High Serum TSH Concentration Research Articles

SAT-426 Macro-Thyroid Stimulating Hormone (TSH) in Children

Macro-TSH is mainly a complex of TSH with anti-TSH autoantibodies. Due to its large molecular size (>150 kDa), it accumulates in the circulation resulting in elevated serum TSH concentrations. Because the bioactivity of macro-TSH is low, treatment with thyroxine is not necessary. The prevalence of macro-TSH is no more than 1% in adult patients with subclinical hypothyroidism. However, the prevalence of macro-TSH in children is not known. We report here two cases of macro-TSH in pediatric setting.[Case reports] Case 1. Six-year and eight-month-Japanese boy visited a pediatric hospital because of hyperactivity disorder. Physical examination revealed that he had a slight mental retardation (IQ 63 by Tanaka-Binet test). Thyroid tests showed that fT4 1.21 ng/dL, TSH 120.4 µU/mL, Tg antibody 1.9 IU/mL, TPO antibody <0.1 IU/mL. His serum was sent to our laboratory to examine the causes of inappropriate high serum TSH concentration. Case 2. Eight-year and three-month-Turkish girl was brought to a pediatric hospital by her parents because of her yellowish palms, which was not identified at the hospital. She did not have any complaints and physical signs attributable to thyroid dysfunction. Laboratory data disclosed that fT4 1.5 ng/dL, TSH 19.6 µU/mL, Tg Ab negative, TPO Ab negative. Levothyroxine treatment started but serum TSH concentration was still high (39.0 µU/mL) after two months. Her serum sample was sent to our laboratory to examine the causes of inappropriate high serum TSH concentrations.[Lab. Tests for macro-TSH]When serum was mixed with the same amount of 25% polyethylene glycol (PEG) and γ-globulin fraction was precipitated, TSH concentration in the supernatant decreased significantly from 109.3 µU/mL to 2.3 µU/mL (PEG precipitation ratio 97.9%) in case 1, and from 17.3 µU/mL to 0.15 µU/mL (PEG precipitation ratio 99.1%) in case 2. HAMA blockers did not significantly change TSH concentration in both cases. High proportion of serum TSH bound to a protein G column, which binds IgG, in case 1 (91.3%) and in case 2 (57.7%), indicating that TSH was associated with IgG. Gel filtration chromatography (GFC) revealed that TSH was mostly eluted at the fraction > 150 kDa rather than 28 kDa of authentic TSH in both cases. Serum was incubated with 37.7 µU of TSH for one hour and subjected to GFC. TSH concentration in the fraction of 150 kDa (macro-TSH) increased from 2.8 µU/mL to 5.6 µU/mL in case 1 and from 0.4 µU/mL to 2.0 µU/mL in case 2, suggesting that macro-TSH was produced by the binding of exogenous TSH to anti-TSH autoantibodies.[Conclusion]Macro-TSH exists in children and careful evaluation is required in patients with inappropriate high serum TSH concentrations to avoid unnecessary treatment.

Postsurgically Hypothyroid Patients on Stable L-T4 Doses in Temperate Climates Have Higher Serum TSH Concentrations During the Coldest Months of the Year

Postsurgically Hypothyroid Patients on Stable L-T₄ Doses in Temperate Climates Have Higher Serum TSH Concentrations During the Coldest Months of the Year

An overall and dose-response meta-analysis for thyrotropin and thyroid cancer risk by histological type.

