Hypothalamic-pituitary-thyroidal axis alterations in bulimic patients

In order to investigate the role of thyrotropin (TSH) in goiter development and maintenance, the serum TSH concentration, the TSH response to thyrotropin-releasing hormone (TRH), and the increase in serum T3 after TRH were measured in 51 normal subjects and in 65 euthyroid patients with idiopathic nontoxic goiter. Fifteen patients had diffuse goiter, 47 multinodular goiter, and 3 an enlarged gland with a single non-functioning nodule. Serum thyrotropin (TSH) concentrations differed significantly in the two groups, the 95% range of the normal subjects was <0.2–2.0 μU/ml, and of the goitrous patients <0.2–4.5 μU/ml, 17 of whom (26%) had TSH values above the normal range (>2.0 μU/ml). There was no correlation between TSH concentrations and nodularity of goiters. Stimulation with TRH was performed in 52 patients and 39 normal subjects. Patients with basal serum TSH values >0.5 (μU/ml had increases in serum TSH after TRH exceeding those of the controls. However, 1/15 patients with diffuse goiter and 10/37 with nodular goiter had impaired or absent TSH responses to TRH. This finding may be a sign of functional autonomy. The normal subjects and the patients showed the same T3 response to TSH during the TRH test, and the T3 response was significantly correlated with the TSH increase after TRH. This was tentatively interpreted as indicating similar sensitivity to TSH in normal subjects and goitrous patients. However, it is not known whether T3 and growth responsiveness to TSH are associated. It is concluded that goiter development was probably TSH dependent in about one-fourth of the patients. In the majority of cases goiter maintenance and growth seemed not to be TSH dependent at the time of study.

To determine the value of the TRH test, we analyzed the unstimulated serum T(4) and TSH concentrations in 54 children with central hypothyroidism. A TRH test was performed in 30 patients. Midline brain defects (septo-optic dysplasia, 28; holoprosencephaly, 2) and combined pituitary hormone deficiencies were present in 30 and 52 patients, respectively. The mean serum free T(4), total T(4), and basal TSH concentrations were 0.6 ng/dl, 4.0 microg/dl, and 2.8 microU/ml, respectively. Five patients demonstrated elevated basal serum TSH concentrations. A normal TRH test [increase (delta) in TSH, 4.5-17.8], based on data from 30 controls, was documented in 23.3% of patients. Brisk (deltaTSH, >17.8), absent/blunted (deltaTSH, <4.5), and delayed responses were documented in 16.7%, 30%, and 30% of patients, respectively. The mean age at diagnosis was 2.8 yr, with 8 patients evolving into TSH deficiency. It was not possible to differentiate patients as having pituitary or hypothalamic disease based solely on the TRH test results. Patients with septo-optic dysplasia were diagnosed earlier and had elevated basal serum TSH and PRL concentrations, diabetes insipidus, and evolving disease. Although full pituitary function assessment is mandatory to identify combined pituitary hormone deficiencies, a TRH test is not essential, and the diagnosis should be made by serial T(4) measurements.

Serum thyrotropin (TSH) responses to thyrotropin-releasing hormone (TRH) in patients with anorexia nervosa and bulimia: Influence of changes in body weight and eating disorders

A sensitive and specific radioimmunoassay for rat thyrotropin (TSH) has been developed which utilizes 125I-mouse thyrotropic tumor TSH, antibovine TSH serum and USP bovine TSH as a standard. TSH in serum and pituitary homogenates was found in fractions corresponding to those previously shown to contain biological activity after gel filtration on Sephadex G-200. Serum TSH in normal rats after decapitation ranged from 15 to 66 μU/ml. During pentobarbital anesthesia, serum TSH was significantly lower (10–37 /μU/ml). Mean normal rat pituitary TSH content was 44 mU/gland. After 50μg thyroxine (T4) every other day for 14 days, serum TSH became undetectable (<6 μU/ml) in 5 of 7 rats, and pituitary content fell to 25 % of normal. Chronic propylthiouracil (PTU) treatment resulted in a progressive increase in serum TSH over a 12-week period. Pituitary TSH content, however, was below normal after 3 weeks of PTU, but rose progressively thereafter to exceed normal at 12 weeks. Following intravenous administration of t...

