TSH Titers Research Articles

Comparison of Thyroid Gland Sonography Index with Serum Antithyroid Peroxidase, Antithyroglobulin, and Thyroid Function Tests in Patients with Hashimoto Thyroiditis.

Ultrasound examination of the thyroid has emerged as a useful diagnostic and prognostic tool, along with measuring serum titers of anti-thyroid peroxidase (TPO), anti-thyroglobulin (Tg), and thyroid hormones, in patients with Hashimoto's thyroiditis. So, we aimed at considering correlations of ultrasonographic, antibodies, and thyroid hormone levels. A total of 149 patients (118 females, 31 males; aged 18-60 years; mean age: 38.60 ± 8.03 years) who were diagnosed with Hashimoto's thyroiditis were enrolled in the study. The blood sample was taken to measure serum titers of free T3 (FT3) and T4 (FT4), TSH, anti-TPO, and anti-Tg antibody titers. The thyroid sonography of each patient was classified into one of the five grades by real-time ultrasound (US) based on echogenicity, thyroid size, and thyroid pattern. We evaluated whether there was a correlation between thyroid characteristics observed via ultrasound and serum levels of thyroid hormones, anti-TPO antibodies, and anti-Tg antibodies. Nodular structures were detected in 54 (36.2%) patients (38 micro-nodular and 16 macro-nodular). Echogenicity was recorded as isoechoic in 15(10.07%) and hypoechoic in 119 (79.87%) subjects. Euthyroid subjects had significantly thicker isthmus than overt and subclinical hypothyroid patients (P=0.018). Mean serum TSH, anti-Tg, and anti-TPO antibody titers showed a significant increase in patients with macro-nodules compared to those with micro-nodules and individuals without nodules (P0.05). The thickness of the isthmus had a significant negative correlation with FT4 (P=0.046; r=0.11) and FT3 (P=0.017; r=0.15), respectively. Thyroid autoantibodies had positive significant correlations with different parameters of thyroid volume (P0.05). Thyroid US findings, in addition to serum anti-Tg and anti-TPO antibody titers, might be correlated with the severity and extent of Hashimoto's thyroiditis, but further evaluations are needed.

Risk factors associated with congenital hypothyroidism: a case-control study in southeast Iran.

Background and aimCongenital hypothyroidism (CH) is known as one of the most common preventable cause of mental retardation. This study aimed to determine factors associated with CH in Iran.MethodsThis case-control study was conducted on 160 children under one year old in Zahedan in southeast Iran in 2016. The neonates who were born from March 1, 2015 to March 19, 2016 and had undergone a screening program for CH were the study population. The neonates with serum TSH > 10mIu/L and T4 < 6.5 or TSH > 30 mIu/L were considered as a case group. Each case was individually matched for sex, age at birth and place of residence with three neonates with normal TSH and T4 titers as a control group. Data was gathered using a standard checklist and analyzed using SPSS 20 and statistical tests, such as Chi-square and Fisher’s exact tests. Multivariable logistic regression analysis was also used to identify independent predictors of CH.ResultsAbout 25 of the 40 patients with CH (62.5%) were male who, in the univariate analysis, the following explanatory factors had no significant association with CH: history of parental consanguinity, type of delivery, weight at birth, height at birth, age of mother, sampling time, nationality, and birth season (p>0.05). Although, multivariate analysis showed no significant association between the studied factors and risk of CH (p>0.05), the likelihood of CH was greater among neonates born to consanguineous parents (AOR: 1.78, 95% CI: 0.82–3.89), those who were born to lower height at birth (AOR: 1.82, 95% CI: 0.85–3.91), neonates born to mothers younger than 18 years (AOR: 2.43, 95% CI: 0.57–10.29) and those who were born in the summer (AOR: 1.76, 95% CI: 0.57–5.44).ConclusionNone of the studied factors were predictors for CH. Since consanguineous marriages are frequent in the province, and it may be a major contributory factor, future studies should be conducted on the genetic causes.

Risk factors of congenital hypothyroidism using propensity score: a matched case-control study.

