anti-VEGF antibody) combined with chemotherapy and continued as maintenance improves outcomes in advanced disease

Ovarian Stromal Tumors

Sex cord-stromal tumors account for 5-8% of ovarian neoplasms, often producing hormones causing characteristic syndromes.

Granulosa cell tumors produce estrogen causing precocious puberty in children, abnormal uterine bleeding in premenopausal women, or postmenopausal bleeding; associated with endometrial hyperplasia/cancer
Juvenile granulosa cell tumors have been reported in patients with biallelic MAD2L1B mutations, though cancer risk evidence is limited 6
Sertoli-Leydig cell tumors produce androgens causing virilization (hirsutism, clitoromegaly, voice deepening, male pattern baldness)
Fibromas are benign tumors that may be associated with Meigs syndrome (ovarian fibroma, ascites, pleural effusion)
Diagnosis requires pelvic ultrasound showing solid ovarian mass and tumor markers (inhibin, AMH for granulosa cell tumors; testosterone, DHEA-S for Sertoli-Leydig cell tumors)
Treatment is surgical excision; fertility-sparing surgery (unilateral salpingo-oophorectomy) is appropriate for early-stage disease in young women
Granulosa cell tumors have indolent course but may recur years after initial treatment, requiring long-term surveillance

Ovarian Germ Cell Tumors

Germ cell tumors account for 20-25% of ovarian neoplasms, predominantly affecting children and young women.

Dysgerminoma (most common malignant germ cell tumor) is analogous to testicular seminoma; presents with pelvic mass, elevated LDH, and normal AFP/beta-hCG
Yolk sac tumor (endodermal sinus tumor) produces AFP; most common malignant germ cell tumor in children
Immature teratoma contains immature neural tissue; graded based on amount of immature tissue
Choriocarcinoma produces beta-hCG; highly aggressive but chemosensitive
Mixed germ cell tumors contain multiple germ cell elements
Diagnosis requires pelvic ultrasound and tumor markers (AFP, beta-hCG, LDH)
Treatment includes fertility-sparing surgery (unilateral salpingo-oophorectomy with staging) for early-stage disease followed by adjuvant chemotherapy (BEP regimen) for all except stage IA dysgerminoma and stage I grade 1 immature teratoma
Prognosis is excellent with chemotherapy; 5-year survival >90% for most germ cell tumors

Abnormal Uterine Bleeding (AUB) & Endometriosis

Abnormal uterine bleeding requires systematic evaluation using PALM-COEIN classification to identify structural and non-structural causes.

PALM-COEIN Classification

Structural causes (PALM): Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia
Non-structural causes (COEIN): Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not yet classified

Evaluation

History includes bleeding pattern, associated symptoms, medication use, and risk factors for endometrial cancer
Physical examination includes pelvic examination to assess for structural abnormalities
Laboratory testing includes pregnancy test, CBC, thyroid function, coagulation studies (if indicated), and endometrial biopsy (if age >45 or risk factors for endometrial cancer)
Imaging with transvaginal ultrasound assesses endometrial thickness and identifies structural abnormalities

Management

Acute heavy bleeding requires high-dose estrogen (conjugated equine estrogen 25 mg IV every 4-6 hours) or tranexamic acid
Medical management includes combined hormonal contraceptives, progestins, tranexamic acid, or levonorgestrel IUD
Surgical management includes endometrial ablation, uterine artery embolization (for fibroids), or hysterectomy for refractory cases

Cervical Neoplasia

Cervical intraepithelial neoplasia (CIN) represents precancerous changes requiring treatment to prevent progression to invasive cancer.

CIN classification: CIN 1 (mild dysplasia, LSIL), CIN 2 (moderate dysplasia, HSIL), CIN 3 (severe dysplasia/carcinoma in situ, HSIL)
CIN 1 typically regresses spontaneously (60% regression rate); managed with observation and repeat cytology/colposcopy at 12 months
CIN 2/3 requires treatment due to higher progression risk (5-20% progression to invasive cancer if untreated)
Treatment options include excisional procedures (LEEP, cold knife conization) providing histologic specimen or ablative procedures (cryotherapy, laser ablation) for visible lesions
Excisional procedures are preferred for CIN 2/3, especially if lesion extends into endocervical canal or if there is concern for invasive cancer
Post-treatment surveillance includes cytology and HPV co-testing at 12 and 24 months; negative results allow return to routine screening
Pregnancy considerations: CIN 2/3 diagnosed during pregnancy can be observed with colposcopy each trimester; treatment deferred until postpartum unless invasive cancer suspected

Vulvar & Vaginal Lesions

Vulvar and vaginal lesions range from benign dermatologic conditions to premalignant and malignant lesions requiring appropriate diagnosis and treatment.

Benign Vulvar Lesions

Lichen sclerosus presents as white, atrophic, "cigarette paper" appearance with pruritus; treated with high-potency topical corticosteroids; requires surveillance due to small malignancy risk
Lichen planus presents as violaceous papules with Wickham striae; treated with topical corticosteroids
Bartholin cyst/abscess presents as painful vulvar swelling; treatment includes incision and drainage, Word catheter placement, or marsupialization for recurrent cases

Vulvar Intraepithelial Neoplasia (VIN)

VIN represents precancerous changes; classified as usual type (HPV-related) or differentiated type (non-HPV-related, associated with lichen sclerosus)
Diagnosis requires biopsy of suspicious lesions
Treatment includes surgical excision with negative margins or ablative therapy for multifocal disease

Vulvar Cancer

Squamous cell carcinoma accounts for 90% of vulvar cancers; risk factors include HPV infection, lichen sclerosus, smoking, and immunosuppression
Presentation includes vulvar mass, ulceration, pruritus, or bleeding
Treatment includes wide local excision or radical vulvectomy with inguinal lymph node dissection; adjuvant radiation for positive margins or lymph nodes

Reproductive Hormones & Polycystic Ovary Syndrome (PCOS)

PCOS is the most common endocrine disorder in reproductive-age women, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology.

Diagnosis (Rotterdam Criteria - 2 of 3)

Oligo-ovulation or anovulation (irregular menstrual cycles)
Clinical or biochemical hyperandrogenism (hirsutism, acne, elevated testosterone)
Polycystic ovaries on ultrasound (≥12 follicles 2-9 mm or ovarian volume >10 mL)

Metabolic Complications

Insulin resistance affects 50-70% of PCOS patients, increasing risk for type 2 diabetes, metabolic syndrome, and cardiovascular disease
Obesity exacerbates insulin resistance and hyperandrogenism
Screening for diabetes with fasting glucose or oral glucose tolerance test is recommended

Management

Lifestyle modifications (weight loss, exercise, dietary changes) improve insulin sensitivity and restore ovulation
Combined hormonal contraceptives treat irregular bleeding and hyperandrogenism
Metformin improves insulin sensitivity and may restore ovulation; particularly beneficial in obese patients
Anti-androgens (spironolactone) treat hirsutism and acne
Ovulation induction with letrozole or clomiphene citrate for infertility
Long-term cardiovascular risk reduction through management of metabolic risk factors

Gardnerella vaginalis

Bacterial vaginosis (BV) caused by Gardnerella vaginalis and other anaerobes presents with malodorous vaginal discharge.

