SUN-432 - Familial Myasthenia Gravis Associated with Autoimmune Adrenal Insufficiency: A Case Report Demonstrating Intergenerational Variability in Age of Onset

Background: Myasthenia gravis is an autoimmune neuromuscular junction disorder that may coexist with other autoimmune diseases. The association with autoimmune adrenal insufficiency is rare, with limited case reports describing sporadic occurrences. Familial cases demonstrating intergenerational variability in disease onset have not been previously documented.

Case Presentation: We report a young adult woman who presented in early adulthood with fluctuating muscle weakness, fatigability, and ptosis. She was diagnosed with generalized myasthenia gravis based on clinical features and confirmatory testing. During follow-up, she developed progressive fatigue, orthostatic intolerance, weight loss, and episodic nausea. Endocrine evaluation confirmed biochemical adrenal insufficiency with findings consistent with an autoimmune etiology. Structural pituitary disease and secondary causes were excluded. She was treated with glucocorticoid replacement therapy with significant clinical improvement. Notably, her father developed myasthenia gravis later in life, with symptom onset in his fifth to sixth decade. He subsequently manifested features of adrenal insufficiency at an advanced age. His disease course was more indolent, with endocrine involvement occurring decades later compared with the proband. No other autoimmune endocrinopathies were identified in the family.

Discussion: Prior literature describes rare associations between MG and adrenal insufficiency, including isolated corticotroph deficiency and primary adrenal failure, but reported cases have been sporadic and non-familial. Population-based studies demonstrate that approximately 15-22% of MG patients develop concurrent autoimmune diseases, with Addison's disease being strongly associated with early-onset MG and the HLA-B8-DR3 haplotype. This case is unique in demonstrating familial clustering with marked intergenerational variability in age of onset. The findings suggest a shared autoimmune susceptibility affecting both neuromuscular and adrenal function, with variable penetrance or modifying factors influencing clinical expression. Genetic factors including HLA-B8-DR3, PTPN22, and CTLA4 variants may contribute to this phenotype.

Conclusion: This case highlights a rare familial association between myasthenia gravis and autoimmune adrenal insufficiency with significant intergenerational variability. Clinicians should maintain a high index of suspicion for adrenal insufficiency in MG patients presenting with systemic symptoms, particularly when a family history of autoimmune disease is present. Recognition of this association has important implications for diagnosis, genetic counseling, and management.

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