ESPE Abstracts

Background: Precocious puberty has a complex and polygenic etiology. To describe genetic factors affecting onset and regulation of puberty and pathophysiology of precocious puberty, further studies are needed. Although, it is reported that ACTH receptor MC4R has impact on premature adrenarche, MC2R is expressed in the adrenal cortex and has a major role on the control of hypothalamo-pituitary-adrenal cortex. Melanocortin signaling system is reported to have leptin mediated affect on the regulation of GnRH neuron activity and has an important role in the onset of puberty and fertility.

Objective and hypotheses: To evaluate the early onset puberty of patients with primary adrenal insufficiency due to Melanocortin receptor 2 (MC2R) gene mutation.

Methods and patients: Four patients (3M,1F) with primary adrenal insufficiency, two of whom are siblings were included in the study. Age of diagnosis was between 6 days-11 months and follow up period was 7.6–20.4 years. The female patient had also congenital hypothyroidism due to dyshormonogenesis and thyroid hormone levels were in normal ranges with L-thyroxine replacement. All the patients were from consanguinous families and there was no family history of precocious puberty. All the patients were term and appropriate for gestational age. Patients had severe MC2R mutation(c\.560delT,p.V187Afs*29) causing adrenal insufficiency In two brothers and the third male patient central precocious puberty started at 8.5, 7.4 and 9.5 years, respectively. Female patient’s central precocious puberty was detected at the age of 8.5 years. LH, T (male)/Estradiol (female) levels of the patients were in pubertal ranges. Puberty had rapid progression in one of the brothers and GnRH analogue was started when he was 11 years old. Precocious puberty was newly detected in his brother and progression is still at follow-up. The third male patient had also completed pubertal progression and his final height was −2.6 SDS (Target height SDS: −1.0). Female patient’s age of menarche was 11 years old and she had completed puberty.

Conclusion: We report that ACTH receptor-MC2R gene mutation and onset and regulation of puberty may be related. We also recommend that these patients must be closely followed for precocious pubertal development.