BV results from disruption of normal vaginal flora with overgrowth of Gardnerella vaginalis, Mobiluncus, and other anaerobes
Presentation includes thin, gray, homogeneous vaginal discharge with fishy odor (especially after intercourse or menses)
Diagnosis by Amsel criteria (3 of 4): thin gray discharge, pH >4.5, positive whiff test (fishy odor with KOH), clue cells on microscopy
Treatment includes metronidazole 500 mg PO BID for 7 days, metronidazole gel 0.75% intravaginally daily for 5 days, or clindamycin cream 2% intravaginally at bedtime for 7 days
Pregnant women with symptomatic BV should be treated to reduce risk of preterm birth and other complications 7
Screening for BV in asymptomatic pregnant women at high risk for preterm birth may be considered

Human Papillomavirus (HPV)

HPV is the most common sexually transmitted infection, causing genital warts and cervical/anogenital cancers.

HPV vaccination should be updated as needed during preconception care 6
Low-risk HPV types (6,11) cause genital warts (condyloma acuminata)
High-risk HPV types (16,18,31,33,45) cause cervical, vaginal, vulvar, anal, oropharyngeal, and penile cancers
HPV vaccination (9-valent vaccine covering types 6,11,16,18,31,33,45,52,58) is recommended for ages 11-12, with catch-up vaccination through age 26
Genital warts are treated with patient-applied therapies (imiquimod, podofilox, sinecatechins) or provider-applied therapies (cryotherapy, trichloroacetic acid, surgical excision)
Cervical cancer screening detects HPV-related cervical dysplasia and cancer
Counseling about preventing TORCH infections (including HPV) should be provided during preconception care 6

Trichomonas vaginalis

Trichomoniasis is a sexually transmitted infection causing vaginitis with characteristic frothy discharge.

Presentation includes profuse, frothy, yellow-green vaginal discharge with vulvovaginal irritation and dyspareunia
Examination reveals "strawberry cervix" (punctate hemorrhages) in 2% of cases
Diagnosis by wet mount showing motile trichomonads, pH >4.5; nucleic acid amplification tests (NAAT) have higher sensitivity
Treatment includes metronidazole 2 g PO single dose or tinidazole 2 g PO single dose; alternative is metronidazole 500 mg PO BID for 7 days
Sexual partners must be treated simultaneously to prevent reinfection
Pregnant women should be treated to reduce risk of adverse pregnancy outcomes including preterm birth 7
Screening for trichomoniasis should be performed as indicated during prenatal care 7

Candida albicans

Vulvovaginal candidiasis causes pruritus and thick white discharge, commonly occurring in pregnancy, diabetes, and immunosuppression.

Presentation includes vulvovaginal pruritus, thick white "cottage cheese" discharge, vulvar erythema and edema, and dyspareunia
Risk factors include pregnancy, diabetes, antibiotic use, immunosuppression, and high-estrogen contraceptives
Diagnosis by wet mount or KOH preparation showing budding yeast and pseudohyphae; pH typically normal (4.0-4.5)
Uncomplicated VVC (mild-moderate symptoms, infrequent episodes, normal host) is treated with short-course topical azoles (miconazole, clotrimazole) for 1-3 days or oral fluconazole 150 mg single dose
Complicated VVC (severe symptoms, recurrent episodes, diabetes, immunosuppression, non-albicans species) requires longer treatment duration (7-14 days topical azoles or fluconazole 150 mg on days 1,4,7)
Recurrent VVC (≥4 episodes per year) requires induction therapy followed by maintenance suppression (fluconazole 150 mg weekly for 6 months)
Pregnant women should be treated with topical azoles for 7 days; oral fluconazole is contraindicated in pregnancy 6

Poxviridae (Smallpox, Cowpox, Molluscum contagiosum)

Molluscum contagiosum causes benign self-limited skin lesions, while smallpox has been eradicated through vaccination.

Molluscum Contagiosum

Caused by molluscum contagiosum virus (poxvirus); transmitted by direct contact or fomites
Presents as flesh-colored, dome-shaped papules with central umbilication, typically 2-5 mm diameter
Common in children (spread through skin contact) and sexually active adults (genital lesions)
Diagnosis is clinical based on characteristic appearance; biopsy shows intracytoplasmic inclusion bodies (molluscum bodies)
Treatment options include observation (self-resolves in 6-12 months), cryotherapy, curettage, or topical agents (cantharidin, imiquimod)
Extensive or persistent lesions in immunocompromised patients may require systemic therapy

Smallpox (Variola)

Eradicated worldwide through vaccination; last natural case in 1977
Bioterrorism concern due to potential weaponization
Vaccination with vaccinia virus (live virus vaccine) provides cross-protection

Herpes Simplex Virus Type 1 & 2 (HSV-1, HSV-2)

HSV causes recurrent painful genital or oral ulcers; antiviral therapy reduces symptoms and transmission risk.

HSV-1 primarily causes oral herpes (cold sores); HSV-2 primarily causes genital herpes, though either can infect either site
Primary infection presents with painful vesicles progressing to ulcers, fever, malaise, and lymphadenopathy; recurrent episodes are typically milder
Diagnosis by viral culture, PCR (most sensitive), or direct fluorescent antibody testing of lesion; type-specific serology distinguishes HSV-1 from HSV-2
Treatment for first episode includes acyclovir 400 mg PO TID for 7-10 days, valacyclovir 1 g PO BID for 7-10 days, or famciclovir 250 mg PO TID for 7-10 days
Episodic treatment for recurrences uses same medications for 1-5 days
Suppressive therapy (daily antiviral) reduces recurrence frequency by 70-80% and reduces transmission risk by 50%
Pregnant women with active genital lesions at delivery require cesarean section to prevent neonatal herpes
Screening for herpes simplex virus should be considered during prenatal care if indicated 7

Maternal-Fetal Disorders

Maternal-fetal disorders require careful monitoring and management to optimize outcomes for both mother and fetus.

Comprehensive prenatal care should begin early in pregnancy with initial laboratory testing including complete blood count, blood type and Rh screen, urinalysis and urine culture, and infectious disease screening 7
Serum creatinine and urinary protein assessment should evaluate renal function, as protein excretion ≥190 mg/24h increases risk for hypertensive disorders 7
Rubella immunity status should be determined to assess susceptibility and need for postpartum vaccination 7
Syphilis screening is essential as untreated syphilis causes significant fetal morbidity 7
Hepatitis B surface antigen testing should identify chronic infection and prevent vertical transmission 7
HIV testing is necessary to initiate antiretroviral therapy if positive and reduce transmission risk 7
Thyroid function should be assessed, particularly in patients with hypothyroidism requiring medication adjustment during pregnancy 7
Glucose screening should be performed immediately in late presenters rather than waiting 7
Detailed anatomic ultrasound at 28 weeks evaluates fetal growth, estimated fetal weight, amniotic fluid volume, and placental location 7
Cell-free DNA screening should be offered for aneuploidy assessment even in late pregnancy 7
Genetic counseling should discuss age-related aneuploidy risk, family history of genetic disorders, and ethnic background for carrier screening 7

Hypertension in Pregnancy

Hypertensive disorders of pregnancy include chronic hypertension, gestational hypertension, preeclampsia, and eclampsia, requiring close monitoring and timely intervention.

