Circulating Thyroid-stimulating Hormone Levels Research Articles

PSAT366 Liquid L-thyroxine (L-T4) Formulation Normalizes TSH in Hypothyroid Patients Treated with Tablets L-T4

Abstract The absorption of L-thyroxine (L-T4) can be affected by different factors, such as the manner of L-T4 assumption (during breakfast, or with food), the age of the patient, the interference with other drugs, absorption kinetics, adherence to therapy, and others. L-T4 tablets malabsorption can occur due to the increased gastric pH in patients in treatment with proton pump inhibitors (PPI; omeprazole, pantoprazole, lansoprazole) for gastritis, gastric ulcer, etc. We enrolled 25 patients in treatment with L-T4 in the tablet formulation, and with elevated serum thyroid-stimulating hormone (TSH) levels; they were switched to the same dose of an oral liquid L-T4 preparation. A normalization, or reduction, of circulating TSH levels occurred after the switch from L-T4 in tablet formulation to the liquid one (at the same dose). Eleven of these subjects who, for different reasons, were switched back again to assume L-T4 in tablets (with the same dosage), had a worsening of TSH levels, reaching the hypothyroid range. Our results show that the pH alteration issue due to PPI could be overcome by the assumption of the oral L-T4 liquid formulation. Other future studies are needed to investigate liquid L-T4 formulation also in other conditions of altered L-T4 absorption. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP598 Liquid levothyroxine (L-T4) maintains more stable TSH levels in hypothyroid patients, than tablet L-T4

Abstract Hypothyroidism affects approximately 5% of the population, mostly women and people over 60 years of age. The standard therapy used for the treatment of hypothyroidism is tablet levothyroxine (L-T4). Thyroid-stimulating hormone (TSH) is monitored, and L-T4 is adjusted as necessary to reach euthyroidism. Upon the stabilization of TSH levels in the normal range, it is recommended to perform an annual testing in treated patients to warrant suitable replacement. Large population studies showed an increased mortality in people with TSH in the hypothyroid range, demonstrating the importance of maintaining a stable TSH level in the normal range. We evaluated the stability of circulating TSH in hypothyroid patients treated with liquid L-T4, with respect to those treated with tablet L-T4. We enrolled patients with normal circulating TSH levels at the basal evaluation, not reporting any malabsorption or drug interference issues, who were in treatment with liquid or tablet L-T4.Six hundred and fifty six hypothyroid patients treated with liquid L-T4 were compared to 328 hypothyroid subjects receiving tablet L-T4 (both groups were matched by age and gender).Patients were followed for two years, and serum TSH, FT3, FT4 levels were assessed after one and two years. At the first abnormal TSH value, the evaluated parameters were: age, gender, body mass index, history of chronic autoimmune thyroiditis, initial TSH, and L-T4 dosage. At the time of initial normal TSH, these parameters were not associated significantly with time to abnormal TSH values. After 1 year, normal TSH values were registered in 86% of the patients who received L-T4 liquid formulation, but only in 81% of patients treated with tablet L-T4. After 2 years, normal TSH values were registered in 84% of patients receiving L-T4 liquid formulation, while only in 74% of those with tablet L-T4 (p<0.05). To sum up, the obtained data suggest that liquid L-T4 maintains more efficiently (than tablet L-T4) normal TSH levels in hypothyroid patients in the long term follow-up. Presentation: No date and time listed

Thyroid Function and COVID-19 Susceptibility and Its Severity: A Two-Sample Mendelian Randomization Study.

