A rare cause of hypertension in a healthy 2-year-old female: Answers

Abstract

This patient has 17α-hydroxylase deficiency, a rare form of congenital adrenal hyperplasia (CAH) and one of the rarer forms of monogenic hypertension. This autosomal recessive disorder results from a complete or partial deficiency of the P450c17 enzyme, which has both 17α-hydroxylase and 17,20-lyase activity (see Fig. 1) [1]. The enzymatic defect leads to impaired formation of cortisol and sex hormones, with retained functioning of the mineralocorticoid pathway. The first case of 17α-hydroxylase deficiency was reported in 1966 by Biglieri, who described a 35-year-old woman who was hypertensive and hypokalemic and had not entered puberty [2]. Since that time, more than 200 cases have been reported in the literature [3]. Overall, 17α-hydroxylase deficiency constitutes approximately 1 % of CAH cases [4]. It has been more commonly identified in certain ethnic populations, including Brazilians and Japanese [5, 6]. As in other forms of CAH, cortisol deficiency stimulates adrenocorticotropic hormone (ACTH) production, ultimately resulting in adrenal gland hyperplasia. In 17αhydroxylase deficiency, this leads to an accumulation of deoxycorticosterone (DOC) and corticosterone (see Fig. 1). In this patient, DOC was elevated at 116 ng/dL (normal range 2–34 ng/dL) and corticosterone was also elevated at 14,948 ng/dL (normal range 135–1860 ng/dL). Hypertension, hypokalemia and metabolic alkalosis result from elevated DOC, which has mineralocorticoid activity. The extent of hypertension may vary significantly in this condition. In one of the larger cohorts described, average blood pressure prior to treatment was 146/100 mmHg at a median age of 18 years [5]. Malignant hypertension may also be seen [7]. Interestingly, 17α-hydroxylase deficiency does not present with adrenal crisis despite the lack of cortisol, as the elevated corticosterone provides sufficient glucocorticoid activity. Although one might anticipate that these patients would have elevated aldosterone levels, the opposite is typically true. 17-α-Hydroxylase deficiency causes a non-aldosterone mineralocorticoid hypertension, also known as pseudoaldosteronism. In this condition, high levels of DOC cause volume expansion, leading to suppression of the renin– angiotensin system and subsequent low levels of renin and aldosterone [8]. It is important to note that hypokalemia is not consistently observed, as demonstrated in this case and previously documented in the literature [5]. Thus, a normal serum potassium should not sway one from considering the diagnosis. As with This article refers to the article that can be found at http://dx.doi.org/ 10.1007/s00467-012-2161-5.