The present study was carried out to evaluate the effectiveness of intramuscular administration of methyl-TRH, a potent analogue of thyrotropin-releasing hormone, for assessing pituitary reserve of TSH and prolactin and for distinguishing euthyroid, hypothyroid and hyperthyroid individuals. Serum samples were taken for 24 hours after intramuscular injection of methyl-TRH, 200 microgram, in 19 euthyroid subjects, 9 hypothyroid men and 9 hyperthyroid men. The mean serum prolactin and TSH concentrations were significantly elevated over baseline levels at 30 min in the euthyroid individuals and remained elevated for 3 to 4 hours. The serum TSH, T3 and T4 responses after intramuscular methyl-TRH in euthyroid subjects were clearly distinguishable from those of hyperthyroid and hypothyroid patients. Significant elevation of the serum T3 and T4 concentrations at 24 hours after intramuscular injection of methyl-TRH shows the sustained effect of this TRH analogue in euthyroid subjects.

Serum T4, T3, rT3, free T4, free T3 and TSH were measured during and after normal pregnancy in 20 women. Special methodological precautions were taken to avoid interference of other hormones and protein alterations in the assays. Serum T4 and T3 were steadily increasing during the last part of the 1st trimester, and remained high and nearly stable during the 2nd and 3rd trimester of the gestation period. The high levels were approximately 1.5 times the values measured 10 weeks post-partum. Serum rT3 was elevated already during the last part of the 1st trimester and remained high throughout pregnancy, compared to the post-partum value. Serum free T4 and free T3 were slightly elevated in early pregnancy. The values decreased gradually during pregnancy and were slightly depressed during the 3rd trimester. A gradual increase in serum TSH was observed during pregnancy and the 2nd and 3rd trimester values were significantly higher than the post-partum value. The mean values for serum TSH, free T4 and free T3 remained always well within the normal range. Thus small variations in serum free iodothyronines and TSH occur during normal pregnancy, the alterations observed in the last trimester of the gestation period resembling those of a slight thyroid insufficiency. These trends in variation of the reference values are worth to remember in the diagnosis of borderline hypo- or hyperthyroidism and in the balanced treatment of pregnant women with thyroid dysfunction.

Adult rats who had neonatal hyperthyroidism (NH) have reduced BW and serum T4, T3, and TSH concentrations. Pituitary TSH responses to TRH administration under basal, T4-suppressed, and propylthiouracil-stimulated conditions suggest that the thyrotroph of these animals is more sensitive to the feedback effects of thyroid hormones. These studies were undertaken to examine, with the use of various thyroid hormone-responsive variables, thyroid status of adult NH rats. NH was induced by 12 daily sc injections of T4 (0.4 microgram/g BW) to neonatal male Sprague-Dawley rats. Adult NH and control rats were then studied at 120 days of age. Adult NH rats had significantly decreased mean BW (P less than 0.001), and serum T4 (P less than 0.005), T3 (P less than 0.001), and TSH (P less than 0.001) concentrations. The percent decreases were 12% for T4, 20% for T3, and 27% for TSH in adult NH rats. Mean pituitary GH concentration and hepatic alpha-glycerophosphate dehydrogenase and malic enzyme activities were significantly decreased in adult NH rats to 54% (P less than 0.005), 52% (P less than 0.025), and 39% (P less than 0.001), respectively, of control values. Mean pituitary TSH concentrations were similar in adult NH and control rats. Mean hepatic T4 5'-deiodinase activity of adult NH rats [200 +/- (SE) 23 fmol T3/min X mg protein] was significantly decreased to 56% of control levels (355 +/- 31 fmol T3/min . mg protein; P less than 0.005). Mean pituitary T4 5'-deiodinase activity of adult NH rats (32.8 +/- 3.3 fmol T3/min . mg protein) was significantly increased compared with that of control rats (21.2 +/- 1.7 fmol T3/min . mg protein; P less than 0.025). These changes are consistent with a hypothyroid state in adult NH rats. The observation of decreased serum TSH concentration and enhanced thyrotroph sensitivity to thyroid hormones in the face of increased pituitary T4 5'-deiodinase activity suggests that increased thyrotroph monodeiodination of T4 may be the central biochemical aberration responsible for the hypothyroid state in adult NH rats.