The aim of this study was to investigate the relationship between congenital hypothyroidism and several variables using two different adjustment methods. This matched case-control study was conducted in Hamadan Province, the west of Iran, in 2012 enrolling neonates born between 2005 and 2011 and covered by screening program for congenital hypothyroidism. The neonates with TSH titer more than 10 mU/l or T4 titer less than 6.4 μg/dl were considered as cases. Each case was individually matched for birth place and year with four neonates with normal TSH and T4 titers as controls. The data were analyzed using two different approaches including propensity score and multiple conditional logistic regression model. Of 1313 enrolled neonates, 277 (159 girls) were cases and 1036 (531 girls) were controls. The most important prognostic factors which had significant effect on congenital hypothyroidism included twin, birth season, maturity, jaundice at birth, birth weight, age at pregnancy, maternal anemia and goiter, gestational age, delivery type, father's education and smoking status, and consanguinity. The associations reported by logistic regression were stronger that of than propensity score analysis in most items, although the differences were not statistically significant. We addressed the effect of numerous potential risk factors on congenital hypothyroiditis and the impact of these factors on the disease occurrence. However, future prospective studies are needed to test these findings and hypothesis and to investigate the true effect of these potential risk factors on congenital hypothyroiditis.

Hashimoto's encephalopathy: Identification and long-term outcome in children

ObjectiveTo identify the clinical findings of Hashimoto's encephalopathy (HE) in children and assess their neurological outcome. MethodsIn this retrospective observational study of 42 children with encephalitis dominated by acute neuro-behavioral features, eight met the diagnostic criteria of HE. Their biological, EEG and brain MRI characteristics were compared to those of the other 34 children. Their clinical outcome was also compared to that of 14 children with Hashimoto's thyroiditis (HT). ResultsAll eight HE children were girls and had high levels of anti-thyroid peroxidase (TPO) antibodies at onset (4043.3 ± 2969.8 IU/mL, inclusion criteria: TPO > 60 IU/mL) despite normal T4 and TSH levels in six of them. All HE children had abnormal EEG and brain MRI was abnormal in four of them. Relapses were observed in five children with a second relapse, despite steroid therapy, occurring sooner after the previous episode (median 18 days (range 17–188) vs 213 days (range 14–518)). Immunosuppressive therapy was started in all five children and two developed sequelae by the last follow-up visit (after 4 ± 1.3 years). Mean anti-TPO antibody titers were significantly higher in HE children than in those with Hashimoto's thyroiditis (HT) (4043.3 ± 2969.8 IU/mL vs 1980.9 ± 3449.9 IU/mL, p = 0.03). Four HE children subsequently developed hypothyroidism whereas only one HT patient presented encephalitis. ConclusionHE is characterized by suggestive clinical symptoms with high levels of anti-TPO antibodies and, in most cases, normal T4 and TSH titers. Despite steroid treatment, relapses and sequelae are frequent. HE may evolve toward HT, but the reverse appears to be rare.

Enhanced oxidative stress in Hashimoto's thyroiditis: Inter-relationships to biomarkers of thyroid function

ObjectivesOxidative stress has been implicated in the pathogenesis of several inflammatory and immune-mediated disorders including Hashimoto's thyroiditis (HT). The objectives of the present cross-sectional investigation were to estimate serum glutathione (GSH) status and the activities of its recycling enzymes in HT and to explore their interrelationships with biomarkers of autoimmunity and thyroid function. Design and methodsNewly diagnosed females with HT (n=44) and 58 matched control subjects were recruited. Thyroid hormone profile, anti-thyroperoxidase anti-body (TPO-AB), anti-thyroglublin antibody (Tg-AB), thyroid volume (Tvol), urinary iodine excretion (UIE), GSH and the activities of glutathione peroxidase (GPx), glutathione reductase and gamma-glutamyltransferase were assessed. ResultsMedian UIE in HT was slightly but not significantly higher than that of controls. HT group exhibited higher levels of TSH, TPO-AB, Tg-AB and larger Tvol when compared with controls (P<0.001). The means of GSH and GPx in HT patients were significantly different from those of controls (P<0.001). In HT subjects, significant associations were seen between Tvol on TSH, GSH on TPO-AB, GSH on TSH and TPO-AB titers on TSH, respectively. ConclusionsThis is the first study to demonstrate a substantial reduction in GSH status in HT subjects. Secondly, the interrelationship between the GSH contents and TPO-AB titers in HT provides a preliminary data to support the notion that GSH diminution is a hallmark of in the events leading to oxidative stress activation and the development of immunological intolerance in HT. Further studies are required to elucidate the role of GSH in the etiology of down-regulation of thyroid function.

