Endocrine Abstracts

JOINT480

Introduction and Background: Allgrove syndrome, also known as "4A syndrome," is a rare autosomal recessive condition characterized by Alacrimia, Achalasia, Adrenal insufficiency, and Autonomic disturbances, among other features.

Case Report: We present the case of a 19-year-old female, born to consanguineous parents, who first exhibited symptoms at age 3 with alacrimia, initially mistaken for an allergic reaction. At 12, she presented with acute gastrointestinal symptoms, generalized hyperpigmentation, hypotension, and growth delays. Hormonal testing confirmed primary adrenal insufficiency (cortisol: 4.5 µg/dl, ACTH: 344 ng/L), and she was treated with hydrocortisone. Etiological investigations revealed a positive Schirmer’s test, confirming alacrimia, and she was started on artificial tears. Achalasia was diagnosed via esophagram, showing impaired cardia motility, and treated with Heller’s myotomy at age 14, leading to good progress. By 16, the patient developed polyradiculoneuropathy, confirmed by EMG findings of sensory and motor demyelination with axonal damage. Treatment with pregabalin, alpha-lipoic acid, acetyl-L-carnitine, and coenzyme Q10 yielded satisfactory results. However, she continues to experience severe learning difficulties. The clinical presentation strongly suggests Allgrove syndrome despite the absence of genetic confirmation.

Discussion: Allgrove syndrome is marked by adrenal insufficiency, alacrimia, and achalasia, often accompanied by progressive neurological impairments. Mutations in the AAAS gene on chromosome 12q13 are implicated. Alacrimia, the earliest and most constant sign, results from cholinergic innervation degeneration. Achalasia occurs in 75% of cases due to absent ganglion cells in the lower esophagus. Adrenal insufficiency, predominantly glucocorticoid defect due to ACTH resistance typically emerges early in life, with mineralocorticoid involvement in 15% of cases. Neurological manifestations include motor neuropathy, amyotrophy, and, rarely, amyotrophic lateral sclerosis or epilepsy.

Conclusion: Early diagnosis and a multidisciplinary approach are critical for managing Allgrove syndrome. Regular monitoring, steroid dose adjustments, and patient education are essential for improving outcomes.