Rise In Thyroid-stimulating Hormone Research Articles

Effect of Pyridostigmine on the Thyroid‐Stimulating Hormone Response to Thyrotropin‐Releasing Hormone in Abstinent Alcoholics

Alcoholism is sometimes associated with a blunted thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH; peak minus baseline < 5 mIU/liter), despite basal TSH and thyroid hormone levels within the normal range. In light of the inhibitory effect of somatostatin on TSH secretion, we examined whether this condition is caused by an increased hypothalamic somatostatinergic tone in alcoholic subjects. To answer this question, 16 euthyroid male alcoholics (aged 38 to 50 years) with normal [n = 8; normal responder alcoholics (NRAs)] or blunted [n = 8; low responder alcoholics (LRAs)] TSH response to TRH were selected in a preliminary TRH test (200 micrograms in an intravenous bolus). In addition, 8 age- and weight-matched normal men were tested with TRH and used as normal controls (NCs). NCs and alcoholic patients showed similar basal serum TSH, free triiodothyronine, and free thyroxine levels. All subjects were tested again with TRH, 60 min after treatment with 180 mg of pyridostigmine orally. According to selection criteria, NCs and NRA groups showed similar TSH responses to TRH, whereas TRH-induced TSH rise was strikingly lower in LRAs than in NCs and the NRA group. Pyridostigmine did not change the basal levels of TSH in any group, whereas it enhanced in a similar manner the TRH-induced TSH rise in the NC and NRA groups. No significant change in the TSH response to TRH was observed in LRA patients after pyridostigmine treatment. These data argue against the possibility that an enhanced somatostatinergic tone is responsible for the blunted TSH response to TRH observed in some alcoholic patients. This phenomenon might be attributed to alcohol-related defects of stimulated pituitary thyrotroph secretory capacity in some individuals, possibly due to genetic vulnerability and/or the toxic effects of prolonged alcohol abuse.

Audit of screening programme for congenital hypothyroidism in Scotland 1979–93

OBJECTIVETo evaluate the efficiency of the screening programme for congenital hypothyroidism in Scotland and to determine the outcome in the cohort of children with positive testing for thyroid stimulating hormone...

Congenital hypothyroidism with delayed rise in serum TSH missed on newborn screening

We report on a female patient with congenital hypothyroidism (CH) missed on a newborn screening test. She is now 10 years old with retarded development. The patient was born premature at 34 weeks of gestation with birth-weight of 1515 g, and was judged to be normal in the screening programme of Niigata Prefecture. However, she gradually suffered from poor weight gain and retarded development with stridor at breathing. Serum thyroid stimulating hormone (TSH) levels were rechecked and showed high values with normal T3 and T4 levels. She was referred to our hospital at the age of 13 months. She was diagnosed as having CH (ectopic thyroid) with a delayed rise in blood TSH concentration, probably due to the prematurity of the hypothalamic-pituitary-thyroid axis. L-thyroxine therapy brought a decline in TSH levels with partial improvement of her symptoms. Regardless of the result of newborn screening, infants with elevated serum TSH levels should be carefully examined for possible CH, even when T3, T4 and free T4 values are in the normal range.

Elevations in Thyroid-Stimulating Hormone in Normal Subjects after Receiving Short-Term Lithium Carbonate

Nine normal, healthy male subjects had significantly elevated thyroid-stimulating hormone (TSH) concentrations while receiving oral lithium carbonate for two weeks. The mean minimum lithium serum concentration was 0.765 mEq/L. The TSH concentrations after 15 days on lithium were significantly correlated to the TSH concentration at baseline. No correlation was found between mean minimum lithium steady-state concentration and TSH concentration after 15 days on lithium. Further research is necessary to determine if a high baseline TSH concentration or an early rise in TSH will predict those patients who will eventually develop hypothyroidism after long-term lithium therapy.

Deficient nocturnal surge of TSH secretion during sleep and sleep deprivation in rapid-cycling bipolar illness

Rapid-cycling bipolar patients have a high prevalence of hypothyroidism, and this disturbance in their hypothalamic-pituitary-thyroid (HPT) function may provide a model for understanding the less severe thyroid dysfunction present in other forms of affective disorder. For these reasons, we investigated HPT function in eight rapid-cycling bipolar patients and eight normal controls by measuring plasma levels of thyroid-stimulating hormone (TSH) and cortisol every 30 min during a baseline 24-h period and during an additional night of sleep deprivation. Thyrotropin-releasing hormone (TRH) (500μg) challenge tests were also performed in the patients. Controls exhibited a significant circadian variation in TSH with a nocturnal rise that was augmented by sleep deprivation. In the rapid cyclers, the nocturnal rise in TSH was absent, and sleep deprivation failed to raise their TSH levels significantly compared with baseline. Low nocturnal TSH levels were associated with blunted TSH responses to TRH infusions; due to the relatively brief sampling interval used in the TRH challenge tests, however, these results do not reliably discriminate between hypothalamic and pituitary dysfunction as an etiology for low nocturnal TSH levels. Additional studies are needed to determine the precise nature of the HPT disturbance in rapid-cycling patients.

