Thyroid-Stimulating Hormone Inhibits Insulin Receptor Substrate-1 Expression and Tyrosyl Phosphorylation in 3T3-L1 Adipocytes by Increasing NF-κB DNA-Binding Activity.

Background: Abundant evidence indicates that thyroid-stimulating hormone (TSH) levels are associated with insulin resistance in adipocytes. However, the potential mechanism of the association remains uncertain. The objective of this study was to determine the potential role of TSH in the suppression of insulin receptor substrate-1 (IRS-1) expression and IRS-1 tyrosyl phosphorylation, which might contribute to insulin resistance. Methods: Mouse 3T3-L1 preadipocytes were differentiated into adipocytes. After treatment with 0.01, 0.1, and 1.0 mIU/ml bovine TSH, the TNF-α concentration in the medium was determined by enzyme-linked immunosorbent assay (ELISA). Nuclear factor-kappa B (NF-κB) DNA-binding activity was quantified by electrophoretic mobility shift assay (EMSA). IRS-1 levels in adipocytes were quantified by Western blotting, and tyrosine phosphorylation was measured by immunoprecipitation. Results: TSH induced TNF-α secretion in a dose-dependent manner. There was a significant positive correlation between NF-κB DNA-binding activity and TNF-α secretion. This effect and correlation were weakened by BAY 11-7082 (a nuclear NF-κB inhibitor) and H89 (an inhibitor of cyclic adenosine monophosphate- (cAMP-) dependent protein kinase A (PKA)). Treatment of cultured adipocytes with TSH inhibited insulin-stimulated IRS-1 tyrosyl phosphorylation but promoted TSH-dependent secretion of TNF-α and activation of NF-κB DNA-binding activity. The effects of TSH were significantly inhibited by BAY 11-7082 and H89 and were completely blocked by the TNF-α antagonist WP9QY. Conclusion: TSH inhibited IRS-1 protein expression and tyrosyl phosphorylation in 3T3-L1 adipocytes by stimulating TNF-α production via promotion of NF-κB DNA-binding activity. TSH might play a pivotal role in the development of insulin resistance.

A practical individualized radiation precaution based on the dose rate at release time after inpatient 131I ablation therapy.

INTRODUCTION: Retained radioactivity of 131I after ablation therapy largely differs in each patient according to factors including the amount of remnant thyroid tissue, renal function, and use of recombinant human thyroid-stimulating hormone. To reduce unnecessary restriction of patient's daily life after inpatient 131I ablation therapy, we propose a practical individualized method for radiation precaution based on dose rate at release time. METHODS: We evaluated 215 patients with differentiated thyroid cancer who underwent inpatient 131I ablation therapy following total thyroidectomy. Effective dose equivalent rates at 1-m distance were measured upon release (EDRR) on day 2 and during delayed whole-body scan (EDRD) visits on day 6‒8 after 131I administration. The biexponential model was designed to estimate total effective dose equivalent to others. To assess conservativeness of our model, EDRD estimated by our model was compared with measured EDRD. EDRR-based periods of precaution not to receiving 1 mSv of radiation exposure were estimated and compared with those based on administered radioactivities on American Thyroid Association (ATA) recommendations. RESULTS: The EDRR ranged from 1.0-48.9 µSv/hr. The measured EDRD were equal to or lower than estimated EDRD in all patients, except for one, indicating that our model is sufficiently conservative. According to our model, no subjects needed additional daytime restriction after release. The maximum permissible times for public transportation use were longer in all patients compared with those based on administered radioactivities. Nighttime restriction periods were significantly shorter than those based on administered radioactivity; median periods requiring sleeping apart were 0 (range, 0‒5), 4 (range, 1‒14), and 3 (range, 2‒13) days after release in patients treated with radioactivity doses of 2.96, 5.50, and 7.40 GBq, respectively, needing 8, 16, and 19 additional days, respectively, based on administered radioactivity. CONCLUSIONS: Radiation safety instructions using proposed method based on EDRR of individual patient could safely reduce the burden of radiation precaution.

