MON-483 Familial Dysalbuminemic Hyperthyroxinemia with False Hypercortisolemia

Abstract

Background: Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant disease characterized by hyperthyroxinemia without symptoms of thyrotoxicosis, due to a high affinity of mutant albumin for thyroxine. No report has described cortisol-albumin binding in FDH patient, and here we present a case of FDH presenting with false hypercortisolemia.Clinical Case: A 46-year man, previously diagnosed with FDH by genetic test (1), was pointed out hypercortisolemia with normal ACTH level (ACTH 64.7 pg/mL, Cortisol 34.7 μg/dL) during the investigation for Parkinson’s syndrome and referred to our department for further examination. Cortisol was 7.1 μg/dL at midnight, 14.9 μg/dL after low dose dexamethasone overnight test, and DDAVP test was positive. ACTH and cortisol responded to CRH load, although basal and peak cortisol levels were high (35.4 and 53.9 μg/dL, respectively). High dose dexamethasone overnight test showed suppressed ACTH and cortisol, and MRI showed no obvious pituitary adenoma.In spite of significant high cortisol level, no Cushing sign’s or metabolic abnormalities were observed and urinary free cortisol was within the normal range (30.7 μg/day), suggesting the presence of factors affecting the laboratory testing. We removed albumin from serum with immunoprecipitation using anti-albumin antibody and measured cortisol with LC-MS/MS. The decrease of cortisol was 4% in control serum but 38% in the patient serum after removing albumin, suggesting the binding rate of cortisol to mutant albumin in the patient was increased, leading to false hypercortisolemia.Conclusion: This is the first case demonstrating the false hypercortisolemia in a FDH patient. Clinicians should consider the possibility of the abnormal cortisol binding to albumin in differential diagnosis of hypercortisolemia with normal ACTH level.Reference: (1) Norio Wada, et al: A Novel Missense Mutation in Codon 218 of the Albumin Gene in a Distinct Phenotype of Familial Dysalbuminemic Hyperthyroxinemia in a Japanese Kindred. Journal of Clinical Endocrinology and Metabolism 1997;82;3246–3250