Hypogonadism, Male

Hypogonadism is one of the most common endocrine disorders in men, and is characterized by low serum testosterone levels with clinical signs and symptoms of the disease.

Epidemiology

• Prevalence
  • Estimated 4-5 million men in U.S. have hypogonadism
  • 20% of men 60 or older have hypogonadism
  • Frequency increases with obesity, type II diabetes mellitus, aging

Etiologies

• Primary (pathology in testes)
  • Autoimmune orchitis
  • Chemotherapy
  • Cryptorchidism
  • Dysgenetic testes
  • Klinefelter syndrome
  • Mumps orchitis
  • Myotonic dystrophy
  • Orchiectomy
  • Radiation
• Secondary (pathology in pituitary)
  • Alcohol abuse
  • Cushing syndrome
  • Drugs (corticosteroids, opiates)
  • Hyperprolactinemia
  • Iron overload
  • Pituitary lesions
  • Severe chronic illness (cancer, chronic liver disease, chronic renal disease, rheumatoid arthritis, diabetes melitis, obesity)
  • Other genetic mutations
• Tertiary (pathology in hypothalamus)
  • Kallman syndrome
  • Prader-Willi syndrome
• Age-related hypogonadism (pathology in testes and hypothalamus)

Pathophysiology

• Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus
• GnRH stimulates the release of leuteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary
• LH promotes secretion of testosterone from Leydig cells
• FSH stimulates spermatogenesis and inhibin B production from Sertoli cells inhibits FSH
• 2% of circulating testosterone is free; 98% is bound 
  • 60% bound to albumin   
  • 40% bound to sex hormone binding globulin
• Bioavailable testosterone = free testosterone plus albumin bound testosterone
• Substantial alterations in sex hormone binding globulin affect total testosterone level
  • Free testosterone and bioavailable testosterone levels more accurately reflect bioactive testosterone under these circumstances

Clinical Presentation

• Manifestations depend on the age of onset of hypogonadism
• Pubertal hypogonadism
  • Eunuchoidal body habitus
  • Gynecomastia
  • Small testes
  • Lack of secondary sexual characteristics
• Postpubertal hypogonadism
• Weakness
  • Decreased libido
  • Depressed mood
  • Impotence
  • Normal penile size
  • Low bone mineral density
  • Gynecomastia
  • Muscle loss
  • Abdominal adiposity

Treatment

• Androgen replacement

Hypopituitarism  

Osteoporosis

Diagnosis

• Indications for testing – signs and symptoms of hypogonadism
• Laboratory testing
  • Screen with serum testosterone concentration (preferably between 8-10 am)
    • For children, use mass spectrometry assay
    • For adult males, use radioimmunoassay (mass spectrometry not necessary) – <300 ng/dL suggests hypogonadism
  • If total testosterone is abnormal, may consider testing for free testosterone concentrations – helpful in determining bioavailable testosterone
  • FSH/LH to differentiate between primary and secondary etiologies
    • Primary – FSH and LH are elevated
• Imaging studies
  • If testosterone <150 ng/dL – consider MRI for pituitary imaging and if  LH is normal to low prolactin may be increased

Differential Diagnosis

• Pituitary lesions
• Dementia
• Hypothyroidism adrenal tumor
• Depression
• Diabetes mellitis
• Hemochromatosis
• Cystic fibrosis

Indications for Ordering

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.
Test Name and Number	Comments
Testosterone, Free & Total (Includes Sex Hormone Binding Globulin), Adult Male 0070109 Method: Electrochemiluminescent Immunoassay The concentration of free testosterone is derived from a mathematical expression based on the constant for the binding of testosterone to sex hormone binding globulin.
Testosterone, Bioavailable & Sex Hormone Binding Globulin (Includes Total Testosterone), Females or Children 0081057 Method: High Performance Liquid Chromatography/Tandem Mass Spectrometry The concentrations of free and bioavailable testosterone are derived from mathematical expressions based on constants for the binding of testosterone to albumin and/or sex hormone binding globulin.	This test is suggested for children due to an improved sensitivity of testosterone by LC-MS/MS
Testosterone Free, Females or Children 0081059 Method: Tandem Mass Spectrometry The concentration of free testosterone is derived from a mathematical expression based on the constant for the binding of testosterone to sex hormone binding globulin.
Sex Hormone Binding Globulin 0099375 Method: Electrochemiluminescent Immunoassay
Testosterone, Urine 0070716 Method: Chemiluminescent Immunoassay
Androstenedione 0070020 Method: Chemiluminescent Immunoassay
5-a-Dihydrotestosterone 0078005 Method: Radioimmunoassay