Immunoreactive TSH Research Articles

Plasma immunoreactive TSH: Spurious elevation due to antibodies to bovine TSH which cross-react with human TSH

A patient with thyroid carcinoma treated by thyroidectomy who received multiple injections of bovine (bTSH) exhibited elevated and nonsuppressible levels of plasma “immunoreactive TSH”. Antibodies to TSH of the IgG class which bound bTSH and human TSH (hTSH) were demonstrated using specific radioimmunoassay and radioimmunoelectrophoretic techniques. Antibodies were present for more than one year and binding of bTSH was greater than that of hTSH throughout this period. Characterization of the antibodies with respect to the binding of human and bovine glycoprotein hormones and subunits revealed two populations of antibodies, one of which bound both bTSH and hTSH and the other which bound only bTSH. Both antibodies appeared to be directed toward antigenic sites on the beta subunit of TSH as both hTSH-β and bTSH-β displaced the binding of intact TSH from antibodies whereas the alpha subunits were virtually unreactive. The binding studies suggest that the cross-reactivity of the antibody to hTSH occurred on the basis of common antigenic determinants on the beta subunits of the two species. Documentation of a true elevation of plasma hTSH was achieved by gel filtration of plasma in which a peak of immunoreactivity co-eluting with [ 125I]-hTSH could be shown. Evidence for suppression of TSH secretion by thyroxine administration in the presence of interfering antibody was obtained by demonstrating that the level of plasma “immunoreactive TSH” did not change in response to TRH administration.

Patterns of TSH response to TRH in children with hypopituitarism

The TSH response to TRH was studied in 42 children with hypopituitarism. Basal TSH was similar to the control group except in seven patients who had elevated values (Group A). These children also had an altered TSH response to TRH but normal increments in T4, T3, and 131I thyroid uptake after administration of bTSH. Three different patterns of TSH responses to TRH were observed in patients with normal basal TSH: delayed and exaggerated response (Group B, n=15), deficient response (Group C, n=4), and normal response (Group D, n=16). Some patients of groups A, B, and C with blunted basal growth velocity had an improved growth rate with T4 therapy. However, a better response was observed when hGH and T4 were administered simultaneously. The following conclusions were drawn: (1) high immunoreactive TSH in the presence of a thyroid gland responding normally to TSH suggests a dissociation between the biologic and immunologic activity of serum TSH; (2) an exaggerated and delayed response to TRH was frequently found in secondary hypothyroidism and suggests hypothalamic TRH deficiency; (3) an impaired TSH response to TRH is less frequent and suggests a pituitary abnormality; (4) patients with a normal response to TRH probably have normal hypothalamic-pituitary thyroid axis. The TRH test is useful in the diagnosis of hypothalamic-pituitary thyroid abnormalities and helps to unmask thyroid dysfunction. A number of such patients with stunted growth benefit from thyroid therapy. The TSH response to TRH was studied in 42 children with hypopituitarism. Basal TSH was similar to the control group except in seven patients who had elevated values (Group A). These children also had an altered TSH response to TRH but normal increments in T4, T3, and 131I thyroid uptake after administration of bTSH. Three different patterns of TSH responses to TRH were observed in patients with normal basal TSH: delayed and exaggerated response (Group B, n=15), deficient response (Group C, n=4), and normal response (Group D, n=16). Some patients of groups A, B, and C with blunted basal growth velocity had an improved growth rate with T4 therapy. However, a better response was observed when hGH and T4 were administered simultaneously. The following conclusions were drawn: (1) high immunoreactive TSH in the presence of a thyroid gland responding normally to TSH suggests a dissociation between the biologic and immunologic activity of serum TSH; (2) an exaggerated and delayed response to TRH was frequently found in secondary hypothyroidism and suggests hypothalamic TRH deficiency; (3) an impaired TSH response to TRH is less frequent and suggests a pituitary abnormality; (4) patients with a normal response to TRH probably have normal hypothalamic-pituitary thyroid axis. The TRH test is useful in the diagnosis of hypothalamic-pituitary thyroid abnormalities and helps to unmask thyroid dysfunction. A number of such patients with stunted growth benefit from thyroid therapy.

