Dissociated response of thyrotropin and prolactin to dopamine receptor blockade with domperidone in hypothyroid subjects.

To investigate the hypothesis of an altered hypothalamic dopaminergic activity in primary hypothyroidism, eight patients with hypothyroidism and seven normal subjects, all female, were studied. All of them were submitted to two tests: TRH stimulation and after the administration of dopamine receptor-blocking drug, Domperidone. The hypothyroid patients with basal TSH values less than or equal to 60 mU/L (4 cases--group 1) had lower PRL levels than the remaining 4 subjects with TSH greater than 60 mU/L (group 2) (p less than 0.001), despite all patients presenting the PRL levels within the normal range. A significant increase occurred for both TSH and PRL after the administration of TRH and Domperidone in normal as well as in the hypothyroid subjects, except for TSH in group 1 after the administration of Domperidone. The area under the curve for PRL response to THR was not different between the normal subjects and both hypothyroid groups, while that under the curve for TSH was greater in the hypothyroidism as a whole than in the normal subjects (p = 0.006) and between the hypothyroid groups, being greater in group 2 than in 1 (p less than 0.009). In relation to Domperidone, the area under the curve for TSH was significantly higher in group 2 when compared to the normal controls (p less than 0.001), while for PRL it was not different between hypothyroid groups in relation to normal controls and when groups I and II were compared. These results suggest that the hypothalamic dopamine activity is not altered in primary hypothyroidism and favor the small relevance of dopamine on the control of TSH secretion.     

The effect of dexamethasone on TSH and prolactin secretion after TRH stimulation

Serum thyrotropin (TSH) and prolactin levels were measured after intravenous administration of 400 μg of synthetic thyrotropin-releasing hormone (TRH) in 13 normal subjects and six hypothyroid patients before and after three days of administration of dexamethasone 2 mg per day. In the normal subjects dexamethasone suppressed baseline serum levels and secretion of TSH after TRH stimulation. On the other hand, it had no effect on the hypothyroid patients. In the control group dexamethasone also suppressed baseline serum levels but not secretion of prolactin after TRH stimulation. Dexamethasone had no effect on prolactin levels in the hypothyroid group. It is concluded that in normal patients short-term administration of dexamethasone has an inhibitory effect on TSH secretion at the pituitary level. As for prolactin, our results could indicate that TRH is a more potent stimulator of prolactin secretion than of TSH secretion, or that TSH and prolactin pituitary thresholds for TRH are different.     

Effects of thyroidectomy, propylthiouracil, and thyroxine on pituitary content and immunocytochemical staining of thyrotropin (TSH) and thyrotropin releasing hormone (TRH)

Previous studies have demonstrated immunocytochemical staining for beta chains of thyroid stimulating hormone (TSH-beta) in rough endoplasmic reticulum of pituitary cells hypertrophied after thyroidectomy ("thyroidectomy cells") (Moriarty CG(1976): J Histochem Cytochem (24:846; Moriarty GC, Tobin RB (1976): J Histochem Cytochem 24:1140). Here we report the localization of thyrotropin releasing hormone (TRH) in serial sections of the same pituitaries to determine if it could be found at similar sites. No staining for TRH was found in hypertrophied TSH cells formed 42 days after the surgery, or after 14, 34, and 70 days of propylthiouracil (PTU) treatment. The loss in immunostaining in the PTU-treated rats was correlated with radioimmunoassay (RIA) measurements that showed a 65% reduction in anterior pituitary TRH content after 34, 70, and 98 days of PTU treatment (from 22.9--7.8 pg/mg wet wt) and a 50% reduction in TSH content after 34 days of treatment. When thyroxine was administered to hypothyroid rats for 3 days before death, our previous studies had demonstrated intense staining for TSH in granules inside the rough endoplasmic reticulum. In this study, the radioimmunoassay showed that TSH content rose dramatically in the hypothyroid animals treated with PTU for 77 days and thyroxine for 2 days before death (from 8.5--64.1 mU/mg wet wt); however, the rise in TRH content was minimal (5.8--9.8 pg/mg wet wt). The immunocytochemical stain for TRH correlated well with the RIA showing a weak reaction mainly on small granules in the cytoplasm. No reaction for TRH was found in rough endoplasmic reticulum. These results suggest that TRH and TSH storage sites are dissimilar in the hypothyroid rat. The presence of stain for TRH in granules in the cytoplasm suggests that it might play a role in the storage or packaging of TSH. Its absence in profiles of rough endoplasmic reticulum staining intensely for TSH suggests that it is not synthesized at this site. No definite conclusions about its origin can be drawn at this time.     