Childhood chronic urticaria and type 1 diabetes

Results We present the case of a 10 year old, otherwise healthy boy, who has a 6-7 year history of persistent chronic urticaria requiring ongoing treatment. His symptoms consist of daily urticarial lesions and angioedema with frequent flares. Upper respiratory viral infections, spring/ fall season and stressful events make his condition worse; however, no food or medication triggers has been found so far. The initial work up of chronic urticaria included CBC, differential, TSH, thyroid antibodies, ANA, C3 and C4 titers, serology for H. Pylori, tryptase level, ESR, stool for O&A, urinalysis, which were entirely negative. A year ago, he developed sudden onset of weight loss, polydipsia and polyuria, and was diagnosed with Type 1 insulin dependent diabetes. He was found to have positive antiGAD antibodies, but thyroid and anti TTG IgA antibodies remained negative. He has been tried on many treatment modalities including various combinations of new and old generation antihistamines, steroids, ketotifen, montelukast, but his condition remains active.

Association between Helicobacter Pylori infection and autoimmune hypothyroidism in Egyptian population

Autoimmune hypothyroidism commonly affecting females is one of the commonest causes of thyroid disease in adults. Among the various autoantibody tests applied in research and clinical practice, the determination of thyroid microsomal antibodies (TPO) and thyroglobulin antibodies (TG Ab) still retains its strong value in the screening for thyroid autoimmunity. Helicobacter pylori (H. pylori) infection plays an important role in the pathogenesis of chronic gastritis, peptic ulcer disease, MALT (Mucosa Associated lymphocyte T) Lymphoma and gastric cancer. Aim of the work: The aim of this work was to study the relationship between H.pylori infection and autoimmune hypothyroidism in Egyptian population. Subjects and Methods: This study was carried out on 147 Egyptian persons divided into 3 groups: Hypothyroid Group: Included 49 patients with autoimmune hypothyroidsm and positive antithyroid antibodies with no history of dyspeptic symptoms or peptic ulcer. H.pylori positive Group: Included 50 patients with dyspeptic symptoms or peptic ulcer with H.pylori positive antibodies with no history of any thyroid disease. Control Group: Included 48 apparently healthy persons serving as control. Serum Free T3, Free T4 and TSH were done for all subjects together with Antimicrosomal antibodies (TPO-Ab), Antithyroglobulin antibodies (TG-Ab) and Helicobacter Pylori antibodies (H. pylori Ab). Result There was no significant difference between all groups as regards age. Also there was significant difference between Hypothyroid and H.pylori positive groups as regarding TSH and Free T3, TG-Ab, TPO-Ab and H. pylori Ab. There is also significant difference between Hypothyroid and control groups regarding TSH, free T3, TG-Ab, TPO-Ab, and H. pylori Ab. There is significant difference between H.pylori positive and control groups regarding FT3 and H. pylori AB. Hypothyroid Group was divided according to the presence of H. pylori Ab into –ve &+ve H. pylori Ab subgroups. There was significant difference between the –ve and +ve subgroups as regard TSH, free T4 and TG-Ab. H.pylori positive Group was divided according to the presence of TG Ab & TPO Ab into–ve and +ve subgroups. There was significant difference between the –ve and +ve cases in TSH, free T4, Free T3, and H.Pylori Antibody. Positive correlation was found between H pylori Ab titer and age, TSH, TG-Ab and TPO-Ab titers. There was also negative correlation between H. pylori Ab titer and free T4. There is no correlation between H. pylori Ab titer and free T3. (Correlation is referred to all subjects of the study = 147). Conclusion This study revealed that patients with positive TG & TPO antibodies, showed (+ve) H. pylori Ab, with significant high titer in their sera. The patients with positive H. Pylori Ab showed high serum titer of TG-Ab. In our study H. pylori-Ab correlates to thyroid function tests and thyroid antibodies.

