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Plasma Adrenocorticotropin (ACTH) Values and Cortisol Response to 250 and 1 µg ACTH Stimulation in Patients with Hyperthyroidism before and after Carbimazole Therapy: Case-Control Comparative Study

Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi 110029, India

Address all correspondence and requests for reprints to: Ravinder Goswami, M.D., D.M., Associate Professor, Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India 110029. E-mail: gosravinder{at}hotmail.com.

Context: Although the production and metabolic clearance rate of cortisol is increased during thyrotoxic state, the net effect on adrenocortical reserves is not clear.

Objective: We assessed circulating ACTH levels, cortisol binding globulin (CBG), and adrenocortical reserves in hyperthyroid patients (before and after carbimazole therapy) and healthy controls.

Design and Setting: This was a case-control investigative study in a tertiary care setting.

Patients and Methods: Plasma ACTH and free cortisol index (FCI; serum cortisol/CBG) were measured in 49 consecutive patients with hyperthyroidism and 50 controls. ACTH_1–24 stimulation tests (250 and 1 µg) were carried out in the first 29 patients and 15 controls. Peak FCI less than the mean –3 SD of healthy controls was considered subnormal. ACTH_1–24 stimulation tests were repeated in 24 patients in the euthyroid state.

Results: The mean basal plasma ACTH and FCI were higher and CBG was lower in thyrotoxic patients in comparison with controls. The peak cortisol was less than 18 µg/dl in 10 of 29 and 14 of 29 on 250 and 1 µg ACTH_1–24 stimulation. Peak FCI was subnormal only in three of 27 (11.1%) and two of 21 (7.4%) on 250 and 1 µg ACTH_1–24 stimulation, respectively. The mean plasma ACTH, basal FCI, and subnormal peak FCI (two of the three) normalized after euthyroidism. Plasma ACTH and FCI did not correlate with severity of thyrotoxicosis.

Conclusions: Up to 11% of thyrotoxics have subnormal peak FCI on ACTH_1–24 stimulation. Such changes occur despite high basal plasma ACTH and FCI. Use of FCI, rather than total cortisol, is required for the interpretation of cortisol values in thyrotoxicosis due to the variation in CBG.