- Author: Karen S Vogt, MD; Chief Editor: Stephen Kemp, MD, PhD more...
A karyotype is recommended to confirm chromosomal sex. If PWS is suspected, methylation studies should be performed, and if positive, further genetic analysis for the specific genetic defect is indicated.
Gonadotropins (LH and FSH) reach pubertal levels in healthy male infants, peaking at age 1-3 months and declining by about age 6 months. Excessively high or low values during this "minipuberty" help to narrow the differential diagnoses.
Anti-M ü llerian hormone (M ü llerian inhibitory substance) and inhibin B are markers of Sertoli cell function and can be useful as indicators of the presence of testicular tissue in the setting of bilateral cryptorchidism.
Testosterone and DHT levels, before and after hCG stimulation, can be measured to evaluate the responsiveness of the testes to gonadotropin stimulation and for 5-alpha reductase deficiency (indicated by an increased testosterone-to-DHT ratio).
Given the possibility of panhypopituitarism, observe all infants with micropenis for hypoglycemia and evidence of other metabolic derangements. If hypoglycemia occurs, obtain a critical sample immediately before intravenous glucose is administered. The critical sample should include glucose, insulin, growth hormone, and cortisol levels.
In infants with hypoglycemia or suspected hypopituitarism, other pituitary hormone function should be evaluated. Evaluation of the thyroid axis should include measurement of total or free thyroxine (T4) as well as thyrotropin stimulating hormone (TSH). Growth hormone and cortisol levels may need to be measured after stimulation (eg, with glucagon for growth hormone and cortisol or ACTH for cortisol).
In situations of genital ambiguity, pelvic ultrasonography is often helpful. The presence of a uterus and ovaries strongly suggests a virilized female (46,XX) infant.
When hypopituitarism is suspected, an MRI of the head should be obtained to evaluate the hypothalamic and pituitary areas. In Kallmann syndrome, abnormalities of the olfactory system may be seen.
Feldman KW, Smith DW. Fetal phallic growth and penile standards for newborn male infants. J Pediatr. 1975 Mar. 86(3):395-8. [Medline].
Bin-Abbas B, Conte FA, Grumbach MM. Congenital hypogonadotropic hypogonadism and micropenis: effect of testosterone treatment on adult penile size why sex reversal is not indicated. J Pediatr. 1999 May. 134(5):579-83. [Medline].
Schonfeld WA, Beebe GW. Normal growth and variation in male genitalia from birth to maturity. J Urol. 1942. 64:759-777.
Wessells H, Lue TF, McAninch JW. Penile length in the flaccid and erect states: guidelines for penile augmentation. J Urol. 1996 Sep. 156(3):995-7. [Medline].
Bhakhri BK, Meena SS, Rawat M, Datta V. Neonatal stretched penile length: relationship with gestational maturity and anthropometric parameters at birth. Paediatr Int Child Health. 2014 Jan 26. [Medline].
Tuladhar R, Davis PG, Batch J. Establishment of a normal range of penile length in preterm infants. J Paediatr Child Health. 1998 Oct. 34(5):471-3. [Medline].
Cohee, L. Endocrinology: Table 10-19: Mean Stretched Penile Length. Tschudy MM, Arcara KM. The Harriet Lane Handbook. 19th ed. Philadelphia, PA: Elsevier; 2012. Chapter 10.
Hughes IA. The Testes: Disorders of Sexual Differentiation and Puberty in the Male. Sperling MA. Pediatric Endocrinology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2008. Chapter 16.
Achermann JC, Hughes IA. Disorders of Sex Development. Melmed. Williams Textbook of Endocrinology. 12th ed. Philadelphia, PA: Elsevier Saunders; 2011. Chapter 23.
Grumbach MM. A window of opportunity: the diagnosis of gonadotropin deficiency in the male infant. J Clin Endocrinol Metab. 2005 May. 90(5):3122-7. [Medline].
Quigley CA. Editorial: The postnatal gonadotropin and sex steroid surge - Insights from the androgen insensitivity syndrome. J Clin Endocrinol Metab. 2002. 87:24-28. [Medline].
Witchel SF, Lee PA. Ambiguous Genitalia. Sperling MA. Pediatric Endocrinology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2008. 127-164. Chapter 4.
Maimon L, Philibert P, Cammas B, et. al. Phenotypical, biological, and molecular heterogeneity of 5-alpha-reductase deficiency: An extensive international experience of 55 patients. J Clin Endocrinol Metab. Feb 2011. 96(2):296-307. [Medline].