Several observational studies have confirmed the relationship between thyroid hormones and coronavirus disease 2019 (COVID-19), but this correlation remains controversial. We performed a two-sample Mendelian randomization (MR) analysis based on the largest publicly available summary datasets. Summary statistics with 49 269 individuals for free thyroxine (FT4) and 54 288 for thyroid stimulating hormone (TSH) were used as exposure instruments. Genome-wide association studies of susceptibility (cases = 38 984; controls = 1 644 784), hospitalization (cases: 9986 = controls = 1 877 672), and very severe disease (cases = 5101; controls = 1 383 241) of COVID-19 were used as the outcome. We used the inverse-variance weighted (IVW) method as the primary analysis, and utilized MR-Egger regression, weighted median, and robust adjusted profile score (RAPS) for sensitivity analysis. Genetic predisposition to higher serum levels of FT4 within the normal range was negatively associated with the risk of COVID-19 hospitalization (odds ratio [OR] = 0.818; 95% CI, 0.718-0.932; P = 2.6 × 10-3) and very severe disease (OR = 0.758; 95% CI, 0.626-0.923; P = 5.8 × 10-3), but not susceptibility. There is no evidence that genetically predicted circulating TSH levels are associated with COVID-19 susceptibility and severity risk. Neither apparent pleiotropy nor heterogeneity were detected in the sensitivity analysis. In summary, we found that higher FT4 levels may reduce the risk of COVID-19 severity, suggesting that thyroid function testing may be required for patients with COVID-19.

Thyroid Stimulating Hormone Levels Are Associated With Genetically Predicted Nonalcoholic Fatty Liver Disease.

Findings from observational studies indicate an association of thyroid hormone levels with the risk of nonalcoholic fatty liver disease (NAFLD); however, conflicting results remain and reverse causality may be a possibility. This study aimed to evaluate the associations between NAFLD and both plasma thyroxine (T4) and thyroid stimulating hormone (TSH) at the phenotypic and genetic levels. We included 14 797 participants, aged 20 to 74 years who had undergone abdominal ultrasonography during the Third National Health and Nutrition Examination Survey (NHANES III). Multivariable logistic regression analyses were used to examine the observational associations of TSH and T4 with NAFLD. Mediation analyses were performed to study whether the relationship between NAFLD and TSH levels was mediated via potential confounders. A bidirectional, two-sample Mendelian randomization (MR) analysis was used to determine the potential causal relationship. Multivariable logistic regression model suggested a "dose-response" relationship between TSH (Q4 vs Q1: OR = 1.29; 95% CI, 1.10-1.52; Ptrend = 0.001) and NAFLD. BMI and ALT partially mediated the association between TSH and NAFLD, while the proportion of the mediation effects of BMI and ALT were 39.1% and 22.3%, respectively. In MR analyses, the inverse-variance weighted method was selected as primary method and suggested a putative causal effect of NAFLD on serum TSH levels (OR = 1.022; 95% CI, 1.002-1.043). The result was further validated in the sensitivity analyses. Circulating TSH levels were associated with the risk of NAFLD. MR analysis suggested a putative causal effect of NAFLD on TSH levels.

SAT-547 Pituitary Thyrotrophs: A Generator of Repetitive Calcium Waves in Freely-Moving Animal Models

Hypothyroidism refers to the pathological state of thyroid hormone (TH) deficiency. It affects between 0.3% and 3.7% of the general population in the USA and between 0.2% and 5.3% in Europe. Hypothyroid patients suffer from extreme fatigue, altered heart rate, depression, weight gain, and difficulty in conceiving. Also, maternal hypothyroidism, which affects 0.5% of all pregnant women, is the leading preventable cause of mental retardation in offspring. Importantly, diagnosis of hypothyroidism is based on a single thyroid-stimulating-hormone (TSH) measurement. TSH secretion by pituitary thyrotrophs is under the positive control of hypothalamic thyrotropin-releasing-hormone (TRH) and negative feedback exerted by THs. Despite the undeniable implication of thyrotrophs in the hypothalamus-pituitary-thyroid (HPT) axis regulation, little is known about the mechanisms underlying adaptive TSH secretion. Being the smallest endocrine cell population of the pituitary (2-4%), thyrotrophs display high plasticity in cell shape, number and network topology throughout development and in disease. Moreover, enzymatically-dispersed thyrotrophs lose their ability to express and secrete TSH in both basal and TRH-stimulated conditions. Altogether, these findings led us to the hypothesis that thyrotrophs form a very finely regulated and highly plastic functionally-organized cell population capable of adapting to physiological (i.e. pregnancy) and pathological (i.e. hypothyroidism) demand. The aim of this study was to investigate how thyrotrophs function in their native environment. Using gradient-index (GRIN) lenses implanted at the pituitary level and a 2g head-mounted miniscope, multicellular calcium activities of the thyrotroph population were monitored in freely-moving TSHβ-crexR26fl-flGCaMP6f mice. Strikingly, thyrotrophs displayed both short-lived calcium spikes of high amplitude, and slowly-evolving calcium waves propagating among the thyrotroph population (n=3). Such calcium waves recurred every 80min during episodes lasting 3min and were interspaced by short-lived activity/silent periods. As TSH displays a 2.722min half-life (n=6), repetitive bouts of calcium-dependent TSH exocytosis would lead to cumulative increase in circulating TSH levels. Hence, the thyrotroph population functions in vivo as a robust generator of repetitive calcium waves which would orchestrate the generation of ultradian TSH fluctuations. Such signaling events could be monitored during longitudinal studies (weeks to months) in which individual animals could be their own controls.