A pre-ablative thyroid-stimulating hormone with 30-70 mIU/L achieves better response to initial radioiodine remnant ablation in differentiated thyroid carcinoma patients.

Our aim was to clarify the optimum pre-ablative thyroid-stimulating hormone (TSH) level for initial radioiodine remnant ablation (RRA) in patients with differentiated thyroid carcinoma (DTC). From December 2015 to May 2019, 689 patients undergone RRA at Nuclear Medicine Department, Second Hospital of Shandong University were included in the study. Patients were categorized by their pre-ablative TSH level grouping of < 30, 30-70 and ≥ 70 mIU/L. Response to RRA were evaluated as complete response (including excellent and indeterminate response) and incomplete response (including biochemical and structural incomplete response) after a follow-up of 6-8 months. Multivariable binary logistic regression model was used to explore the optimum pre-ablative TSH level range and independent factors associated with response to RRA. Rates of complete response to RRA were 63.04%, 74.59% and 66.41% in TSH level groups of < 30, 30-70 and ≥ 70 mIU/L, separately. With multivariate analysis, the study found that pre-ablative TSH levels, gender and lymph node dissection were independent predictors of response to RRA. TSH between 30 and 70 mIU/L had a higher rate of complete response compared with TSH < 30 mIU/L, OR 0.451 (95% CI 0.215-0.958, P = 0.036). A pre-ablative TSH level of 30-70 mIU/L was appropriate for patients with DTC to achieve a better response to RRA.

Postoperative thyroid hormone supplementation rates following thyroid lobectomy.

BACKGROUND: Thyroid lobectomy is performed for symptomatic benign nodules, indeterminate nodules, or low-risk well differentiated thyroid cancer. We aimed to determine factors associated with thyroid stimulating hormone over goal (TH) following lobectomy. METHODS: We performed a retrospective single-institution cohort study of patients undergoing thyroid lobectomy from January 2016 to December 2017. TH was defined as need for thyroid hormone in accordance with guidelines. Univariate and multivariate logistic regression analysis was performed. RESULTS: One hundred patients were included and 47% developed. TH: 73% of those with cancer, 38% with benign pathology (p = 0.002). Patients with TH were more likely to have thyroiditis 26% versus 3.8% (p = 0.002); higher preoperative TSH: mean 1.88mIU/L (SD 1.17) versus 1.16mIU/L (SD 0.77) (p = 0.0002), and smaller remnant thyroid lobe adjusted for body surface area 2.99ml/m2 versus 3.72ml/m2 (p = 0.003). CONCLUSIONS: After thyroid lobectomy, TH is associated with preoperative TSH level, thyroiditis, remnant thyroid volume, and malignancy. The majority of patients with final pathology of carcinoma will require thyroid hormone supplementation to achieve TSH goal.

Recombinant Human Thyroid-Stimulating Hormone Increases the Percentages of Natural Killer T Cells and B Lymphocytes in Human Peripheral Blood In Vivo.

Multiple cellular and humoral components of the immune system play a significant role in the physiology and pathophysiology of various organs including the thyroid. On the other hand, both thyroid hormones and thyroid-stimulating hormone (TSH) have been shown to exert immunoregulatory activities, which are difficult to assess independently in vivo. In our study we employed a unique clinical model for the assessment of TSH biological function in humans. The structure of peripheral blood mononuclear cell populations was investigated, using flow cytometry, in athyroid patients (n = 109) after treatment because of the differentiated thyroid carcinoma (DTC) at two time-points: directly before and five days after recombinant human TSH (rhTSH) administration. The analysis revealed significant increase in the percentage of natural killer T cells and B lymphocytes in the peripheral blood of rhTSH treated patients, whereas, we did not observe any effects on investigated subpopulations of dendritic cells and monocytes, T cells and natural killer cells. The findings of the study indicate the immune regulatory role of TSH, directed specifically on selected cell subtypes.

