Genetic Disease Models

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As summarized in Table 2, disturbance of GnRH causes hypogonadism in Kallmann's syndrome by affecting the Kal-X gene, but GnRH is also affected in the Prader-Lahart-Willi syndrome and idiopathic hypogonadotrophic hypogonadism. Tumors, infiltrations, trauma, irradiation, ischemia, and surgery may cause hypothalamic or pituitary dysfunction.1,2 Isolated FSH deficiency is found with the Pasqualini syndrome.

Defects in primary testicular function are also summarized in Table 2. The causes range from congenital and chromosomal to acquired. There are also disorders of testosterone synthesis, metabolism, and action. Androgen-resistant syndromes range from complete androgen resistance to male infertility.

Table 2 Differential diagnosis of hypogonadotropic and hypergonadotropic hypogonadism

Hypogonadotropic hypogonadism (HH)

Congenital HH

Idiopathic hypogonadotropic hypogonadism (IHH) Kallmann syndrome Adult-onset IHH Fertile eunuch syndrome Adrenal hypoplasia congenita Genetic defects of the gonadotropin subunits HH associated with other pituitary hormone deficiencies HH associated with obesity Prader-Willi syndrome Laurence-Moon-Biedl syndrome

Acquired HH Structural Tumors

Craniopharyngiomas

Pituitary adenomas (e.g., prolactinoma, nonfunctioning tumor) Germinoma, glioma, meningioma Infiltrative disorders

Sarcoidosis, hemochromatosis, histiocytosis X Head trauma Radiation therapy Pituitary apoplexy Primary hypothyroidism Functional Exercise Dieting

Anabolic steroids Glucocorticoid therapy Narcotics

Critical illness (cancer) Diabetes

Metabolic syndrome Obesity

Aging (mixed with Leydig cell dysfunction)

Hypergonadotropic hypogonadism

Klinefelter's sydrome 47, XYY syndrome Dysgenetic testes Androgen receptor defects Testicular feminization Reifenstein's syndrome 5-a-reductase deficiency Androgen synthesis defects

Acquired

Myotonic dystrophy Cryptorchidism Vanishing testes syndrome Hemochromatosis Trauma

Mumps orchitis

Radiation

Chemotherapy

Autoimmune

Sertoli cell only syndrome

Human immunodeficiency virus (HIV)

Hepatic cirrhosis

Chronic renal failure

Idiopathic

Aging

Diabetes

Metabolic

Table 3 Laboratory testing of hypogonadism

Hypothalamic Primary Seminiferous tubule Leydig cell failure Pituitary disease Hypothalamic hypogonadism disease disease

Testosterone

Low

Normal

Low

Low

Low

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