Achermann JC, Ozisik G, Meeks JJ. Genetic causes of human reproductive disease. J Clin Endocrinol Metab. 2002. 87:2447-2454. [Medline].
Hayes FJ, Seminara SB, Crowley WF. Hypogonadotropic hypogonadism. Endocrinol Metab Clin North Am. 1998. 27:739-763. [Medline].
Pallais JC, Au M, Pitteloud N, et al. Kallmann Syndrome. GeneReviews. Available at http://www.ncbi.nlm.nih.gov/books/NBK1334/. Accessed: 3 July 2011.
Toogood AA, Stewart PM. Hypopituitarism: clinical features, diagnosis, and management. Endocrinol Metab Clin North Am. 2008 Mar. 37(1):235-61, x. [Medline].
Melmed S, Kleinberg D, Ho K. Pituitary Physiology and Diagnostic Evaluation. Melmed S. Williams Textbook of Endocrinology. 12th ed. Philadelphia, PA: Elsevier Saunders; 2011. Chapter 8.
Tsigos C, Latronico C, Chrousos GP. Luteinizing hormone resistance syndromes. Ann N Y Acad Sci. 1997 Jun 17. 816:263-73. [Medline].
Boehmer AL, Brinkmann AO, Sandkuijl LA, et al. 17Beta-hydroxysteroid dehydrogenase-3 deficiency: diagnosis, phenotypic variability, population genetics, and worldwide distribution of ancient and de novo mutations. J Clin Endocrinol Metab. 1999 Dec. 84(12):4713-21. [Medline].
Lee YS, Kirk JM, Stanhope RG, et al. Phenotypic variability in 17beta-hydroxysteroid dehydrogenase-3 deficiency and diagnostic pitfalls. Clin Endocrinol (Oxf). 2007 Jul. 67(1):20-8. [Medline].
Gad YZ, Nasr H, Mazen I. 5 alpha-reductase deficiency in patients with micropenis. J Inherit Metab Dis. 1997 Mar. 20(1):95-101. [Medline].
Sinnecker GH, Hiort O, Dibbelt L. Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency. Am J Med Genet. 1996 May 3. 63(1):223-30. [Medline].
Palmer JS. Genitourinary manifestations in boys and girls associated with genetic disease. J Men's Health Gend. March 2006. 3(1):71-79.
Cassidy SB, Schwartz S. Prader-Willi Syndrome. GeneReviews. Available at http://www.ncbi.nlm.nih.gov/books/NBK1330/. Accessed: 2 July 2011.
Waters AM, Beales PL. Bardet-Biedl Syndrome. GeneReviews. Available at http://www.ncbi.nlm.nih.gov/books/NBK1363/. Accessed: 2 July 2011.
Allanson JE. Noonan Syndrome. GeneReviews. Available at http://www.ncbi.nlm.nih.gov/books/NBK1124/. Accessed: 2 July 2011.
Ragan DC, Casale AJ, Rink RC. Genitourinary anomalies in the CHARGE association. J Urol. 1999 Feb. 161(2):622-5. [Medline].
Lalani SR, Hefner MA, Belmont JW et al. CHARGE Syndrome. GeneReviews. Available at http://www.ncbi.nlm.nih.gov/books/NBK1117/. Accessed: 2 July 2011.
Bourgeois MJ, Jones B, Waagner DC. Micropenis and congenital adrenal hypoplasia. Am J Perinatol. 1989 Jan. 6(1):69-71. [Medline].
Becker D, Wain LM, Chong YH, et al. Topical dihydrotestosterone to treat micropenis secondary to partial androgen insensitivity syndrome (PAIS) before, during, and after puberty - a case series. J Pediatr Endocrinol Metab. 2016 Feb. 29 (2):173-7. [Medline].
Calikoglu AS. Should boys with micropenis be reared as girls? [editorial]. J Pediatr. 1999 May. 134(5):537-8. [Medline].
Wisniewski AB, Migeon CJ, Gearhart JP, et. al. Congenital micropenis: Long-term medical, surgical, and psychosexual follow-up of individuals raised male or female. Hormone Research. 2001. 56:3-11. [Medline].
Drugs: Testosterone. MD Consult. Available at http://www.mdconsult.com. Accessed: 2 July 2011.
Menon RK, Trucco M, Stratakis CA. Molecular Endocrinology and Endocrine Genetics. Sperling MA. Pediatric Endocrinology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2008. Chapter 1.
Styne DM, Grumbach MM. Puberty: Ontogeny, Neuroendocrinology, Physiology, and Disorders. Melmed S. Williams Textbook of Endocrinology. 12th ed. Philadelphia, PA: Elsevier Saunders; 2011. Chapter 25.