Association between Helicobacter Pylori infection and autoimmune hypothyroidism in Egyptian population

Autoimmune hypothyroidism commonly affecting females is one of the commonest causes of thyroid disease in adults. Among the various autoantibody tests applied in research and clinical practice, the determination of thyroid microsomal antibodies (TPO) and thyroglobulin antibodies (TG Ab) still retains its strong value in the screening for thyroid autoimmunity. Helicobacter pylori (H. pylori) infection plays an important role in the pathogenesis of chronic gastritis, peptic ulcer disease, MALT (Mucosa Associated lymphocyte T) Lymphoma and gastric cancer. Aim of the work: The aim of this work was to study the relationship between H.pylori infection and autoimmune hypothyroidism in Egyptian population. Subjects and Methods: This study was carried out on 147 Egyptian persons divided into 3 groups: Hypothyroid Group: Included 49 patients with autoimmune hypothyroidsm and positive antithyroid antibodies with no history of dyspeptic symptoms or peptic ulcer. H.pylori positive Group: Included 50 patients with dyspeptic symptoms or peptic ulcer with H.pylori positive antibodies with no history of any thyroid disease. Control Group: Included 48 apparently healthy persons serving as control. Serum Free T3, Free T4 and TSH were done for all subjects together with Antimicrosomal antibodies (TPO-Ab), Antithyroglobulin antibodies (TG-Ab) and Helicobacter Pylori antibodies (H. pylori Ab). Result There was no significant difference between all groups as regards age. Also there was significant difference between Hypothyroid and H.pylori positive groups as regarding TSH and Free T3, TG-Ab, TPO-Ab and H. pylori Ab. There is also significant difference between Hypothyroid and control groups regarding TSH, free T3, TG-Ab, TPO-Ab, and H. pylori Ab. There is significant difference between H.pylori positive and control groups regarding FT3 and H. pylori AB. Hypothyroid Group was divided according to the presence of H. pylori Ab into –ve &+ve H. pylori Ab subgroups. There was significant difference between the –ve and +ve subgroups as regard TSH, free T4 and TG-Ab. H.pylori positive Group was divided according to the presence of TG Ab & TPO Ab into–ve and +ve subgroups. There was significant difference between the –ve and +ve cases in TSH, free T4, Free T3, and H.Pylori Antibody. Positive correlation was found between H pylori Ab titer and age, TSH, TG-Ab and TPO-Ab titers. There was also negative correlation between H. pylori Ab titer and free T4. There is no correlation between H. pylori Ab titer and free T3. (Correlation is referred to all subjects of the study = 147). Conclusion This study revealed that patients with positive TG & TPO antibodies, showed (+ve) H. pylori Ab, with significant high titer in their sera. The patients with positive H. Pylori Ab showed high serum titer of TG-Ab. In our study H. pylori-Ab correlates to thyroid function tests and thyroid antibodies.

Thyroid autoimmunity role in the evolution of endemic goiter in rural area, Fars, Iran.

WHO reports indicate no iodine insufficiency in Iran, however, goiter is still endemic in Fars Province. This study evaluates the role of thyroid autoimmunity in the evolution of endemic goiter. A total of 516 permanent residents of Akbarabad County of the Kavar area in Fars Province, Iran were selected by simple random sampling. Patients with thyroid malignancy and dysfunction, and those who consumed drugs affecting thyroid function were excluded. After signing a written consent form and undergoing a thyroid examination, 5 cc of blood were drawn to measure free T3 and T4 (RIA), TSH (IRMA), and anti-thyroid peroxidase (competitive RIA) levels. Moreover, samples of 50 cc morning urine were collected for the measurement of urinary iodine excretion (UIE; chloridric acid digestion). Data were analyzed by SPSS (version 13). P<0.05 was significant. The prevalence of goiter was 38.4% by WHO classification. The prevalence of children with UIE 2-4.9 µg/dL was 5.8%, which indicated sufficient iodine intake. Goiter was more prevalent in females, as well as in patients with positive anti-TPO or higher TSH titers (P<0.01). The prevalence of positive anti-TPO was higher in goiterous patients than healthy persons (P=0.002), which increased with an increase in age, grade of thyromegaly or TSH (P<0.02). Regression analysis showed the odds ratio for diagnosing goiter in females was 2.4 (P<0.001), in those with positive anti-TPO it was 1.87 (P=0.03) and in those with TSH>5.2 mIU/mL the odds ratio was 2.74 (P=0.01). In adolescents compared to children the odds ratio was 0.36 (P=0.01) and the odds ratio in adults to children was 0.33 (P=0.001). This study indicates that despite normal UIE, goiter is endemic in Akbarabad County. Some degree of goiter endemicity may be due to thyroid autoimmunity.