Thyrotropin (TSH) is thought as a risk factor for thyroid cancer. However, the effect of serum TSH might depend on histological types of thyroid cancer. We searched for related studies including serum TSH as an exposure and thyroid cancer as a result in PUBMED, EMBASE and Chinese National Knowledge Infrastructure up to April 21, 2016. This meta-analysis included 22 articles with 53,538 participants. When comparing all histological thyroid cancer, the pooled odds ratios of thyroid cancer in patients with nodules was found to increase significantly with higher serum TSH concentrations for differentiated thyroid carcinoma (1.88 vs .1.48, P = 0.0000) and papillary thyroid carcinoma (2.08 vs. 1.48, P = 0.0006). Each 1 mU/L increase of serum TSH was associated with 14% greater risk of thyroid cancer for all histological thyroid cancer, 16% for differentiated thyroid carcinoma and 22% for papillary thyroid carcinoma. In addition, high serum TSH was associated with a reduced risk for follicular thyroid carcinoma (OR = 0.73, 95% CI: 0.52, 1.02). This meta-analysis suggested high serum TSH concentration is risky for papillary thyroid carcinoma but not for follicular thyroid carcinoma.

Thyroid Hormone and Thyrotropin Concentrations and Responses to Thyrotropin Releasing Hormone in Ageing Horses

Reasons for performing studyThyroid hormones (THs) decrease with age in healthy dogs and cats, although they tend to remain within established reference ranges. Thyrotropin (TSH) is increased in elderly people, with or without mild alterations in THs.ObjectivesTo test the hypothesis that geriatric horses will have lower THs and/or higher TSH compared with younger horses.Study designCross‐sectional study.MethodsResting THs and TSH, and responses to thyrotropin releasing hormone (TRH) were compared between young and old horses. Data from 71 normal, healthy horses that had participated in prior research projects were examined, and found to contain 42 horses 3–10 years of age, 16 horses &gt;15 years and 10 horses &gt;20 years. All samples had been assayed in the same previously validated radioimmunoassays. Statistical analysis was performed with commercial software.ResultsAlthough lower, THs were not significantly different between young and old horses when compared with the Mann–Whitney rank sum test. However, TSH concentration was significantly higher in horses aged &gt;20 (median 0.52 ng/ml) or &gt;15 years (0.44 ng/ml) compared to younger horses (0.33 ng/ml). TRH stimulation tests were performed in 19 of the younger horses, 7 of the horses &gt;20, and 11 of the horses &gt;15. Two‐way repeated measures ANOVA on ranks revealed no significant differences in TH responses to TRH. The TSH response to TRH appeared to be slightly greater in the older horses, but did not quite reach significance (P = 0.06).ConclusionSimilar to reports in elderly humans, aged horses have higher serum TSH concentrations than younger horses.Ethical animal research: All horses in this study were part of a NCSU IACUC approved study. Owners gave informed consent for their horses' inclusion in the study. Sources of funding: College of Veterinary Medicine North Carolina State University, USA Equestrian. Competing interests: None declared.

Progress in the study of pathogenesis, diagnosis and therapeutics in thyroid hormone insensitivity syndrome

Thyroid hormone insensitivity syndrome is an inherited syndrome characterized by high serum concentrations of thyroid hormone,accompanied by normal or slightly high serum TSH concentration due to the reduced responsiveness of target tissues to thyroid hormone.Thyroid hormone insensitivity syndromes are related to gene mutations of thyroid hormone receptors,thyroid hormone cell transport defect,and thyroid hormone metabolism defect.This article reviews the progress of pathogenesis,diagnosis,and therapeutics of thyroid hormone insensitivity syndrome. Key words: Thyroid hormone insensitivity syndrome; Receptors; Gene mutation

The association between serum TSH concentration and thyroid cancer

There is mounting evidence that the serum concentration of TSH is an independent predictor for the diagnosis of thyroid malignancy in patients with nodular thyroid disease. Furthermore, preoperative serum TSH concentrations are higher in patients with more aggressive tumors, suggesting a potential role for TSH in the progression of differentiated thyroid cancer. Based on these observations, patients with higher serum TSH concentrations and borderline cytological results may require more aggressive investigation and treatment when compared with those with lower baseline TSH levels. The mechanisms underlying the finding of higher serum TSH in patients with thyroid cancer remain unexplained. According to the analysis of the relationship of TSH and frequency of papillary thyroid cancer, found significantly increased levels of TSH in patients with thyroid cancer compared with benign tumors. They found significantly higher TSH concentrations in patients who were subsequently diagnosed with thyroid cancer compared with those with benign disease. In addition, they found that the development of autonomous thyroid function (TSH&lt;0.4 mU/ml) was associated with a reduction in the risk of papillary thyroid carcinoma. In this review we present evidence for an association between TSH and thyroid cancer.

