From the Guidelines
The workup of secondary hypogonadism should begin with confirming the diagnosis through morning total testosterone levels (drawn before 10 AM) on two separate occasions, along with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements, as recommended by the most recent guidelines 1.
Initial Evaluation
The initial evaluation of secondary hypogonadism involves laboratory tests to confirm the diagnosis and identify potential causes.
- Morning total testosterone levels should be measured on two separate occasions, along with LH and FSH measurements, to confirm the diagnosis of secondary hypogonadism.
- Additional laboratory tests should include:
- Prolactin levels to rule out hyperprolactinemia, a common cause of secondary hypogonadism.
- Thyroid function tests to evaluate for hypothyroidism or hyperthyroidism.
- Complete blood count and comprehensive metabolic panel to identify any underlying medical conditions.
- Hemoglobin A1c to assess for diabetes mellitus.
Pituitary Function Assessment
Pituitary function should be assessed with morning cortisol and free T4 levels to evaluate for any pituitary dysfunction.
- Magnetic resonance imaging (MRI) of the pituitary gland is indicated to rule out pituitary tumors or other structural abnormalities, as recommended by the Endocrine Society Clinical Practice Guideline 1.
Additional Testing
Additional testing may include:
- Bone mineral density testing to evaluate for osteoporosis, a common complication of hypogonadism.
- A detailed history focusing on medications, substance use, chronic illnesses, and symptoms of pituitary dysfunction is essential to identify any underlying causes of secondary hypogonadism.
- Physical examination should assess for signs of hypogonadism and evaluate visual fields if a pituitary tumor is suspected.
Treatment
Once the diagnosis is confirmed and the underlying cause identified, treatment can be directed at the specific etiology or, if not reversible, testosterone replacement therapy can be initiated with monitoring of hematocrit, PSA (in men over 40), and bone density, as recommended by the American Urological Association Education and Research, Inc. 1. It is essential to note that exogenous testosterone therapy should be avoided in males pursuing or planning to pursue family building in the near future, as it can inhibit spermatogenesis and impair fertility 1.
From the FDA Drug Label
INDICATIONS AND USAGE ... Selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to a pituitary deficiency) in males. The workup for secondary hypogonadism (hypogonadotropic hypogonadism) is not explicitly stated in the provided drug label. Key points to consider in the workup of secondary hypogonadism include:
- Evaluation of pituitary function
- Assessment of gonadotropin levels However, the FDA label does not provide specific guidance on the workup for secondary hypogonadism. 2
From the Research
Diagnostic Workup for Secondary Hypogonadism
The diagnostic workup for secondary hypogonadism (hypogonadotropic hypogonadism) involves:
- A comprehensive history and physical examination 3
- Measurement of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels to differentiate between primary and secondary hypogonadism 3, 4, 5
- Investigation of pituitary function 3
- Imaging procedures, such as MRI or CT scans, to rule out pituitary tumors or other abnormalities 3, 6
- GnRH stimulation test to assess the function of the hypothalamic-pituitary-gonadal axis 3
- Genetic analyses to identify any genetic mutations that may be contributing to the condition 3
- Olfactory test to assess the function of the olfactory system, which can be affected in some cases of hypogonadotropic hypogonadism 3
Laboratory Tests
Laboratory tests that may be used to diagnose secondary hypogonadism include:
- Total testosterone levels: <200 ng/dl indicates hypogonadism 7
- Free testosterone levels: may be measured to confirm the diagnosis of hypogonadism 7
- LH and FSH levels: low levels indicate secondary hypogonadism, while high levels indicate primary hypogonadism 4, 5
- Inhibin B levels: may be measured to assess the function of the Sertoli cells in the testes 6
- Prostate-specific antigen (PSA) levels: may be measured to rule out prostate cancer before starting testosterone replacement therapy 5, 7
Clinical Evaluation
A clinical evaluation should include:
- A detailed medical history to identify any underlying medical conditions that may be contributing to the hypogonadism 7
- A physical examination to assess for any signs of hypogonadism, such as decreased muscle mass, decreased facial hair, and gynecomastia 6
- Questionnaires to assess symptoms of hypogonadism, such as decreased libido, erectile dysfunction, and decreased sense of well-being 7