What tests should be done for an adult male experiencing unexplained episodes of heat intolerance?

Diagnostic Testing for Heat Intolerance in Adult Males

For an adult male with unexplained heat intolerance, begin with thyroid function testing (TSH and free T4) and a comprehensive medication review, followed by alpha-galactosidase A enzyme assay if initial workup is unrevealing, as Fabry disease is a critical but under-recognized cause of heat intolerance in males. 1, 2, 3

Initial Laboratory Evaluation

First-Line Tests

• Thyroid function tests (TSH and free T4) to exclude hyperthyroidism, which causes heat intolerance accompanied by fine tremor, warm moist skin, lid lag, nervousness, insomnia, weight loss, and diarrhea 1, 3
• Comprehensive medication and substance review for sympathomimetics (decongestants), stimulants, caffeine, cocaine, amphetamines, neuropsychiatric agents, and other drugs that cause heat intolerance with fine tremor, tachycardia, and sweating 1, 2, 3
• Urinary drug screen if illicit drug use is suspected based on clinical presentation 1, 3

Critical Diagnostic Consideration: Fabry Disease

Alpha-galactosidase A enzyme level in plasma or peripheral leukocytes should be obtained if the above tests are unrevealing, as Fabry disease presents with unexplained heat intolerance in adult males and is frequently missed 1

Key clinical features suggesting Fabry disease include:

• Heat intolerance with hypohidrosis (decreased sweating) 1, 4
• Chronic pain or discomfort in extremities 1
• Angiokeratomas (characteristic skin lesions) 1
• Unexplained renal dysfunction or proteinuria 1
• Cardiomyopathy, especially left ventricular hypertrophy 1
• Characteristic corneal opacities on ophthalmologic examination 1
• Unexplained fatigue 1

The enzyme assay is highly reliable in males, showing markedly deficient or absent alpha-galactosidase A activity when Fabry disease is present 1

Secondary Evaluation for Specific Clinical Contexts

If Exertional Heat Intolerance

• Serum creatine kinase to evaluate for exertional rhabdomyolysis, which may indicate underlying myopathy or malignant hyperthermia susceptibility 1
• Consider heat tolerance testing in specialized centers if history of exertional heat stroke requiring hospitalization, particularly after excluding predisposing factors 1, 5, 6

If Systemic Symptoms Present

• Serum tryptase (baseline, when asymptomatic) if episodes are paroxysmal with flushing, as systemic mastocytosis can present with heat intolerance and anaphylaxis-like symptoms 1
• Serum calcium and parathyroid hormone if hypercalcemia is detected, as primary hyperparathyroidism rarely causes heat intolerance 1

Physical Examination Findings to Guide Testing

• Skin examination for angiokeratomas (Fabry disease), café-au-lait spots (pheochromocytoma/neurofibromatosis), or telangiectasias 1, 4
• Cardiovascular examination for blood pressure differential between upper and lower extremities (coarctation), absent femoral pulses, or continuous murmur 1
• Neurological examination for delayed ankle reflexes (hypothyroidism) or fine tremor (hyperthyroidism, sympathomimetics) 1, 3
• Assessment of sweating pattern: generalized anhidrosis suggests Fabry disease or Sjögren's syndrome, while normal sweating with heat intolerance suggests other etiologies 1, 7, 4

Common Pitfalls

• Failing to consider Fabry disease in males with unexplained heat intolerance, as it is under-recognized despite being a treatable multisystemic disorder with significant morbidity if untreated 1
• Overlooking medication-induced causes, particularly over-the-counter sympathomimetics, caffeine, and herbal supplements containing ephedra 1, 2
• Not obtaining alpha-galactosidase A levels before invasive evaluations when Fabry disease is suspected, as this simple blood test can establish the diagnosis 1
• Assuming heat intolerance after previous heat stroke is purely physiological without excluding underlying metabolic or genetic disorders 1, 8