The effect of thyrotoxicosis on adrenocortical reserve.
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.


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 0800h with ACTH(1-24) (Cortrosyn; 0.1microg/kg body weight, i.v.) following overnight suppression of the HPA axis with dexamethasone (1mg per os at 2300h). Serum cortisol was assayed at -15, 0, 15, 30, 60 and 90min after the administration of ACTH.


RESULTS
The mean (+/-s.d.) peak and delta cortisol responses to ACTH (634.5+/-164nmol/l and 618+/- 196nmol/l respectively), as well as the net area under the response curve (36769+/-12188nmol/lx min) in the hyperthyroid patients were significantly lower compared with the values when the same patients were euthyroid (911+/-157nmol/l, 905+/-160nmol/l and 57652+/-10128nmol/lxmin respectively; P<0.005). Subnormal peak cortisol responses (<500nmol/l) were observed in two severely toxic patients. The findings were independent of the cause of thyrotoxicosis.


CONCLUSIONS
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.
Tsatsoulis
A
A
Endocrine Unit, Department of Medicine, University of Ioannina School of Medicine, Ioannina, 451 10, Greece. atsatsou@cc.uoi.gr
Johnson
E O
EO
Kalogera
C H
CH
Seferiadis
K
K
Tsolas
O
O
D000302:Adrenal Cortex / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000378:metabolism*; D000328:Adult; D000906:Antibodies / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013961:Thyroid Gland / Q000276:immunology; D013963:Thyroid Hormones / Q000097:blood; D013971:Thyrotoxicosis / Q000097:blood* / Q000209:etiology; D013972:Thyrotropin / Q000097:blood; D013997:Time Factors
D000906:Antibodies; D013963:Thyroid Hormones; D000324:Adrenocorticotropic Hormone; D013972:Thyrotropin; D006854:Hydrocortisone