Background: Familial male-limited precocious puberty (FMPP) or testotoxicosis is a rare form of gonadotrophin-independent precocious puberty. There is a paucity of data on final adult height in these patients and no consensus on what constitutes appropriate treatment. Our aim was to assess the management and final height of patients with FMPP under our care as well as those reported in the literature.
Methods: Growth data were obtained from notes of four local patients with FMPP. We then undertook a literature search (June 2017) to extract data on reported cases of FMPP where final height data were available using Ovid Medline and PubMed. The keywords testotoxicosis or familial male-limited precocious puberty or familial male precocious puberty or male-limited gonadotropin-independent precocious puberty were used. Treatment and height data were extracted from published cases and UK 90 population data used to calculate S.D. scores.
Results: Final height data were available on 25 men with FMPP of whom 21 were treated with agents that impair steroidogenesis (ketoconazole; n=12), anti-androgens (cyproterone, spironolactone, medroxyprogesterone, flutamide; n=11), aromatase inhibitors (AI-Letrozole, Anastrozole, Testolactone; n=4), GnRH analogues (n=6) and growth hormone (n=2). The final height SDS of patients ranged from −3.8 to +1.52 with a median of −1.5 S.D., which was not significantly different to the mid-parental target of −0.6 S.D. (P=0.1). Seven patients (28%) were short with a height more than 2 S.D. below the mean, all receiving anti-androgen ± ketoconazole. Eight patients (32%) had a final height above the mid-parental target, three of whom received an AI. The median height S.D. of the four untreated patients was −0.03 and of the four receiving an AI was +0.5 S.D.. All eight of these patients had a height within normal limits.
Conclusions: Treatment with a third generation aromatase inhibitor is associated with a positive height outcome but untreated FMPP is not always associated with a height below parental target. The impact of the various interventions is complicated by polypharmacy, variation in treatment duration and a likely difference in underlying clinical phenotype. Clinicians need to be cautious when counselling families about the potential impact of medication on final adult height.