Impact of Lifestyle Changes During Ramadan on Thyroid Function Tests in Hypothyroid Patients Taking Levothyroxine

Objective: The holy month of Ramadan poses a challenge for levothyroxine-treated patients due to altered eating habits and time restrictions. The aim of this study was to examine the impact of lifestyle changes during Ramadan on thyroid function tests in hypothyroid patients taking levothyroxine in the United Arab Emirates.Methods: Retrospective design whereby levothyroxine-treated hypothyroid patients who had thyroid function tests within 3 months pre-Ramadan and within 2 months post-Ramadan were included. We looked at adherence to levothyroxine, eating pattern, and levothyroxine administration in relation to meal times during Ramadan. Pre- and post-Ramadan thyroid function tests and the potential impact of independent variables using a random-intercept mixed effects linear model were examined.Results: A total of 112 patients (89 females) were recruited in the study, with a mean age ± standard error (SE) of 44.70 ± 1.36 years (range, 19.0 to 79.0 years). The mean thyroid-stimulating hormone (TSH) within 3 months before Ramadan was 1.809 ± 0.094 mIU/L (median, 41.5 days; interquartile range [IQR], 25.0 to 73.0 days), while the mean TSH within 2 months post-Ramadan was higher at 3.072 ± 0.312 mIU/L (median, 27.5 days; IQR, 14.0 to 42.0 days). Post-Ramadan, 36 out of 112 patients had a plasma TSH outside of the normal reference range. The independent variable outcomes model showed that older patients and males were more likely to have an increased plasma TSH post-Ramadan. There was no relationship between the time of levothyroxine administration and change in TSH level.Conclusion: Levothyroxine-treated hypothyroid patients showed a significant increase in plasma TSH post-Ramadan, amounting to 2.525 standard deviations, with older patients and males more likely to be affected.Abbreviations: IQR = interquartile range; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Thyreotrophic hypophysial function after surgery for euthyroid goiter or autonomous adenoma

44 euthyroid patients with nodular goiter and 23 patients with autonomous adenomas were treated by hemithyrectomy or subtotal thyrectomy. Thyroid function was followed over 6 weeks post-operation by TRH tests, which were performed before and at the 5th, 14th, 28th and 42nd day after operation. Bilateral subtotal thyrectomized patients with euthyroid goiter showed a continous increase of basal and TRH stimulated TSH level into the hypothyroid range. 19 of 25 patients were hypothyroid 6 weeks after operation. In contrast, 14 of 19 hemithyrectomized patients with euthyroid goiters remained euthyroid during the time investigated; 5 patients showed a transient TSH increase into the hypothyroid range but were euthyroid again after 6 weeks. TSH levels obtained from patients operated for autonomous adenoma may not yet reflect thyroid function during the time interval investigated here. We conclude that all patients with euthyroid goiter after bilateral subtotal thyrectomy should receive hormone substitution because they are at high risk to develop recurrency. However, we propose that in patients hemithyrectomized for euthyroid goiters the decision of long term hormone substitution should be cased on the result of a TRH-test 3--4 month after operation. Substitution with thyroid hormone should be preferred to iodide because it is unclear yet how far a failure in iodide organification and hormone synthesis is the reason for goiter recurrency.     

Differential regulation of thyrotropin-releasing hormone receptor mRNA levels by thyroid hormone in vivo and in vitro (GH3 cells).

We studied the effect of thyroid status on thyrotropin-releasing hormone receptor (TRH-R) mRNA levels both in vivo and in vitro (GH3 cells) using a cloned rat TRH-R cDNA by RT-PCR. Experimental hypothyroid rats were produced by total thyroidectomy and were then killed 7 days after the operation. TRH receptor binding in the anterior pituitary and serum TSH level were elevated approximately 2-fold and 8-fold, respectively, in 7 day thyroidectomized rats. TRH-R mRNA levels in hypothyroid rats were also increased significantly compared with those of normal rats. In GH3 cells, however, no significant change of TRH-R mRNA level was observed between cultures treated with triiodothyronine (T3, 10(-9) and 10(-7) M) and the untreated group. The present data indicate that 1) the in vivo effects of thyroid status on TRH-R mRNA levels differ from the in vitro one, and that 2) the down regulation of TRH-R binding by thyroid hormone in GH3 cells may be mediated by translational or post-translational mechanisms.     

