Given a hypotensive (BP 94/56 mmHg), euthermic female with hypothyroidism, hypercholesterolemia, menopause, multiple prior surgeries, allergies to amoxicillin (nausea/vomiting), vitamin C lotion (swelling/hives), and T3 (nausea/vomiting/abdominal pain), currently taking gabapentin, dexamphetamine sulfate sustained‑release, levothyroxine, progesterone intrauterine device, estradiol gel 0.6 mg (started 1 week ago with breast tenderness), norethindrone, metocarbamol, acetaminophen, ibuprofen, vitamin D, zinc, probiotics, collagen, cortisone, lion’s mane, turkey tail, selenium (started last week), and presenting with nausea not relieved by antacids, constant dull epigastric ache, shortness of breath on exertion, and sinus rhythm with first‑degree atrioventricular block, what additional history questions should be asked, what is the differential diagnosis, and what SOAP‑style treatment plan should be provided?

SOAP Note: Complex Medical History with New-Onset Symptoms

SUBJECTIVE

Chief Complaint: Nausea, constant dull epigastric pain, and shortness of breath on exertion since starting estradiol gel one week ago.

History of Present Illness:

• Female patient with baseline hypotension (BP 94/56 mmHg), hypothyroidism, hypercholesterolemia, and menopause
• Started estradiol gel 0.6 mg and selenium one week ago
• Developed breast swelling/tenderness (expected estrogen effect) followed by persistent nausea without vomiting, constant dull epigastric ache, and exertional dyspnea 1
• Nausea not relieved by antacids 2
• Denies fever (temperature 36°C), chest pain, or syncope
• Current vital signs: HR 84, SpO2 98%, BP 94/56 mmHg (baseline)
• ECG shows sinus rhythm with first-degree AV block

Allergies:

• Amoxicillin (nausea/vomiting)
• Vitamin C lotion (swelling/hives)
• T3 thyroid hormone (nausea/vomiting/abdominal pain)

Past Medical History:

• Hypothyroidism on levothyroxine
• Chronic low blood pressure (baseline 94/56)
• Hypercholesterolemia
• Menopause with progesterone IUD (2 years ago)
• Degenerative disc disease (cervical and lumbar L4-L5, L5-S1)
• Prior shingles
• Multiple prior surgeries (fibro-epithelial neoplasm removal, rhinoplasty, breast augmentation, spinal procedures)

Family History:

• Mother: breast cancer, hypertension
• Sister: myocardial infarction
• Father: unknown

Social History:

• Social alcohol use
• Vapes

Current Medications:

• Gabapentin 1200 mg daily
• Dexamphetamine sulfate SR 10 mg
• Levothyroxine (dose not specified)
• Progesterone IUD
• Estradiol gel 0.6 mg (started 1 week ago)
• Norethindrone
• Methocarbamol 6 mg
• Acetaminophen, ibuprofen
• Vitamin D, zinc, probiotics, collagen, cortisone, lion's mane, turkey tail, selenium (started last week)

ASSESSMENT

Primary Differential Diagnosis

1. Estradiol-Induced Gastrointestinal Side Effects (Most Likely)

• Nausea, vomiting, breast tenderness, and abdominal pain are well-documented adverse effects of estrogen overdosage or sensitivity 1
• Temporal relationship: symptoms began within one week of starting estradiol gel 1
• The FDA label specifically lists nausea, vomiting, breast tenderness, and abdominal pain as overdosage symptoms 1

2. First-Degree AV Block Related to Hypothyroidism (Requires Urgent Evaluation)

• First-degree AV block in the setting of hypothyroidism can progress to higher-degree AV block and warrants immediate attention 3, 4
• Hypothyroidism is a reversible cause of AV block, but 88% of patients with AV block and thyroid dysfunction ultimately require permanent pacemaker despite thyroid normalization 3
• The combination of exertional dyspnea, fatigue, and first-degree AV block raises concern for progression to higher-degree block 5
• Profound first-degree AV block (PR >300 ms) can cause "pseudo-pacemaker syndrome" with fatigue, exertional intolerance, decreased cardiac output, and increased pulmonary capillary wedge pressure 5

3. Cardiac Etiology of Exertional Dyspnea (Must Exclude)

• Palpitations with exertional dyspnea in a patient with family history of myocardial infarction and first-degree AV block requires aggressive cardiac investigation 6
• Differential includes supraventricular tachycardia, atrial fibrillation, hypertrophic cardiomyopathy, or early heart failure 6
• Sister's history of myocardial infarction increases pretest probability of cardiac disease 6

4. Medication-Induced Nausea

• Multiple medications can cause nausea including gabapentin, dexamphetamine, and NSAIDs 2
• However, temporal relationship with estradiol gel initiation makes this less likely 1

5. Gastrointestinal Pathology

• Peptic ulcer disease, gastritis, or biliary pathology possible given epigastric pain 2
• Less likely given acute onset and temporal relationship with medication change 2

Critical Findings Requiring Immediate Action

• First-degree AV block in hypothyroid patient (risk of progression) 5, 3
• Exertional dyspnea with family history of cardiac disease 6
• Baseline hypotension (94/56 mmHg) limits treatment options 5

PLAN

Additional History Questions Needed

Cardiac Symptoms:

• Quantify exertional dyspnea: how many stairs/blocks before symptoms? 6
• Any palpitations, chest pain, or near-syncope? 6
• Any orthopnea, paroxysmal nocturnal dyspnea, or lower extremity edema? 5
• Baseline exercise tolerance before estradiol initiation? 6

Thyroid Management:

