Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Hypogonadism Testing Algorithm
Clinical Background
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
See Also
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Hypogonadism Testing Algorithm
Diagnosis
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
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Hypogonadism Testing Algorithm
Tests generally appear in the order most useful for common clinical situations
| Test name: Testosterone, Adult Male
|
| ARUP #: 0070130 |
| Methodology: Electrochemiluminescent Immunoassay
|
| Use: Diagnose and monitor hypogonadism |
| Limitations: This test is not recommended for females or children |
| Follow-up:
|
| Test name: Luteinizing Hormone and Follicle Stimulating Hormone
|
| ARUP #: 0070193 |
| Methodology: Electrochemiluminescent Immunoassay
|
| Use: Diagnose and monitor hypogonadism |
| Limitations: |
| Follow-up:
|
| Test name: Testosterone, Bioavailable & Sex Hormone Binding Globulin (Includes Total Testosterone), Adult Male
|
| ARUP #: 0070102 |
Methodology: Electrochemiluminescent Immunoassay
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.
|
Use: Diagnose and monitor hypogonadism
Use for patients with suspected plasma protein abnormalities
|
| Limitations: This test is not recommended for females or children |
| Test name: Testosterone Free, Females or Children
|
| ARUP #: 0081059 |
Methodology: 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.
|
| Use: Diagnose and monitor hypogonadism |
| Limitations: |
| Follow-up:
|
| Test name: Testosterone Free, Adult Male
|
| ARUP #: 0070111 |
Methodology: 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.
|
| Use: Diagnose and monitor hypogonadism |
| Limitations: Not recommended for testing children |
| Follow-up:
|
Additional Tests Available
| Test name: Testosterone, Free & Total (Includes Sex Hormone Binding Globulin), Adult Male
|
| ARUP #: 0070109 |
Methodology: 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.
|
| Comments: |
| Test name: Testosterone, Bioavailable & Sex Hormone Binding Globulin (Includes Total Testosterone), Females or Children
|
| ARUP #: 0081057 |
Methodology: 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.
|
| Comments: This test is suggested for children due to an improved sensitivity of testosterone by LC-MS/MS |
| Test name: Testosterone Free, Females or Children
|
| ARUP #: 0081059 |
Methodology: 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.
|
| Comments: |
| Test name: Sex Hormone Binding Globulin
|
| ARUP #: 0099375 |
| Methodology: Electrochemiluminescent Immunoassay
|
| Comments: |
| Test name: Testosterone, Urine
|
| ARUP #: 0070716 |
| Methodology: Chemiluminescent Immunoassay
|
| Comments: |
| Test name: Androstenedione
|
| ARUP #: 0070020 |
| Methodology: Chemiluminescent Immunoassay
|
| Comments: |
| Test name: 5-a-Dihydrotestosterone
|
| ARUP #: 0078005 |
| Methodology: Radioimmunoassay
|
| Comments: |
References
Guidelines
American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients--2002 update. Endocr Pract.
2002;
8(
6):
440-456.
General References
Darby E, Anawalt BD. Male hypogonadism : an update on diagnosis and treatment. Treat Endocrinol.
2005;
4(
5):
293-309.
Morales A, Buvat J, Gooren LJ, Guay AT, Kaufman JM, Tan HM, Torres LO. Endocrine aspects of sexual dysfunction in men. J Sex Med.
2004;
1(
1):
69-81.
Ohl DA, Quallich SA. Clinical hypogonadism and androgen replacement therapy: an overview. Urol Nurs.
2006;
26(
4):
253-9, 269.
Rogol AD. Pubertal androgen therapy in boys. Pediatr Endocrinol Rev.
2005;
2(
3):
383-390.
Sampson N, Untergasser G, Plas E, Berger P. The ageing male reproductive tract. J Pathol.
2007;
211(
2):
206-218.
Seftel A. Male hypogonadism. Part II: etiology, pathophysiology, and diagnosis. Int J Impot Res.
2006;
18(
3):
223-228.
Seftel AD. Male hypogonadism. Part I: Epidemiology of hypogonadism. Int J Impot Res.
2006;
18(
2):
115-120.
References from the ARUP Institute for Clinical and Experimental Pathology Research®
Kushnir MM, Rockwood AL, Roberts WL, Pattison EG, Bunker AM, Fitzgerald RL, Meikle AW. Performance characteristics of a novel tandem mass spectrometry assay for serum testosterone. Clin Chem.
2006;
52(
1):
120-128.
Medical Reviewers
Meikle, A. Wayne, M.D. Medical Director, RIA and Endocrinology at ARUP Laboratories; Professor of Internal Medicine and Pathology, University of Utah
Roberts, William L. , M.D., Ph.D. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor, Pathology, University of Utah
Comprehensive Review: July 2008
Last Update: July 2008
