What is the cause of polycythemia in a 39-year-old male with elevated hemoglobin (hyperglycemia not present, normal Thyroid-Stimulating Hormone (TSH)) and a Body Mass Index (BMI) of 36?

Obstructive Sleep Apnea (OSA) is the Most Likely Cause

In this 39-year-old obese male (BMI 36) with chronic fatigue and polycythemia (hemoglobin 17.4), obstructive sleep apnea is the most probable diagnosis and should be evaluated with polysomnography. 1, 2

Clinical Reasoning

Key Clinical Features Point to OSA

• Obesity (BMI 36) is the strongest risk factor for obstructive sleep apnea, which causes chronic intermittent hypoxia leading to compensatory erythrocytosis 3, 1

• Chronic fatigue despite "adequate sleep" is a classic presentation of OSA, as patients are unaware of their sleep fragmentation and nocturnal hypoxemia 1, 2

• Normal TSH excludes hypothyroidism as a cause of both fatigue and potential secondary polycythemia 1

• Occupation as home renovation contractor may involve exposure to dust/irritants that could compound any underlying sleep-disordered breathing, though this is less likely the primary cause 3

Why This is Secondary Polycythemia, Not Primary

• Hemoglobin of 17.4 g/dL represents mild polycythemia that is more consistent with secondary causes than polycythemia vera, which typically presents with more marked elevations 3

• Absence of other myeloproliferative features (no mention of splenomegaly, thrombocytosis, leukocytosis, pruritus, or erythromelalgia) makes polycythemia vera unlikely 3

• Hypoxia-driven secondary polycythemia from sleep apnea is far more common in obese patients than primary polycythemia 1, 2

Diagnostic Approach

Immediate Next Steps

• Order polysomnography (sleep study) to confirm obstructive sleep apnea as the cause of chronic hypoxemia 1, 2

• Check serum erythropoietin (EPO) level - expect it to be elevated or high-normal in hypoxia-driven secondary polycythemia, though levels may normalize after hemoglobin stabilizes at a higher baseline 1, 2

• Arterial blood gas or pulse oximetry can document hypoxemia, though nocturnal oximetry during sleep study is more diagnostic 1

If Sleep Apnea is Confirmed

• CPAP therapy is the primary treatment, which should resolve the polycythemia by eliminating nocturnal hypoxemia 1, 2

• Weight loss is essential as it directly addresses the underlying pathophysiology of OSA 1

If Sleep Study is Negative

• Consider JAK2 V617F mutation testing to evaluate for polycythemia vera, though this is less likely given the clinical presentation 3, 1

• Evaluate for other hypoxia-driven causes: chronic lung disease (though he doesn't smoke), high oxygen-affinity hemoglobinopathy (congenital, would have family history) 3, 1

• Screen for hypoxia-independent causes: renal ultrasound for renal cell carcinoma or cysts, liver imaging for hepatocellular carcinoma (though these are uncommon in a 39-year-old) 3, 1

Critical Pitfalls to Avoid

• Do not assume "adequate sleep" rules out sleep apnea - patients with OSA are typically unaware of their sleep fragmentation and nocturnal arousals 1, 2

• Do not overlook obesity as the key clinical clue - BMI 36 dramatically increases OSA risk and is the most important finding in this case 1, 2

• Do not rush to diagnose polycythemia vera without first excluding secondary causes, especially in an obese patient with fatigue 3, 1, 2

• Do not misinterpret normal or mildly elevated EPO levels - in chronic hypoxic states, EPO may normalize after compensatory hemoglobin elevation has occurred 1, 2

• Do not perform unnecessary red cell mass measurements when the clinical context strongly suggests a specific secondary cause like OSA 3, 1