Suppression of serum thyrotropin (TSH) concentrations following thyroidectomy and cold exposure by passive immunization with antiserum to thyrotropin-releasing hormone (TRH) in rats

Although a normal serum thyrotropin (TSH) concentration is generally considered to be the most important finding to support the clinical impression of euthyroidism in patients with nonthyroidal diseases and decreased serum triiodothyronine (T(3)), the regulation of TSH secretion in sick patients has not been studied previously. Accordingly, we studied the regulation of TSH secretion in 23 patients with nonthyroidal diseases; 15 of the patients had decreased serum T(3). TSH regulation was studied by measuring the TSH response to injected thyrotropin-releasing hormone (TRH) before and after effecting a small decrease in serum thyroxine (T(4)) and/or T(3) concentrations by iodide treatment, 262 mg daily for 10 d. Iodide treatment significantly decreased (> 10%) the free T(4) index (FT(4)-I) and/or free T(3) index (FT(3)-I) in all patients. FT(4)-I values were correlated (0.611, P < 0.001), with free T(4) concentration determined by equilibrium dialysis. Despite decreased FT(4)-I and/or FT(3)-I after iodide treatment in all patients, the TSH response to TRH after iodide treatment was augmented in only 8 of 15 patients who had decreased serum T(3) (group 1) and in only 5 of 8 patients who had a normal serum T(3). Mean base-line TSH concentration was increased significantly (P < 0.05) from 0.9+/-0.1 to 1.5+/-0.3 muU/ml in group 1 only. Comparison of the mean TSH response to TRH showed that there was no significant difference between groups 1 and 2. Moreover, no significant difference in thyroidal parameters was observed between patients who had augmented TSH response to TRH after iodides and those who had either similar or decreased TSH response irrespective of the initial serum T(3). These studies show that an augmented TSH response to TRH in response to a small reduction in serum T(4) and T(3) concentration occurred in only 57% of the entire group of patients with nonthyroidal diseases and that the presence or absence of a normal TSH response to this stimulus did not seem to be related to the base-line serum T(3) concentration. Because an increase in serum TSH in response to decreased serum T(4) and T(3) did not occur in about one-half of patients with nonthyroidal diseases, normal serum TSH may not be a reliable index of the euthyroid state in these patients.

Short term cooling of adult human subjects fails to stimulate TSH release, whereas a prompt increase in serum TSH is observed in infants and children in response to cooling. Heat loss in infants is known to be augmented in response to cold exposure and it is possible that more effective catecholamine thermogenesis in the adult obviates the TSH response. To test this hypothesis the serum TSH response to cooling at 2 to 4° C was measured in adolescent and young adult subjects with and without administration of alpha or beta adrenergic receptor blocking drugs. Neither drug augmented the TSH response although significant hypothermia occurred. Thus, it seems that the hypothalamus of the adult has become refractory to the acute cold stimulus. Although cooling fails to evoke an acute TSH release in adults, some delayed TSH response to cooling can be observed probably in response to increased thyroxine utilization.

Follow-up studies of a woman with hyperthyroidism due to excessive TSH secretion, previously reported (1), are described. For most of the ensuing years, she has been treated with methimazole. On several occasions, methimazole was discontinued; each time elevations of serum TSH, T4, and T3 concentrations, similar in magnitude to those originally present, occurred. Initially, her serum TSH concentrations fell substantially after dexamethasone administration and did not change after TRH. The same responses have occurred on several occasions during the follow-up period. Serum glycoprotein alpha-subunit and TSH-beta concentrations were normal and did not change after TRH administration, but serum alpha-subunit declined during dexamethasone and increased slightly after gonadotropin-releasing hormone. No increase in serum TSH occurred after TRH administration when TSH secretion was decreased by dexamethasone administration. No evidence of pituitary enlargement has developed during the 7-yr follow-up period. The cause of this patient's excessive TSH secretion remains unknown, but her TSH secretory dynamics are most consistent with those found in patients who had TSH-secreting pituitary adenomas reported in recent years.

