Comprehensive Endocrinology Notes for MCCQE1 Exam
1. DIABETES MELLITUS
Type 1 Diabetes
- Autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency 1
- Presents with polyuria, polydipsia, weight loss, and lethargy 2
- Cannot be treated with metformin alone - requires insulin therapy 1
- Risk of diabetic ketoacidosis (DKA) with high ketones in blood/urine 1
Type 2 Diabetes
- Insulin resistance with relative insulin deficiency 1
- Metformin is first-line: decreases hepatic glucose production, decreases intestinal glucose absorption, improves peripheral insulin sensitivity 1
- Metformin dosing: Start 500 mg once or twice daily with meals, titrate by 500 mg weekly up to maximum 2550 mg/day 1
- Metformin reduces FPG by ~53 mg/dL and HbA1c by ~1.4% 1
- Contraindications to metformin: kidney disease, liver disease, heart failure, age >80 without kidney function testing, alcohol abuse 1
Diabetic Emergencies
Diabetic Ketoacidosis (DKA)
- Hyperglycemia, ketosis, metabolic acidosis 3
- Management: IV fluids, insulin therapy, electrolyte replacement, treat precipitating factors 3
- Check urine/blood ketones, acid-base status, electrolytes immediately 2
Hyperosmolar Hyperglycemic State (HHS)
- Severe hyperglycemia, hyperosmolality, dehydration without significant ketosis 3
- Management: aggressive fluid resuscitation, insulin, electrolyte replacement 3
Severe Hypoglycemia
- Blood glucose <54 mg/dL with neurological symptoms 3
- Management: IV glucose (D50W) for unconscious patients, glucagon if no IV access 3
2. THYROID DISORDERS
Hypothyroidism
Primary Hypothyroidism
- Elevated TSH with low free T4 2
- Levothyroxine dosing for patients <70 years without cardiac disease: ~1.6 mcg/kg/day based on ideal body weight 2
- For patients >70 years or with cardiac disease/frailty: start 25-50 mcg daily and titrate up 2
- Monitor TSH every 4-6 weeks during titration 2
- Overtreatment indicated by low TSH - reduce or discontinue dose 2
Central (Secondary) Hypothyroidism
- Low TSH with low free T4 - indicates pituitary/hypothalamic dysfunction 2
- Goal free T4 in upper half of reference range (TSH not accurate for monitoring) 2
- Evaluate for hypophysitis 2
Hyperthyroidism/Thyrotoxicosis
Thyroiditis (Most Common with Immune Checkpoint Inhibitors)
- Low TSH with elevated free T4 2
- Grade 1 (mild): Beta-blocker (atenolol or propranolol) for symptoms, monitor thyroid function every 2-3 weeks 2
- Grade 2 (moderate): Consider holding treatment, beta-blocker, hydration, endocrine consultation 2
- Grade 3-4 (severe): Hold treatment, hospitalize, beta-blocker, consider steroids/SSKI/thionamides 2
- Usually self-limited, resolves in weeks, often progresses to hypothyroidism 2
Graves' Disease
- Persistent thyrotoxicosis with TSH receptor antibodies 2
- Physical exam: ophthalmopathy, thyroid bruit 2
- Treatment: antithyroid drugs (methimazole/propylthiouracil), radioactive iodine, or surgery 2
Thyroid Storm
- Life-threatening severe thyrotoxicosis with multi-organ dysfunction 3
- Management: beta-blockers, thionamides, hydration, supportive care 3
Myxedema Coma
- Life-threatening severe hypothyroidism with altered mental status and hypothermia 3
- Management: ventilatory support if needed, careful fluid management, treat precipitating factors 3
3. ADRENAL DISORDERS
Primary Adrenal Insufficiency
Diagnosis
- AM cortisol <3 mg/dL with elevated ACTH (>2-3× ULN) 2
- Check basic metabolic panel (Na, K, CO2, glucose), renin, aldosterone 2
- ACTH stimulation test if AM cortisol 3-15 mg/dL 2
- Adrenal CT for metastasis or hemorrhage 2
Management
- Grade 1 (mild): Hydrocortisone 15-20 mg daily in divided doses (2/3 morning, 1/3 early afternoon) 2
