Primary adrenal insufficiency at the crossroads of autoimmunity and immunodeficiency

Abstract

Background: Primary adrenal insufficiency may occur in the setting of complex autoimmune or immune-dysregulation conditions, where its nonspecific clinical manifestations can be obscured by pre-existing multisystem disease. The diagnostic challenge may be further amplified in patients with underlying humoral immunodeficiency, in whom conventional autoimmune serology may be falsely reassuring.

Case summary: A young male with childhood-onset coeliac disease and primary immunodeficiency disorder, characterized by chronic diarrhea, recurrent respiratory and ear infections, presented with progressive weight loss and generalized hyperpigmentation over three years. He had profound growth impairment, hypotension, and striking mucocutaneous hyperpigmentation involving the buccal mucosa, lips, and extremities. Biochemical evaluation confirmed primary adrenal insufficiency; there was no evidence of additional endocrine gland failure. Adrenal 21-hydroxylase and thyroid autoantibodies were negative. Immunological assessment demonstrated persistent IgA, IgG, and IgE deficiency with a markedly reduced CD4/CD8 ratio. The diagnostic complexity was compounded by a previous markedly elevated sweat chloride concentration obtained during evaluation for chronic diarrhea and recurrent respiratory infections, which had prompted consideration of cystic fibrosis. However, the absence of a concordant clinical phenotype or characteristic radiological features made cystic fibrosis less compelling. Positive sweat chloride test might reflect aldosterone-deprived sodium wasting rather than concurrent cystic Fibrosis. Glucocorticoid replacement resulted in hemodynamic stabilization and subsequent weight gain.

Conclusion: This case highlights the importance of recognizing adrenal insufficiency in patients with established multisystem disease when otherwise unexplained weight loss, hyperpigmentation, and hypotension emerge. Importantly, negative adrenal autoantibodies should not be interpreted as excluding autoimmune adrenal disease in patients with significant humoral immunodeficiency, in whom impaired antibody production may attenuate serological responses. The case also raises an important diagnostic consideration regarding interpretation of sweat chloride concentrations in the setting of adrenocortical insufficiency. When biochemical findings suggest cystic fibrosis but the clinical phenotype is discordant, reassessment following correction of adrenal insufficiency may be warranted.

[J Assoc Clin Endocrinol Diabetol Bangladesh, 2026;5(Suppl 1): S53]