The effect of thyrotoxicosis on adrenocortical reserve

Objective: Variations in thyroid function are known to be associated with c hanges in adrenocortical activity. Previous studies in animals have suggest ed that long-standing hyperthyroidism may be associated with diminished adr enal functional reserve despite a continuing hyperactivity of the hypothala mic-pituitary-adrenal (RPA) axis. In humans, there has been no direct asses sment of adrenal secretory reserve in clinical thyrotoxicosis. This study a imed to assess adrenocortical reserve in response to low-dose ACTH, followi ng 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 toxi c nodular goitre (n = 4) were studied at diagnosis and again when in a stab le euthyroid state following drug therapy for 8-12 months. All patients und erwent ACTH stimulation tests at 0800 h with ACTH(1-24) (Cortrosyn; 0.1 mu g/kg body weight, i.v.) following overnight suppression of the HPA axis wit h 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 hyper thyroid patients were significantly lower compared with the values when the same patients were euthyroid (911 +/- 157 nmol/l, 905 +/- 160 nmol/l and 5 7 652 +/- 10 128 nmol/l x min respectively; P < 0.005). Subnormal peak cort isol 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 r esponse to low-dose ACTH stimulation, following dexamethasone suppression, is lower in the hyperthyroid than in the euthyroid state. It appears that t hyrotoxicosis is associated with subtle impairment of adrenocortical reserv e.