ESPE Abstracts (2022) 95 P2-70

ESPE2022 Poster Category 2 Diabetes and Insulin (43 abstracts)

Familial Genetic Syndrome of Severe Insulin Resistance and Hyperandrogenemia in a young girl with Polycystic Ovary Morphology

Gheorghita Patriciu Zubascu 1 , Andrada Florina Predescu 1 , Ana Maria Stancu 1 , Mihaela Tarna 1 , Luminita Nicoleta Cima 1,2 , Osama Alnuaimi 3 , Aida Tincuta Petca 4,2 , Vasilica Plaiasu 5 & Simona Fica 1,2

1Department of Endocrinology, Elias University Emergency Hospital, Bucharest, Romania; 2”Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania; 3Department of Imaging and Radiology, Elias University Emergency Hospital, Bucharest, Romania; 4Department of Ginecology, Elias University Emergency Hospital, Bucharest, Romania; 5Departament of Genetics, National Institute for Mother and Child Health "Alessandrescu-Rusescu", Bucharest, Romania

Introduction: Signs of hyperandrogenemia are common through adolescent and young females, hirsutism affecting 5% of reproductive -aged women. The most common cause of hyperandrogenemia and insulin resistance (IR) is polycystic ovary syndrome (PCOS) (1). The differential diagnosis includes congenital adrenal hyperplasia (CAH) (2), androgen secreting tumors, but also very rare genetic syndromes of IR.

Case report: A 13 year-old girl presented to our Paediatric Endocrinology Department for severe hirsutism, primary amenorrhea, alopecia and progressive deepening of the voice. Family history revealed that her mother and also her maternal grandmother and great-grandmother had hirsutism and type 2 diabetes mellitus. Physical examination showed a height at presentation of 153,54 cm (-0,72 SD), BMI=17,2 kg/m2(P=23%), B3P5 Tanner stage, androgenic alopecia, clitoromegaly (~ 2,5 cm) and severe hirsutism (Preauricular hairiness, upper-lip, white line, chin and on the back). Laboratory exams revealed elevated testosterone level (3x UN), severe hyperinsulinemia (basal insulin > 21uIU/ml, insulin in OGTT> 215uIU/ml), altered glucose tolerance and an elevated 17-OH basal progesterone. Therefore, the Synacthen stimulation test was performed in order to exclude CAH (60 minutes 17-OH progesterone=9,6 ng/ml). The serum concentration of DHEA sulfate, androstenedione and cortisol were within normal limits. Pelvic ultrasound revealed infantile uterus and polycystic ovary morphology. Because the level of testosterone was very high, we decided to perform an abdominal-pelvic MRI that revealed no evidence of ovarian or adrenal masses. Genetic tests identified 46, XX Karyotype and a mutation of P453S (c.1657C>T) CYP21A2. Because of her family history and abnormal levels of basal and stimulated insulin a syndrome of IR was suspected and we decided to continue the genetic evaluation. Treatment with metformin was recommended along with an androgen receptor-blocking agent (spironolactone) to control hirsutism and ensure glycemic homeostasis with a good clinical and biochemical outcome.

Conclusions: Hyperinsulinemia contributes to the marked magnitude of hyperandrogenemia and is a determinant of the severity of hirsutism. There’s a group of rare congenital conditions described as inherited severe IR syndromes that can lead to severe hyperandrogenism associated with altered glucose tolerance. Therefore, detailed family history and genetic counselling should be done in such cases.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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