The association between serum TSH concentration and thyroid cancer

There is mounting evidence that the serum concentration of TSH is an independent predictor for the diagnosis of thyroid malignancy in patients with nodular thyroid disease. Furthermore, preoperative serum TSH concentrations are higher in patients with more aggressive tumours, suggesting a potential role for TSH in the progression of differentiated thyroid cancer. Based on these observations, patients with higher serum TSH concentrations and borderline cytological results may require more aggressive investigation and treatment when compared with those with lower baseline TSH levels. The mechanisms underlying the finding of higher serum TSH in patients with thyroid cancer remain unexplained. In this issue of Endocrine-Related Cancer, Fiore et al. have analysed the relationship between serum TSH and diagnosis of papillary thyroid cancer in 10 178 patients with nodular thyroid disease who were investigated by fine-needle aspiration biopsy. They found significantly higher TSH concentrations in patients who were subsequently diagnosed with thyroid cancer compared with those with benign disease. In addition, they found that the development of autonomous thyroid function (TSH<0.4 muU/ml) was associated with a reduction in the risk of papillary thyroid carcinoma. In this commentary, the evidence regarding the association between serum TSH and thyroid cancer is discussed placing these new findings into context.

Loss-of-Function Mutations in the Thyrotropin Receptor Gene as a Major Determinant of Hyperthyrotropinemia in a Consanguineous Community

Resistance to TSH (RTSH) is a condition of impaired responsiveness of the thyroid gland to TSH, characterized by elevated serum TSH, low or normal thyroid hormone levels, and hypoplastic or normal-sized thyroid gland. The aim of the study was to evaluate the clinical course and the genotype-phenotype relationship of RTSH caused by two different TSH receptor (TSHR) gene mutations in a consanguineous population. We conducted a clinical and genetic investigation of 46 members of an extended family and 163 individuals living in the same town. In vitro functional studies of the mutant TSHRs were also performed. Two TSHR gene mutations (P68S and L653V) were identified in 33 subjects occurring as homozygous L653V (five subjects), heterozygous L653V (20 subjects), heterozygous P68S (four subjects), and compound heterozygous L653V/P68S (four subjects). With the exception of one individual with concomitant autoimmune thyroid disease, all homozygotes and compound heterozygotes presented with compensated RTSH (high TSH with free T(4) and T(3) in the normal range). Only nine of 24 heterozygotes had mild hyperthyrotropinemia. The L653V mutation resulted in a higher serum TSH concentration and showed a more severe in vitro abnormality than P68S. Haplotype analysis predicted a founder of the L653V six to seven generations earlier, whereas the P68S is older. Cross-sectional and prospective longitudinal studies indicate that TSH and T(4) concentrations remain stable over time. High frequency hyperthyrotropinemia in an Israeli Arab-Muslim consanguineous community is attributed to two inactivating TSHR gene mutations. Concordant genotype-phenotype was demonstrated clinically and by in vitro functional analysis. Retrospective and prospective studies indicate that in the absence of concomitant autoimmune thyroid disease, elevated TSH levels reflect stable compensated RTSH.