Thyroid Stimulating Hormone and Prolactin Secretion: Reduced Sensitivity to TRH-Stimulated Prolactin Release after Midpregnancy in Rats

Prolactin (PRL) and thyroid stimulating hormone (TSH) plasma concentrations were measured during the latter part of the dark period in early and mid-late pregnancy in the rat. On Days 4-5 and 7-8 of pregnancy, plasma PRL concentrations surged between 22:00 and 06:00 hr and TSH values increased between 22:00 and 02:00 hr. While the TSH pattern was maintained during the second-half of pregnancy, surges in PRL release ceased and PRL levels remained at less than 10 ng/ml. The effects of thyrotropin releasing hormone (TRH) administration on PRL and TSH secretion were then measured to determine whether the second-half of pregnancy is associated with a decrease in sensitivity to an agent that can stimulate PRL release. Injection (iv) of cannulated pregnant rats with a low dosage (20 ng) of TRH stimulated a twofold increase in plasma TSH during both early (Days 5-9) and later (Days 14-18) pregnancy but did not change plasma PRL levels. Treatment with a high dosage (2 micrograms) of TRH induced a sixfold rise in plasma TSH during both phases of gestation. The higher dose of TRH also stimulated elevations in plasma PRL during early and mid-late pregnancy; however, both the absolute increase in the amount of PRL in plasma and the percentage increase over baseline levels were greater from Days 5-9 than from Days 14-16 of gestation. These data indicate that the neuroendocrine sensitivity to factors that stimulate PRL secretion changes as pregnancy progresses, and suggest that nocturnal secretion of PRL and TSH during pregnancy may be regulated, in part, by a common trophic factor.

Inhibition of cold-induced TSH release by benzodiazepines

Diazepam (1–5 mg/kg, i.p.) did not alter basal thyroid-stimulating hormone (TSH) release in rats; however, both diazepam (2 mg/kg, i.p.) and clonazepam (1 mg/kg, i.p.) blocked the 3–5-fold increase in TSH induced by cold exposure. The benzodiazepine antagonist, Ro15-1788 (10 mg/kg, i.p.) was effective in reversing clonazepam inhibition of cold-induced TSH release, but when administered alone had no effect on either basal TSH levels or the rise in TSH following cold exposure. Diazepam did not affect the ability of TRH to increase TSH secretion.

Impaired dopaminergic control of thyroid stimulating hormone secretion in chronic renal failure.

After administration of intravenous metoclopramide, a dopaminergic receptor blocking agent, no rise in thyroid stimulating hormone (TSH) could be found in patients with chronic renal failure, in contrast to non-uraemic controls. Basal TSH values were normal in the uraemic patients but the TSH response to thyrotrophin-releasing hormone (TRH) was significantly reduced. These results suggest that a discrete abnormality in the hypothalamo-pituitary axis exists in uraemia which may in part be due to interference with central dopaminergic control by a uraemic toxin.

Thyrotropin-releasing hormone is not required for thyrotropin secretion in the perinatal rat.

To determine the role of thyrotropin-releasing hormone (TRH) in the regulation of thyroid-stimulating hormone (TSH) secretion in the perinatal period, a physiological approach of neutralizing circulating TRH in the fetal and early neonatal rat was employed. TRH-antiserum (TRH-AS) raised in rabbits and administered daily to low iodine-propylthiouracil (LID-PTU)-fed pregnant rats from days 12 to 19 of gestation markedly impaired the rise in serum TSH to LID-PTU when compared with normal rabbit serum-treated controls. In contrast, fetal serum TSH was unaffected by TRH-AS. The binding capacity of TRH-AS in the fetal serum (111 ng/ml) far exceeded circulating TRH in the fetus. Similarly, acute TRH-AS administration to the pregnant rat fed LID-PTU markedly decreased the serum TSH concentration in the mother, but not in the fetus, 60 min after TRH-AS administration. Chronic TRH-AS administration to neonatal rats whose nursing mothers were fed LID-PTU was in-effective in decreasing the elevated serum TSH in the neonate through day 8 of life, whereas a slight but significant decrease in serum TSH was observed on day 10. Chronic daily TRH-AS administration to neonatal rats through day 10 of life had no effect on the later development of the hypothalamic-pituitary-thyroid axis. These findings suggest that TRH does not participate in TSH regulation during the perinatal life in the rat and that thyroid hormones are probably the main regulators of TSH secretion during this period. Placental TRH is not important in regulating TSH secretion in the fetal rat. Furthermore, TRH "deprivation" during neonatal life does not prevent normal later development of the hypothalamic-pituitary-thyroid axis.

