Endocrine Abstracts

Introduction: It has been generally accepted that adrenal function might be impaired in patients with primary hypothyroidism. A transitory low glucocorticoid production has been identified in cases with severe hypothyroidism. We tried to evaluate adrenocortical glucocorticoid function using the low-dose Synacthen test, in patients with primary hypothyroidism. The primary endpoint was to contrast the cortisol response to low-dose Synacthen before L-T4 replacement and after normalization of thyroid function tests.

Patients and methods: Seven patients (2 men and 5 women), aged 18 to 70 years, with a diagnosis of primary hypothyroidism and naïve to L-T4 treatment, were included. Primary hypothyroidism was documented by the results of a High TSH levels >4.5 mUI/L and positive antibodies to thyroid peroxidase confirmed Hashimoto disease. We excluded individuals with other endocrinopathies, glucocorticoid use in the last 24 months, and current use of oral/nonoral contraceptives or drugs that may interfere with cortisol metabolism, transport, or the hypothalamo-pituitary-adrenal axis. A low dose Synacthene 1 ug was performed before and 6 months after LT4 replacement. Blood samples for serum cortisol were taken at T0, T30 and 60 min. A serum cortisol value equal to or greater than 180 ng/L at 30 or 60 min after stimulation was defined as a normal glucocorticoid response.

Results: When cases were compared before and after L-T4 therapy, mean serum cortisol values were lower before thyroid hormone normalization. Statistical significance was found only at 30-minute time (112.6±33.1 versus 253.2±38.3 ng/L). Taking 180 ng/L or more as the normal cortisol response at 30 or 60 minutes after Synacthene stimulation, 4 out of 7 cases had insufficient glucocorticoid reserve before L-T4 treatment. After L-T4 therapy, 3 out of 4 cases reached a normal cortisol response and the other case stayed with glucocorticoid insufficiency.

Conclusion: Patients with primary hypothyroidism showed, using the low-dose Synacthene test, an improved cortisol response after normalization of thyroid hormone levels. The mechanism of impaired cortisol secretion in cases with hypothyroidism still has to be elucidated but our data support an adrenal rather than a pituitary affection. The incidence of adrenal insufficiency was 6.7–18.3% and more than 50% of the cases had a normal cortisol response after L-T4 therapy. This finding could have important clinical implications especially in the setting of acute stress situations occurring during the period while a euthyroid state is still not achieved.