Thyrotoxicosis and a Thyrotropin-Secreting Pituitary Tumor Causing Unilateral Exophthalmos

Hyperthyroidism due to a TSH-secreting pituitary tumor has been noted by a number of investigators. We describe a unique case in which a 17-yr-old female presented with clinical hyperthyroidism, a goiter, and unilateral exophthalmos. Serum T4, free T4, and T3 (RIA) were consistently elevated along with elevated TSH levels (range, 10-100 microunits/ml). Skull x-rays and computed tomography scan revealed a tumor invading the right orbit. Other pituitary function studies were normal and LATs was undetectable. Surgery performed resulted in 70% removal of the pituitary tumor and confirmed the presence of tumor infiltration into the right orbit. TRH tests done pre- and postoperatively (patient still clinically hyperthyroid with elevated T4 and TSH levels) showed TSH and PRL responsiveness. Electron microscopy of the tumor demonstrated features typical of pituitary thyrotrophs. Monolayer cultures of pituitary cells released TSH over time into the media but did not respond to TRH stimulation. Pituitary adenoma tissue content of immunoreactive TSH was 65 microunits/g wet tissue and demonstrated immunosimilarity with human standard. We conclude that the patient had a TSH-secreting pituitary tumor responsive to TRH stimulation.

Pituitary resistance to thyroid hormone in cystinosis.

Eleven children with nephropathic cystinosis without clinical features of hyperthyroidism or hypothyroidism had elevated serum levels of immunoreactive TSH. The mean TSH level (+/- SE) was 37.4 +/- 12.3 microM/ml. Serial determinations of thyroid function during 1 yr were: mean (+/- SE) serum T4, 10.8 +/- 0.7 microgram/dl; free T4, 2.1 +/- 0.2 ng/dl; and T3, 239 +/- 6 ng/dl. After 500 microgram TRH iv, the peak TSH level exceeded 100 microU/ml in 6 of 10 patients, whereas T3 responses were variable. Studies of parameters influenced by thyroid hormone, including red cell sodium content, serum cholesterol, and 24-h urinary hydroxylysine excretion, were consistent with euthyroidism. On the other hand, the mean pulse wave arrival time was significantly reduced, consistent with hyperthyroidism. Three control patients, 2 with Lowe's syndrome and 1 with benign cystinosis, had normal thyroid studies. Eight of the patients were given either exogenous L-T4 or T3 in doses which were increased at weekly intervals. The serum TSH concentrations were suppressed to normal only after elevation of serum levels of thyroid hormones and with high exogenous thyroid replacement doses. The data suggest abnormal pituitary resistance to feedback by thyroid hormone in patients with cystinosis. We believe this to be the first description of the association of a heritable metabolic disease with such pituitary resistance.

Effect of time, temperature and freezing on the stability of immunoreactive LH, FSH, TSH, growth hormone, prolactin and insulin in plasma

1. Endogenous LH, FSH, TSH, growth hormone, prolactin and insulin were measured by radioimmunoassay in human plasma samples stored at 4 degrees, 20 degrees and 37 degrees for up to 8 days or repeatedly frozen and thawed. 2. At 4 degrees, the concentrations of all hormones were stable for at least 8 days; at 20 degrees only LH, FSH and TSH were stable for 8 days; at 37 degrees only TSH was stable for 8 days. 3. All the hormones except insulin were stable during 5 freeze-thaw cycles.