The Long-Term Impact Of Controlled Ovarian Hyperstimulation On Thyroid Function

Objective: Evidence on the long-term impact of controlled ovarian hyperstimulation (COH) on thyroid function is scarce. To investigate this, we report on serum thyroid-stimulating hormone (TSH) modifications in euthyroid and hypothyroid women during COH and 3 months after the end of the stimulation cycle.Methods: Women who underwent in vitro fertilization (IVF) and who did not become pregnant were eligible. Cases were women with treated hypothyroidism and basal serum TSH <2.5 mIU/L. Controls were euthyroid women matched to cases by age and basal serum TSH. Women could be included if serum TSH was available at 4 time points: prior to initiating COH (time 1); at the time of human chorionic gonadotropin (hCG) administration (time 2); 16 days after hCG administration (time 3); and 3 months after the end of the IVF cycle (time 4).Results: Thirty-seven case-control pairs were included. Serum TSH at times 1, 2, 3, and 4 was 1.7 ± 0.6, 3.1 ± 1.4, 3.1 ± 1.3, and 2.7 ± 1.7 mIU/L, and 1.7 ± 0.6, 2.9 ± 1.0, 2.7 ± 1.0, and 1.9 ± 0.7 mIU/L among cases and controls, respectively. A statistically significant difference emerged at time 4 (P<.001). In both groups, serum TSH was higher at time 4 compared to time 1. Serum TSH exceeded the recommended threshold of 2.5 mIU/L at time 4 in 51% of cases (95% confidence interval &lsqb;CI], 35 to 68%) and in 16% of controls (95% CI, 4 to 28%) (P = .003).Conclusion: COH seems to have a long-term impact on TSH levels. The magnitude of this effect is particularly pronounced in hypothyroid women.Abbreviations:CI = confidence intervalCOH = controlled ovarian hyperstimulationFT4 = free thyroxinehCG = human chorionic gonadotropinIVF = in vitro fertilizationT4 = thyroxineTBG = thyroxine-binding globulinTGAb = anti-thyroglobulin antibodiesTPOAb = anti-thyroperoxidase antibodiesTSH = thyroid-stimulating hormone     

Effect of bromocryptine on the secretion of thyrotropic hormone (TSH), prolactin (Pr), human growth hormone (HGH), thyroxine (T4) and triiodothyroxine (T3) in hypothyroidism.

Bromocryptine (CB-154) virtually abolished the rise of serum Pr after TRH stimulation in hypothyroid and euthyroid subjects. The response of serum TSH to TRH stimulation was significantly depressed in hypothyroid but not in euthyroid subjects. No significant changes of serum HGH, T4 and T3 after CB-154 were observed. The dual mode of action of CB-154 in pituitary and hypothalamus is discussed.     

Comparison of TSH Levels with Liquid Formulation Versus Tablet Formulations of Levothyroxine in the Treatment of Adult Hypothyroidism

ObjectiveA great number of factors can interfere with levothyroxine (LT4) tablet absorption, leading to increased serum thyroid-stimulating hormone (TSH) levels and, accordingly, to increased LT4 requirements. LT4 oral solution (LT4-OS) is a novel formulation with a pharmacokinetics profile different from those of tablets. The aim of this study was to retrospectively evaluate whether serum TSH levels were decreased after switching adult hypothyroid patients from the tablet to LT-OS.MethodsWe retrospectively evaluated 53 outpatients on LT4 replacement therapy (consumed within 1 hour before breakfast) who switched from LT4 tablets to LT4-OS without changing the daily dose. We compared preswitch TSH (TSH1) with TSH level 60 to 90 days after the switch (TSH2) and examined the clinical differences between the patients whose TSH did and did not drop after the switch.ResultsAfter the switch, TSH levels decreased from a median value of 3.04 (interquartile range [IQR] 1.75-6.80) to 2.30 (IQR 1.21-3.81) μIU/mL, and the difference was significant (P = .0034). We observed a TSH reduction (TSH2/TSH1 ratio < 1) in 36/53 (67.9%) of patients; the median TSH2/TSH1 ratio was 0.71 (IQR 0.37-1.14). In the group of patients whose TSH dropped, we observed an increased frequency of factors interfering with LT4 absorption (P = .014). The median TSH2/TSH1 ratios were 0.50 (IQR 0.31-0.72) and 0.85 (IQR 0.65-1.36) for patients with and without interfering factors, respectively.ConclusionOur study confirms that LT4-OS could have an increased absorption rate in comparison to LT4 tablets, especially in the presence of other factors interfering with LT4 absorption. (Endocr Pract. 2014;20:657-662)     