Serum thyroxine, triiodothyronine and thyroid stimulating hormone after prolonged heavy excerise

Serum thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) was measured before, immediately after and on the following days after a 70 km cross-country ski race in two groups of ten well-trained men, one aged 21--29 years, taking 5.01--7.03 h, and one aged 51--57 years, taking 6.07--7.38 h. T4 was definitely increased immediately after the race, but fell to below the initial level on the following day and was not restored to the pre-race level until 4 days after the race. T3 showed essentially the same pattern, though less pronounced, a major part of the changes being possibly due to plasma volume variations. TSH showed a tendency to rise immediately after the race, but rose further to 175% of the initial level on the following day and was not restored to the initial level 4 days after the race. The pattern of changes were independent of age. It is suggested that the prolonged rise in TSH is probably due to an exercise-induced increased peripheral need for thyroid hormone.

Effect of quipazine and d-fenfluramine, two serotonin-like drugs, on TSH secretion in basal and cold stimulated conditions in the rat

The effects of two serotonin-like drugs, quipazine and d-fenfluramine, on thyroid stimulating hormone (TSH) secretion in basal and cold stimulated conditions were investigated in male rats. Both drugs are able to decrease TSH secretion in basal conditions and to inhibit the TSH rise elicited by cold exposure (CE). These effects were antagonized by a pretreatment with metergoline, a serotonin receptor blocker. These results appear to suggest that serotonin may play an inhibitory role in the control of TSH secretion in the rat.

Partial target organ resistance to thyroid hormone.

An 8-year old boy with a small goiter, normal basal metabolic rate (BMR), and elevated serum thyroid hormone levels (thyroxine [T(4)] 19.5 mug per 100 ml, free T(4) 4 ng per 100 ml, triiodothyronine [T(3)] 505 ng per 100 ml) was studied. He had measurable serum thyroid-stimulating hormone (TSH) levels (average 5.5 muU per ml), and the thyroxine-binding proteins, hearing, and epiphyseal structures were normal. There was no parental consanguinity nor were there thyroid abnormalities either in the parents or six siblings.Methimazole, 50 mg daily, depressed thyroxine synthesis (T(4) 10.5, free T(4) 2.5) and caused a rise in TSH to 11 muU per ml. After discontinuation of treatment, TSH declined to 4.2 muU per ml and chemical hyperthyroidism returned (T(4) 21.0 mug per 100 ml, free T(4) 4.2, and total T(3) 475 ng per 100 ml, radioactive iodine [RAI] uptake 68%), but studies of BMR and insensible water loss showed the patient to be clinically euthyroid. Thyrotropin-releasing hormone (TRH), 200 mug i.v., caused a brisk rise in TSH to 28 muU per ml, with T(4) rising to 28 mug per 100 ml, free T(4) to 5.6, and T(3) to 730 ng per 100 ml, thus indicating that the pituitary-thyroid system was intact and that the patient's TSH was biologically active. The unusual sensitivity of the pituitary cells to TRH in spite of the markedly elevated serum thyroid hormone levels also suggested that the pituitary was insensitive to suppression by T(3) or T(4). Serum dilution studies gave immunochemical evidence that this patient's TSH was normal. Neither propranolol, 60 mg, chlorpromazine, 30 mg, nor prednisone, 15 mg daily, influenced thyroid indices. Steroid treatment, however, suppressed the pituitary response to TRH, T(3) in doses increased over a period of 12 days to as much as 150 mug daily caused a rise in serum T(3) to above 800 ng per 100 ml, a decline of T(4) to euthyroid levels (T(4) 9.5 mug per 100 ml, free T(4) 1.6 ng per 100 ml), suppression of the RAI uptake from 68% to 35%, and marked blunting of the responses to TRH, but the BMR and insensible water loss remained normal. The data suggest that the patient's disorder is due to partial resistance to thyroid hormone.