- Grade 2 (moderate): Oral pulse dose therapy, clinic evaluation for volume repletion 2
- Grade 3-4 (severe): Hold treatment, hospitalize, IV stress-dose steroids 2
- All patients need: stress dosing education, emergency injectable, medical alert bracelet 2
Adrenal Crisis
Presentation
- Severe hypotension (refractory to fluids), shock, electrolyte abnormalities 3
- Fever, altered mental status, hyponatremia, hyperkalemia 3
- Triggers: infections, surgery, injuries, severe allergic reactions 3
Management
- Immediate hydrocortisone 100 mg IV bolus 3
- Followed by 100-300 mg/day as continuous infusion or divided every 6-8 hours 3
- Rapid IV isotonic saline (0.9%) at 1 L/hour initially 3
- Evaluate for precipitating cause 2
Secondary (Central) Adrenal Insufficiency
- Low ACTH with low cortisol 2
- Manage as hypophysitis (see below) 2
- No aldosterone deficiency (renin-angiotensin system intact) 2
4. PITUITARY DISORDERS
Hypophysitis
Diagnosis
- Low TSH with low free T4 suggests central hypothyroidism 2
- Check AM ACTH, cortisol, TSH, free T4, LH, FSH, testosterone/estrogen 2, 3
- MRI brain with pituitary cuts: shows pituitary enlargement, stalk thickening, suprasellar convexity 2
- Most common: central hypothyroidism (>90%), central adrenal insufficiency (>75%), panhypopituitarism (50%) 2
Management
- All grades: Endocrine consultation, stress dosing education, medical alert bracelet 2
- Grade 1: Consider holding treatment, corticosteroid replacement (hydrocortisone 15-20 mg divided), thyroid hormone replacement, sex hormone replacement if needed 2
- Grade 2: Consider holding treatment, clinic evaluation, oral pulse dose steroids 2
- Grade 3-4: Hold treatment, hospitalize, IV stress-dose steroids 2
- Critical: Initiate adrenal replacement before thyroid replacement to avoid precipitating adrenal crisis 2
Pituitary Apoplexy
- Acute hemorrhage/infarction of pituitary tumor 3
- Sudden headache, visual disturbances, hormonal deficiencies 3
- Management: immediate high-dose glucocorticoids, neurosurgical evaluation for decompression, hormone replacement 3
5. CALCIUM DISORDERS
Hypocalcemia
In 22q11.2 Deletion Syndrome Context
- Occurs in ~60% of children with 22q11.2DS 2
- May present as transient neonatal hypocalcemia or hypocalcemic seizures 2
- Can recur during stress: perioperative, acute illness, puberty, pregnancy, decreased oral intake 2
- Symptoms: fatigue, irritability, seizures, paresthesias, muscle cramps, tremors, rigidity 2
Severe Hypocalcemia
- Serum calcium <7.5 mg/dL or symptomatic 3
- Management: IV calcium gluconate for severe symptoms, vitamin D supplementation, treat underlying cause 3
Hypercalcemia
Severe Hypercalcemia
- Serum calcium >14 mg/dL or symptomatic 3
- Management: aggressive IV fluid resuscitation, bisphosphonates, calcitonin, treat underlying cause 3
6. PARATHYROID DISORDERS
Hypoparathyroidism
- Most common endocrine issue in 22q11.2DS 2
- Monitor with TSH and free T4 every 1-2 years 2
- Can be complete or partial 2
7. GROWTH DISORDERS
Growth Hormone Deficiency
- Rare but responds well to growth hormone therapy when present 2
- Growth restriction pattern: early deceleration of weight/stature, weight recovery with less stature catch-up 2
- Mean height at age 19: females and -0.72 SD for males 2
- Measure height/weight regularly, consider parental height 2
8. REPRODUCTIVE ENDOCRINOLOGY
Hypogonadism
- Evaluate LH, testosterone in males; FSH, estrogen in premenopausal females with fatigue, loss of libido, mood changes, oligomenorrhea 2
- Testosterone or estrogen therapy if needed in those without contraindications (prostate cancer, breast cancer, DVT history) 2