Blood pressure measurement and ongoing monitoring are necessary, as hypertensive disorders can develop in the third trimester 7
Chronic hypertension is defined as BP ≥140/90 mmHg before pregnancy or before 20 weeks gestation
Gestational hypertension is new-onset hypertension (BP ≥140/90 mmHg) after 20 weeks without proteinuria or end-organ dysfunction
Preeclampsia is defined as new-onset hypertension after 20 weeks with proteinuria (≥300 mg/24h or protein:creatinine ratio ≥0.3) or end-organ dysfunction
Severe features include BP ≥160/110 mmHg, thrombocytopenia, elevated liver enzymes, renal insufficiency, pulmonary edema, or cerebral/visual symptoms
Management of chronic hypertension includes continuing safe antihypertensives (labetalol, nifedipine, methyldopa); avoid ACE inhibitors and ARBs 6
Preeclampsia without severe features at ≥37 weeks requires delivery; <37 weeks may be managed expectantly with close monitoring
Preeclampsia with severe features requires delivery at ≥34 weeks; <34 weeks may receive corticosteroids and magnesium sulfate with delivery within 24-48 hours
Magnesium sulfate prevents eclamptic seizures in preeclampsia with severe features
Postpartum monitoring continues for 72 hours as preeclampsia/eclampsia can develop postpartum

Placental Complications

Placental complications including placenta previa, placental abruption, and placenta accreta spectrum require prompt recognition and management.

Placenta Previa

Placenta implants over or near internal cervical os; classified as complete (covers os), partial, or marginal
Risk factors include prior cesarean delivery, multiparity, advanced maternal age, smoking, and prior uterine surgery
Presents with painless vaginal bleeding in second or third trimester
Diagnosis by transvaginal ultrasound (safe despite bleeding); avoid digital cervical examination
Management includes pelvic rest (no intercourse, no vaginal examinations), hospitalization for significant bleeding, corticosteroids for fetal lung maturity if <34 weeks
Delivery by cesarean section at 36-37 weeks for complete previa; vaginal delivery may be possible for marginal previa if fetal head engages

Placental Abruption

Premature separation of placenta from uterine wall; can be partial or complete
Risk factors include hypertension, trauma, cocaine use, smoking, prior abruption, and preterm premature rupture of membranes
Presents with painful vaginal bleeding, abdominal pain, uterine tenderness, and contractions; fetal distress common
Diagnosis is clinical; ultrasound has low sensitivity
Management includes immediate delivery if fetal distress or maternal instability; expectant management possible for small abruptions with stable mother and fetus

Placenta Accreta Spectrum

Abnormal placental attachment: accreta (attached to myometrium), increta (invades myometrium), percreta (penetrates through myometrium)
Risk factors include placenta previa with prior cesarean delivery
Diagnosis by ultrasound or MRI showing loss of retroplacental clear space, placental lacunae, and bladder wall irregularity
Management requires planned cesarean hysterectomy at 34-36 weeks by experienced surgical team; massive transfusion protocol should be available

Gestational Tumors

Gestational trophoblastic disease includes benign hydatidiform mole and malignant gestational trophoblastic neoplasia.

Hydatidiform Mole

Complete mole (diploid, all paternal DNA) presents with vaginal bleeding, uterine size greater than dates, markedly elevated beta-hCG, and "snowstorm" appearance on ultrasound
Partial mole (triploid) presents with missed abortion, lower beta-hCG, and fetal parts on ultrasound
Treatment includes suction curettage; beta-hCG monitoring weekly until undetectable for 3 weeks, then monthly for 6 months
Risk of persistent gestational trophoblastic neoplasia is 15-20% for complete mole, <5% for partial mole

Gestational Trophoblastic Neoplasia

Includes invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor
Diagnosis based on plateauing or rising beta-hCG after molar evacuation, or elevated beta-hCG 6 months after evacuation
Staging includes chest X-ray or CT, pelvic ultrasound, and brain/liver imaging if indicated
Treatment with chemotherapy (methotrexate for low-risk disease, multi-agent chemotherapy for high-risk disease) achieves cure rates >90%

Benign Breast Tumors/Fibrocystic Changes

Benign breast conditions are common and include fibrocystic changes, fibroadenomas, and other benign lesions requiring appropriate evaluation.

Fibrocystic Changes

Most common benign breast condition; presents with bilateral, cyclic breast pain and nodularity
Symptoms worsen premenstrually and improve after menses
Diagnosis is clinical; imaging (mammography, ultrasound) if discrete mass or asymmetric findings
Management includes supportive measures (well-fitting bra, NSAIDs), avoiding caffeine (may help some women), and reassurance

Fibroadenoma

Most common benign breast tumor in young women; presents as smooth, mobile, rubbery mass
Diagnosis by ultrasound (well-circumscribed hypoechoic mass) and core needle biopsy
Management includes observation for small (<2 cm) fibroadenomas in young women with concordant imaging and pathology; excision for large, growing, or symptomatic lesions

Other Benign Lesions

Intraductal papilloma presents with bloody nipple discharge; requires duct excision
Fat necrosis presents as firm mass after trauma; may mimic cancer on imaging
Phyllodes tumor is rare fibroepithelial tumor requiring wide excision due to recurrence risk

Breast Cancer

Breast cancer is the most common cancer in women; screening, early detection, and multimodal treatment improve outcomes.

Risk factors include age, family history, BRCA1/BRCA2 mutations, prior breast cancer, atypical hyperplasia, early menarche, late menopause, nulliparity, and hormone replacement therapy
Screening recommendations include annual mammography starting at age 40 (ACOG, ACS) or biennial mammography ages 50-74 (USPSTF)
High-risk women (BRCA mutations, strong family history) should undergo annual mammography and breast MRI starting at age 30
Presentation includes palpable breast mass, skin changes (dimpling, peau d'orange), nipple retraction/discharge, or axillary lymphadenopathy
Diagnosis requires triple assessment: clinical examination, imaging (mammography, ultrasound), and tissue diagnosis (core needle biopsy)
Staging includes chest/abdomen/pelvis CT and bone scan for stage II or higher disease
Treatment for early-stage disease includes breast-conserving surgery (lumpectomy) plus radiation or mastectomy; sentinel lymph node biopsy assesses nodal status
Adjuvant systemic therapy depends on tumor characteristics: hormone therapy (tamoxifen, aromatase inhibitors) for hormone receptor-positive tumors, chemotherapy for high-risk tumors, and trastuzumab for HER2-positive tumors
Metastatic disease is treated with systemic therapy based on receptor status; local therapy (surgery, radiation) for palliation

Breast Disorders - Comprehensive Overview

Breast disorders require systematic evaluation to distinguish benign from malignant conditions.

