Background: Automimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is an extremely rare autoimmune condition caused by AIRE (autoimmune regulator) gene mutations and characterised by a classic triad of 1) chronic mucocutaneous candidiasis, 2) hypoparathyroidism and 3) adrenal insufficiency. APECED can involve any endocrine or non-endocrine organ. Consequently, clinicians need to be mindful of the great variability in presentation. Although adrenal insufficiency has been described as the initial endocrine manifestation of APECED syndrome, hypoaldosteronism without cortisol deficiency is not a recognised manifestation of APECED. We describe a young boy with atypical initial endocrine presentation.
Case: A 3-year-old British Caucasian male presented to the Emergency Department with a 3-month history of candida stomatitis resistant to nystatin and bilateral athlete’s foot. Weight and height were on the 90th centile, and the child was normotensive with no other abnormalities identified on full examination. Initial investigations for persistent candidiasis showed normal full blood count, renal, bone and liver profile, normal immunoglobulins and vaccine responses and negative Human Immunodeficiency virus screen. Unexpected low serum sodium (lowest value 128 mmol/L) resulted in specific investigations, which showed inappropriately elevated urinary sodium (44mmol/L). Paired serum and urine osmolalities were 276 mOsm/kg and 320mOsm/kg respectively. Serum ACTH (14ng/L) and cortisol (489 nmol/L) were normal. Low serum aldosterone (78pmol/L) and high renin (790mU/L) pointed towards isolated hypoaldosteronism. However, urine steroid profile did not show evidence of aldosterone synthase defect. Treatment with fludrocortisone (100micrograms daily) normalised serum sodium In view of uncertain diagnosis of primary adrenal insufficiency due to normal serum ACTH and cortisol, we measured anti-adrenal antibodies (21-hydroxylase and 17-hydroxylase) which were elevated. Subsequent genetic testing confirmed compound heterozygous mutation in AIRE (c.769C>T p.(Arg257*) pathogenic variant and c.967_979del p.(Leu323Serfs*51) pathogenic variant). Monitoring with 3-monthly serum cortisol and ACTH confirmed development of cortisol deficiency approximately 6 months after diagnosis of hypoaldosteronism (ACTH 2080ng/L; Cortisol 0 min 205nmol/l, 30 minutes 190nmol/l and 60 minutes 126nmol/L). Hydrocortisone replacement was commenced. To date the child has had normal bone profile and no other autoimmune endocrine or non-endocrine dysfunction.
Discussion: Hypoaldosteronism is a rare first endocrine presentation of APECED. APECED may pose a diagnostic conundrum even for experienced clinicians due to heterogenicity in presentation. Presence of treatment resistant candidiasis in addition to any auto-immune endocrine disorder should act as a red flag prompting for consideration of APECED.
15 Sep 2022 - 17 Sep 2022