Higher Serum Thyroid Stimulating Hormone Level in Thyroid Nodule Patients Is Associated with Greater Risks of Differentiated Thyroid Cancer and Advanced Tumor Stage

TSH is a known thyroid growth factor, but the pathogenic role of TSH in thyroid oncogenesis is unclear. The aim was to examine the relationship between preoperative TSH and differentiated thyroid cancer (DTC). The design was a retrospective cohort. Between May 1994 and January 2007, 1198 patients underwent thyroid surgery at a single hospital. Data from the 843 patients with preoperative serum TSH concentration were recorded. Serum TSH concentration was measured with a sensitive assay. Diagnoses of DTC vs. benign thyroid disease were based on surgical pathology reports. Twenty-nine percent of patients (241 of 843) had DTC on final pathology. On both univariate and multivariable analyses, risk of malignancy correlated with higher TSH level (P=0.007). The likelihood of malignancy was 16% (nine of 55) when TSH was less than 0.06 mIU/liter vs. 52% (15 of 29) when 5.00 mIU/liter or greater (P=0.001). When TSH was between 0.40 and 1.39 mIU/liter, the likelihood of malignancy was 25% (85 of 347) vs. 35% (109 of 308) when TSH was between 1.40 and 4.99 mIU/liter (P=0.002). The mean TSH was 4.9+/-1.5 mIU/liter in patients with stage III/IV disease vs. 2.1+/-0.2 mIU/liter in patients with stage I/II disease (P=0.002). The likelihood of thyroid cancer increases with higher serum TSH concentration. Even within normal TSH ranges, a TSH level above the population mean is associated with significantly greater likelihood of thyroid cancer than a TSH below the mean. Shown for the first time, higher TSH level is associated with advanced stage DTC.

Subclinical thyroid disorders – Consequences and implications for treatment

Subclinical hyperthyroidism is characterized by low circulating TSH concentrations, together with normal concentrations of free T4 and free T3. The clinical significance of low but detectable TSH values is likely to be different from undetectable TSH values. The question remains as to whether endogenous and exogenous (iatrogenic) causes of low serum TSH have the same clinical significance. Subclinical hypothyroidism is characterized by high serum TSH concentrations, together with normal free T4 values.

Rapid regulation of thyroid sodium–iodide symporter activity by thyrotrophin and iodine

Transport of iodide into thyrocytes, a fundamental step in thyroid hormone biosynthesis, depends on the presence of the sodium-iodide symporter (NIS). The importance of the NIS for diagnosis and treatment of diseases has raised several questions about its physiological control. The goal of this study was to evaluate the influence of thyroid iodine content on NIS regulation by thyrotrophin (TSH) in vivo. We showed that 15-min thyroid radioiodine uptake can be a reliable measurement of NIS activity in vivo. The effect of TSH on the NIS was evaluated in rats treated with 1-methyl-2-mercaptoimidazole (MMI; hypothyroid with high serum TSH concentrations) for 21 days, and after 1 (R1d), 2 (R2d), or 5 (R5d) days of withdrawal of MMI. NIS activity was significantly greater in both MMI and R1d rats. In R2d and R5d groups, thyroid iodide uptake returned to normal values, despite continuing high serum TSH, possibly as a result of the re-establishment of iodine organification after withdrawal of MMI. Excess iodine (0.05% NaI for 6 days) promoted a significant reduction in thyroid radioiodide uptake, an effect that was blocked by concomitant administration of MMI, confirming previous findings that iodine organification is essential for the iodide transport blockade seen during iodine overload. Therefore, our data show that modulation of the thyroid NIS by TSH depends primarily on thyroid iodine content and, further, that the regulation of NIS activity is rapid.

Iodine status remains critical in mother and infant in Central Anatolia (Kayseri) of Turkey.

