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This version published online on February 27, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-2090
A more recent version of this article appeared on May 1, 2007
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Submitted on September 25, 2006
Accepted on February 20, 2007

Plasma 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

Sunil Kumar Mishra MD, Senior Research Fellow, Nandita Gupta PhD, Additional Professor, and Ravinder Goswami MD, DM, Associate Professor*

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

* To whom correspondence should be addressed. E-mail: gosravinder{at}hotmail.com.

Context: Though 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: 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. 250- and 1-µg ACTH1-24 stimulation tests were carried out in first 29 patients and 15 controls. Peak FCI < mean - 3SD of healthy controls was considered subnormal. ACTH1-24 stimulation tests were repeated in 24 patients in euthyroid state.

Results: The mean basal plasma ACTH and FCI were higher and CBG was lower in thyrotoxic patients in comparison to controls. The peak cortisol was <18 µg/dl in 10/29 and 14/29 on 250- and 1-µg ACTH1-24 stimulation. Peak FCI was subnormal only in 3/27 (11.1%) and 2/21(7.4%) on 250- and 1-µg ACTH1-24 stimulation respectively. The mean plasma ACTH, basal FCI and subnormal peak FCI (two of the three) normalized following euthyroidism. Plasma ACTH and FCI did not correlate with severity of thyrotoxicosis.

Conclusion: Up to 11% of thyrotoxics have subnormal peak FCI on ACTH1-24 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.
Key words: Hyperthyroidism • ACTH • Free cortisol index






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