Levothyroxine Liquid Solution Versus Tablet for Replacement Treatment in Hypothyroid Patients

BackgroundAlthough replacement treatment with L-thyroxine (LT4) seems easy to manage, about one-third of hypothyroid patients show thyroid-stimulating hormone (TSH) values outside the normal range.ObjectivesTo explore whether LT4 liquid formulation (monodose vials or drops) affects TSH stability values and to assess its ability to maintain TSH within the normal range compared to tablets.MethodsA total of 100 hypothyroid patients on replacement treatment with LT4 liquid solution were enrolled (Liquid Group) at a follow-up visit (revisit). The inclusion criteria were 1) treatment for surgical hypothyroidism for at least 2 years or autoimmune hypothyroidism for at least 5 years, 2) normal TSH at the previous visit 12 months before enrollment (baseline visit), and 3) maintenance of the same LT4 dosage during the time interval between the baseline and the follow-up visit. Using the same selection process, we also enrolled 100 hypothyroid patients on replacement treatment with LT4 tablets (Tablet Group).ResultsAt the follow-up visit, 19 patients of the Tablet Group and 8 patients of the Liquid Group had abnormal TSH values (P = .023). Weekly and daily LT4 dosage per kilogram were higher in Tablet Group (P = .016 and .006, respectively). The magnitude of TSH change from baseline to follow-up visit was greater in the Tablet Group (P < .001).ConclusionThe use of LT4 liquid formulation compared to tablet resulted in a significantly higher number of hypothyroid patients who maintained the euthyroid state in a 12-month follow-up period and a reduced variability in TSH values. (Endocr Pract. 2014;20:901-906)     

Visfatin Levels in Subclinical Hypothyroidism

Alterations in thyroid function are associated with changes in body weight, metabolism, and low-grade inflammation abnormal thyroid function may be associated with disturbances in the production of adipokines also. Although there have been studies showing changes in visfatin levels in thyroid dysfunction, exact relationship between them was still unclear. Our aim was to evaluate serum concentrations of visfatin in patients with subclinical thyroid dysfunction before and after normalization of thyroid function tests. The study included 43 patients (mean age 50.1 ± 10.6 years) with subclinical hypothyroidism. Serum insulin, visfatin, TSH, free T4 (FT4) and free T3 (FT3) levels of subjects were analyzed. Visfatin levels were measured in all patients before starting therapy and after normalization of thyroid function. Serum visfatin levels of subclinical hypothyroid patients were 0.99 ± 0.45 and they were similar after normalization of thyroid function (p = 0.394). Serum visfatin levels were negatively correlated with FT4 levels before treatment (r = ?0.329 p < 0.05). There was no significant correlation between serum levels of visfatin and the serum levels of TSH and FT3. Serum visfatin levels did not correlate with insulin, fasting blood glucose, total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride levels. In this study, it was shown visfatin levels did not change after replacement therapy in patients with subclinical hypothyroidism. Subclinical hypothyroid state may be an earlier stage regarding the changes of adipocytokines specifically the visfatin secretion as seen in overt hypothyroidism.     

