Primary amenorrhoea with hypertension: undiagnosed 17‐α‐hydroxylase deficiency

Abstract

Clinical recordA 22-year-old Taiwanese woman on a working holiday in Australia was admitted to hospital in March 2011 with a cervical spine fracture from a motor vehicle accident. During her hospital stay it was noted that she had metabolic alkalosis with significant hypokalaemia.Her past medical history included,presentation at 16 years of age with primary amenorrhoea that was attributed to pubertal delay.At that time, she was given oestrogen-progesterone replacement therapy, which induced withdrawal bleeding. She noted an increase in stature after commencing hormone replacement therapy, growing to the height of her two brothers. She was diagnosed with Mild hypertension-at a pre-immigration health check in Taiwan. After arriving in Australia, 12 months before the accident, she had stopped taking,hormonal therapy and experienced complete cessation of withdrawal bleeds. She was ethnically Han Chinese with no family history of consanguinity.Physical examination revealed she was tail and thin, with height 174 cm and body mass index 19.6 kg/m(2). Her blood-pressure was elevated, with a-maximal reading of 190/120 mmHg. In addition to bruising consistent with her injury, she had hyperpigmentation of the oral mucosa and axillary areas (Box 1). Pubic and axillary hair were absent, and-breast development was minimal (Tanner stage 2). An abdominal computed tomography scan showed bulky adrenal glands and an atrophic uterus. Her potassium level was 2.4 mmol/L and an-initial electrocardiogram showed sinus rhythm and hypokalaemic changes, including a prolonged corrected QT interval, but no left ventricular hypertrophy.The medical team prescribed verapamil 80 mg three times daily. Potassium replacement in excess of 120 mmol/day was required to maintain a potassium level of 2.7-3.0 mmol/L. Advice was sought from endocrinologists.On review, given the patient's history, clinical signs and biochemistry profile, an upstream block in steroid synthesis was suspected. Further biochemical testing showed low levels of serum cortisol, oestradiol and testosterone and high levels of adrenocorticotrophic hormone, gonadotrophins and progesterone. Serum aldosterone and renin levels were low (Box 2). These results are consistent with 17-alpha-hydroxylase deficiency. This diagnosis was further supported by steroid Metabolite levels in a spot urine sample. Pregnanediol (a progesterone metabolite), tetrahydrocorticosterone and tetrahydro compound A (deoxycorticosterone metabolites) were elevated. In addition, decreased 11-deoxycortisol and cortisol metabolites (tetrahydrodeoxycortisol, tetrahydrocortisone and tetrahydrocortisol) and decreased androstenedione metabolites (etiocholanolone and androsterone) were observed.Sequencing of CYP17A1 demonstrated homozygosity for a non-synonymous-mutation (ie, one that changes the amino acid sequence of the protein) previously described in the Chinese population. A karyotype analysis was not performed, owing to the patient's history of withdrawal bleeds with hormone replacement therapy and visualisation of the uterus on imaging that was performed because of her traumatic injuries.The patient was-commenced-on prednisolone 10 mg twice daily and spironolactone 25 mg daily. Hypokalaemia and hypertension resolved rapidly, and potassium supplementation, spironolactone and verapamil were no longer required. Recommencement of sex hormone replacement and weaning of prednisone to a physiological dose were planned for after her return to Taiwan.