Severe iodine deficiency disorders have been eradicated in many parts of the world, but milder forms still exist and may escape detection. Turkey has long been known to be a mild to moderate iodine deficiency area. The aim of this study was to assess the iodine nutritional status and the thyroid function of pregnant women and their neonates in the region of Kayseri (central Anatolia of Turkey) that appeared to be iodine deficient in previous studies performed before the introduction of mandatory salt iodization. A cross-sectional voluntary screening study was performed in the Maternity Unit of a university hospital. A total of 70 mothers and their healthy full-term neonates were included in this study. Urinary iodine concentration was estimated in spot urine samples obtained from mothers and their neonates on day 5. All the neonates were breastfed. The iodine content was determined in the breast milk of all mothers on day 5. Serum concentrations of TSH, thyroglobulin (Tg), free triiodothyronine (FT3) and free thyroxine (FT4) were investigated in the cord serum of neonates and compared to those of mothers immediately after parturition The median urinary iodine on day 5 in mothers and their babies were 30.20 and 23.80 microg/l, respectively. These figures are much lower than normal for these age groups (150-200 microg/l). The median iodine content of breast-milk was 73 microg/l. It is again much lower than in iodine sufficient areas, indicating that the status of iodine nutrition of pregnant and lactating women is clearly insufficient. The median concentrations (and ranges) of neonatal TSH, Tg, FT3 and FT4 were 7.44 mU/l, 71.62 ng/ml, 1.30 pg/ml and 1.34 ng/dl respectively. The corresponding levels for the mothers during labor were 2.19 mU/l, 25.65 ng/ml, 1.31 pg/ml and 1.23 ng/dl respectively. The median neonatal serum concentrations of TSH and Tg were significantly higher than the corresponding maternal levels (P < 0.0001, P < 0.0001, respectively) and 27.1% of the neonates had serum TSH concentrations above 10 mU/l and 57.1 % had cord blood serum Tg concentrations above 54 ng/ml. None of the mothers showed TSH concentrations above 5 mU/l and 41.4% had serum Tg concentrations above 30 ng/ml. Iodine deficiency with low urinary iodine excretion and high serum Tg and TSH concentrations were recognized among pregnant women and their babies in Kayseri in spite of the program of salt iodization. National measures are urgently required for improving the correction of iodine deficiency in Turkey. This includes regular supplementation with iodine, starting at preconception or in early pregnancy and continuing during the period of nursing in this region.

Transient Congenital Hypothyroidism due to maternal autoimmune thyroid disease

The neonatal screening program for congenital hypothyroidism (CH) in Greece shows an overall incidence of the disease of 1:2321. The cases with permanent CH have an incidence of 1:2542, whereas the transient forms of CH account for 8.7% of all cases diagnosed as CH. Transplacental passage of maternal thyrotropin receptor-blocking antibodies is a rare cause of transient CH. In our program, a retrospective analysis of 508,358 screened newborns revealed 6 infants with transient CH caused by maternal thyroid autoimmunity, representing 2.7% of all cases of CH. All the newborns with transient CH, due to maternal autoimmune thyroid disease, had high serum TSH concentration (ranging from 98 to 689 mU/L), whereas serum thyroxine (T4) values were low normal to normal in 3 of them. Replacement therapy with L-thyroxine was initiated at a mean age of 6.5 days. The newborns with transient CH belonged to 4 families, one of which had 4 and another 2 children with the same pathology. Thyrotropin-receptor antibodies (TSH-R Abs), present at the initial examination in newborns' serum, had disappeared from the infants' circulation by the third month of life. One mother carried the Abs for at least 8 years during which period she delivered four babies. The diagnosis of transient CH should be suspected if the mother has autoimmune thyroid disease, if there are siblings with transient CH or if there is no need for an increase in L-thyroxine dose with advancing age. The diagnosis is very important for genetic counseling, early treatment initiation of subsequent offspring and adequate control of the mother's thyroid function during subsequent pregnancies so that any neurodevelopmental abnormality of the fetus could be avoided.