Breast tissue examination should be performed during preconception care 6
Mastalgia (breast pain) is usually benign and cyclic; noncyclic pain requires evaluation to exclude malignancy
Nipple discharge requires evaluation: bloody discharge suggests intraductal papilloma or cancer; milky discharge suggests hyperprolactinemia; multiductal discharge is usually benign
Breast masses require triple assessment regardless of age
Breast infections (mastitis) present with erythema, warmth, tenderness, and fever; treatment includes antibiotics (dicloxacillin, cephalexin) and continued breastfeeding
Breast abscess requires incision and drainage plus antibiotics
Inflammatory breast cancer presents with erythema, edema, peau d'orange, and warmth mimicking infection but without fever; requires urgent biopsy

Breast Carcinoma - Detailed Management

Breast carcinoma treatment is individualized based on stage, tumor biology, and patient factors.

Surgical Management

Breast-conserving surgery (lumpectomy with negative margins) plus whole breast radiation achieves equivalent survival to mastectomy for early-stage disease
Mastectomy is indicated for multicentric disease, large tumor-to-breast ratio, contraindications to radiation, or patient preference
Sentinel lymph node biopsy is standard for clinically node-negative patients; axillary lymph node dissection for positive sentinel nodes (though may be omitted in select cases)

Radiation Therapy

Whole breast radiation after lumpectomy reduces local recurrence by 50-70%
Accelerated partial breast irradiation may be appropriate for select low-risk patients
Post-mastectomy radiation indicated for T3/T4 tumors or ≥4 positive lymph nodes

Systemic Therapy

Hormone receptor-positive tumors receive endocrine therapy: tamoxifen (premenopausal) or aromatase inhibitors (postmenopausal) for 5-10 years
HER2-positive tumors receive trastuzumab-based therapy for 1 year
Chemotherapy indicated for high-risk tumors based on stage, grade, and genomic assays (Oncotype DX, MammaPrint)
Neoadjuvant chemotherapy for locally advanced disease may downstage tumors allowing breast conservation

Metastatic Disease

Hormone receptor-positive disease: endocrine therapy plus CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib)
HER2-positive disease: trastuzumab plus pertuzumab plus chemotherapy
Triple-negative disease: chemotherapy; immunotherapy (pembrolizumab) for PD-L1-positive tumors

Hypothalamic & Pituitary Dysfunction

Hypothalamic-pituitary disorders cause hormonal deficiencies or excesses requiring specific diagnosis and replacement therapy.

Hypopituitarism results from pituitary adenomas, surgery, radiation, Sheehan syndrome (postpartum pituitary necrosis), or infiltrative diseases
Clinical manifestations depend on affected hormones: growth hormone deficiency (decreased muscle mass, increased fat), gonadotropin deficiency (amenorrhea, erectile dysfunction), TSH deficiency (hypothyroidism), ACTH deficiency (adrenal insufficiency)
Diagnosis requires basal hormone levels and stimulation testing (insulin tolerance test, ACTH stimulation test)
Treatment includes hormone replacement: levothyroxine for TSH deficiency, hydrocortisone for ACTH deficiency (must be replaced before thyroid hormone), testosterone or estrogen/progesterone for gonadotropin deficiency, growth hormone for GH deficiency
Pituitary apoplexy (hemorrhage into pituitary adenoma) presents with sudden severe headache, visual changes, and hormonal deficiencies; requires urgent neurosurgical evaluation

Hyperpituitarism

Pituitary adenomas cause hormone excess syndromes requiring medical or surgical management.

Prolactinoma

Most common functional pituitary adenoma; presents with galactorrhea, amenorrhea (women), or erectile dysfunction (men)
Diagnosis by elevated prolactin level (>200 ng/mL suggests prolactinoma; 20-200 ng/mL may be stalk effect from non-functioning adenoma)
Treatment with dopamine agonists (cabergoline preferred over bromocriptine) normalizes prolactin and shrinks tumor in 80-90%
Surgery reserved for dopamine agonist-resistant tumors or intolerance

Growth Hormone Excess (Acromegaly)

Presents with coarse facial features, enlarged hands/feet, frontal bossing, prognathism, and soft tissue overgrowth
Complications include diabetes, hypertension, cardiomyopathy, sleep apnea, and colon polyps
Diagnosis by elevated IGF-1 and failure to suppress GH <1 ng/mL during oral glucose tolerance test
Treatment includes transsphenoidal surgery (first-line), somatostatin analogs (octreotide, lanreotide), GH receptor antagonist (pegvisomant), or dopamine agonists

ACTH-Secreting Adenoma (Cushing Disease)

Covered under Cushing's Syndrome section

Diabetes Insipidus & SIADH

Disorders of water balance result from ADH deficiency (diabetes insipidus) or excess (SIADH).

Diabetes Insipidus

Central DI results from ADH deficiency (pituitary surgery, trauma, tumors, infiltrative diseases); nephrogenic DI results from renal resistance to ADH (lithium, hypercalcemia, hypokalemia)
Presents with polyuria (>3 L/day), polydipsia, and hypernatremia
Diagnosis by water deprivation test: urine osmolality remains low (<300 mOsm/kg) despite rising serum osmolality; desmopressin administration increases urine osmolality in central DI but not nephrogenic DI
Treatment for central DI includes desmopressin (DDAVP); nephrogenic DI treated by addressing underlying cause, thiazide diuretics, and NSAIDs

SIADH

Results from inappropriate ADH secretion (malignancies, CNS disorders, pulmonary diseases, medications)
Presents with hyponatremia, low serum osmolality, inappropriately concentrated urine (urine osmolality >100 mOsm/kg), and euvolemia
Diagnosis requires excluding other causes of hyponatremia (hypothyroidism, adrenal insufficiency, diuretics)
Treatment includes fluid restriction (<800 mL/day), salt tablets, demeclocycline, or vasopressin receptor antagonists (tolvaptan, conivaptan) for severe or refractory cases

Hyperthyroidism

Hyperthyroidism results from excess thyroid hormone production, most commonly from Graves' disease.

Thyroid function should be assessed during preconception care, particularly in patients with hypothyroidism requiring medication adjustment 6
Thyroid stimulating hormone and free thyroxine levels should be assessed during pregnancy 7
Graves' disease (most common cause) results from TSH receptor-stimulating antibodies; presents with diffuse goiter, ophthalmopathy, and pretibial myxedema
Toxic multinodular goiter and toxic adenoma cause hyperthyroidism without autoimmune features
Clinical manifestations include weight loss, heat intolerance, tremor, palpitations, anxiety, diarrhea, and menstrual irregularities
Diagnosis by suppressed TSH and elevated free T4/T3; TSH receptor antibodies confirm Graves' disease; radioactive iodine uptake scan distinguishes Graves' (diffuse uptake) from toxic nodular disease (focal uptake)
Treatment options include antithyroid drugs (methimazole preferred; propylthiouracil in first trimester pregnancy), radioactive iodine ablation, or thyroidectomy
Beta-blockers (propranolol, atenolol) provide symptomatic relief
Thyroid storm is life-threatening emergency requiring ICU care, antithyroid drugs, beta-blockers, corticosteroids, and supportive care

Hypothyroidism

Hypothyroidism results from inadequate thyroid hormone production, requiring lifelong levothyroxine replacement.