Hypothyroidism in the Elderly: Who Should Be Treated and How?

Hypothyroidism is among the most frequent chronic diseases in the elderly, and levothyroxine (l-T4) is worldwide within the 10 drugs more prescribed in the general population. Hypothyroidism is defined by increased serum thyroid-stimulating hormone (TSH) values and reduced circulating free thyroid hormones, whereas subclinical hypothyroidism (sHT) is characterized by free hormone fractions within the normal ranges and has been divided into two classes, depending on circulating TSH levels (above or below 10 mIU/L). Given that during aging, a natural trend toward higher values of circulating TSH has been reported, it is necessary to verify carefully the diagnosis of sHT to tailor an appropriate follow-up and ad hoc therapy, avoiding unnecessary or excessive treatment. In the current review, we evaluate the state of the art on hypothyroidism in the elderly with special focus on the effect of sHT on cognition and the cardiovascular system function. We also summarize the recommendations for a correct diagnostic workup and therapeutic approach to older people with an elevated TSH value, with special attention to the presence of frailty, comorbidities, and poly therapy. In conclusion, personalized therapy is crucial in good clinical practice, and in the management of older patients with sHT, multiple factors must be considered, including age-dependent TSH cutoffs, thyroid autoimmunity, the burden of comorbidities, and the possible presence of frailty. l-T4 is the drug of choice for the treatment of hypothyroid older people, but the risk of overtreatment, potential adverse drug reactions, and patient compliance should always be considered and thyroid status periodically reassessed.

Thyroid Stimulating Hormone and Bone Mineral Density: Evidence From a Two-Sample Mendelian Randomization Study and a Candidate Gene Association Study.

With population aging, prevalence of low bone mineral density (BMD) and associated fracture risk are increased. To determine whether low circulating thyroid stimulating hormone (TSH) levels within the normal range are causally related to BMD, we conducted a two-sample Mendelian randomization (MR) study. Furthermore, we tested whether common genetic variants in the TSH receptor (TSHR) gene and genetic variants influencing expression of TSHR (expression quantitative trait loci [eQTLs]) are associated with BMD. For both analyses, we used summary-level data of genomewide association studies (GWASs) investigating BMD of the femoral neck (n = 32,735) and the lumbar spine (n = 28,498) in cohorts of European ancestry from the Genetic Factors of Osteoporosis (GEFOS) Consortium. For the MR study, we selected 20 genetic variants that were previously identified for circulating TSH levels in a GWAS meta-analysis (n = 26,420). All independent genetic instruments for TSH were combined in analyses for both femoral neck and lumbar spine BMD. In these studies, we found no evidence that a genetically determined 1-standard deviation (SD) decrease in circulating TSH concentration was associated with femoral neck BMD (0.003 SD decrease in BMD per SD decrease of TSH; 95% CI, -0.053 to 0.048; p = 0.92) or lumbar spine BMD (0.010 SD decrease in BMD per SD decrease of TSH; 95% CI, -0.069 to 0.049; p = 0.73). A total of 706 common genetic variants have been mapped to the TSHR locus and expression loci for TSHR. However, none of these genetic variants were associated with BMD at the femoral neck or lumbar spine. In conclusion, we found no evidence for a causal effect of circulating TSH on BMD, nor did we find any association between genetic variation at the TSHR locus or expression thereof and BMD. © 2018 The Authors. Journal of Bone and Mineral Research Published by WileyPeriodicals, Inc.