PRIMARY HYPOTHYROIDISM CAUSES DECREASED EXPRESSION OF THYROID TRANSCRIPTIONAL FACTOR-1 AND SURFACTANT PROTEIN-C IN FETAL MOUSE LUNG. † 2063

Thyroid hormones play an important role in mammalian fetal lung development. Delayed fetal lung ultrastructural maturation is observed in the Hyt/Hyt mouse which has primary hypothyroidism due to a point mutation(Pro-556-Leu) in the β subunit of the TSH receptor (Ped. Res.380-386,1994). Thyroid transcriptional factor 1 (T.T.F.-1) and surfactant protein C (SP-C) play an important role in fetal lung function and type II cell differentiation. The effect of primary hypothyroidism on the developmental expression of lung SP-C or TTF-1 has not been studied. Hypothyroid (Hyt/Hyt) mice, characterized by high serum TSH and low serum free T4 concentration, were made euthyroid by T3 supplementation. These mice were mated to produce hypothyroid (Hyt/hyt) pups. Balb-c mice served as euthyroid controls. Mice were killed on d 18 of pregnancy (term≈19d, vaginal plug=d 1). Immunostaining of fetal lung for SP-C was done using polyclonal antibody. The intensity of the immunoreactivity for SP-C was scored on a scale of 0 to 3 in 0.5 increments. Fetal lung gene expression for T.T.F.-1 and SP-C was determined by Northern analysis and densitometry. All data Mean ±SEM, * P<0.02 There was a linear relationship between the gene expression for T.T.F.-1 and SP-C in these mice (r=0.86). We conclude that primary hypothyroidism causes a delay in the gene expression for TTF-1 and SP-C in the fetal lung. Table

Delayed ultrastructural lung maturation in the fetal and newborn hypothyroid (Hyt/Hyt) mouse.

Thyroid hormones influence fetal and neonatal lung growth and maturation. However, the effect of naturally occurring, genetically determined hypo- or hyperthyroidism on fetal or neonatal lung maturation has not been examined. In the hyt/hyt mouse, primary hypothyroidism, which is characterized by a high serum TSH concentration, is transmitted as an autosomal recessive trait. It occurs due to a mutational defect in the beta-subunit of the TSH receptor. We studied the lung ultrastructure of the fetal [18-d-gestation (term = approximately 19.5 d)] and neonatal (< 1-d-old) hyt/hyt mouse. In addition, disaturated phosphatidylcholine and total phospholipid contents of newborn hyt/hyt mouse lungs were determined. Male and female hyt/hyt mice with a high serum TSH concentration were made euthyroid by adding 3,5,3'-triiodothyronine to drinking water and then mated. Balb-c mice served as euthyroid controls. Fetal and neonatal hyt/hyt mice had a higher serum TSH concentration than the Balb-c controls. Fetal hyt/hyt mouse lungs showed a large amount of intracellular glycogen and fewer lamellar bodies in epithelial type II cells compared with Balb-c fetal mouse lungs. The neonatal hyt/hyt mouse also showed signs of lung immaturity such as persistent epithelial cell glycogen, few lamellar bodies, reduced disaturated phosphatidylcholine content, and absent tubular myelin. We conclude that fetal and neonatal lung maturation is delayed in the hyt/hyt mouse with primary hypothyroidism.

ENDOCRINE AND MORPHOLOGIC STUDIES OF PITUITARY ADENOMAS SECONDARY TO PRIMARY HYPOTHYROIDISM

Two patients with enlarged pituitary fossae presented with a number of features in their medical history and laboratory workup suggesting the diagnosis of “non-functioning” pituitary adenoma. Both patients had low serum thyroxine (T4) concentrations and resin T3 uptake, and one patient showed a high titer of microsomal thyroid antibodies. Both patients had high serum TSH concentrations before and after stimulation with TRH. After pituitary surgery, the serum TSH levels diminished but remained abnormally high and were suppressed by thyroid hormone administration. Light microscopic studies of the tumors, including differential staining and immunocytochemical procedures for the demonstration of TSH cells, showed cells indistinguishable from those of chromophobic adenomas. Ultrastructurally, the adenoma cells contained relatively few granules, similar to those described in “non-functioning” chromophobic tumors. Our investigations suggest that some of the patients diagnosed as having “non-functioning” pituitar...

Cytological changes of the pituitary basophils in rats slowly infused with thyrotropin-releasing hormone (TRH).