Plasma thyrotropin responses to thyrotropin-releasing hormone after injection into the third ventricle, systemic circulation, median eminence and anterior pituitary.

To determine whether the cerebrospinal fluid provides a potential route by which hypothalamic hypophysiotropic hormones might be transported to the anterior pituitary, thyrotropin releasing hormone (TRH) was injected into the third ventricle and plasma radioimmunoassayable thyroid stimulating hormone (TSH) measured. Comparisons were made with injections into the median eminence, anterior pituitary and a peripheral vein. In one series of experiments, intraventricular TRH did not increase plasma TSH significantly above baseline, but did prevent the expected post—anesthetic fall. In a second series, intraventricular TRH caused a small but significant increase in plasma TSH. By contrast injections of similar amounts into the systemic circulation, median eminence and anterior pituitary led to a much greater rise in plasma TSH at five min post injection: third ventricular 27.9 ± 12.7, iv 70.8 ± 21, median eminence 107 ± 35, and pituitary 188 ± 22.6 mU TSH/100 ml. These studies indicate that TRH can reach the an...

Effect of thyrotropin-releasing factor on serum thyroid-stimulating hormone. An approach to distinguishing hypothalamic from pituitary forms of idiopathic hypopituitary dwarfism.

To test the hypothesis that the primary defect in some patients with idiopathic hypopituitary dwarfism is failure to secrete hypothalamic hypophysiotropic-releasing factors, synthetic thyrotropin-releasing factor (TRF), 500 mug, wa given intravenously, and timed venous samples obtained for determination of the concentration of plasma TSH by radioimmunoassay in three groups of subjects: (a) 11 patients without evidence of endocrine or systemic disease, (group I) (b) 8 with isolated growth hormone deficiency and normal thyroid function, (group II) and (c) 9 patients with idiopathic hypopituitary dwarfism and thyroid-stimulating hormone (TSH) deficiency (group III). The mean fasting plasma TSH value was 4.1 muU/ml in group I, and 3.9 muU/ml in group II; in both groups there was a brisk rise in plasma TSH to peak levels of 12-45 muU/ml at 30-45 min, and a fall toward base line levels at 120 min. All children in group III had basal TSH levels of < 1.5 muU/ml; one failed to respond to TRF; eight exhibited a rise in plasma TSH with peak values comparable with those in groups I and II. In four of eight children in group III who responded to TRF, the TSH response was delayed and the initial rise in plasma TSH was not detectable until 10-60 min. In these four patients, plasma TSH levels continued to rise at 120 min. The mean fasting concentration of plasma thyroxine iodide (T(4)) in subjects with normal thyroid function (groups I and II) was 5.6 mug/100 ml, and the mean plasma T(4) level at 120 min was 6.6 mug/100 ml. This difference between fasting and postTRF plasma T(4) was significant (P < 0.001) by paired analysis. Mean fasting plasma T(4) concentration in group III patients was 1.3 mug/100 ml; after TRF a significant rise in T(4) concentration was not detected in this group. The results indicate that TRF test is useful in distinguishing between primary hypothalamic and pituitary forms of TSH deficiency. In light of the evidence of TRF deficiency in eight of nine patients with idiopathic hypopituitary dwarfism, it seems likely that in these patients, other pituitary hormone deficiencies may be attributable to deficiency of their respective releasing factors.

Further observations on the effect of synthetic thyrotropin-releasing hormone in man.

Synthetic thyrotrophin-releasing hormone (TRH) given intravenously in doses of 50 mug or more causes a significant rise in serum thyroid-stimulating hormone (TSH) levels but has no effect on serum growth hormone, plasma luteinizing hormone, or plasma 11-hydroxycorticosteroids under carefully controlled basal conditions.The peak TSH response to intravenous TRH occurs at 20 minutes. The mild and transient side effects, which occur only after intravenous TRH, include nausea, a flushing sensation, a desire to micturate, a peculiar taste, and tightness in the chest. There is considerable variability in response to a given dose of TRH in the same subject on different occasions and in different subjects. Oral administration of TRH in doses of 1 mg and above causes a rise in serum TSH, maximal at two hours, a consistent response being obtained at doses of 20 mg and above. A rise in serum protein-bound iodine (P.B.I.) follows that of TSH, a consistent response being observed at 40-mg doses of TRH orally. Measurements of serum TSH after intravenous administration of TRH or of serum TSH or serum P.B.I. after oral TRH should prove useful tests of pituitary TSH reserve.