What is the workup for elevated progesterone (a steroid hormone) in a male patient?

Workup for Elevated Progesterone in a Male Patient

The workup for elevated progesterone in a male patient should begin with a comprehensive endocrine evaluation to identify potential adrenal, testicular, or neoplastic causes, as progesterone elevation in males is uncommon and warrants thorough investigation.

Initial Evaluation

Laboratory Tests

• Comprehensive hormone panel:
  • Testosterone (total and free)
  • Estradiol
  • Luteinizing hormone (LH)
  • Follicle-stimulating hormone (FSH)
  • Prolactin
  • Dehydroepiandrosterone sulfate (DHEAS)
  • 17-hydroxyprogesterone
  • Androstenedione
  • Cortisol (morning)

Adrenal Function Assessment

• 1 mg overnight dexamethasone suppression test to evaluate for autonomous cortisol secretion 1
• 24-hour urinary free cortisol if Cushing's syndrome is suspected
• Plasma ACTH to determine if progesterone elevation is ACTH-dependent 1

Secondary Evaluation

Imaging Studies

• CT scan of adrenal glands to evaluate for adrenal masses, which could be a source of hormonal abnormalities 1
• Testicular ultrasound to evaluate for testicular masses or abnormalities 2
• MRI of pituitary if hypogonadotropic hypogonadism or pituitary tumor is suspected 2

Additional Tests Based on Initial Findings

• Aldosterone/renin ratio if hypertension or hypokalemia is present 1
• Plasma or 24-hour urinary metanephrines if pheochromocytoma is suspected (especially with adrenal mass >10 HU on non-contrast CT) 1
• Tumor markers (AFP, β-hCG) if testicular or extragonadal germ cell tumor is suspected 1

Differential Diagnosis Considerations

Adrenal Causes

• Adrenal adenoma or carcinoma - may produce excess steroid hormones including progesterone 1
• Congenital adrenal hyperplasia - particularly late-onset forms with enzyme deficiencies
• Cushing's syndrome - can alter the entire steroid hormone pathway

Testicular Causes

• Leydig cell tumors - can produce various steroid hormones
• Germ cell tumors - may alter hormone production 1

Other Causes

• Liver disease - impaired hormone metabolism
• Medications - certain drugs can affect steroid hormone levels
• Obesity - can alter hormone metabolism and increase peripheral conversion

Interpretation and Management

• Progesterone in males is primarily produced by the adrenal glands, with some contribution from the testes 3
• Unlike in females, there are no significant age-dependent changes in serum progesterone concentrations in men 3
• Elevated progesterone may be part of a broader pattern of steroid hormone abnormalities
• If adrenal tumor is identified, consider surgical resection for functional adrenal masses 1
• For hypogonadotropic hypogonadism, consider appropriate hormone replacement therapy 2

Important Considerations

• Progesterone levels should be interpreted in the context of other hormonal abnormalities
• Single elevated value should be confirmed with repeat testing
• Diurnal variation should be considered when interpreting results
• Progesterone may originate from adrenal cortex and be modulated by ovarian factors even in males 4
• Elevated progesterone may not always indicate pathology but could represent a variant of normal in some cases

Remember that while progesterone is often considered a "female hormone," it plays important roles in men including effects on spermiogenesis, testosterone biosynthesis, CNS function, and other systems 3. Therefore, abnormal levels warrant appropriate investigation to identify underlying causes.