Abstract: Familial male-limited precocious puberty (FMPP) is an autosomal-dominant form of gonadotropin-independent precocious puberty resulting from a heterozygous activating mutation in the gene encoding the luteinizing hormone (LH) receptor. Affected males usually show evidence of virilization and accelerated linear growth by 1 to 3 years of age. Untreated, affected males experience premature epiphyseal fusion and compromised adult height. Establishing the diagnosis of FMPP is straightforward when a positive family history is present. In the absence of a positive family history, mutation analysis of the LH receptor can be performed once other etiologies of precocious puberty have been excluded. There are 2 primary treatment approaches to FMPP. The first is oral administration of ketoconazole to block sex steroid synthesis. This approach suppresses puberty until the addition of GnRH analog is necessary for suppression of secondary GnRH-dependent precocious puberty. Occasionally, serious dose-independent hepatotoxicity results from ketoconazole therapy. The second treatment approach involves a combination of spironolactone and testolactone to block androgen effect and estrogen synthesis. Again, addition of GnRH analog is necessary once secondary GnRH-dependent puberty is present. Long-term treatment with spironolactone, testolactone, and GnRH analog normalizes rate of growth and bone maturation and improves adult height in boys with FMPP.
Program Director, Type 1 Diabetes TrialNet, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Division of Diabetes, Endocrinology, and Metabolic Diseases, Bethesda, Maryland.
The author has disclosed that she has no significant relationships with or financial interests in any commercial company that pertains to this educational activity.
The author discloses that spironolactone and testolactone have not been approved by the U.S. Food and Drug Administration for use in the treatment of familial male-limited precocious puberty.
Reprints: Ellen Leschek, MD, National Institutes of Health, 6707 Democracy Boulevard, Room 603, MSC 5460, Bethesda, MD 20892–5460. E-mail: LeschekE@extra.niddk.nih.gov.
Chief Editor’s Note: This article is the 17th of 36 that will be published in 2004 for which a total of up to 36 Category 1 CME credits can be earned. Instructions for how credits can be earned precede the CME Examination at the back of this issue.