What is the differential diagnosis and recommended workup for a 56‑year‑old postmenopausal woman with a one‑month history of intermittent flushing and dizziness, normal inflammatory markers, normal thyroid function, hypokalemia, normal 5‑hydroxyindoleacetic acid and urine metanephrines, and a postmenopausal hormone profile?

Differential Diagnosis and Workup for Postmenopausal Flushing and Dizziness

Most Likely Diagnosis

Based on the hormone profile (FSH 37, LH 19.33, estradiol <24, progesterone <0.50) and the exclusion of carcinoid syndrome and pheochromocytoma, this patient's symptoms are most consistent with postmenopausal vasomotor symptoms (hot flushes). 1

Differential Diagnosis

The key differential diagnoses for flushing and dizziness in this clinical context include:

1. Postmenopausal Vasomotor Symptoms (Most Likely)

• The hormone profile confirms postmenopausal status with elevated FSH/LH and low estradiol 1
• Flushing is reported in 50-70% of postmenopausal women and can be severe with abrupt hormonal changes 1
• Dizziness may accompany vasomotor episodes due to vasodilation and blood pressure fluctuations 1

2. Carcinoid Syndrome (Effectively Ruled Out)

• Normal 5-HIAA excludes functional carcinoid tumor 1, 2
• Carcinoid syndrome typically presents with flushing (70%), diarrhea (50%), and abdominal pain (70%) at diagnosis 1
• Critical pitfall: Over-the-counter 5-hydroxytryptophan (5-HTP) supplements can cause false-positive 5-HIAA elevation—ensure the patient was not taking these 3

3. Pheochromocytoma (Effectively Ruled Out)

• Normal urine metanephrines exclude pheochromocytoma 1
• Pheochromocytoma typically presents with episodic hypertension, headache, and palpitations 1

4. Thyroid Dysfunction (Ruled Out)

• Normal TSH (1.057) excludes hyperthyroidism as a cause of flushing 1

5. Medication-Induced Flushing

• Review all medications for niacin, nicotine, catecholamines, ACE inhibitors, alcohol, or vancomycin 1
• These agents can induce flushing independent of underlying pathology 1

6. Vasodepressor (Vasovagal) Reaction

• Distinguished from other causes by bradycardia (not tachycardia), pallor, weakness, nausea, and lack of urticaria or pruritus 1
• Typically triggered by specific situations (prolonged standing, emotional stress) 1

7. Adrenal Insufficiency (Requires Evaluation)

• The hypokalemia (3.2 mEq/L) is concerning and warrants further investigation 4, 5
• Adrenal insufficiency can present with dizziness, weakness, and electrolyte abnormalities 4
• However, hypokalemia is present in only ~50% of primary adrenal insufficiency cases; hyponatremia is more common (90%) 4

Additional Workup Required

Immediate Priority: Evaluate Hypokalemia

The potassium of 3.2 mEq/L requires systematic evaluation:

1. Assess acid-base status and measure urine potassium-creatinine ratio (K/C) 5

   • K/C ratio <1.5 suggests poor intake, GI losses, or intracellular shift 5
   • K/C ratio >1.5 suggests renal losses 5

2. Check blood pressure (supine and standing) 5

   • Metabolic alkalosis with K/C >1.5 and hypertension suggests primary hyperaldosteronism, Cushing syndrome, or renal artery stenosis 5
   • Metabolic alkalosis with K/C >1.5 and normal BP suggests diuretic use, Bartter syndrome, or Gitelman syndrome 5

3. Measure serum magnesium 5

   • Hypomagnesemia can cause refractory hypokalemia through increased urinary potassium losses 5

Consider Adrenal Insufficiency Workup If:

• Patient has orthostatic hypotension, unexplained weight loss, fatigue, nausea, or salt craving 4
• Hyponatremia is present (check if not already done) 4
• Morning cortisol and ACTH should be measured if clinical suspicion exists 4
• Critical: A morning cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH is diagnostic of primary adrenal insufficiency 4
• If morning cortisol is indeterminate (5-18 μg/dL), perform cosyntropin stimulation test 4

Additional Considerations

1. Serum tryptase (if episodes are acute and severe)

   • To evaluate for systemic mastocytosis or anaphylaxis 1
   • Should be measured 1-2 hours after symptom onset 1

2. Complete medication review

   • Specifically ask about niacin, ACE inhibitors, over-the-counter supplements (especially 5-HTP), and alcohol use 1, 3

3. Evaluate for other autoimmune conditions (if adrenal insufficiency is confirmed)

   • Screen for thyroid antibodies, celiac disease, and pernicious anemia 4

Management Approach

For Postmenopausal Vasomotor Symptoms:

Offer SNRIs (venlafaxine), SSRIs (avoiding paroxetine if on tamoxifen), or gabapentin as first-line pharmacologic therapy 1

• Venlafaxine has been shown to be safe and effective in reducing hot flushes 1
• Gabapentin 300-900 mg daily is also effective 1
• Lifestyle modifications: cool environment, layered clothing, avoid triggers (spicy foods, caffeine, alcohol) 1
• Systemic hormone therapy is rarely given to patients with breast cancer history but may be considered in select cases 1

For Hypokalemia:

• Correct underlying cause based on workup results 5
• Replete potassium and magnesium as needed 5
• Monitor for cardiac arrhythmias if severe 5

Critical Pitfalls to Avoid

1. Do not assume all flushing is benign postmenopausal symptoms—always exclude secondary causes first 1
2. Do not overlook medication-induced flushing, especially over-the-counter supplements like 5-HTP that can confound testing 3
3. Do not ignore hypokalemia—it requires systematic evaluation and may indicate serious underlying pathology 5
4. Do not delay treatment of suspected adrenal crisis if patient becomes hypotensive or acutely ill—give IV hydrocortisone 100 mg immediately 4
5. Absence of hyperkalemia does not rule out adrenal insufficiency—it is present in only ~50% of cases 4