What is the pathophysiology of microphallus?

Updated: Nov 30, 2020
  • Author: Karen S Vogt, MD; Chief Editor: Sasigarn A Bowden, MD  more...
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Fetal production of testosterone and its peripheral conversion to dihydrotestosterone (DHT) is necessary for normal male development. Early in gestation, placental human chorionic gonadotropin (hCG) stimulates the developing testes to produce testosterone by binding to the luteinizing hormone (LH) receptor. By approximately 14 weeks' gestation, the fetal hypothalamic-pituitary-gonadal axis is active, and testosterone production falls under the control of fetal LH. Penile growth after the first trimester depends on fetal gonadotropin production. Testosterone is peripherally converted by the enzyme 5-alpha reductase to the more potent androgen DHT, which is responsible for virilization of the male external genitalia. Finally, intact peripheral androgen receptors are necessary for normal male development. [10, 11]

After an initial surge of LH and testosterone at birth, lasting about 12 hours, gonadotropin (LH and follicle stimulating hormone [FSH]) and testosterone levels are low during the first few days of life. At about 1 week of age, gonadotropin and testosterone levels begin to rise to pubertal levels, peaking at age 1-3 months, and then decreasing to prepubertal levels by age 6 months. [12, 13] After age 6 months, the little subsequent penile growth that occurs parallels general somatic growth. With the onset of puberty penis growth resumes because of increased testosterone production. Growth hormone also plays a role in penis growth as micropenis has been observed in children with isolated growth hormone deficiency.

Micropenis may be caused by a defect anywhere along the hypothalamic-pituitary-gonadal axis, a defect in peripheral androgen action, isolated growth hormone deficiency, a primary structural anomaly, or may be part of a genetic syndrome. The most common cause of micropenis is abnormal hypothalamic or pituitary function. In the absence of normal hypothalamic or pituitary function, a normally shaped penis may develop due to maternal hCG effect on fetal testosterone production, but adequate penile growth does not occur after 14 weeks' gestation when testosterone production depends on intact fetal pituitary LH secretion. Failure of adequate testosterone production toward the end of gestation due to a primary testicular disorder can also result in inadequate penis growth.

Micropenis can also occur in children with LH-receptor defects and defects in testosterone biosynthesis (e.g. 17-beta hydroxysteroid dehydrogenase deficiency). [12] The genitalia of individuals with LH-receptor defects vary from normal female-appearing to male-appearing with micropenis. Individuals with 17-beta hydroxysteroid dehydrogenase deficiency most often have female-appearing genitalia and, less often, ambiguous genitalia. [14]

Defects in peripheral androgen action include 5-alpha reductase deficiency (failure of conversion of testosterone to DHT) and partial androgen insensitivity syndrome (PAIS) due to an androgen receptor defect. However, most children with these conditions have varying degrees of incomplete labioscrotal fusion, resulting in hypospadias and genital ambiguity. [14, 15]

Lastly, genetic syndromes in which micropenis may be a feature include Prader-Willi, Klinefelter, and Noonan syndromes, among others (see Causes). [14, 16]

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