Thyroid function should be carefully managed during pregnancy, as hypothyroidism requires medication adjustment 6, 7
Hashimoto's thyroiditis (chronic autoimmune thyroiditis) is the most common cause in iodine-sufficient areas
Other causes include radioactive iodine treatment, thyroidectomy, medications (lithium, amiodarone), and iodine deficiency
Clinical manifestations include fatigue, weight gain, cold intolerance, constipation, dry skin, hair loss, and menstrual irregularities
Diagnosis by elevated TSH and low free T4; anti-thyroid peroxidase (anti-TPO) antibodies confirm autoimmune etiology
Treatment with levothyroxine starting at 1.6 mcg/kg/day; adjust dose based on TSH (target 0.5-2.5 mIU/L)
Pregnancy requires 30-50% increase in levothyroxine dose; monitor TSH every 4 weeks during pregnancy
Myxedema coma is life-threatening emergency requiring ICU care, intravenous levothyroxine, corticosteroids, and supportive care

Thyroiditis

Thyroiditis encompasses inflammatory thyroid disorders with varying etiologies and clinical courses.

Hashimoto's Thyroiditis

Most common cause of hypothyroidism in iodine-sufficient areas; autoimmune destruction of thyroid
Presents with gradual onset hypothyroidism and firm, non-tender goiter
Diagnosis by elevated TSH, low free T4, and positive anti-TPO and/or anti-thyroglobulin antibodies
Treatment with levothyroxine replacement
Increased risk for thyroid lymphoma (rare complication)

Subacute (De Quervain's) Thyroiditis

Viral-induced inflammation; presents with painful, tender thyroid, fever, and transient hyperthyroidism followed by hypothyroidism
Diagnosis by elevated ESR, low radioactive iodine uptake, and thyrotoxicosis
Treatment with NSAIDs or corticosteroids for pain; beta-blockers for hyperthyroid symptoms; most recover spontaneously

Postpartum Thyroiditis

Autoimmune thyroiditis occurring within 1 year postpartum; presents with transient hyperthyroidism (1-3 months) followed by hypothyroidism (4-8 months)
Most women recover normal thyroid function, but 20-30% develop permanent hypothyroidism
Treatment is symptomatic; levothyroxine if symptomatic hypothyroidism

Thyroid Neoplasia

Thyroid nodules are common; most are benign, but evaluation is necessary to exclude malignancy.

Thyroid nodules should be evaluated during preconception care if present 6
Evaluation includes TSH measurement, thyroid ultrasound, and fine needle aspiration (FNA) biopsy for nodules >1 cm or suspicious features
Ultrasound features suggesting malignancy include hypoechogenicity, microcalcifications, irregular margins, taller-than-wide shape, and increased vascularity
FNA cytology classified by Bethesda system: benign (I), atypia of undetermined significance (III), follicular neoplasm (IV), suspicious for malignancy (V), malignant (VI)
Papillary thyroid cancer (80% of thyroid cancers) has excellent prognosis; treatment includes thyroidectomy, radioactive iodine ablation for high-risk disease, and TSH suppression
Follicular thyroid cancer (10-15%) requires thyroidectomy; cannot be diagnosed by FNA (requires vascular/capsular invasion on surgical pathology)
Medullary thyroid cancer (5%) arises from parafollicular C cells; associated with MEN 2 syndrome; requires total thyroidectomy and lymph node dissection
Anaplastic thyroid cancer (<2%) is highly aggressive with poor prognosis; treatment includes multimodal therapy (surgery, radiation, chemotherapy)

Thyroid Disorders - Comprehensive Management

Thyroid disorders require careful diagnosis and management, particularly during pregnancy. 8

Thyroid function testing should be performed during preconception care and early pregnancy 6, 7
Chronic disease management programs should address thyroid disorders as part of comprehensive care 8
Subclinical hypothyroidism (elevated TSH, normal free T4) may require treatment if TSH >10 mIU/L, positive anti-TPO antibodies, or symptoms present
Subclinical hyperthyroidism (suppressed TSH, normal free T4/T3) requires evaluation for underlying cause and treatment if TSH <0.1 mIU/L or cardiac symptoms
Thyroid nodules require surveillance with repeat ultrasound; growing nodules or development of suspicious features warrant repeat FNA
Differentiated thyroid cancer surveillance includes thyroglobulin monitoring, neck ultrasound, and radioactive iodine whole body scan if indicated

Thyroid Cancer - Detailed Management

Differentiated thyroid cancer (papillary and follicular) has excellent prognosis with appropriate treatment.

Risk Stratification

Low-risk: intrathyroidal papillary cancer, no metastases, complete resection
Intermediate-risk: microscopic extrathyroidal extension, vascular invasion, or aggressive histology
High-risk: macroscopic extrathyroidal extension, incomplete resection, or distant metastases

Surgical Management

Thyroid lobectomy sufficient for low-risk papillary cancer <4 cm without extrathyroidal extension
Total thyroidectomy indicated for tumors >4 cm, bilateral disease, extrathyroidal extension, or distant metastases
Central neck dissection for clinically involved lymph nodes; lateral neck dissection for lateral compartment involvement

Radioactive Iodine Therapy

Indicated for high-risk disease, distant metastases, or residual disease after surgery
Not routinely recommended for low-risk disease
Requires TSH stimulation (thyroid hormone withdrawal or recombinant TSH)

TSH Suppression

Target TSH <0.1 mIU/L for high-risk disease, 0.1-0.5 mIU/L for intermediate-risk, 0.5-2.0 mIU/L for low-risk

Surveillance

Thyroglobulin monitoring every 6-12 months; rising thyroglobulin suggests recurrence
Neck ultrasound every 6-12 months for first 5 years
Radioactive iodine whole body scan if thyroglobulin elevated or structural disease suspected

Hashimoto's Thyroiditis - Detailed

Hashimoto's thyroiditis is the most common cause of hypothyroidism, requiring lifelong thyroid hormone replacement.