E449X mutation in the thyroid hormone receptor β associated with autoimmune thyroid disease and severe neuropsychomotor involvement

To report the clinical and molecular aspects of a patient with a diagnosis of Resistance to Thyroid Hormone (RTH) harboring the E449X mutation associated with autoimmune thyroid disease and severe neuropsychomotor retardation. We present a case report including clinical and laboratory findings, and molecular analysis of a Brazilian patient with RTH. A 23-year old male presented hyperactivity disorder, attention deficit, delayed neuropsychomotor development, and goiter. Since the age of 1 year and 8 months, his mother had sought medical care for her son for the investigation of delayed neuropsychomotor development associated with irritability, aggressiveness, recurrent headache, profuse sudoresis, intermittent diarrhea, polyphagia, goiter, and low weight. Laboratory tests revealed normal TSH, increased T3, T4, antithyroglobulin and antimicrosomal antibody titers. Increasing doses of levothyroxine were prescribed, reaching 200 microg/day, without significant changes in his clinical-laboratory picture. Increasing doses of tiratricol were introduced, with a clear clinical improvement of aggressiveness, hyperactivity, tremor of the extremities, and greater weight gain. Molecular study revealed a nonsense mutation in exon 10, in which a substitution of a guanine to tyrosine in nucleotide 1345 (codon 449) generates the stop codon TAA, confirming the diagnosis of RTH. This patient has severe neuropsychomotor retardation not observed in a single previous report with the same mutation. This may reflect the lack of a genotype-phenotype correlation in affected cases with this syndrome, suggesting that genetic variability of factors other than beta receptor of thyroid hormone (TRbeta) might modulate the phenotype of RTH.

Thyroid Function and Intellectual Development of Infants Nursed by Mothers Taking Methimazole

For many years, breast-feeding was forbidden if antithyroid drugs were being used. Recently, limited studies have shown the relative safety of propylthiouracil and methimazole (MMI). It is not known whether MMI therapy of lactating mothers for 1 yr is safe for breast-fed infants and does not cause alterations in thyroid function and intellectual development. Between 1988 and 1998, 139 thyrotoxic lactating mothers and their infants were studied. Fifty-one thyrotoxic lactating mothers were treated with MMI during pregnancy, and MMI was continued during breast-feeding. Eighty-eight mothers were given 10 mg MMI (n = 46) or 20 mg MMI (n = 42) daily for 1 month, 10 mg daily for the second month, and 5–10 mg daily thereafter. Serum T4, T3, and TSH concentrations were measured in thyrotoxic lactating mothers and their infants, before and at 1, 2, 4, 8, and 12 months. Serum MMI was measured in the infants of thyrotoxic lactating mothers taking 20 mg MMI. Thyroid function, urinary iodine, thyroid antibodies, intelligence quotient (IQ), verbal and functional components (Wechsler and Goodenough tests) were performed on 14 children of thyrotoxic lactating mothers between 48 and 74 months of age and on 17 controls. Mean ± SD of FT4I in thyrotoxic lactating mothers treated with 10 mg MMI for 1 month decreased from 19.4 ± 4.1 to 11.6 ± 4.4 and from 20.5 ± 4.7 to 9.8 ± 1.5 when treated with 20 mg MMI. Values for FT3I decreased from 462 ± 52 to 194 ± 52 with 10 mg MMI and from 481 ± 92 to 171 ± 38 with 20 mg MMI. FT4I and FT3I were normal from the third to the twelfth months. In all infants FT4I, FT3I, and TSH concentrations were normal before and up to 12 months of MMI therapy in their lactating mothers. The lowest T4 and T3 values were 108 and 1.87 nmol/L, and the highest TSH value was 4.0 mU/L. Serum MMI levels in infants were less than 0.03 μg/mL. Six mothers receiving 20 mg MMI had increased serum TSH concentrations ranging from 26 – 135 mU/L after 1 month of treatment. Their infants were euthyroid with serum TSH values less than 2.6 mU/L. At 48–74 months of age, height, weight, FT4I, FT3I, TSH, and antithyroid antibody titers were not different than controls. The mean IQ was 107 ± 14 vs. 106 ± 16 (Goodenough test) and 103 ± 10 vs. 103 ± 16 (Wechsler test) for infants of thyrotoxic lactating mothers and control infants, respectively. Similarly, there was no difference in verbal and performance IQ and their components between infants of thyrotoxic lactating mothers and control children. No deleterious effects occur in thyroid function and physical and intellectual development of breast-fed infants whose lactating mothers were treated with doses of MMI up to 20 mg daily.