Changes in the Contents! of Multiple Components of Rat Pituitary Thyrotropin in Altered Thyroid States

Anterior pituitary glands from normal and hypothyroid rats were analyzed for the distribution of immunoreactive TSH using isoelectric focusing. More than four distinct components of immunoreactive TSH were present in the normal rat pituitary, mostly distributed over a region of isoe ectric point (pI) between pH 6.6–8.3. When rats were rendered hypothyroid by treatment with 6-methyl-2-thiouracil (MTU), the distribution pattern of these components as well as the total TSH content in the pituitary changed considerably. All of the TSH components in the pituitary decreased during the first week of MTU treatment and reaccumulated thereafter. Acidic TSH (pI 8.2) decreased to a lesser extent initially, returned to the normal level by 2 weeks, and exceeded it by 90% at 3 weeks of MTU treatment. Median TSH (pI 7.9) almost paralleled the variation in the total TSH content in...

Thyroid-stimulating activity of chorionic gonadotropin and luteinizing hormone.

While recent evidence indicates that the hCG molecule has intrinsic thyroid-stimulating activity (TSA), it is not clear whether a thyrotropic molecule other than hCG accounts for some of the TSA apparent in the crude or highly purified hCG. To determine if a thyrotropic factor is excluded from crude urinary hCG during purification of hCG, the ratio of interstitial cell-stimulating activity (ICSA) to TSA was determined in the starting material used for hCG preparation as well as in the highly purified hCG preparation. The ratio of the two biological activities did not change significantly during purification, suggesting that no factor present in crude hCG other than hCG itself accounts for the TSA. The highly purified hCG preparation was gel-filtered on Sephadex G-100 and the main protein peak was divided into three fractions. The ratio of TSA to ICSA was the same in each fraction, further indicating that these activities are intrinsic to the same molecule. If hCG has intrinsic thyrotropic activity, as these data indicate, then thyrotropic activity would be expected to be a secondary biological activity of LH, since there are strong structural and functional similarities between LH and hCG. In order to assess the LH molecule for intrinsic TSA, an LH preparation with minimal TSH contamination was prepared by recombining subunits exhibiting minimal TSH immunoreactivity. The LH molecule formed from the recombination of highly purified hCG alpha and ovine LH beta subunits exhibited TSA in the bioassay that was 25 times greater than that expected based on the immunoreactive TSH contamination. There was no evidence to support the existance of a thyrotropic factor other than hCG in either crude or highly purified hCG preparations. Our finding that a hybrid LH molecule structurally similar to hCG with potent ICSA also exhibits intrinsic TSA further extends and supports the hypothesis that TSA is an intrinsic property of the hCG molecule.

Plasma immunoreactive thyrotropin releasing hormone (TRH) values in normal newborns.

The study reported here extends investigation on the pituitary thyroid axis in newborn infants, including the assay of plasma immunoreactive TSH levels at different intervals after delivery. Blood samples were collected at birth and after 30, 60, 120 minutes, 6, 24 and 48 hours. Plasma TRH levels were also estimated in normal adult subjects and pregnant women. No significant difference was observed with regard to sex, pregnancy or age, except for a marked increase in newborn infants after delivery. Plasma TRH values, already moderately high at birth (mean 46 pg/ml, range 34-57) reached rapidly a peak of 78 pg/ml (range 60-93) 30 minutes after delivery, decreased rapidly between 30 minutes and 2 hours post-partum, then fell gradually to normal range at 24 hours. A comparison of plasma TRH and TSH levels measured simultaneously suggests that the acute TSH surge at delivery is mediated by TRH secretion.