Serum trace elements are interrelated with hormonal imbalance in men with acute ischemic stroke

The objective of the present study was to assess hormonal and trace element status in men suffering from acute ischemic stroke. Methods21 acute ischemic stroke patients and 21 age- and body mass index-matched healthy volunteers were enrolled in the study. Serum trace elements were assessed using inductively coupled plasma mass spectrometry. Serum hormones and brain damage markers were estimated using enzyme-linked immunosorbent assay. ResultsIschemic stroke patients are characterized by significantly higher levels of total and free triiodothyronine (T3), anti-thyroid peroxidase antibodies (Anti-TPO-Ab), prolactin, and cortisol, whereas the level of thyroid stimulating hormone (TSH) was decreased. Serum B, Cu, Li, Mn, Ni, Pb, Se, V, and Zn in stroke significantly exceeded the control values, whereas the level of Co and Fe was decreased. Correlation analysis revealed a significant association between serum B and T3, Anti-TPO-Ab, and iodine concentration; serum Li and Sr levels − with circulating TSH, free T3, and Anti-TPO-Ab; and V concentration − with total T3 and I levels. The following positive relationships were also revealed: Co − TSH, Mn − free T3, Zn − free T3. Multiple linear regression demonstrated that Co, I, and Li were directly related to circulating TSH levels, whereas V concentration was negatively interrelated. In turn, only serum Li levels were characterized by a significant direct relationship with free T3 values. ConclusionGenerally, the obtained data demonstrate that altered serum trace elements are associated with thyroid dysfunction in acute ischemic stroke patients. However, the causal relationship should be estimated.

Cholesterol Synthesis Increased in the MMI-Induced Subclinical Hypothyroidism Mice Model.

Subclinical hypothyroidism (SCH) is defined as increased serum thyroid-stimulating hormone (TSH) concentrations and normal serum thyroid hormone (TH) levels as well as an increased serum cholesterol level, which is an important cause of secondary hypercholesterolemia and cardiovascular diseases. Some studies have demonstrated a direct effect of TSH on cholesterol metabolism via in vivo and in vitro experiments. However, because no suitable SCH model has been established until now, the changes in cholesterol synthesis that occur in SCH patients remain unknown. Here, we establish an SCH mouse model by using long-term low-dose MMI administered in drinking water. Compared with the control group, the MMI-treated mice had elevated circulating TSH levels, but the serum FT3 levels in these mice did not change. Additionally, the TC levels increased in both the serum and liver of the experimental mice. Both the protein expression and activity of hepatic HMGCR, the rate-limiting enzyme for cholesterol synthesis in the liver, increased in these mice. We also found that the SCH mice had decreased phospho-HMGCR and phospho-AMPK expression, while the expression of AMPK showed no change. In conclusion, we established a suitable SCH model in which cholesterol synthesis is increased.

Carriers of a VEGFA enhancer polymorphism selectively binding CHOP/DDIT3 are predisposed to increased circulating levels of thyroid-stimulating hormone

BackgroundLevels of serum thyroid-stimulating hormone (TSH) indicate thyroid function, because thyroid hormone negatively controls TSH release. Genetic variants in the vascular endothelial growth factor A (VEGFA) gene are associated with...