Analysis of pulsatile secretion of thyrotropin and growth hormone in the hypothyroid rat.

To characterize the role of TRH in the generation of TSH pulsatility as well as the effect of hypothyroidism on episodic GH secretion, blood was constantly withdrawn (30-60 microliters/min) from rats treated with 0.02% methimazole in the drinking water for 8-10 days. This treatment significantly reduced circulating levels of both T3 and T4 and elevated plasma TSH; however, since thyroid hormone titers were still detectable (T3, 39.6 +/- 5.3 vs. 89.8 +/- 5.3 ng/dl in euthyroid animals), methimazole-treated rats were referred to as being mildly hypothyroid. TSH was found to be secreted in secretory bursts, consisting of one to several peaks in these rats. Pulsar analysis of TSH secretory profiles revealed a mean pulse frequency of 2.8 pulses/h, a mean pulse amplitude of 10 ng/pulse, and a mean pulse duration of 0.2 h. Euthyroid rats exhibited similar fluctuations of circulating TSH levels; however, due to the variability of the TSH RIA in the range of euthyroid TSH titers, no significant pulsatility was detected by Pulsar. Mean plasma TSH levels in eu- and hypothyroid rats were 2.3 +/- 0.3 and 14.6 +/- 1.8 ng/ml, respectively. To confirm that the TRH antiserum (TRH-AS) used in the present study for passive immunization had sufficient binding capacity to absorb endogenous TRH release, euthyroid rats were pretreated with either normal rabbit serum or TRH-AS, followed by the injection of clonidine (100 micrograms/kg BW, iv). This alpha 2-adrenergic agonist caused a significant (P < 0.01) 12.7-fold rise in plasma TSH levels in normal rabbit serum-treated animals, which was completely abolished by TRH-AS pretreatment, indicating that clonidine stimulates TSH secretion via activation of hypothalamic TRH release. When TRH-AS was slowly infused into hypothyroid rats that were sampled frequently for the detection of TSH pulsatility, it caused a significant (60.3%; P < 0.01) decrease in mean TSH levels, with TSH titers approaching euthyroid concentrations 1 h after the infusion of TRH-AS. The antiserum treatment also caused the disappearance of statistically significant (Pulsar) TSH secretory pulses. Mild hypothyroidism shifted the GH secretory profiles from a low frequency, high amplitude in euthyroid animals to a high frequency, low amplitude pattern in hypothyroid rats. Mean GH levels in hypothyroid rats were 76% lower than those in euthyroid controls. These findings show that TSH is secreted in a pulsatile fashion in the hypothyroid rat and that TRH is predominantly responsible for the generation of TSH pulsatility.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of barbital on the pituitary-thyroid axis.

Barbital (diethylbarbituric acid), administered via the drinking water (0.1% solution), elicited mild goitrogenic responses in rats (p less than 0.05), accompanied by a slight depression in serum T4 titers (p less than 0.02). The goitrogenic responses appeared to be the result of slight elevations in the serum TSH levels and in the case of neonate rats, whose mothers were fed barbital during pregnancy and lactation, the elevations of TSH in the circulation were pronounced (p less than 0.01). However, continuation of barbital treatment beyond puberty resulted in mean serum TSH titers declining to twice the mean control values so that only the variances between the data were different(p less than 0.05). This group of young adults showed endocrine profiles which resembled those of more mature rats. The latter group included the mothers of these young adults and of the neonates. In contrast to the action of barbital, feeding rats 0.05% propylthiouracil (PTU) in the drinking water caused substantial increases in mean serum levels of TSH (p less than 0.001) and goiter size (p less than 0.001). Moreover, the precipitous declines in serum T4 elicited by PTU were of far greater magnitude than that caused by barbital (p less than 0.001).

Pituitary thyrotroph function in hypothyroid rats.

