What is the appropriate diagnosis and treatment for a patient with hypertension, iron deficiency anemia, and hypothyroidism?

Diagnosis and Management

This patient requires urgent evaluation for pheochromocytoma or secondary hypertension, treatment of iron deficiency, and thyroid hormone replacement for hypothyroidism—addressing all three conditions is critical to prevent cardiovascular morbidity and mortality.

Primary Concern: Episodic Hypertension with Dizziness

The presentation of "random bouts of high blood pressure" causing dizziness in a 43-year-old smoker demands immediate investigation for secondary causes of hypertension, particularly pheochromocytoma/paraganglioma (PPGL). 1

Key diagnostic steps:

• Measure 24-hour urinary metanephrine and normetanephrine or plasma metanephrines immediately, as these are the preferred screening tests for PPGL due to their constitutive secretion pattern (unlike the highly variable catecholamine secretion). 1
• Consider screening for obstructive sleep apnea (OSA) given the episodic hypertension pattern—OSA affects up to 60% of patients with resistant hypertension and should be suspected in patients with non-dipping blood pressure patterns. 1
• Screen for primary aldosteronism with aldosterone-to-renin ratio, as this is a common form of secondary hypertension. 1

Common pitfall: Do not dismiss episodic hypertension as "white coat syndrome" or anxiety in a smoker—the combination of episodic symptoms with dizziness warrants exclusion of catecholamine-secreting tumors before initiating standard antihypertensive therapy.

Iron Deficiency Without Anemia

The labs reveal iron deficiency without overt anemia: ferritin 30.9 ng/mL, iron saturation 15%, TIBC 470 mg/dL, with normal hemoglobin (16.1 g/dL) and hematocrit (47.2%). 1

Important distinction: This patient has iron deficiency (ferritin <100 ng/mL, saturation <20%) but the hemoglobin is normal, indicating early iron depletion before frank anemia develops. 1

Treatment approach:

• Initiate oral iron supplementation with 60-120 mg elemental iron daily, as this patient has mild iron deficiency without severe anemia and likely has adequate absorption. 1
• Investigate the source of iron loss: Given the patient is 43 years old with elevated FSH (46.5) and LH (39.4) suggesting perimenopause/menopause transition, menstrual blood loss is the most likely etiology. However, gastrointestinal blood loss must be excluded with stool guaiac testing. 1
• If oral iron is not tolerated or ineffective after 4 weeks (failure to increase hemoglobin by 1 g/dL), consider intravenous iron therapy. 1

Clinical significance: Iron deficiency can contribute to fatigue and may exacerbate hypothyroid symptoms, making treatment essential even without anemia. 2, 3

Hypothyroidism

The thyroid function tests indicate primary hypothyroidism: TSH 4.38 mIU/L (elevated), Free T4 0.76 ng/dL (low-normal to low), Free T3 2.96 pg/mL, with negative TPO antibodies (1.3). 4

Treatment protocol:

• Initiate levothyroxine replacement therapy at a conservative starting dose given the patient's cardiovascular risk factors (smoker, hypertension). Start with 25-50 mcg daily rather than full replacement dose due to increased cardiovascular disease risk. 4
• Monitor TSH and Free T4 in 6-8 weeks after initiation, then adjust dosage by 12.5-25 mcg increments until TSH normalizes. 4
• Target TSH within normal reference range (typically 0.5-4.5 mIU/L). 4

Critical consideration: In patients with cardiovascular disease or risk factors (this patient has hypertension and is a smoker), initiate levothyroxine at lower doses to avoid precipitating cardiac arrhythmias or angina. Atrial fibrillation is the most common arrhythmia with levothyroxine overtreatment. 4

Interaction Between Conditions

The three conditions are interconnected:

• Iron deficiency can impair thyroid hormone synthesis and worsen hypothyroid symptoms, as iron is required for thyroid peroxidase activity. 3
• Hypothyroidism can contribute to anemia through multiple mechanisms including bone marrow depression and decreased erythropoietin production. 3
• Both iron deficiency and hypothyroidism can cause fatigue, potentially masking or exacerbating each other's symptoms. 2, 3

Hypertension Management Algorithm

Once secondary causes are excluded:

1. First-line therapy: ACE inhibitor or ARB (avoid alpha-blockers which can worsen heart failure and cause fluid retention). 1
2. Second-line: Add thiazide diuretic if blood pressure remains uncontrolled. 1
3. Third-line: Add amlodipine or other dihydropyridine calcium channel blocker if needed. 1

Avoid: Moxonidine (increased mortality risk) and alpha-adrenoceptor antagonists (neurohumoral activation, fluid retention). 1

Monitoring Plan

• Recheck iron studies in 4 weeks to assess response to oral iron supplementation. 1
• Recheck TSH and Free T4 in 6-8 weeks after starting levothyroxine. 4
• Follow up on secondary hypertension workup (metanephrines, aldosterone-to-renin ratio) within 1-2 weeks. 1
• Smoking cessation counseling is essential given cardiovascular risk. 1