Endocrine Abstracts

P450 Oxidoreductase (POR) deficiency is a rare autosomal recessive disorder of steroidogenesis with varied clinical presentation. POR is the electron donor for all microsomal enzymes involved in steroidogenesis namely P450c 17(17 hydroxylase/17,20 lyase), P450c 21 (21 –hydroxylase), and P450 aro(aromatase). POR deficiency can cause genital ambiguity in both sexes, impaired steroidogenesis and skeletal malformations. Here we present a patient with ovarian cysts and delayed puberty with a novel mutation in the POR gene. A 14 year old girl born of 3^rd degree consanguineous marriage presented with acute abdominal pain, on evaluation found to have torsion of large right hemorrhagic ovarian cyst requiring surgical intervention with oophorectomy. 3 to 4 months later patient presented with recurrence of abdominal pain, investigation revealed large cyst in left ovary for which cystectomy was done, subsequent serial ultrasonography evaluation for the next 6months revealed increase in size of ovarian cysts. At this point endocrinology consultation was sought for not attaining menarche. History of acne eruption in the mother during pregnancy but no hirsutism. Her height was 164 cm (75-90^th centile), weights 69 kg (90-97^th centile), arm span – 171 cms, US/LS ratio-0.85:1. Sexual maturation is A1 P3 B1. No facial dysmorphism, no features of androgen excess, normotensive. Short 4^th metatarsal left foot, no other skeletal deformities. Normal external genitalia. Karyotype is 46, XX. Prolactin is 12.8 ng/ml, FSH 13.8, LH 33.7, T3- 1.66, T4- 10.5, TSH -1.10, Estradiol 24.22 pg/ml, AMH-0.45 ng/ml and testosterone 14.40 ng/dl. 8 AM serum cortisol is 12.62 mg/dl, 17 hydroxy progesterone 21.7 ng/ml, post ACTH stimulation serum 17 OHP is 22.8 ng/ml, serum cortisol 9.74 mgldl. Bone age-14 years. USG pelvis uterus 30x20x15 mm, ET 4.5mm, bulky left ovary with multiple cysts. Genetic testing showed homozygous mutation in POR (NM_000941.2), (Chr7:75615521); Exon 15; c.1860G>T (p.Trp620Cys). She was advised estrogen replacement and hydrocortisone cover during stress. In conclusion our case presented with normal genitalia, no skeletal abnormalities, no hyper androgenic features with large ovarian cysts and delayed puberty(suggestive of aromatase deficiency) with high 17(OH) progesterone and subnormal rise in cortisol and 17(OH) progesterone post ACTH stimulation consistent with POR deficiency. The wide range of phenotypic presentation may be explained by the differential inhibition of POR dependent enzymes. Given the varied clinical presentation and the risk of hypocortisolism, clinicians should be aware and alert to this diagnosis.