Endocrine Abstracts

Background: Combined pituitary hormone deficiency (CPHD) is characterized by multiple pituitary hormone deficiencies, due to mutations of pituitary transcription factors involved in pituitary ontogenesis. The genetic basis for CPHD is complex, involving a variety of syndromic and non-syndromic presentations with variable degrees of phenotype-genotype correlations. In male infants with CPHD, gonadotropin deficiency is suggested by the presence of a microphallus and undescended testes, as the growth of the penis and normal testicular descent are dependent upon the normal secretion of fetal LH in the second and the third trimesters. However, more severe genital abnormalities, such as hypospadias or ambiguous genitalia, indicate a defect of hCG-driven androgen secretion and/or action in early fetal life, before the initiation of endogenous hypothalamic-pituitary-gonadal axis activity. Herein, we describe a clinical case of a 15-year-old and 5 months male with a history of premature delivery, ambiguous genitalia at birth (Prader stage 3), who was admitted to the Department of Endocrinology due to underdeveloped genitalia and delayed puberty. Postnatally, it was suspected apartial 46XYDSD after chromosome analysis. Physical examination revealed an overweight patient of normal height, Taner stage 1, micropenis, bifid scrotum, penoscrotal hypospadias, palpable prepubertal gonads in the scrotum (after orchidopexy). Hormonal assayse stablished the combined deficiencies of pituitary hormones: GH, TSH, ACTH, and gonadotropins. The provocative tests revealed no response to GnRH but a significant increase in testosterone level after hCG. Ultrasound imaging didn’t find either Mullerian structures or adrenal hyperplasia; the testicular structure was normal, but with a hypoplasic aspect. Brain MRI showed a normal adenohypophysis, a hypoplasic and ectopic neurohypophysis, and a thin pituitary stalk with interruptions. The hand radiogram revealed a bone age of 12. The genetic testing results are at work.

Conclusion: This case illustrates an atypical presentation of CPDH with normal growth despite GH deficiency and genital anomalies indicating an androgen deficiency in early fetal life. It also highlights the need to evaluate the hypothalamic-pituitary axis in selected cases of intersex, and questions the prevailing assumptionsabout the mechanisms underlying the control of testosterone secretion during embryogenesis.