Impact of Ramadan Fasting on Thyroid Status and Quality of Life in Patients with Primary Hypothyroidism: a Prospective Cohort Study from karachi,pakistan

Objective: Ramadan is the ninth month in the lunar calendar, during which Muslims fast from predawn to sunset and major changes occur in their dietary, sleep, and physical activity patterns. Most patients with hypothyroidism are unable to comply with the proper timings of levothyroxine (LT4) administration. The objective of the study was to determine the change in thyroid-stimulating hormone (TSH) level and quality of life (QOL) before and after Ramadan in patients with primary hypothyroidism.Methods: This prospective cohort study included adult patients on stable doses of LT4 who fasted for at least 20 days during the month of Ramadan in the Islamic year 1437 Hijri (June/July 2016). Baseline characteristics and TSH levels were recorded on all consenting patients within 6 weeks prior to Ramadan. Post-Ramadan TSH was tested within 1 to 2 weeks after Eid-ul-Fitr.Results: During the study period, 64 patients with hypothyroidism were enrolled, of which 58 were female. The mean age of participants was 44.2 ± 13.2 years. Average daily dose of LT4 was 95.3 ± 35.4 μg. On average, patients fasted for 26.5 days and missed a dose of LT4 on 1.27 days. Mean TSH pre-Ramadan was 2.37 ± 1.35 mIU/L, and post-Ramadan, it was 4.69 ± 3.87 mIU/L. Mean difference between TSH pre- and post-Ramadan was 2.32 ± 3.80 mIU/L (P<.001). However, the difference in TSH was not significantly different between those who were compliant with meals and LT4 interval versus those who were not (compliant, 2.04 mIU/L; noncompliant, 3.15 mIU/L; P = .30). Overall, an increase in QOL scores in the domains of physical health, psychological health, and social relationships was observed after Ramadan.Conclusion: We observed statistically significant changes in TSH concentrations after the month of Ramadan in hypothyroid patients who fasted. The change in TSH was not affected by timing of LT4 intake and interval from meal.Abbreviations: AKUH = Aga Khan University Hospital; LT4 = levothyroxine; QOL = quality of life; TSH = thyroid-stimulating hormone     

Thyroid hormone levels during a 3-week professional road cycling competition

AIMS: The aim of this investigation was to examine the thyroid hormone levels of professional cyclists during a 3-week stage competition (Vuelta a Espa?a 1998). METHODS: The study population was made up of 16 male cyclists from two world-leading professional teams. Four blood samples were drawn (between 07:00 and 09:00 a.m.) from each participant before and at the end of the 1st, 2nd and 3rd weeks of competition. 3,5,3'(-Triiodothyronine (T(3)), free T(3) (FT(3)), thyroxine (T(4)), free T(4) (FT(4)) and thyroid-stimulating hormone (TSH) were determined in each blood sample by radioimmunoassay. RESULTS: Serum T(4), FT(4) and FT(3) levels showed a significant increase (p < 0.05) by the last week of competition while concentrations of TSH and T(3) remained unchanged. CONCLUSION: In conclusion, 3 weeks of competition provokes changes in basal thyroid hormone concentrations in professional road cyclists.     

The use of intramuscularly administered methyl-TRH to evaluate the pituitary-thyroid axis.

The present study was carried out to evaluate the effectiveness of intramuscular administration of methyl-TRH, a potent analogue of thyrotropin-releasing hormone, for assessing pituitary reserve of TSH and prolactin and for distinguishing euthyroid, hypothyroid and hyperthyroid individuals. Serum samples were taken for 24 hours after intramuscular injection of methyl-TRH, 200 microgram, in 19 euthyroid subjects, 9 hypothyroid men and 9 hyperthyroid men. The mean serum prolactin and TSH concentrations were significantly elevated over baseline levels at 30 min in the euthyroid individuals and remained elevated for 3 to 4 hours. The serum TSH, T3 and T4 responses after intramuscular methyl-TRH in euthyroid subjects were clearly distinguishable from those of hyperthyroid and hypothyroid patients. Significant elevation of the serum T3 and T4 concentrations at 24 hours after intramuscular injection of methyl-TRH shows the sustained effect of this TRH analogue in euthyroid subjects.     

Elements in erythrocytes of population with different thyroid hormone status

The contents of elements K, Ca, Fe, Cu, Zn, Se, and Rb in erythrocytes of 78 cases with different thyroid hormone status have been measured by proton-induced X-ray emission and neutron activation analysis. According to the status of thyroid hormones T₃, T₄, TSH, FT₃, and FT₄ detected by radioimmunoassay, the experiment subjects were divided into four groups (i.e., hyperthyroid, hypothyroid, critical [one of thyroid hormones was abnormal], and normal). Elements contents and hormones levels of four groups were analyzed by one-way analysis of variance and correlation using an SPSS/PC statistical package. The results showed that the Se contents of four groups were not significantly different (p<0.05). Zn content of hypothyroid group was significantly higher than those of hyperthyroid and critical groups. The Zn content of the normal group was higher than that of the hypothyroid group and lower than that of the hyperthyroid and critical groups. In the hyperthyroid group, there were significant correlations between elements contents and thyroid hormones levels (except TSH), but not between elements contents and levels of thyroid hormones. However, in the hypothyroid group, relatively strong correlations have been found between elements contents and thyroid hormones levels, especially between Zn and the T₃/T₄ ratio, and between Zn and TSH.     