Élaboration d’un questionnaire sur les cognitions alimentaires

Prolactin, growth hormone and thyroid stimulating hormone responses to thyrotropin releasing hormone (TRH) and metoclopramide were determined in 12 alcoholic men with biopsy proven liver disease and were compared to those of 8 age matched normal controls. All subjects were challenged with TRH (400 micrograms) and metoclopramide (10 mg) given as an intravenous bolus each on a separate day. Alcoholics had increased basal prolactin and growth hormone levels compared to controls. Alcoholics had a brisk and statistically significant (p less than 0.01) response for each of the 3 hormones studied in response to TRH. In contrast to the alcoholics, the controls did not demonstrate a growth hormone response to TRH. Moreover, the TSH response to TRH of the alcoholics was exaggerated (p less than 0.05) compared to that of the controls. In response to metoclopramide, alcoholics had a brisk prolactin response, failed to demonstrate a TSH response, and had a decline in growth hormone when compared to controls. These results for alcoholics with liver disease differ from those reported for individuals with renal failure while those for the controls are similar to previously reported normal responses. These data suggest that liver disease and renal disease must differ in terms of their patterns of hypothalamic-pituitary neuroregulation as documented by their differing pituitary hormone responses to TRH and metoclopramide.

Serum thyroglobulin (Tg), T4, T3, FT4, FT3, TSH concentrations and TSH response to iv TRH (delta TSH) were measured in 56 consecutive patients with (multi) nodular goiter from a severely iodine-deficient endemic goiter area in Northeastern Sicily and in 11 non goitrous euthyroid individuals living in the same area. Serum Tg concentrations were sharply increased in goitrous subjects (453 +/- 476 ng/ml) and related to thyroid size and the presence of nodules (chi 2 = 43.5, p less than 0.0005). Serum TSH levels measured in goitrous patients (2.1 +/- 0.9 microU/ml) were significantly lower than those measured in nongoitrous iodine deficient subjects (3.1 +/- 0.9 microU/ml, p less than 0.001) and decreased with increasing goiter size and nodularity (chi 2 = 27.3, p less than 0.05). A similar pattern was shown by the analysis of the delta TSH (chi 2 = 43.1, p less than 0.0005). These results suggest that at least a part of the largest and multinodular goiters become autonomously functioning with duration and growing in size. In 13 goitrous patients with absent or impaired response to TRH, a significant direct relation was apparent between log-Tg and goiter size and nodularity (r = 0.64) with an inverse relationship between serum FT3 and delta TSH (r = 0.73). A computed program analysis based on the combination of different independent variables (x) including age, thyroid size and nodularity, serum TSH, log-Tg and FT3, indicated the existence of a significant negative relationship between these variables and the TSH response to TRH (r = 0.75, p = 0).(ABSTRACT TRUNCATED AT 250 WORDS)

Recent reports of altered TSH responsiveness to its releasing hormone (TRH) in women with premenstrual syndrome (PMS) suggested that subclinical hypothyroidism may be responsible for the mood changes, such as depression, that occur in these women. In this study we measured basal and TRH-stimulated serum TSH and PRL levels in 15 women with PMS and in 19 age-matched normal women. The mean baseline serum TSH concentrations were similar in the 2 groups in both the follicular [normal, 1.3 +/- 0.2 (+/- SE); PMS, 0.9 +/- 0.2 mU/L] and luteal (normal, 1.1 +/- 0.2; PMS, 1.1 +/- 0.2 mU/L) phases of the cycle. The mean baseline serum PRL levels also were similar in the 2 groups in the follicular (normal, 16 +/- 2; PMS, 13 +/- 2 micrograms/L) and luteal (normal, 13 +/- 2; PMS, 14 +/- 2 micrograms/L) phases of the cycle. After TRH administration, peak serum PRL and TSH levels were reached at 15 and 30 min, respectively, and the response curves were virtually identical in the 2 groups in both phases of the cycle. One normal woman had elevated basal and TRH-stimulated TSH concentrations compatible with subclinical hypothyroidism, but had normal noncyclic scores on her prospective rating scales. Our findings suggest that PMS is not associated with thyroid dysfunction or abnormal PRL secretion and that thyroid hormone replacement therapy is not indicated in this condition.