An X-traordinary stroke

Abstract

In January, 2010, a 60-year-old non-smoking, white man with mild intellectual disability, presented with acuteonset diplopia and ataxic gait. There was no consanguinity or relevant family history. CT of the brain showed a left cerebellar infarct. Blood tests showed he had polycythaemia with haemoglobin of 220 g/L (normal range 130–170). Investigations to fi nd a cause for the polycythaemia showed that although his erythropoietin concentration was normal and JAK2 mutation screening negative, serum total testosterone concentration was high at 29·1 nmol/L (normal 550 nmol/L at 30 min or 60 min), high serum concentrations of 17-hydroxyprogesterone 66·9 nmol/L (<5 nmol/L) and of androstendione, 31·6 nmol/L (2·0–9·1). His urinary steroid profi le was consistent with 21-hydroxylase defi ciency. A diagnosis of congenital adrenal hyperplasia was made. Our patient’s polycythaemia was treated with regular venesection, and glucocorticoid therapy was initiated to decrease corticotropin concentrations. Adrenal size decreased substantially within weeks of glucocorticoid initiation. The importance of glucocorticoid therapy to prevent future adrenal crises and androgen excess was emphasised. He may need testosterone therapy to maintain virilisation in the future. In September, 2010 at last follow-up he was stable. Congenital adrenal hyperplasia is the most common cause of antenatal virilisation in females. 95% of cases are due to defi ciency of 21-hydroxylase, an enzyme necessary for the synthesis of cortisol. Low serum cortisol concentrations stimulate secretion of corticotropin, which leads to excess production of androgenic steroids. Treatment is with glucocorticoids to prevent adrenal crisis and to normalise corticotropin concentrations, preventing excess androgen production. Excessive use of glucocorticoids should be avoided, because it can lead to growth retardation and iatrogenic Cushing’s syndrome. Our patient’s congenital adrenal hyperplasia was untreated for decades, and the sustained high concentrations of corticotropin caused severe adrenal hyperplasia with increased androgen production. Androgen excess during growth resulted in his short stature because of premature closure of the epiphyses. Androgen excess leads to polycythaemia through stimulation of erythropoiesis. Although polycythaemia is a well-described risk factor for stroke, androgenic polycythaemia in congenital adrenal hyperplasia has been reported only rarely. Androgen excess should be considered as a cause for poly cythaemia. Our patient’s case highlights the harmful eff ects of unfettered androgen excess in untreated congenital adrenal hyper plasia, and is also an important reminder on the importance of a genital examination as a part of a complete physical examination.