To Thyrotropin-releasing Hormone In Patients Research Articles

Influence of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in uremic patients

Several alterations in growth hormone (GH) secretion have been reported in patients with chronic renal failure. The aim of the present report has been to assess the effect of acutely administered recombinant human erythropoietin (rHuEPO) infusion on GH responses to thyrotropin-releasing hormone (TRH) in uremic patients. Twelve male patients (mean age 46.2 years, range 24 to 69) were studied. Seven of them were on continuous ambulatory peritoneal dialysis (CAPD), two on chronic hemodialysis (HD) and two in pre-dialysis (PreD). None had been treated before with rHuEPO. Each patient was tested with TRH (400 micrograms i.v. in bolus), and with TRH plus rHuEPO (40 U/kg in constant infusion for 30 min) on different days. TRH administration provoked a paradoxical response of GH (peak > 5 micrograms/liter) in nine (5 CAPD, 2 HD, 2 PreD) out of 12 patients. In this group of patients with anomalous GH responses, rHuEPO infusion produced an abolishment of the paradoxical responses (GH peak < 5 micrograms/liter) in eight patients and a marked decrease in a further one. On the contrary, in patients with no paradoxical GH response, stimulation with TRH plus rHuEPO did not induce any change in GH release compared with that observed after TRH alone. rHuEPO had no effect on TRH-induced thyrotropin release. These results suggest that the paradoxical GH response to TRH in patients with chronic renal failure is blocked by rHuEPO administration. This rHuEPO action might be mediated by an increased release of somatostatin or an inhibited GH-releasing hormone secretion.

Corticotropin-releasing hormone inhibition of paradoxical growth hormone response to thyrotropin-releasing hormone in insulin-dependent diabetics

A paradoxical growth hormone (GH) response to thyrotropin-releasing hormone (TRH) has been observed in type 1 diabetic patients and was hypothetically attributed to a reduced hypothalamic somatostatin tone. We have previously reported that corticotropin-releasing hormone (CRH) inhibits GH response to growth hormone-releasing hormone (GHRH) in normal subjects, possibly by an increased release of somatostatin. To study the effect of CRH on anomalous GH response to TRH, we tested with TRH (200 μg intravenously [IV]) and CRH (100 μg IV) + TRH (200 μg IV) 13 patients (six males and seven women) affected by insulin-dependent diabetes mellitus. A paradoxical GH response to TRH was observed in seven of 13 patients, one man and six women. In these subjects, the simultaneous administration of CRH and TRH significantly reduced the GH response to TRH, as assessed by both the maximal GH mean peak ± SE (2.18 ± 0.67 v 9.2 ± 1.26μg/L, P < 0.005) and the area under the curve (AUC) ± SE (187 ± 32 v 567 ± 35μg · min/L, P < .001). CRH had no effect on TRH-induced thyroid-stimulating hormone (TSH) release. Our data demonstrate that the paradoxical GH response to TRH in patients with type 1 diabetes mellitus is blocked by CRH administration. This CRH action may be due to an enhanced somatostatin release. Our data also show that exogenous CRH has no effect on TSH response to TRH, thus suggesting the existence of separate pathways in the neuroregulation of GH and TSH secretion.

TSH and prolactin responses to TRH in patients with premenstrual syndrome.

The thyroid-stimulating hormone (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH), administered during the follicular and luteal phases of the menstrual cycle, were examined in 14 women with prospectively confirmed premenstrual syndrome and in nine control subjects. There were no differences in basal or maximum increase in TSH or prolactin values between menstrual cycle phases in patients or in control subjects or between patients and control subjects in either phase. However, there was significantly greater variability in TSH response to TRH among symptomatic patients (seven of 10 patients: three with blunted and four with augmented response) than among control subjects (none of nine patients).

Prolactin response to thyrotropin-releasing hormone in early and advanced human breast cancer.