Association of High Vitamin D Status with Low Circulating Thyroid-Stimulating Hormone Independent of Thyroid Hormone Levels in Middle-Aged and Elderly Males

Background. A recent study has reported that high circulating 25-hydroxyvitamin D [25(OH)D] is associated with low circulating thyroid-stimulating hormone (TSH) levels, but only in younger individuals. The goal of the present study was to explore the relationship between vitamin D status and circulating TSH levels with thyroid autoimmunity and thyroid hormone levels taken into consideration in a population-based health survey of middle-aged and elderly individuals. Methods. A total of 1,424 Chinese adults, aged 41–78 years, were enrolled in this cross-sectional study. Serum levels of 25(OH)D, TSH, thyroid hormones, and thyroid autoantibodies were measured. Results. The prevalence of vitamin D insufficiency was 94.29% in males and 97.22% in females, and the prevalence of vitamin D deficiency was 55.61% in males and 69.64% in females. Vitamin D status was not associated with positive thyroid autoantibodies after controlling for age, gender, body mass index, and smoking status. Higher 25(OH)D levels were associated with lower TSH levels after controlling for age, FT4 and FT3 levels, thyroid volume, the presence of thyroid nodule(s), and smoking status in males. Conclusion. High vitamin D status in middle-aged and elderly males was associated with low circulating TSH levels independent of thyroid hormone levels.

Quantitative Histological Assessment of Xenobiotic-Induced Liver Enzyme Induction and Pituitary-Thyroid Axis Stimulation in Rats Using Whole-Slide Automated Image Analysis

Preclinical evaluation of a new compound, RO2910, identified a hypertrophic response in liver, thyroid gland, and pituitary gland (pars distalis). We aimed to develop and validate automated image analysis methods to quantify and refine the interpretation of semi-quantitative histology. Wistar-Han rats were administered RO2910 for 14 days. Liver, thyroid, and pituitary gland tissues were processed for routine histology and immunolabeled with anti-thyroid stimulating hormone (TSH) antibody (pituitary) and anti-topoisomerase II antibody (thyroid). Glass slides were scanned, image analysis methods were developed and applied to whole-slide images, and numerical results were compared with histopathology, circulating hormone levels, and liver enzyme mRNA expression for validation. Quantitative analysis of slides had strong individual correlation with semi-quantitative histological evaluation of all tissues studied. Hepatocellular hypertrophy quantification also correlated strongly with liver enzyme mRNA expression. In the pars distalis, measurement of TSH weak-staining areas correlated with both hypertrophy scores and circulating TSH levels. Whole-slide image analysis enabled automated quantification of semi-quantitative histopathology findings and a more refined interpretation of these data. The analysis also enabled a direct correlation with non-histological parameters using straightforward statistical analysis to provide a more refined dose- and sex-response relationship and integration among affected parameters. These findings demonstrate the utility of our image analysis to support preclinical safety evaluations.

Phosphodiesterase 8B Gene Variants Are Associated with Serum TSH Levels and Thyroid Function

Thyroid-stimulating hormone (TSH) controls thyroid growth and hormone secretion through binding to its G protein-coupled receptor (TSHR) and production of cyclic AMP (cAMP). Serum TSH is a sensitive indicator of thyroid function, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over a life span. By genotyping 362,129 SNPs in 4,300 Sardinians, we identified a strong association (p = 1.3 x 10(-11)) between alleles of rs4704397 and circulating TSH levels; each additional copy of the minor A allele was associated with an increase of 0.13 muIU/ml in TSH. The single-nucleotide polymorphism (SNP) is located in intron 1 of PDE8B, encoding a high-affinity cAMP-specific phosphodiesterase. The association was replicated in 4,158 individuals, including additional Sardinians and two genetically distant cohorts from Tuscany and the Old Order Amish (overall p value = 1.9 x 10(-20)). In addition to association of TSH levels with SNPs in PDE8B, our genome scan provided evidence for association with PDE10A and several biologically interesting candidates in a focused analysis of 24 genes. In particular, we found evidence for association of TSH levels with SNPs in the THRB (rs1505287, p = 7.3 x 10(-5)), GNAQ (rs10512065, p = 2.0 x 10(-4)), TG (rs2252696, p = 2.2 x 10(-3)), POU1F1 (rs1976324, p = 3.9 x 10(-3)), PDE4D (rs27178, p = 8.3 x 10(-3)), and TSHR (rs4903957, p = 8.6 x 10(-3)) loci. Overall, the results suggest a primary effect of PDE8B variants on cAMP levels in the thyroid. This would affect production of T4 and T3 and feedback to alter TSH release by the pituitary. PDE8B may thus provide a candidate target for the treatment of thyroid dysfunction.

