The effect of thyrotoxicosis on adrenocortical reserve

Abstract

Objective. Variations in thyroid function are known to be associated with changes in adrenocortical activity. Previous studies in animals have suggested that long-standing hyperthyroidism may be associated with diminished adrenal functional reserve despite a continuing hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. In humans, there has been no direct assessment of adrenal secretory reserve in clinical thyrotoxicosis. This study aimed to assess adrenocortical reserve in response to low-dose ACTH, following dexamethasone suppression, in patients with severe thyrotoxicosis. Design and methods: Ten patients (four men and six women, 30- 45 years) with severe long-standing thyrotoxicosis due to Graves' disease (n = 6) or toxic nodular goitre (n = 4) were studied at diagnosis and again when in a stable euthyroid state following drug therapy for 8-12 months. All patients underwent ACTH stimulation tests at 0800 h with ACTH1-24 (Cortrosyn; 0.1 μg/kg body weight, i.v.) following overnight suppression of the HPA axis with dexamethasone (1 mg per os at 2300 h). Serum cortisol was assayed at -15, 0, 15, 30, 60 and 90 min after the administration of ACTH. Results: The mean (± S.D.) peak and delta cortisol responses to ACTH (634.5 ± 164 nmol/l and 618 ± 196 nmol/l respectively), as well as the net area under the response curve (36 769 ± 12 188 nmol/l x min) in the hyperthyroid patients were significant lower compared with the values when the same patients were euthyroid (911 ± 157 nmol/l, 905 ± 160 nmol/l and 57652 ± 10128 nmol/l x min respectively; P<0.005). Subnormal peak cortisol responses (<500 nmol/l) were observed in two severely toxic patients. The findings were independent of the cause of thyrotoxicosis. Conclusion: In patients with severe thyrotoxicosis, cortisol secretion in response to low-dose ACTH stimulation, following dexamethasone suppression, is lower in the hyperthyroid than in the euthyroid state. It appears that thyrotoxicosis is associated with subtle impairment of adrenocortical reserve.