ABSTRACT The suggestion has been made that the substantial increases in pituitary thyrotrophin (TSH) concentration reported in hypothyroid rats by some workers might be attributable to incomplete surgical thyroidectomy or partial goitrogen block. An attempt, therefore, was made to correlate the severity of hypothyroidism with the storage and release rate of TSH. Female and male Long-Evans rats were made hypothyroid either by surgical thyroidectomy or by administration of propylthiouracil (PTU). Rats were also surgically or chemically thyroidectomized and injected daily with subnormal doses of thyroxine (T4) so as to ameliorate the hypothyroidism. Pituitary and serum levels of TSH were quantified, both by bioassay (stasis tadpole), and radioimmunoassay. The results showed TSH reduced in the pituitary of the severely hypothyroid rat. In both females and males, amelioration of the hypothyroidism with small chronic doses of T4 did not increase bioassayable or immunoassayable TSH stores. Paradoxially, bioassay showed serum TSH titers increased in females inversely proportional to the apparent severity of the hypothyroidism. However, radioimmunoassay of the sera of males, whose hypothyroidism was ameliorated by T4, revealed no significant increases in TSH over thyroidectomy controls. Therefore, the results were unclear as to whether subnormal quantities of T4 increase TSH release from the pituitary. The differences in serum TSH concentration between hypothyroid-ameliorated females and males are not attributable to sex or to differences in the reliability between the bioassay and immunoassay. However, bioassayable increases in TSH stores may perhaps reflect an influence exerted by pituitary gonadotrophins or sex steroids.

Simultaneous effects of estradiol on TSH secretion and adrenocortical function in male and female rats.

Sex differences in TSH secretion and adrenal function were revealed in adult male and female Sprague-Dawley rats after chronic administration (14 days) of estradiol benzoate (EB). The effect of the steroid on the pituitarythyroid and adrenocortical systems was dose dependent. Relatively little change in the various indices of adrenal function (gland weight, plasma and adrenal corticosteroids) was seen in the female rat with all dose levels of EB treatment (.1, 1, 10 and 50 μg daily). TSH content of the enlarged pituitary progressively declined, however. Plasma TSH titers also fell. This was accompanied by histological alterations indicative of reduced secretion in the thyroid. The response of the adrenal in estradiol-treated male rats was biphasic. Lower doses (10 and 50 μg) produced adrenal hypertrophy and sharp elevation in plasma and adrenal corticosteroid concentrations. With higher doses of EB (150 μg), all indices of adrenal activity remained normal. TSH content of plasma and adenohypophysis was not...

Chronic effects of triiodothyronine on thyrotrophin levels in thyroidectomized rats.

ABSTRACT In order to study the mechanism of the paradoxical potentiating effect of small doses of thyroid hormone on propylthiouracil goiter growth in rats, serum and pituitary thyrotrophin (TSH) titers were measured after small and larger doses of triiodothyronine (T3) in thyroidectomized rats. A small dose of T3, 4 μg daily, sufficient to maintain normal oxygen consumption, caused elevated pituitary and serum TSH titers when compared to controls. Reduced titers of TSH resulted from a larger dose of T3, 16 μg daily. It is concluded that the goitrogenic action of small doses of thyroid hormone is not limited to an interaction peculiar to propylthiouracil administration but may be the result of direct stimulation of increased synthesis and secretion of TSH by the pituitary gland and is seen even in the absence of thyroid tissue or propylthiouracil. It is hypothesized that small amounts of thyroid hormone are necessary for optimal or maximal synthesis and secretion of TSH. These effects may be mediated directly at the pituitary gland or at a suprapituitary level. It was also found that stalk-median eminence TSH titers were significantly increased in the thyroidectomized rats that received a large dose of T3, as compared to those that received no T3, i. e. the effects were the opposite of those seen in the pituitary gland.

TSH rebound phenomenon in the rat adenohypophysis.

The dynamics of pituitary TSH secretion have been studied in the female rat throughout prolonged goitrogencsis (3 weeks to one year) and during readjustment of the pituitary-thyroid system after removal of the goitrogenic stimulus (2–21 days). TSH levels in sera of rats 5–15 months old are relatively constant but hormone concentration in the adenohypophysis is more variable and falls substantially in the old animal. With chronic PTU treatment, blood thyrotrophin levels increase 70-300% and pituitary hormonal stores decrease to less than 5% of normal. Goitrogen withdrawal results in heightened accumulation of hormone stores in the pituitary (4–8 fold increase) with peak of rebound at 6–12 days. TSH rebound in the adenohypophysis is associated with return of AF-positive glycoprotein granulation in the thyroidectomy cell. Blood TSH titers during pituitary repletion remain at nearly normal levels. Doses of triiodothyronine and thyroxine which normally induce almost complete disappearance of thyrotrophin from ...