Addison-like Clinical Phenotype Without Adrenal Insufficiency: A Rare Manifestation of Pernicious Anemia

Severe vitamin B12 deficiency can clinically mimic Addison disease, with hyperpigmentation despite preserved adrenal function. We report a 34-year-old woman presenting with fatigue, an unintended weight loss of about 20 kg, and mucocutaneous hyperpigmentation raising concern for primary adrenal insufficiency. Examination showed pallor, mild scleral icterus, and elevated blood pressure. Laboratory testing demonstrated severe cobalamin deficiency with macrocytic anemia and biochemical evidence of intramedullary hemolysis, whereas morning cortisol and ACTH levels excluded adrenal failure. Intrinsic factor antibodies confirmed pernicious anemia. Notably, cancer antigen 15-3 was elevated at presentation but normalized after intramuscular vitamin B12 replacement, indicating a benign hematologic rather than oncologic etiology. Treatment triggered an appropriate reticulocyte response with subsequent hematologic recovery and gradual resolution of the hyperpigmentation. Pernicious anemia should be considered in the differential diagnosis of Addison-like pigmentation without adrenal insufficiency. Recognizing that tumor marker elevation may occur in severe megaloblastic anemia is essential to prevent unnecessary oncologic workup.

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Journal
JCEM Case Reports
Published
2025-12-05
DOI
https://doi.org/10.1210/jcemcr/luaf312
Primary Topic
Folate and B Vitamins Research
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article
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article

Addison-like Clinical Phenotype Without Adrenal Insufficiency: A Rare Manifestation of Pernicious Anemia

Ivan Gagliardi Castilho, Nalisson Thiago Neves Araújo, Daniela Marinho Vila Real Araújo
JCEM Case Reports
Folate and B Vitamins Research
article

Addison-like Clinical Phenotype Without Adrenal Insufficiency: A Rare Manifestation of Pernicious Anemia

Ivan Gagliardi Castilho, Nalisson Thiago Neves Araújo, Daniela Marinho Vila Real Araújo
article en

Abstract

Severe vitamin B12 deficiency can clinically mimic Addison disease, with hyperpigmentation despite preserved adrenal function. We report a 34-year-old woman presenting with fatigue, an unintended weight loss of about 20 kg, and mucocutaneous hyperpigmentation raising concern for primary adrenal insufficiency. Examination showed pallor, mild scleral icterus, and elevated blood pressure. Laboratory testing demonstrated severe cobalamin deficiency with macrocytic anemia and biochemical evidence of intramedullary hemolysis, whereas morning cortisol and ACTH levels excluded adrenal failure. Intrinsic factor antibodies confirmed pernicious anemia. Notably, cancer antigen 15-3 was elevated at presentation but normalized after intramuscular vitamin B12 replacement, indicating a benign hematologic rather than oncologic etiology. Treatment triggered an appropriate reticulocyte response with subsequent hematologic recovery and gradual resolution of the hyperpigmentation. Pernicious anemia should be considered in the differential diagnosis of Addison-like pigmentation without adrenal insufficiency. Recognizing that tumor marker elevation may occur in severe megaloblastic anemia is essential to prevent unnecessary oncologic workup.

JCEM Case ReportsVol. 4(2)
Southampton General Hospital (GB), Western Regional Hospital (NP), Hospital de Clínicas Universidade Federal do Paraná (BR)
Good health and well-being
Openalex Percentile: Top 24%
Folate and B Vitamins Research
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Addison-like Clinical Phenotype Without Adrenal Insufficiency: A Rare Manifestation of Pernicious Anemia — Ivan Gagliardi Castilho, Nalisson Thiago Neves Araújo, et al. · JCEM Case Reports (2025) | TGRS Research Map | TGRS