Mode of action of thyroid tumor formation in the male Long-Evans rat administered high doses of alachlor.

Chronic administration of alachlor in the diet at a level of 126 mg/kg/day has previously been shown to cause an increase in benign thyroid follicular cell tumors in male Long-Evans rats. Studies were conducted to elucidate the mechanism of the alachlor-induced thyroid tumors in the male rat by evaluating changes in parameters that are collectively associated with a hormonally mediated mode of action for thyroid neoplasia. Male Long-Evans rats were administered 126 mg alachlor/kg body wt/day via the diet for up to 120 days. One group of animals was removed from alachlor-treated diet after 60 days and received untreated diet for an additional 60 days. Liver and thyroid weights and serum levels of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH), as well as hepatic uridine diphosphate glucuronosyl transferase (UDPGT) activity, were determined at 7, 14, 28, 60, and 120 days of treatment. Liver and thyroid weights, hepatic UDPGT activity, and circulating levels of TSH were significantly increased in animals administered alachlor. These increases were seen as early as 7 days after alachlor administration. Circulating levels of T4 in alachlor-treated animals were significantly decreased compared with controls at 7 days, but had returned to control levels by 60 days. T3 levels were elevated at all time points except at 28 days. The changes in TSH and T3 levels, hepatic UDPGT activity, and liver weights were all reversible on elimination of alachlor from the diet. Thyroid weights did not completely return to control levels after removal of alachlor from the diet, although some recovery was evident. The results of this study clearly suggest that alachlor-induced thyroid neoplasia, observed in previous chronic bioassays with alachlor, was associated with increases in circulating TSH levels. Increased metabolism of T4 via hepatic enzymatic conjugation (i.e., T4-UDPGT) appeared to be responsible for the increased TSH levels. These effects were shown to be reversible on cessation of exposure to alachlor. In summary, evidence is presented for a hormonally mediated process for the development of thyroid follicular cell tumors.

Immunocytochemical Demonstration of Chicken Hypophyseal Thyrotropes and Development of a Radioimmunological indicator for Chicken TSH Using Monoclonal and Polyclonal Homologous Antibodies in a Subtractive Strategy

The production and characterization of monoclonal antibodies (mAbs) toward the chicken pituitary glycoproteins are described. MAbs were first subdivided on an immunocytochemical (ICC) basis: one category of mAbs reacts with both thyrotropic and gonadotropic cells whereas another stains exclusively gonadotropic cells. The hypothesis that the former are anti-glycoprotein α and that the latter are anti-βLH and/or anti-βFSH mAbs was further elaborated in a homologous tracer binding assay. The putative anti-β gonadotropin mAbs exclusively recognize iodinated USDA-cLH-I-1, whereas the supposed anti-α mAbs react with both USDA-cLH-I-1 and USDA-cFSH-I-1. The ICC localization of pituitary thyrotropes has been achieved in a double-staining protocol using an anti-LH mAb to subtract specifically the gonadotropic cells from the complete α-subunit-containing cell population. The result is a strictly cephalic cell population that is densely granulated in hyperthyroid and hardly detectable in hypothyroid birds. A similar subtractive approach was used to develop a thyroid-stimulating hormone (TSH)-indicator in RIA. The total titer of α-containing molecules is first quantified with an anti-α mAb. The contribution of both LH and FSH to this titer is then measured by homologous USDA-RIA and subtracted from the total α-immunoreactivity to give an indication of the TSH level of the sample. The direct effect of thyroid-releasing hormone on pituitary TSH release in vitro in juvenile chicks and the effect of hypo- and hyperthyroidism on circulating TSH levels in vivo in juvenile broilers have been demonstrated.