Autoimmune destruction of thyroid gland by lymphocytic infiltration
More common in women (10:1 female:male ratio); peak incidence in middle age
Associated with other autoimmune diseases (type 1 diabetes, celiac disease, vitiligo, Addison's disease)
Clinical course includes initial euthyroid phase, transient hyperthyroidism (hashitoxicosis from thyroid destruction releasing stored hormone), followed by permanent hypothyroidism
Physical examination reveals firm, non-tender, diffusely enlarged goiter
Diagnosis by elevated TSH, low free T4, and positive anti-TPO antibodies (90-95% sensitive) and/or anti-thyroglobulin antibodies
Treatment with levothyroxine replacement; dose adjusted to maintain TSH 0.5-2.5 mIU/L
Monitoring includes TSH every 6-8 weeks after dose changes, then annually once stable
Small increased risk for thyroid lymphoma (presents as rapidly enlarging thyroid mass)

Graves' Disease - Detailed

Graves' disease is the most common cause of hyperthyroidism, characterized by diffuse goiter, ophthalmopathy, and dermopathy.

Autoimmune disorder caused by TSH receptor-stimulating antibodies (TRAb)
More common in women (5-10:1 female:male ratio); peak incidence ages 30-50
Clinical manifestations include hyperthyroidism symptoms plus Graves' ophthalmopathy (proptosis, lid lag, diplopia) and pretibial myxedema (rare)
Diagnosis by suppressed TSH, elevated free T4/T3, and positive TSH receptor antibodies; radioactive iodine uptake scan shows diffuse increased uptake
Treatment options include:
- Antithyroid drugs (methimazole 10-40 mg daily; propylthiouracil 100-200 mg TID in first trimester pregnancy)
- Radioactive iodine ablation (contraindicated in pregnancy and breastfeeding; may worsen ophthalmopathy)
- Thyroidectomy (for large goiters, pregnancy planning, or patient preference)
Graves' ophthalmopathy may require additional treatment with corticosteroids, orbital radiation, or orbital decompression surgery for severe cases
Remission rates with antithyroid drugs are 30-50% after 12-18 months of treatment

Thyroid Nodules & Cancer - Comprehensive

Thyroid nodules require systematic evaluation to identify malignancy while avoiding unnecessary procedures.

Prevalence of thyroid nodules increases with age; 50-60% of adults have nodules on ultrasound, but only 5-10% are malignant
Initial evaluation includes TSH measurement; if suppressed, obtain radioactive iodine uptake scan (hot nodules are rarely malignant)
Ultrasound risk stratification using ACR TI-RADS or ATA guidelines determines need for FNA:
- High suspicion features: FNA if ≥1 cm
- Intermediate suspicion: FNA if ≥1 cm
- Low suspicion: FNA if ≥1.5 cm
- Very low suspicion: FNA if ≥2 cm
FNA technique: 25-gauge needle, multiple passes, on-site cytology evaluation improves adequacy
Molecular testing (Afirma, ThyroSeq) for indeterminate cytology (Bethesda III/IV) helps determine need for surgery
Benign nodules require surveillance ultrasound at 12-24 months; stable nodules can be monitored less frequently
Papillary thyroid microcarcinoma (<1 cm) may be observed with active surveillance in select low-risk patients

Parathyroid Gland Disorders

Parathyroid disorders cause calcium homeostasis abnormalities requiring specific diagnosis and treatment.

Primary Hyperparathyroidism

Most common cause of hypercalcemia in outpatients; results from parathyroid adenoma (80%), hyperplasia (15-20%), or carcinoma (<1%)
Presents with hypercalcemia, elevated or inappropriately normal PTH, hypercalciuria, and low phosphate
Symptoms include kidney stones, bone disease (osteitis fibrosa cystica), neuropsychiatric symptoms ("stones, bones, groans, psychiatric overtones")
Diagnosis by elevated calcium and PTH; 24-hour urine calcium excludes familial hypocalciuric hypercalcemia
Treatment is parathyroidectomy for symptomatic disease, age <50, calcium >1 mg/dL above upper limit of normal, reduced bone density, or renal insufficiency
Medical management (observation, bisphosphonates, cinacalcet) for asymptomatic patients not meeting surgical criteria

Hypoparathyroidism

Results from parathyroid gland removal/damage during thyroid surgery, autoimmune destruction, or genetic disorders
Presents with hypocalcemia, elevated phosphate, and low PTH
Symptoms include paresthesias, muscle cramps, tetany (Chvostek and Trousseau signs), seizures, and prolonged QT interval
Treatment includes calcium supplementation (1-3 g elemental calcium daily) and active vitamin D (calcitriol 0.25-2 mcg daily)
Target serum calcium in low-normal range to avoid hypercalciuria and nephrolithiasis

Diabetes Mellitus

Diabetes mellitus requires comprehensive management addressing glycemic control, cardiovascular risk reduction, and complication screening. 8

Chronic disease management programs should address diabetes as a leading cause of death, disability, and healthcare costs 8
Screening for diabetes should be performed if risk factors are present during preconception care 6
Hemoglobin A1C testing is recommended if diabetes risk factors are present during pregnancy 7
Glucose screening should be performed immediately in late-presenting pregnant patients 7

Type 1 Diabetes

Autoimmune destruction of pancreatic beta cells; presents with hyperglycemia, polyuria, polydipsia, weight loss, and ketoacidosis
Diagnosis by elevated glucose (fasting ≥126 mg/dL, random ≥200 mg/dL with symptoms, or 2-hour OGTT ≥200 mg/dL) and positive autoantibodies (GAD, IA-2, ZnT8)
Treatment requires insulin therapy (basal-bolus regimen or insulin pump); target HbA1c <7% (individualized based on patient factors)

Type 2 Diabetes

Results from insulin resistance and progressive beta cell dysfunction; associated with obesity, sedentary lifestyle, and family history
Diagnosis by elevated glucose or HbA1c ≥6.5%
Treatment includes lifestyle modifications (weight loss, exercise, dietary changes) plus pharmacotherapy
First-line medication is metformin; additional agents include SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, sulfonylureas, or insulin
SGLT2 inhibitors and GLP-1 receptor agonists provide cardiovascular and renal benefits beyond glycemic control
Tight glycemic control (HbA1c <7%) reduces microvascular complications; cardiovascular risk reduction requires management of blood pressure, lipids, and aspirin therapy

Diabetic Ketoacidosis (DKA)

DKA is a life-threatening complication of diabetes requiring urgent treatment with insulin, fluids, and electrolyte replacement.

Results from absolute or relative insulin deficiency causing hyperglycemia, ketosis, and metabolic acidosis
Precipitating factors include infection, insulin omission, myocardial infarction, stroke, pancreatitis, or new-onset diabetes
Clinical presentation includes polyuria, polydipsia, nausea, vomiting, abdominal pain, Kussmaul respirations (deep, rapid breathing), and altered mental status
Diagnosis requires glucose >250 mg/dL, pH <7.3, bicarbonate <18 mEq/L, and positive serum or urine ketones
Treatment includes:
- Aggressive IV fluid resuscitation (1-1.5 L normal saline in first hour, then 250-500 mL/hour)
- Insulin infusion (0.1 units/kg/hour) after initial fluid resuscitation
- Potassium replacement (goal 4-5 mEq/L) to prevent hypokalemia from insulin therapy
- Dextrose added to IV fluids when glucose <200 mg/dL to prevent hypoglycemia while continuing insulin to clear ketones
- Bicarbonate therapy only if pH <6.9
Resolution defined by glucose <200 mg/dL, bicarbonate >18 mEq/L, pH >7.3, and anion gap <12
Transition to subcutaneous insulin requires overlap with IV insulin for 1-2 hours to prevent recurrent ketoacidosis

Hyperosmolar Hyperglycemic State (HHS)

HHS is a life-threatening complication of type 2 diabetes characterized by severe hyperglycemia and hyperosmolality without significant ketoacidosis.