Young male rats were slowly infused with synthetic TRH, 1 microgram/hr, for 1, 3, 24, 48 and 72 hr, respectively. In the control rats, the basophils of the pituitaries can be divided, in their cytological properties, into the II- (classical thyrotrophs), II/III-,III, (classical LH-cell), and III/IV-type cell. The typical IV-type cells (classical FSH-cell), however, are scarcely found in the young rats. Following 1-hr infusion of TRH, the II-type cells decrease in number with the advancement of granular release, but morphological changes are not yet concrete on the other types of basophils. The II-type cells are quickly invisible following a 3-hr infusion, while the III- and III/IV-type cells remain without any significant changes. The III- and III/IV-type cells are progressively degranulated after a 24-hr infusion. The diameter of secretory granules is reduced to 100--150 nm. The smallest ones below 50 nm in diameter, are disintegrated to disperse into the ground matrix. After degranutlaion, the III/IV-type cells appear to revert to the polygonal or stellate cells with the identical fine structure with the II-type cells. There is evidence that the thyroidectomy cells may develop from the III/IV-type cells only after a 48-hr infusion. After 72 hr, most basophils are provided with the uniform structure of "reversionary II-type cells". In reference to the high serum TSH concentration and no significant change of pituitary TSH concentration under the same experimental condition (Soji, 1978), the present author conclusively postulates that the degranulation of the III/IV-type cells may mainly reflect the conspicuous elevation of serum TSH concentration. The above morphological results are contradictory a plausible view that TRH acts only upon the thyrotrophs to release TSH. The fact that all the basophils ultimately take an appearance of "reversionary II-type cells" in the gland by the prolonged infusion of TRH may not only suggest the share of responsiveness of all the basophils to TRH, but also support the hypothesis of secretory cycle of the basophils.

Serum thyrotropin and thyroid hormone levels in humans receiving chronic potassium iodide.

Serum thyroxine (T4), triiodothyronine (T3) and thyrotropin (TSH) concentrations were measured in 13 patients with chronic obstructive pulmonary disease receiving saturated solution of potassium iodide (SSKI). All had a low serum T4 and a high serum TSH concentration. However, serum T3 levels were normal in eight. Recovery of normal thyroid function was observed in each of the seven patients in whom the iodide was discontinued. The same hormones were measured in four normal subjects who received 30 drops of SSKI daily for 11 weeks. An increase in serum TSH levels was preceded by a fall in serum concentrations of T4 and to some extent, T3. Upon SSKI withdrawal subsequent increases in the serum concentrations of both thyroid hormones, but particularly T3, resulted in the return of serum TSH to baseline levels. None of the subjects developed clinical hypothyroidism. It is not apparent why the normal subjects did not exhibit clinical or laboratory evidence of hypothyroidism while the patients with chronic pulmonary disease did. A younger age and the shorter duration of iodide administration in the normal subjects may have played a role.

Late effects of neonatal undernutrition and overnutrition on pituitary-thyroidal and gonadal function.

Neonatal rats were underfed or overfed and then, at weaning, placed on a normal diet and allowed to mature. Although overfed rats were obese at weaning, they were of normal weight when mature. The underfed rats remained smaller all their lives. The endocrine organs did not share in this retardation, and were actually larger in several instances when expressed per 100 g body weight. Underfed rats also had delayed eye-opening, normal puberty and normal estrous cycles. Pituitary, hypothalamic and serum TSH concentrations were normal, or even increased (in the underfed females). The responses to propylthiouracil and to thyrotropin-releasing hormone (TRH) were both normal. Thus the tertiary hypothyroidism reported in underfed rats 16 days old did not persist into adult life. In all comparisons the males had higher serum TSH concentrations than females and usually had a greater response to TRH stimulation. The various persistent endocrine abnormalities resulting from neonatal thyrotoxicosis differ from those seen after neonatal caloric deprivation in all pertinent regards except that both have reduced body weights.