Dopaminergic control of TSH secretion in endogenous depression

To evaluate whether the inhibitory control exerted by endogenous dopamine on thyroid-stimulating hormone (TSH) secretion is altered in patients with major depressive disorder, 11 depressed patients and 9 normal controls were tested with the dopaminergic receptor antagonist domperidone (10 or 20 mg i.v.). The administration of domperidone induced a significant increase in circulating TSH levels in the normal controls, but not in the depressed patients. These data excluded the possibility that the dopaminergic inhibition of TSH secretion is enhanced in depression. To establish whether domperidone failure was due to reduced dopaminergic tone, domperidone was administered before stimulation of TSH secretion with thyrotropin-releasing hormone (TRH) (200 μg i.v.). The TSH response to TRH was significantly lower in the depressed than in the control subjects, regardless of domperidone priming. However, in both groups domperidone enhanced the TSH-induced TSH release by 50%. These data suggest that the dopaminergic control of TSH secretion is not altered in patients with endogenous depression and that a reduced capacity of the pituitary to secrete TSH might be responsible for the reduced TSH responsiveness to TRH and domperidone.

Effect of endogenous thyroid stimulating hormone levels on the secretion of thyroid hormones in man.

The effect of endogenous thyroid stimulating hormone (TSH) on the thyroid secretion of triiodothyronine (T3) and thyroxine (T4) was evaluated by serial determinations of serum T3. T4 and TSH concentrations in the following groups of patients: a) three patients submitted to surgical removal of a solitary, autonomous thyroid nodule which had completely inhibited the extranodular tissue; b) five subjects, with the same disease, in whom functional recovery of the extranodular tissue was induced by increased circulating TSH levels, produced by treatment with methimazole; c) one patient submitted to hemithyroidectomy for multinodular goitre; d) two hyperthyroid patients who had been treated with methimazole. In all these patients serum T3 and T4 levels progressively decreased, with a consequent progressive increase in serum TSH concentrations, leading to stimulation of the thyroid gland. During this TSH-induced stimulation of thyroid tissue, a significant positive correlation was found between the serum TSH concentrations and the corresponding ratio between the serum levels of T3 and T4 (T3/T4), both within each patient group (P less than 0.001) and among all patients (P less than 0.001). The same correlation also governs the relationship between the TSH and the T3/T4 values of 34 euthyroid control subjects and one patient with incipient hypothyroidism. These data strongly suggest that endogenous TSH can induce a preferential secretion of T3 over T4 by the human thyroid.

Developmental and patterns of pituitary and plasma TSH in the normal and hypothyroid female rat.

The developmental patterns of thyroid-stimulating hormone (TSH) was examined in female Long-Evans rats by radioimmunoassay of pituitary and plasma from 5 through 80 days of age. The effects of hypothyroidism on normal TSH levels were examined in animals radiothyroidectomized at birth. Control animals showed a peak in circulating TSH levels at day 12 followed by lower levels through day 30, and even lower levels at day 80 when values were those of adult animals. Hypothyroid females had higher plasma TSH levels than controls from days 10 through 30 with no distinct peak at day 12. Pituitary content reached a peak at day 18 and was always higher in control than hypothyroid animals.

A new in vitro assay for thyroid-stimulating hormone.

SUMMARY A new in vitro assay for thyroid-stimulating hormone (TSH) is described. The parameter of TSH action is the discharge of radioactive iodine from mouse thyroid glands labelled with 131I in vivo. The assay is sensitive to human TSH and gave consistent results during 1 yr. without seasonal variation. A potent preparation of long-acting thyroid stimulator gave a dose-response line parallel with human TSH. Fresh human serum was toxic to the assay preparation so that circulating TSH levels cannot be measured.