• Current levothyroxine dose and most recent TSH/free T4 levels? 3, 4
• When was thyroid function last checked? 3
• Any symptoms of hypothyroidism (cold intolerance, weight gain, constipation)? 3

Medication History:

• Exact timing and dose of estradiol gel application? 1
• Any other new medications or supplements beyond selenium? 2
• Compliance with levothyroxine (taking on empty stomach, separated from other medications)? 3

Gastrointestinal Symptoms:

• Character of epigastric pain (burning, cramping, constant vs. intermittent)? 2
• Relationship to meals? 2
• Any melena, hematochezia, or hematemesis? 2

Diagnostic Testing (In Order of Priority)

Immediate (Today):

1. 12-lead ECG with measurement of PR interval to quantify degree of first-degree AV block and assess for progression 5
2. Thyroid function tests (TSH, free T4) to assess adequacy of levothyroxine replacement 3, 4
3. Basic metabolic panel to evaluate electrolytes (hyponatremia, hyperkalemia suggest adrenal insufficiency), renal function, and glucose 5
4. Complete blood count to assess for anemia as cause of exertional dyspnea 6
5. Brain natriuretic peptide (BNP) to exclude heart failure 6

Within 24-48 Hours:

1. Transthoracic echocardiogram to assess for structural heart disease, systolic/diastolic function, hypertrophic cardiomyopathy, and valvular disease given exertional dyspnea and family history 6
2. 24-hour Holter monitor to assess for paroxysmal arrhythmias and quantify burden of first-degree AV block 5

If Initial Workup Inconclusive:

1. Cardiopulmonary exercise testing (CPET) is the definitive test to distinguish cardiac, pulmonary, vascular, and deconditioning causes of exertional dyspnea 5, 6

Therapeutic Interventions

Immediate Management:

1. Discontinue Estradiol Gel

• Stop estradiol gel immediately as nausea, vomiting, breast tenderness, and abdominal pain are signs of estrogen overdosage 1
• Treatment of estrogen overdosage consists of discontinuation with institution of symptomatic care 1
• Symptoms should improve within 24-48 hours if estrogen-related 1

2. Antiemetic Therapy

• Start ondansetron 8 mg PO/IV as first-line antiemetic 7
• Ondansetron is recommended for patients with multiple drug allergies due to lack of cross-reactivity and high efficacy 7
• Can repeat every 8 hours as needed 7
• If inadequate response after 2 doses, add metoclopramide 10 mg IV 7
• Avoid diphenhydramine given multiple drug allergies 7

3. First-Degree AV Block Management

• Do NOT initiate beta-blockers despite family cardiac history until AV block is fully evaluated 5
• Beta-blockers can worsen AV block and cause bradycardia requiring dose reduction or discontinuation 5
• Monitor for symptoms of dizziness, lightheadedness, or syncope suggesting progression to higher-degree block 5
• First-degree AV block with PR >300 ms can cause symptoms and may require pacing 5

4. Thyroid Optimization

• Ensure levothyroxine dose is adequate based on TSH results 3, 4
• Hypothyroidism lengthens effective refractory period of AV node and can cause or worsen AV block 4
• However, note that even after achieving euthyroid state, 88% of patients with AV block and thyroid dysfunction require permanent pacemaker 3

5. Blood Pressure Management

• Given baseline hypotension (94/56 mmHg), avoid medications that lower blood pressure 5
• Hypotension can be asymptomatic but may produce dizziness, lightheadedness, or blurred vision 5
• Ensure adequate hydration 5

Medication Adjustments:

• Hold norethindrone temporarily (can contribute to nausea) 2
• Continue levothyroxine (critical for hypothyroidism management) 3
• Continue other medications unless contraindicated by test results 2

Follow-Up Plan

24-Hour Reassessment:

• Repeat vital signs including orthostatic blood pressures 5
• Assess response to ondansetron and estradiol discontinuation 7, 1
• Review laboratory results and ECG findings 5, 3

48-72 Hour Follow-Up:

• Review echocardiogram and Holter monitor results 6
• If PR interval >300 ms or symptoms of exertional intolerance persist, refer to cardiology for pacemaker evaluation 5
• If thyroid function abnormal, adjust levothyroxine and recheck in 6 weeks 3

1-Week Follow-Up:

• Reassess nausea and epigastric pain (should resolve if estrogen-related) 1
• Reassess exertional dyspnea 6
• If symptoms persist despite estradiol discontinuation and normal cardiac workup, consider upper endoscopy for gastrointestinal evaluation 2

Cardiology Referral Indications (Urgent)

• PR interval >300 ms on ECG 5
• Any progression to second- or third-degree AV block 5
• Abnormal echocardiogram findings 6
• Persistent exertional dyspnea despite treatment 6
• Paroxysmal arrhythmias on Holter monitor 5

Critical Pitfalls to Avoid

1. Do not assume first-degree AV block is benign in hypothyroid patients - 88% ultimately require pacemaker despite thyroid normalization 3

2. Do not restart estradiol without cardiology clearance - estrogen can worsen cardiac symptoms and the patient has multiple cardiac risk factors 1

3. Do not initiate beta-blockers for family cardiac history without addressing AV block first - beta-blockers worsen conduction abnormalities 5

4. Do not use diphenhydramine for nausea given multiple drug allergies - use ondansetron instead 7

5. Do not overlook cardiac causes in women with exertional dyspnea - women are at risk for underdiagnosis of cardiac pathology 6

6. Do not delay pacemaker referral if PR >300 ms with symptoms - "pseudo-pacemaker syndrome" causes significant morbidity 5

7. Do not attribute all symptoms to menopause - this patient has multiple serious conditions requiring evaluation 6