Adrenoleukodystrophy and Secondary Hyperaldosteronism; A Clinical Demonstration of the Zona Glomerulosa Persistence

Abstract

Adrenoleukodystrophy (ALD) is a peroxisomal disorder which leads to the accumulation of very long-chain fatty acids in all tissues. Age at onset of symptoms vary depending on the phenotype severity. It can present with progressive symptoms of neurological defects and/or primary adrenal insufficiency.We report a case of 31 yo man diagnosed in childhood with ALD and treated with hydrocortisone and fludrocortisone who eventually developed resistant hypertension due to secondary hyperaldosteronism.He was diagnosed with ALD at 9-year-old and have received an allogenic hematopoietic cell graft 4 years later. After transplantation, he developed a bronchiolitis obliterans which was treated with high dose of glucocorticoids for 3 years.In 2014, at first evaluation with our team, he was on hydrocortisone 10mg/m2 and fludrocortisone 0.05 mg daily. Fludrocortisone was started at 14 yo for a clinical suspicion of mineralocorticoids deficiency. At that time, the patient was normokaliemic (3.8 mmol\\L), his aldosterone was, 2 days apart, 245pmol/L lying down and 68 pmol/L (N 138 - 413) sitting, his renin activity was 0.11 ng/L/s (N 0.14 - 0.31) and no orthostatic hypotension was documented.In July 2015, high blood pressure (BP) was noticed, and fludrocortisone was decreased at 0.05 mg every other day. However, his BP continued to increase progressively, thereby fludrocortisone was discontinued in June 2018. Thereafter, amlodipine 10 mg daily, hydrochlorothiazide 12.5 mg daily and terazosin 2 mg daily were progressively introduced. Even with those three anti-hypertensive drugs his BP wasn’t controlled (190/100 mmHg) and he also developed persistent hypokalemia (3.0 - 3.3 mmol/L). Furthermore, significant aortic atheromatosis was described on abdominal computed tomography. In that context, his serum aldosterone/renin ratio was measured. The aldosterone was 632 pmol/L (N < 350) and the renin mass was 93.4 ng/L (N 3 - 16). An assessment of renal arteries was done by doppler ultrasonography, which was compatible with a hemodynamically significant right renal artery stenotic lesion. The patient had never smoke, had no diabetes (HbA1c 5.1%) or dyslipidemia (LDL 2.02 mmol/L). Based on the diagnosis of secondary aldosteronism, spironolactone was introduced in June 2020. Spironolactone was titrated to 37.5 mg daily and BP significantly improved with values around 136/75 and potassium return in normal range (3.8 mmol/L).This interesting case illustrates 1) the persistence of a functioning zona glomerulosa in some patient with ALD and the possible development of secondary hyperaldosteronism in response to renovascular disorder and 2) the particularly high burden of atherosclerosis in this young patient, without classic risk factor, raises questions on the effect of the metabolic defect of ALD itself on the development of atheromatosis.