Effect of Altered Thyroid Hormone Levels on Hypothalamic-Pituitary-Adrenal Function*

Abstract

To determine whether alterations in serum thyroid hormone levels affect hypothalamic-pituitary-adrenal function, we measured the plasma immunoreactive (IR) ACTH and IR-cortisol responses to 1 microgram/kg BW ovine CRH (oCRH) given iv in the late afternoon and the plasma IR-ACTH, IR-cortisol, and IR-11-deoxycortisol responses to 2 g metyrapone given orally at midnight in 10 athyreotic patients during T4 treatment and 1 month after stopping T4 when they were biochemically, but not clinically, hypothyroid. Mean serum TSH increased from 0.7 +/- 0.9 (+/- SD) mU/L (normal range 0.5-4.9 mU/L) during T4 therapy to 107 +/- 82 mU/L after stopping T4. The serum total T4 level and free T4 index fell from 165 +/- 37 nmol/L and 1.9 +/- 0.4, respectively (normal range, 59-154 nmol/L and 0.9-2.5, respectively), to 19 +/- 9 and 0.2 +/- 0.1, respectively, after stopping T4. Basal plasma IR-ACTH and IR-cortisol levels at 0800 and 1630 h were similar during and after stopping T4 therapy. Peak plasma IR-ACTH and IR-cortisol levels after oCRH were significantly greater after stopping T4 (20 +/- 9.2 pmol/L and 880 +/- 260 nmol/L, respectively) than during T4 therapy (9.7 +/- 4.7 pmol/L and 720 +/- 190 nmol/L; P less than 0.01 and P less than 0.05, respectively). The mean integrated plasma IR-ACTH and IR-cortisol responses to oCRH were also significantly greater P less than 0.01 and P less than 0.05, respectively) after stopping T4 than during T4 therapy. Plasma IR-ACTH the morning after metyrapone was slightly (1.6-fold) but not significantly greater during therapy than after stopping T4 therapy (100 +/- 86 vs. 65 +/- 54 pmol/L, respectively). The plasma IR-11-deoxycortisol responses to metyrapone during and after stopping T4 therapy were similar (720 +/- 250 and 750 +/- 330 nmol/L, respectively), presumably because plasma IR-ACTH concentrations were maximally stimulating in both instances. These results indicate that thyroid hormone deficiency of short duration 1) increases corticotroph sensitivity to oCRH, 2) may diminish the plasma ACTH response to metyrapone-induced hypocortisolemia, and 3) has no apparent effect on the acute adrenal response to ACTH. These data together with those of previous studies that have shown reduced responses of the hypothalamic-pituitary-adrenal axis to metyrapone and hypoglycemia in hypothyroid patients suggest that the release of hypothalamic CRH and/or other ACTH secretagogues may be decreased in hypothyroidism.

Stress-Induced Inhibition of the Hypothalamic-Pituitary-Thyroid Axis Is Attenuated in the Aged Fischer 344/N Male Rat

“…Hypothyroid patients off replacement therapy exhibit increased adrenocorticotropic hormone and cortisol re sponses to oCRH, responses that have been explained as compatible with CRH and/or other adrenocorticotropic segretagogue deficiency in hypothyroidism [51], In agree ment with this, experimental hypothyroidism in the rat is associated with reduced basal CRH mRNA concentra tions in the PVN [Kamilaris et al, unpubl. observation].…”

Novel neuroanatomical pathways for thyroid hormone action in the human anterior pituitary

“…LH, FSH and GH levels are often increased during hyperthyroidism (37,38). CRH responsiveness of the corticotrope is increased in hypothyroid patients (39). The presence of TRs in somatotropes, corticotropes and gonadotropes indicates that changes in pituitary glycoproteins may be based, at least partly, upon a direct action of thyroid hormone on these hormone-secreting cells in the anterior pituitary.…”

Morphofunctional Characteristics of Pituitary Adrenocorticotropes in An Animal Model of Heat Stress

“…Considering the data about decreased concentration of serum corticosterone found in this study, we assume that the decreased activity of ACTH cells may be due, in some part, to the negative feed-back mechanism of glucocorticoids upon the HPA axis, and therefore, upon ACTH cells. Generally, there is a synergistic relationship between the adrenal and thyroid gland through the HP axis (27,28). The data from Rousset et al (25) have shown suppression of thyroid activity in the first two days of exposure to 34°C, and therefore decreased activity of the CRH and ACTH (27).…”