Endocrine Abstracts

JOINT3288

Introduction: X-linked adrenoleukodystrophy (X-ALD) is a rare peroxisomal disorder caused by mutations in the ABCD1 gene, leading to impaired beta-oxidation of very-long-chain fatty acids (VLCFAs) and their accumulation in the brain, spinal cord, gonads, and adrenal glands. It should always be considered in the etiology of primary adrenal insufficiency in males. Here, we present a case of X-ALD with diagnostic challenges.

Case: A 17-year-old male presented with fatigue, exhaustion, diarrhea after an active day, followed by confusion and syncope the next morning. He was evaluated at a center in Rome, Italy, where hypoglycemia, hyponatremia, metabolic acidosis, and hypocalcemia were detected. Low serum cortisol and markedly elevated ACTH levels suggested primary adrenal insufficiency, hypocalcemia was considered to be due to hypoparathyroidism, which led to a diagnosis of autoimmune polyglandular syndrome. Intravenous hydrocortisone infusion, oral fludrocortisone, calcium, and calcitriol was initiated. The patient was subsequently transferred to our hospital via air ambulance. In the history the patient reported fatigue, difficulty during physical exertion or severe illnesses, and significant skin darkening over the course of 2 years. Parents were first-degree cousins. On physical examination, height, weight SDS were normal. There was hyperpigmentation on extensor surfaces. Puberty was consistent with Tanner stage 5. Autoimmune markers for celiac disease and thyroid autoantibodies were negative. The treatment initiated in Italy was continued. Over the course of his treatment serum phosphate levels were within normal limits, suggesting that hypocalcemia might be linked to critical illness rather than hypoparathyroidism, and original diagnosis was reconsidered. Etiological evaluation for primary adrenal insufficiency revealed elevated plasma VLCFA levels. Calcitriol was discontinued, and hypocalcemia did not recur. Genetic analysis (hemizygous ABCD1 c.1876G>A (p.Ala626Thr mutation) proved a diagnosis of X-ALD. There were no cognitive abnormalities, behavior changes, handwriting issues, or neurological symptoms. MRI findings of the brain and spinal cord were unremarkable. During the last follow-up, mild sensory loss was noted on physical.

Conclusion: Clinical course of hypocalcemia in critical illness may lead to a misdiagnosis of hypoparathyroidism. Reassessment is important during follow-up.

Key Words: Critical illness hypoparathyroidism, primary adrenal insufficiency, primary hypothyroidism, X-linked adrenoleukodystrophy