Adenohypophysial necrosis in rats following destructionof the pituitary stalk

Adenohypophyses of adult male rats have been investigated by light microscopy, immunocytology and electron microscopy 30 minutes, 1, 2, 4, 6 and 24 hours following electrolyte destruction of the pituitary stalk. Light microscopy revealed massive ischemic infarction of the adenohypophysis. Immunoreactive growth hormone, prolactin, TSH, FSH and LH were demonstrated up to 24 hours after surgery in necrotic adenohypophysial cells by the immunoperoxidase technique. Fine structural abnormalities were already noticeable 30 minutes following stalk lesion. The changes rapidly progressed and within 2 hours unmistakable signs of cellular necrosis became evident. Mitochondria, especially those of growth hormone cells, seemed to be affected at an early stage, whereas alterations in rough-surfaced endoplasmic reticulum membranes developed later. Nuclear changes, formation of cytoplasmic vacuoles and disruption of cell membranes were conspicuous findings. No evidence, indicating the participation of lysosomes in the development of cellular damage, was obtained. Secretory granules were prominent and well preserved even in cells which showed advanced necrosis. The failure of discharge and degradation of secretory granules in the necrotic cells suggest that factors accounting for their intracellular migration and extrusion are very sensitive to ischemia and are paralyzed at an early phase.

Effect of a large dose of thyrotrophin releasing factor on pituitary and thyroid function in patients with Parkinsonism.

Thyrotrophin releasing factor (TRF) was given intravenously in doses of 0-5 mg and 20 mg to six patients with Parkinsonism treated with L-dopa. Plasma thyrotrophin (TSH), prolactin, lutenizing hormone (LH), follicle stimulating hormone (FSH), thyroxine (T4) and triiodothyronine (T3) were measured before and after TRF infusion. The observation that FSH and LH did not change in response to either dose of TRF confirmed specificity of the effects TRF for certain anterior pituitary functions. The plasma TSH and prolactin levels achieved after 20 mg TRF were considerably greater and were maintained longer than those after 0-5 mg TRF. However, despite a seven fold increase in the overall TSH response, the T4 and T3 responses to 20 mg TRF were not significantly greater than those to 0-5 mg TRF. The explanation for this discrepancy between immunoreactive TSH levels and apparent biologic effect is unclear.

Plasma Immunoreactive T3, TSH and ACTH Before and After Provocative Tests in Idiopathic Hypopituitary Dwarfism

The somatotropic, thyrotropic and corticotropic functions were investigated in 8 patients with idiopathic pituitary dwarfism. Particularly interesting were the results obtained from studies of the thyrotropic function. In the absence of clinical and conventional laboratory indices of hypothyroidism, measurement of plasma immunoreactive T3 and TSH before and after iv administration of 400 μg of TRH suggested the presence of borderline hypothyroidism. Basal plasma T3 values ranged from 20 to 55 ng/100 ml with a mean of 36.2 vs 55–160 ng/100 ml with a mean of 107. Moreover, plasma T3 response to TRH, although present, was markedly lower than in the controls (20–90 ng/100 ml with a mean of 62 vs 100–175 ng/100 ml with amean of 127). Plasma TSH response to TRH appeared markedly delayed and prolonged (maximal rise at 60 min instead of at 20 min). Also of interest were the results obtained from studies of the corticotropic function. The maximal plasma ACTH values after insulin-induced hypoglycemia was 91 + 17.5 ...

Endocrine function in an anencephalic infant.

ABSTRACT The endocrine function in a fullterm 2.1 kg female anencephalic infant was studied by measuring immunoreactive ACTH, growth hormone, insulin, TSH, T4, and T3 concentrations in umbilical cord blood and serial venous plasma samples obtained at 10–30-min intervals until death. In addition, plasma cortisol and T4 concentrations were determined by competitive protein binding. The following materials were given: TRF (100 mg, iv) at 86 mins; lysinevasopressin (LVP) (2.5U, iv) at 125 mins; α1-24 ACTH (1 mg, im) at 160 min; and TSH (5U, im) at 221 min. Plasma TSH and ACTH concentrations were low in the infant until stimulation by TRF and LVP, respectively. Plasma TSH and ACTH concentrations then increased significantly. There were no corresponding changes in plasma T4, T3, or cortisol concentrations following the elevation in plasma TSH and ACTH concentration. A spike in plasma insulin concentration occurred following injection of vasopressin with a subsequent fall in the plasma glucose concentration. The...