Endocrine Abstracts

We present the case of a 28-year old woman who presented with menstrual irregularity and hirsutism since menarche at age 11. She had been diagnosed with polycystic ovarian syndrome and treated with the oral contraceptive pill for 12 years, despite BMI of 21 kg/m². Blood pressure was 101/66 mmHg. Baseline electrolytes showed sodium 140 mmol/L, potassium 3.6 mmol/L. Short synachthen test confirmed the biochemical diagnosis of congenital adrenal hyperplasia (CAH) [cortisol 275 nmol/L (0min), 335 nmol/L (30 min), 371 nmol/L (60 min) and 17-hydroxyprogesterone of 32.5 nmol/L (0 min), 173.5 nmol/L (30 min), 201.2 nmol/L (60 min)]. Long synachthen test revealed cortisol of 356 nmol/L (0 min), 389 nmol/L (30 min), 488 nmol/L (60 min), 534 nmol/L (240 min), 586 nmol/L (360 min), 815 nmol/L (440 min), 279 nmol/L (2880 min). Prolonged oral glucose tolerance test was performed, as she complained of hypoglycaemia-like symptoms, confirming hypoglycaemia at 3 hours post-glucose load (glucose 2.1 mmol/L) with appropriate spontaneous recovery (glucose 4.1 mmol/L at 300 min). Genetic testing confirmed non-classical CAH due to 21-hydroxylase deficiency. She was heterozygous for c.89C and c.841G with normal CYP21A2 copy number. She started Dexamethasone 0.25 mg daily and responded well. Androstenedione levels decreased to 11.4 nmol/L. She still complains of fatigue in early evening and a cortisol day curve is scheduled to investigate need for a second dose of dexamethasone. Non-classic CYP21A2 deficiency is one of the most common autosomal recessive diseases. Despite general correlations, the CYP21A2 deficiency phenotype does not always correlate precisely with the genotype, suggesting that other genes influence the clinical manifestations. Women with late-onset form may be compound heterozygotes (classic mutation and a variant allele) or heterozygotes with two variant alleles, allowing for 20–60% of normal enzymatic activity. Women who are compound heterozygotes for two different CYP21A2 mutations usually have the phenotype associated with the less severe of the two genetic defects.