SAT315 A Case Of PAI "Do Not Miss This Rare Cause"

• Published in: Journal of the Endocrine Society Vol. 7; no. Supplement_1
• Main Authors: Alshantti, Raeda, Musurakis, Clio, Rafat, Ummara, Akhter, Wajeeha, Gilden, Janice L, Moid, Alvia
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 05-10-2023
• Subjects: Adrenal (Excluding Mineralocorticoids)
• ISSN: 2472-1972; 2472-1972
• DOI: 10.1210/jendso/bvad114.319

Abstract
Disclosure: R. Alshantti: None. C. Musurakis: None. U. Rafat: None. W. Akhter: None. J.L. Gilden: None. A. Moid: None.
Background: Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a mutation in the ABCD1 gene, located at Xq28. This impairs beta-oxidation and breakdown of very long chain fatty acids (VLCFAs) which then accumulate in the CNS, adrenal cortex, and Leydig cells of the testes, leading to three main phenotypes of X-ALD: childhood cerebral ALD, adrenomyeloneuropathy AMN, and adrenal insufficiency (AI). AI presents in 47% of X-ALD cases by age 10 years. X-ALD represents a spectrum of phenotypes that vary in age of onset, severity, and clinical characteristic. AI may predate, occur simultaneously with, or follow the onset of the neurologic deterioration. While in the majority, it is inherited in an X-linked manner, at least 4.1% of individuals with X-ALD have a de novo pathogenic variant of ABCD1. Case Description: A 30-year-old male, previously healthy, was found to have adrenal nodule on CT renal during the evaluation of a transient episode of acute abdominal pain. Further evaluation of the adrenal nodule with a CT adrenal protocol showed a 1.5 cm x 1.0 cm right adrenal nodule, HU 22, washout of 66.7% consistent with an adrenal adenoma. Evaluation of adrenal hormones failed to show abnormal hypersecretion, but rather suggested insufficiency. Lab tests: RENIN FRZ PLS 45.76 ng/mL/h (0.25 - 5.82), ALDOSTERONE <1 ng/dL, ACTH >1250 pg/mL (0 - 47), SALIV CORT 0.06 mcg/dL, DHEAS 28.19 ug/dL (34.5 - 568.9). The patient was referred to endocrinology. Only reported symptom was poor exercise tolerance. Diagnosis of primary adrenal insufficiency was confirmed by low AM cortisol of 7.91 ug/dL, and very high ACTH of >1250 H pg/mL. He was started on glucocorticoid & mineralocorticoid replacements. An evaluation to determine the etiology of PAI was conducted. The patient was not taking any medications or drugs. Family history was noncontributory. 21 OH Ab was negative. Quantiferron was negative. Our patient had no risk factors or clinical manifestations to suggest TB or fungal infections. No bleeding disorders. CT adrenal findings did not suggest infiltrative, infectious, hemorrhage, or malignant etiologies. Blood tests for VLCFAs showed elevations in phytanic, C22:0, C24:0, C26:0, C24/C22, & C26/C22. These are consistent with X-linked adrenomyeloneuropathy. Genetic testing has confirmed the diagnosis; POSITIVE for a hemizygous pathogenic variant in ABCD1, consistent with a diagnosis of X-linked adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN). Conclusion: Our case highlights the importance of a comprehensive evaluation to determine the cause of PAI. When autoimmunity and infectious etiologies are ruled out in male patients, it is crucial to consider X- ALD regardless of age at presentation, family history, or presence/absence of neurologic symptoms. This diagnosis is particularly important not to miss, since X-ALD can have devastating implications not only for the patient but also the family.
Presentation: Saturday, June 17, 2023