Opiate receptor subtypes in the regulation of thyrotropin and prolactin secretion in the rat

In the present study both MR 2034 (kappa-agonist) and DAMME (mu-agonist) decreased thyrotropin (TSH) secretion stimulated by cold in the rat when infused into the 3rd ventricle. After infusion into the posterior hypothalamus (PH), a small dose of MR 2034 increased the TSH response to cold whereas other doses did not. The stimulatory (at PH) but not the inhibitory (at 3rd ventricle) effect of MR 2034 was antagonized by naloxone. DAMME had no statistically significant effect at this location. Both the mu- and kappa-agonist stimulated prolactin secretion when infused into the 3rd ventricle, but DAMME was more effective than MR 2034. Furthermore, the stimulatory effect of DAMME, but not that of MR 2034, on prolactin secretion was antagonized by naloxone.     

Lack of An Association between BMI and TSH in Treated Hypothyroid Patients and Euthyroid Controls

Objective: The standard treatment for primary hypothyroidism is replacement with levothyroxine to achieve a thyroid-stimulating hormone (TSH) level within the normal range, (0.45–4.5 mIU/L), which is known to prevent complications including weight gain. While the normal TSH range includes the 95% confidence intervals, it is not known if there is an association between weight and TSH within this interval in treated hypothyroid patients.Methods: We conducted a retrospective analysis of patients treated within the Cooper Health System from January 1 to August 31, 2014. A sample of 245 treated hypothyroid patients and 162 euthyroid controls were studied. Data collected included age, sex, race/ethnicity, height, weight, levothyroxine dose, and diabetes and smoking history.Results: Hypothyroid and control groups were similar in height, weight, body mass index (BMI), and the number of patients with diabetes. There were more females, Caucasians, and nonsmokers in the hypothyroid group. The average TSH was slightly higher in the treated hypothyroid patients versus nonhypothyroid controls (median 1.87 vs. 1.55, P<.01). There was no significant relationship between TSH and BMI in the treated hypothyroid patients or the euthyroid controls.Conclusion: Since no significant relationship was found between BMI and TSH in treated hypothyroidism, there may be no weight reduction benefit gained by adjusting TSH to the lower end of normal range. Patients should be counseled that properly treated hypothyroidism is unlikely to contribute to weight gain. Other treatments such as nutrition and exercise counseling should be offered instead.Abbreviations:BMI = body mass indexTSH = thyroid stimulating hormone     

Variations in the serum levels of thyroid hormones and TSH after intake of a dose of L-thyroxine in euthyroid subjects and in adequately-treated hypothyroid patients

The aim of the present study was to determine whether the temporary variations in blood thyroid hormone levels secondary to a therapeutic dose administration of L-thyroxine observed in adequately treated hypothyroid patients also occur in spontaneously euthyroid subjects under analogous conditions. Serum levels of T3, T4, FT3, FT4 and TSH were measured over 6 hours following a single oral administration of L-thyroxine (dosage 85 mcg/mq body surface area) in a group of 18 euthyroid volunteers and 8 hypothyroid patients adequately compensated with replacement therapy. In the euthyroid subjects there was a significant increase in T4 and a significant fall in TSH values at 60', while a significant decrease in FT3 and FT4 as compared to initial values was observed at 120'. In the treated hypothyroid patients serum T3 and T4 increased at 120', while FT4 concentrations, already significantly higher at 120', still remained higher than initial levels at 360'. The different behaviour of the hypothyroid patients, in spite of being compensated with therapeutic doses of L-thyroxine, reflects the persistence of a thyroid-metabolic condition substantially different to the physiological feature, which appears to be realized by means of a reduced iodothyronine clearance and a lower sensitivity in TSH feedback.