Familial Testotoxicosis: Outcome and Possible Relation to Testicular Malignancies

ICL Kremer Hovinga, AA Verrijn Stuart

Research output: Contribution to conferencePosterOther research output


Background: Testotoxicosis or familial male-limited precocious puberty (FMPP) is a rare disease caused by an autosomal dominant activating mutation of the luteinizing hormone receptor gene, leading to early gonadotrophin-independent precocious puberty. Phenotypic expression is limited to males. Treatment evolved over the last decades and nowadays consists of a combination of a potent anti-androgen agent and a third-generation aromatase inhibitor. Since the identification of etiologic gene mutations in 1993, pre-symptomatic genetic testing provides the opportunity of early diagnosis and treatment without diagnostic delay.

Objective and hypotheses: Evaluation of clinical course and outcomes in FMPP families.

Method: Nine affected males; two generations in four families were evaluated. Information was gathered on clinical course, therapy and mutation analysis.

Results: All four affected fathers were diagnosed based on clinical symptoms. One of them remained untreated and reached a final height of 165 cm. Three others were treated and attained normal final heights (183, 187 and 189 cm). Regarding their offspring, one family opted for pre-symptomatic genetic testing, revealing FMPP in two brothers. Early onset of treatment (age 1.5 years) resulted in a final height in the lower part of target height range. In three other families, diagnosis of FMPP in offspring was made after onset of clinical symptoms at the age of 3–5 years. Treatment was started subsequently. These boys have not yet reached final height, however treatment resulted already in a decrease of both growth rate and skeletal maturation rate. Two affected adults developed testicular cancer in their twenties (embryonal carcinoma and non-seminoma).

Conclusion: In these families, pre-symptomatic genetic analysis has not led to increased final height. Furthermore, concern is raised by the fact that 50% of adults developed testicular malignancies. We therefore suggest surveillance of adult FMPP patients after treatment in childhood.
Original languageEnglish
Number of pages1
Publication statusPublished - 2016
Event55th Annual ESPE Meeting: ESPE 2016 - Paris, France
Duration: 10 Sept 201612 Sept 2016


Conference55th Annual ESPE Meeting


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