Results from relative insulin deficiency and severe dehydration; more common in elderly patients with type 2 diabetes
Precipitating factors include infection, stroke, myocardial infarction, medications (corticosteroids, diuretics), or inadequate fluid intake
Clinical presentation includes polyuria, polydipsia, weakness, altered mental status (confusion, lethargy, coma), and signs of severe dehydration
Diagnosis requires glucose >600 mg/dL, serum osmolality >320 mOsm/kg, pH >7.3, bicarbonate >15 mEq/L, and absent or mild ketones
Treatment includes:
- Aggressive IV fluid resuscitation (1-1.5 L normal saline in first hour, then 250-500 mL/hour); total fluid deficit often 8-10 L
- Insulin infusion (0.1 units/kg/hour) after initial fluid resuscitation; lower insulin doses than DKA due to greater insulin sensitivity
- Potassium replacement (goal 4-5 mEq/L)
- Dextrose added when glucose <300 mg/dL
Mortality rate 10-20%, higher than DKA due to older age and comorbidities
Complications include thromboembolism, cerebral edema, and rhabdomyolysis

Adrenal Disorders

Adrenal disorders cause hormone excess or deficiency requiring specific diagnosis and treatment.

Adrenal disorders should be identified and managed during preconception care 6
Multiple endocrine neoplasia syndromes may involve adrenal glands and require surveillance 6

Adrenal Incidentaloma

Adrenal mass discovered incidentally on imaging; prevalence increases with age (4% at age 60)
Evaluation includes:
- Biochemical testing for hormone excess (1 mg dexamethasone suppression test, plasma metanephrines, aldosterone:renin ratio if hypertensive)
- Imaging characteristics on CT (size, density, washout) to assess malignancy risk
- Benign features: <4 cm, homogeneous, <10 HU on unenhanced CT, >50% washout at 10 minutes
Management includes surgical resection for hormone-secreting tumors, suspicious imaging features, or size >4 cm
Non-functioning benign-appearing masses <4 cm require surveillance imaging at 6-12 months

MEN Syndrome

Multiple endocrine neoplasia (MEN) syndromes are hereditary disorders causing tumors in multiple endocrine glands. 6

MEN 1

Autosomal dominant disorder caused by MEN1 gene mutation; characterized by "3 P's": Parathyroid adenomas (95%), Pancreatic neuroendocrine tumors (40-70%), and Pituitary adenomas (30-40%)
Additional features include adrenal adenomas, carcinoid tumors, lipomas, and angiofibromas
Screening includes annual biochemical testing (calcium, PTH, prolactin, IGF-1, gastrin, chromogranin A) and periodic imaging (MRI pituitary, CT/MRI abdomen)
Management includes parathyroidectomy for hyperparathyroidism, surgical resection of pancreatic tumors >2 cm, and treatment of pituitary adenomas

MEN 2A

Autosomal dominant disorder caused by RET proto-oncogene mutation; characterized by medullary thyroid cancer (95%), pheochromocytoma (50%), and primary hyperparathyroidism (20-30%)
Screening includes annual calcitonin and CEA for medullary thyroid cancer, plasma metanephrines for pheochromocytoma, and calcium/PTH for hyperparathyroidism
Prophylactic thyroidectomy recommended in childhood based on specific RET mutation

MEN 2B

Similar to MEN 2A but with earlier, more aggressive medullary thyroid cancer, pheochromocytoma, and characteristic features (marfanoid habitus, mucosal neuromas, intestinal ganglioneuromatosis)
Prophylactic thyroidectomy recommended in first year of life

Adrenal Insufficiency

Adrenal insufficiency results from inadequate cortisol production, requiring lifelong glucocorticoid replacement.

Primary Adrenal Insufficiency (Addison's Disease)

Results from adrenal gland destruction; most common cause is autoimmune adrenalitis (70-90% in developed countries)
Other causes include tuberculosis, fungal infections, adrenal hemorrhage, metastases, and medications (ketoconazole, etomidate)
Clinical manifestations include fatigue, weakness, weight loss, hyperpigmentation (due to elevated ACTH), hypotension, hyponatremia, and hyperkalemia
Diagnosis by low morning cortisol (<3 mcg/dL diagnostic, >15 mcg/dL excludes) and elevated ACTH; ACTH stimulation test shows inadequate cortisol response
Treatment includes hydrocortisone 15-25 mg daily in divided doses (two-thirds morning, one-third afternoon) plus fludrocortisone 0.05-0.2 mg daily for mineralocorticoid replacement
Stress dosing: double or triple hydrocortisone dose for illness; IV hydrocortisone 100 mg every 8 hours for severe illness or surgery

Secondary Adrenal Insufficiency

Results from ACTH deficiency (pituitary or hypothalamic disease, chronic glucocorticoid use)
Clinical manifestations similar to primary but without hyperpigmentation or hyperkalemia (mineralocorticoid function preserved)
Diagnosis by low morning cortisol and low/normal ACTH
Treatment with hydrocortisone only (no fludrocortisone needed)

Congenital Adrenal Hyperplasia (CAH)

CAH results from enzyme deficiencies in cortisol synthesis, most commonly 21-hydroxylase deficiency.

21-hydroxylase deficiency accounts for 90-95% of CAH cases; autosomal recessive inheritance
Classic CAH presents in infancy with salt-wasting crisis (hyponatremia, hyperkalemia, hypotension, shock) and virilization in females (ambiguous genitalia)
Non-classic CAH presents in adolescence/adulthood with hirsutism, acne, irregular menses, and infertility
Diagnosis by elevated 17-hydroxyprogesterone (>1000 ng/dL diagnostic for classic CAH; 200-1000 ng/dL suggests non-classic CAH requiring ACTH stimulation test)
Treatment includes hydrocortisone replacement to suppress ACTH and reduce androgen excess; fludrocortisone for salt-wasting form
Genetic counseling and prenatal diagnosis available for affected families
Management of known CAH before and during pregnancy is critical 6

Hyperaldosteronism

Primary hyperaldosteronism causes hypertension and hypokalemia from autonomous aldosterone production.

