Thyroid hormone therapy modulates hypothalamo-pituitary-adrenal axis

Abstract

Thyroid hormones (thyroxine, T4; triiodothyronine, T3) have intricate effects in different organs [1,2]. Subclinical hyperthyroidism, characterized by low thyroid stimulating hormone (TSH) and normal free thyroid hormone concentrations in serum, has been associated with an independent risk factor for Alzheimer's disease, cognitive dysfunction and cardiovascular diseases [3][4][5].We have previously demonstrated that hyperthyroid patients have an adrenocorticotropin (ACTH) hypersensitivity to human corticotropin-releasing hormone (hCRH) [6]. On the other hand, another study showed a decreased response of cortisol to ACTH administration, which may be due to diminished adrenocortical reserve [7]. These findings indicate that hyperthyroidism modulates hypothalamo-pituitary-adrenal (HPA) axis. Patients on thyroid suppression therapy due to differentiated thyroid cancer usually have subclinical hyperthyroidism, which may increase the risks of a mild irreg- Abstract. To observe the influence of thyroid hormone therapy on hypothalamo-pituitary-adrenal (HPA) axis, a group of 14 athyreotic women due to thyroid cancer treatment were studied before and after thyroid suppression therapy with thyroxine (T4). Changes in plasma adrenocorticotropin (ACTH) and cortisol levels in response to human corticotropinreleasing hormone (hCRH; 100μg, i.v.) were estimated under hypothyroid conditions and after T4 suppression therapy with 2.5µg/kg/day for two months (n=14). A group of seven healthy women was evaluated as a control group. A greater increase in ACTH levels by hCRH was observed in patient group both before and after suppression therapy compared than that of control group. Plasma cortisol levels after hCRH stimulation were also greater in patient group both before and after suppression therapy than that of control group. In conclusion, both hypothyroidism and subclinical hyperthyroidism with suppressive doses of thyroid hormone induced a hypersensitivity of ACTH to hCRH. Considering the role of thyroid hormone on HPA axis, the mechanisms of ACTH hypersensitivity may be different between these two conditions.Key words: Adrenocorticotropin, hCRH, Cortisol, Thyroid hormone, Hypothalamo-pituitary-adrenal axis ular heart rhythms and decrease in bone density [8].However, a small number of studies have examined the consequences of thyroid suppression therapy on HPA axis [9]. In order to investigate the changes in HPA axis following thyroid hormone therapy, a group of hypothyroid patients was studied before and after administration of L-T4 (levothyroxine) suppressive doses (2.5µg/ kg/day) for two months. Methods PatientsFourteen hypothyroid women aged between 30 and 57 years (mean age 42.9±3.2 years) were studied. All patients had an ablative therapy for a thyroid cancer with total surgical thyroidectomy and I 131 therapy. During the study, a total body I 131 scan was negative for thyroid remnants, and plasma thyroglobulin levels were below detectable concentration. One month after the ablative therapy, patients reached to hypothyroid s...

Comparison of Salivary Cortisol, Serum Cortisol, Plasma ACTH and Urinary Free Cortisol Levels in Thyrotoxic and Hypothyroid Patients

“…There is substantial evidence that hypothyroidism may alter cortisol levels due to an imbalance between cortisol synthesis and cortisol degradation. [6][7][8][9][10][11] Therefore, there are contrary reports with respect to cortisol levels in hypothyroid patients. Hypothyroidism may decrease cortisol levels.…”

“…Another thyroid dysfunction, hypothyroidism, may alter cortisol levels. [6][7][8][9][10][11] In one report, hypothyroidism has no effect on cortisol levels. 7 In others, hypothyroidism may either decrease 8,9 or increase serum cortisol levels.…”

“…lthough, previous studies have examined the effects of altered thyroid function on the secretion and metabolism of adrenocortical hormones, there are still conflicting results with regard to cortisol levels in thyrotoxicosis and hypothyroid patients. [1][2][3][4][5][6][7][8][9][10][11] There are limited studies regarding the association between thyrotoxicosis and hypothalamo-pituitary-adrenal (HPA) axis. Circulating cortisol levels were higher, 1,2 lower 3,4 or normal 5,7 in patients with thyrotoxicosis compared to healthy controls.…”

Modulation of central glucocorticoid receptors in short- and long-term experimental hyperthyroidism

“…Our previous in vivo studies have demonstrated that both short-and long-term experimentally induced hyperthyroidism was associated with sustained hyperactivity of the HPA axis [4,[16][17][18][19] (Table 1). We have previously reported that basal corticosterone binding globulin (CBG) concentrations are significantly increased in short-and long-term hyperthyroid rats, and by 60 days, cerebral spinal fluid (CSF) corticosterone levels are also significantly increased [16].…”

“…Despite the sustained hyperactivity of the HPA axis and the significant increase in adrenal weights, longterm hyperthyroidism appears to be associated with diminished adrenal functional reserve of corticosterone [16,17]. Examination of the functional integrity of each component of the HPA axis reveal abnormalities that occur either as a direct consequence of thyroid hormone excess or as a secondary change in one or more component(s) of the adrenal axis [4,[16][17][18][19].…”