Introduction: We report a rare case of hyperandrogenism associated with portal hypertension as a result of Alagille syndrome.
Case report: 21-yr old female presented with primary amenorrhoea and mild hirsutism. There was no history of delayed puberty or acne. Past medical history: Alagille syndrome (biliary tree hypoplasia, liver disease, portal hypertension, splenomegaly, Barretts oesophagus and pulmonary stenosis). Drug history: creon, ursodeoxycholic acid, alimemazine, vitamins. Her mother and sister have mild Alagille syndrome. Her mother also has PCOS. On examination: BMI of 24.2 kg/m2 (160 cm, 62 kg), mild hirsutism, tanner 5 breast and pubic hair, and absent cliteromegaly.
Investigations: Total testosterone range 8 to 13 nmol/L (0.23.0), androstenedione 26 nmol/L (710.8), DHEAS 1.4 μmol/L (0.9 12), LH 18 iu/L (210), FSH 8.9 iu/L (2-10), 17-OH-progesterone 3.4 nmol/L (18.7), 17-β-Oestradiol 253 pmol/L, SHBG 116 nmol/L (3075) , Free Androgen index 10% (<7.2), Bilirubin 33 μmol/L (021), ALP 342 iu/L (30130). Low dose dexamethasone suppression test did not suppress testosterone (8 to 6.6). MR and ultrasound: normal adrenals, PCO appearances and 4 mm endometrium. Karyotyping was normal. Increased 24-hr urinary androstenetriol 1115 μg/24 h (mean 294) and α-cortolone 1339 μg/24 h (mean 675) noted, which are reported biochemical markers of portal hypertension.
Progress: Endometrium responded to progesterone challenge. Given liver transplantation is under consideration, 3 to 4 monthly oral progesterone challenge is planned.
Discussion: Relative increase in androgens is hypothesised as result of portovenal shunting of androgens from reduced liver catabolism of androgenic steroids, possibly aggravated by excess release from polycystic ovaries. Congenital portosystemic shunt causing hyperinsulinaemia may drive the ovaries to produce excess androgens.
Learning points: 1. Hyperandrogenism can be caused by impaired hepatic steroid metabolism and increased urinary androstenetriol is believed to be the marker of this process. 2. Liver transplantation is definitive treatment, but triphasic oral contraceptives utility is reported in literature.