ESPE Abstracts

Background: A thirty-four months old boy was referred for precocious puberty. He was the first child of healthy non-consanguineous parents. His family history was unremarkable. He had no exposure to oestrogenic endocrine-disrupting chemicals. He had presented secondary sexual characteristics for five months: pubic hair, enlarged testicular volume to 6 ml (Tanner stage P2A1G2) and enlarged penile size. He had a deepening voice and aggressive behavior. He had a significant growth acceleration with an advanced bone age (six years according to the Grulich and Pyle atlas). His height was 103 cm (2 SDS).

Laboratory investigations: Testosterone level was high: 190 ng/dl. The gonadotrophin hormone-releasing hormone stimulation test revealed baseline LH and FSH levels at 0.1 UI/l and LH and FSH peaks at 2.6 UI/l and at 1.2 UI/l respectively. AMH level was 26.6 ng/ml. Inhibin B level was 189 ng/ml. IGF-1 level was high at 306 ng/ml (3 DS). The adrenal function was normal. Tumor markers were normal. Ultrasound analysis of testes and adrenal did not reveal any tumor. Brain MRI excluded a hypothalamic tumor.

Evolution and management: The diagnosis of central precocious puberty was made and a treatment with monthly intramuscular injections of gonadotrophin releasing hormone analog (GnRHa) was started. Three months later, no clinical improvement was noticed: testicular volume progressed to 8ml, and height was 109 cm (4 DS). LH and FSH Baseline levels were 0.7 UI/l, and 0.1 UI/l respectively. The testosterone level increased to 310 ng/dl with a lowering AMH level at 12.3 ng/ml. GnRHa treatment was switched to long action every three months associated to cyproterone acetate.

Genetic analysis: Found a mutation of the LH-receptor gene (Met398Thr) already reported to constitutively activate the LH receptor. The diagnosis of peripheral precocious puberty was made.

Conclusion: This case of testotoxicosis is unusual as it initially presented as a central precocious activation of the gonadotropic axis at a very young age. Due to resistance to GnRH agonist treatment, the diagnosis of constitutive activation of the LH receptor was then suspected and confirmed by molecular genetics. It questions about the cellular mechanism of the central activation of the gonadotropic axis.