Pubertal Development
- Hormones orchestrate sexual development, sexuality, reproduction through life history transitions, contextual responses, cyclical patterns 4
9. IMMUNE CHECKPOINT INHIBITOR-RELATED ENDOCRINOPATHIES
General Principles
- Endocrine dysfunction can be managed with hormone replacement - may not require stopping immunotherapy 2
- Organ failure managed with replacement rather than immunosuppression 2
- High-dose corticosteroids have not shown benefit for pituitary hormone recovery 2
Checkpoint Inhibitor-Associated Diabetes Mellitus (CIADM)
- Autoimmune pathophysiology similar to type 1 diabetes 2
- New-onset hyperglycemia without type 2 diabetes risk factors should raise concern 2
- Acute onset: polyuria, polydipsia, weight loss, lethargy 2
- Check urine ketones, acid-base status, electrolytes for DKA screening 2
- Send antibodies, insulin, C-peptide but don't delay treatment 2
- Treat with insulin - no immunosuppressive strategies approved 2
- Endocrinology consultation appropriate; hospitalize if outpatient consultation unavailable 2
10. PERIOPERATIVE ENDOCRINE MANAGEMENT
Stress-Dose Steroids for Surgery
- Patients with adrenal insufficiency: Hydrocortisone 100 mg IV at surgery start, followed by 200 mg/24 hours infusion 3
- Endocrine consultation before surgery or high-stress treatments 2
11. MONITORING AND LABORATORY INTERPRETATION
Routine Monitoring
- Before starting immune checkpoint inhibitors: TSH, free T4, AM ACTH, cortisol, glucose, HbA1c 2
- Before each cycle: TSH, free T4, basic metabolic panel 2
- Consider monthly for 6 months, then every 3 months for 6 months, then every 6 months for 1 year: AM ACTH and cortisol 2
Pre-analytical Considerations
- Patient history, clinical assessment, and laboratory investigations form diagnostic basis 5
- Pre-analytical and analytical variability affects clinical significance 5
12. ENDOCRINE SYSTEM OVERVIEW
Hormonal Regulation
- Hypothalamus produces releasing/inhibiting hormones acting on pituitary 6
- Pituitary hormones act on target glands (adrenal, gonads, thyroid) or directly on target organs 6
- Regulatory cascades: hypothalamic hormone → pituitary hormone(s) → target gland hormone(s) 6
Major Endocrine Glands
- Adrenal glands: primarily cortisol 6
- Gonads (ovaries/testes): sex hormones 6
- Thyroid: thyroid hormone 6
- Parathyroid: parathyroid hormone 6
- Pancreas: insulin and glucagon 6
13. SPECIAL POPULATIONS
Children (Ages 10-16)
- Metformin effectively lowers glucose in children with type 2 diabetes 1
- Not studied in children <10 years 1
- Not studied in combination with other oral agents or insulin in children 1
Pregnancy
- Unknown if metformin harms unborn baby - discuss best blood sugar control options 1
- Hypocalcemia can recur during pregnancy in those with hypoparathyroidism 2
Breastfeeding
- Unknown if metformin passes into breast milk - discuss feeding options 1
14. KEY CLINICAL PITFALLS
Thyroid
- Elevated TSH in recovery phase of thyroiditis - monitor asymptomatic patients with normal free T4 for 3-4 weeks before treating 2
- TSH not accurate in central hypothyroidism - use free T4 for monitoring 2
Adrenal
- Distinguish primary vs secondary adrenal insufficiency by ACTH-cortisol relationship 2
- Always replace adrenal hormones before thyroid hormones to avoid precipitating adrenal crisis 2
Diabetes
- New hyperglycemia without type 2 risk factors - consider CIADM and check for DKA 2
- Metformin contraindicated in kidney disease, liver disease, heart failure 1
Calcium
- Hypocalcemia can recur during biologic stress even after initial resolution 2