Causes include aldosterone-producing adenoma (35%), bilateral adrenal hyperplasia (60%), and rarely adrenal carcinoma or familial hyperaldosteronism
Clinical manifestations include hypertension (often resistant to treatment), hypokalemia, metabolic alkalosis, and muscle weakness
Screening indicated for resistant hypertension, hypertension with hypokalemia, adrenal incidentaloma with hypertension, or early-onset hypertension
Diagnosis by elevated aldosterone:renin ratio (>20-30); confirmatory testing with oral sodium loading or saline infusion test
Adrenal CT distinguishes unilateral adenoma from bilateral hyperplasia; adrenal vein sampling confirms lateralization before surgery
Treatment for unilateral adenoma is laparoscopic adrenalectomy; bilateral hyperplasia treated with mineralocorticoid receptor antagonists (spironolactone, eplerenone)

Hypercortisolism (Cushing's Syndrome)

Cushing's syndrome results from chronic glucocorticoid excess, requiring identification of etiology for appropriate treatment.

Clinical Manifestations

Central obesity, moon facies, buffalo hump, supraclavicular fat pads, purple striae, easy bruising, proximal muscle weakness, hypertension, diabetes, and osteoporosis

Diagnosis

Screening tests (need 2 abnormal tests): 24-hour urine free cortisol (>3 times upper limit of normal), late-night salivary cortisol (elevated), or 1 mg overnight dexamethasone suppression test (cortisol >1.8 mcg/dL)
Distinguish ACTH-dependent (pituitary or ectopic ACTH) from ACTH-independent (adrenal) by measuring ACTH
ACTH-dependent: high-dose dexamethasone suppression test and CRH stimulation test distinguish pituitary (Cushing's disease) from ectopic ACTH
Pituitary MRI for Cushing's disease; chest/abdomen CT for ectopic ACTH source; adrenal CT for adrenal causes

Treatment

Cushing's disease: transsphenoidal pituitary surgery (first-line); medical therapy (ketoconazole, metyrapone, pasireotide) or bilateral adrenalectomy if surgery unsuccessful
Ectopic ACTH: surgical resection of ACTH-secreting tumor if localized; medical therapy if unresectable
Adrenal adenoma/carcinoma: surgical resection

Pheochromocytoma & Neuroblastoma

Pheochromocytoma is a catecholamine-secreting tumor requiring careful preoperative preparation before surgical resection.

Pheochromocytoma

Arises from adrenal medulla chromaffin cells; 10% are extra-adrenal (paraganglioma), 10% bilateral, 10% malignant, and 10% familial (MEN 2, von Hippel-Lindau, neurofibromatosis type 1, succinate dehydrogenase mutations)
Classic triad: episodic headaches, sweating, and palpitations; also causes hypertension (sustained or paroxysmal), anxiety, and tremor
Diagnosis by elevated plasma free metanephrines or 24-hour urine metanephrines and catecholamines
Imaging with CT or MRI shows adrenal mass; functional imaging (MIBG scan, PET) localizes extra-adrenal tumors
Preoperative preparation requires alpha-blockade (phenoxybenzamine or doxazosin) for 10-14 days, followed by beta-blockade (only after adequate alpha-blockade to prevent unopposed alpha stimulation)
Treatment is surgical resection (laparoscopic adrenalectomy); intraoperative hypertensive crises managed with nitroprusside or phentolamine
Genetic testing recommended for all patients due to high rate of hereditary syndromes

Neuroblastoma

Most common extracranial solid tumor in children; arises from neural crest cells
Presents with abdominal mass, bone pain, periorbital ecchymoses, or opsoclonus-myoclonus syndrome
Diagnosis by elevated urine catecholamines and imaging; biopsy confirms diagnosis
Treatment includes surgery, chemotherapy, and radiation based on risk stratification

Multiple Endocrine Neoplasia (MEN) - Detailed

MEN syndromes require lifelong surveillance and early intervention to prevent complications. 6

Cancer screening and surveillance should be updated for children with genomic instability disorders including MEN syndromes 6
Multidisciplinary team approach is essential for managing MEN syndromes 6
Genetic testing should be offered to all first-degree relatives of affected individuals
Surveillance protocols should be individualized based on specific syndrome and genetic mutation
Prophylactic surgery (thyroidectomy for MEN 2) prevents cancer development in high-risk individuals
Patient education about signs and symptoms of endocrine tumors enables early detection
Sharing latest information and limitations of current knowledge helps patient decision-making 6

This comprehensive overview addresses the requested medical topics with evidence-based information, prioritizing guidelines and high-quality research while maintaining clinical relevance and practical applicability.

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Comprehensive Medical Topics Overview

Carcinogenesis

Endogenous vs. Exogenous Factors

Tumor Progression

Phenylketonuria (PKU)

Galactosemia

Cystic Fibrosis

Sudden Infant Death Syndrome (SIDS)

Exocrine Pancreas Function

Acute Pancreatitis

Chronic Pancreatitis

Pancreatic Cancer

Pancreatic Islet Cell Tumors

Glomerulonephritis Principles

Membranoproliferative Glomerulonephritis (MPGN)

Nephrotic Syndrome

Nephritic Syndrome

Tubulointerstitial Disease

Urinary Tract Infection (UTI)

Acute Renal Failure (Acute Kidney Injury)

Chronic Renal Failure (Chronic Kidney Disease)

Renal Function Tests & Acute Kidney Injury

Acute Tubular Necrosis (ATN)

Tubulointerstitial Nephritis

Chronic Kidney Disease (CKD) - Detailed Management

Nephrolithiasis (Kidney Stones)

Calcium Oxalate & Calcium Phosphate Stones

Magnesium Ammonium Phosphate (Struvite), Uric Acid, & Cystine Stones

Struvite (Magnesium Ammonium Phosphate) Stones

Uric Acid Stones

Cystine Stones

Renal Neoplasia

Nephroblastoma (Wilms Tumor)

Cystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Hydronephrosis & Urinary Tract Obstruction

Renal Cell Carcinoma - Detailed Management

Lower Urinary Tract Carcinoma (Bladder Cancer)

Testicular Tumors

Penile Disorders

Scrotal Disorders

Testicular Cancer - Detailed Management

Benign Prostatic Hyperplasia (BPH)

Prostate Cancer

Vaginal Cancer

Cervical Cancer

Endometrial Disorders

Endometriosis

Endometrial Cancer

Ovarian Cysts

Ovarian Epithelial Tumors

Ovarian Stromal Tumors

Ovarian Germ Cell Tumors

Abnormal Uterine Bleeding (AUB) & Endometriosis

PALM-COEIN Classification

Evaluation

Management

Cervical Neoplasia

Vulvar & Vaginal Lesions

Benign Vulvar Lesions

Vulvar Intraepithelial Neoplasia (VIN)

Vulvar Cancer

Reproductive Hormones & Polycystic Ovary Syndrome (PCOS)

Diagnosis (Rotterdam Criteria - 2 of 3)

Metabolic Complications

Management

Gardnerella vaginalis

Human Papillomavirus (HPV)

Trichomonas vaginalis

Candida albicans

Poxviridae (Smallpox, Cowpox, Molluscum contagiosum)

Molluscum Contagiosum

Smallpox (Variola)

Herpes Simplex Virus Type 1 & 2 (HSV-1, HSV-2)

Maternal-Fetal Disorders

Hypertension in Pregnancy

Placental Complications