While prolactin (PRL) has been shown to stimulate the development of mammary carcinoma in several animal species, its role in human breast cancer remains to be established. To further investigate PRL secretion in human breast cancer, its basal levels and response to thyrotropin-releasing hormone (TRH) were evaluated in 16 patients (6 with no metastases and 10 with metastatic locations). The control group consisted of 19 healthy women. High PRL basal concentrations were seen in 2 patients only; no significant differences were found between the other patients and the normal subjects. The PRL increase induced by TRH administration was significantly higher in patients than in controls. Finally a change in the hormonal secretion was found after chemotherapy in 3 of the 5 patients in whom PRL response to TRH was evaluated either before or 10-12 days after a cycle of intravenous CMF adjuvant chemotherapy. These results demonstrate the existence of an exaggerated response of PRL to TRH in patients with breast cancer, even in the presence of normal basal levels. Moreover, they would seem to suggest a possible influence of CMF on PRL response to TRH stimulation.

Blunted TSH Response to TRH in Patients with Central Nervous System Disease

Seven euthyroid and four hypothyroid patients with central nervous system (CNS) disease had blunted thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) compared with corresponding control subjects who had no neural pathology. There was no significant difference in circulating thyronines (T3 and T4) among the groups. As the CNS pathology was the only detectable difference between the patients and their neurologically intact controls, we concluded that this blunted TSH response to TRH is a result of neural dysfunction.

Effect of lithium on prolactin responses to thyrotropin releasing hormone in patients with manic state.

The plasma thyrotropin (TSH) and prolactin (PRL) responses to thyrotropin releasing hormone (TRH) were studied before and during lithium treatment for 3-4 weeks in 6 patients with manic states and 8 control subjects. The plasma TSH responses to TRH were not different between the two groups before lithium treatment. Lithium administration did not alter non-stimulated secretion of TSH in any groups, but resulted in exaggerated responses of plasma TSH to TRH in both groups. No difference between two groups was observed in plasma TSH responses to TRH. The basal plasma PRL concentration did not differ between the two groups and was not affected by lithium administration to either group. The plasma PRL responses to TRH in female subjects were greater than those in male subjects. In females, the plasma PRL responses to TRH in manic patients were significantly higher than those in control subjects before the treatment. Lithium administration caused enhanced responses to TRH in patients when compared to pretreatment levels, but not in control subjects. Although the small number of male subjects limits conclusions, pretreatment plasma PRL responses to TRH in male manic patients were apparently greater than those in control subjects. However, lithium administration appeared not to affect the responses of plasma PRL to TRH in manic patients when compared to pretreatment levels. The augmented responses of plasma PRL to TRH in patients with manic states suggest the existence of some abnormality in the hypothalamo-pituitary axis. Thus, the effect of the anti-manic agent on PRL secretion in manic patients may suggest the mechanism by which the drug affects manic symptoms.

Effect of triiodothyronine administration on the plasma TSH and prolactin responses to TRH in patients with hypothalamic-pituitary insufficiency.

A study was carried out in 10 patients with multiple pituitary hormone deficiencies to determine the response of thyroid-stimulating hormone (TSH) and prolactin (PRL) to thyrotropin-releasing hormone (TRH) and their suppressibility by treatment with triiodothyronine (T3) given at a dose of 60 microgram/day for 1 week. In 3 patients the basal tsh values were normal and in 7 patients, 2 of whom had not received regular thyroid replacement therapy, they were elevated. The response of TSH to TRH was normal in 6 patients and exaggerated in 4 (of these, 1 patient had not received previous substitution therapy and 2 had received only irregular treatment). The basal and stimulated levels of TSH were markedly suppressed by the treatment with T3. The basal PRL levels were normal in 7 and slightly elevated in 3 patients. The response of PRL to TRH stimulation was exaggerated in 2, normal in 6 and absent in 2 patients. The basal PRL levels were not suppressible by T3 treatment but in 4 patients this treatment reduced the PRL response to TRH stimulation. From these findings the following conclusions are drawn: (1) T3 suppresses TSH at the pituitary level, and (2) the hyperreactivity of TSH to TRH and the low set point of suppressibility are probably due to a lack of TRH in the type of patients studied.