Factores clínicos y bioquímicos asociados con la tirotropina en embarazadas aparentemente sanas / Clinical and biochemical factors associated with thyrotropin in seemingly healthy pregnant women

Introducción: Los valores de tirotropina (TSH) pueden modificarse marcadamente durante el embarazo, en relación con diversos factores clínicos y bioquímicos. Objetivo: Identificar los factores clínicos y bioquímicos asociados con la tirotropina en embarazadas aparentemente sanas. Métodos: Estudio descriptivo, transversal, con 247 gestantes aparentemente sanas del municipio Plaza de la Revolución., en el periodo comprendido de septiembre de 2015 a enero de 2019. Variables analizadas: edad materna y gestacional, trimestre del embarazo, color de la piel, paridad, hábito de fumar, antecedentes familiares de enfermedad tiroidea (APF), consumo de suplementos con yodo, índice de masa corporal (IMC), presencia de bocio al examen físico, TSH, tiroxina total (T4t) y libre (T4l), triyodotironina total (T3t) y libre (T3l), gonadotropina coriónica (hCG), anticuerpos contra la peroxidasa tiroidea (AcTPO) y la tiroglobulina (AcTg) y yoduria. Resultados: La TSH (1,66 ± 0,91mUI/L) tuvo una asociación negativa con la edad materna (r = -0,17; p = 0,008), la paridad (nulíparas 1,80 ± 0,90 mUI/L, multíparas 1,45 ± 0,89 mUI/L; p = 0,003), los APF (positivos 1,56 ± 0,91 mUI/L, negativos 1,81 ± 0,89 mUI/L; p = 0,03), la T4t (r = -0,15; p = 0,02), la T4l (r = -0,23; p = 0,000) y la hCG (r = -0,52; p = 0,001). Mostraron una relación directa la edad gestacional (r = 0,25; p = 0,000) y el uso de suplementos yodados (consumo 1,96 ± 0,72mUI/L, no consumo 1,62 ± 0,93 mUI/L; p = 0,03). Conclusiones: La tirotropina presenta una relación inversa con la edad materna, la paridad, los antecedentes familiares de enfermedad tiroidea, la T4 total y libre, y la gonadotropina coriónica, y una relación directa con la edad gestacional y el consumo de suplementos con yodo(AU)

Introduction: Thyrotropin (TSH) values can be sharply modified during pregnancy, in relation to various clinical and biochemical factors. Objective: Identify clinical and biochemical factors associated with thyrotropin in seemingly healthy pregnant women. Methods: Descriptive, cross-sectional study with 247 seemingly healthy pregnant women from Plaza de la Revolution municipality in the period from September 2015 to January 2019. Variables analyzed: maternal and gestational age, trimester of pregnancy, skin color, pregnancies, smoking habit, family history of thyroid disease (APF), consumption of iodine supplements, body mass index (BMI), presence of goiter to physical examination, TSH, total and free (T4l) thyroxine (T4t), total (T3t) and free (T3l) triiodothyronine, chorionic gonadotropin (hCG), antibodies against thyroid peroxidase (AcTPO) and thyroglobulin (AcTg) and urinary iodine. Results: TSH (1.66 ± 0.91mUI/L) had a negative association with maternal age (r = -0.17; p x 0.008), pregnancy (nulliparas 1.80 ± 0.90 mUI/L, 1.45 ± 0.89 mUI/L; p x 0.003), APF (positive 1.56 ± 0.91 mUI/L, negative 1.81 ± 0.89 mUI/L; p x 0.03), the T4t (r = -0.15; p s 0.02), the T4l (r = -0.23; p x 0.000) and the hCG (r = -0.52; p x 0.001). They showed a direct relationship with gestational age (r x 0.25; p x 0.000) and the use of iodine supplements (consumption 1.96 ± 0.72mUI/L, not consumption 1.62 ± 0.93 mUI/L; p x 0.03). Conclusions: Thyrotropin has an inverse relationship with maternal age, pregnancies, family history of thyroid disease, total and free T4, and chorionic gonadotropin, and a direct relationship with gestational age and consumption of iodine supplements(AU)

Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials.

A potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.

Thyroid function testing and management during and after pregnancy among women without thyroid disease before pregnancy.

BACKGROUND: Screening in pregnancy for subclinical hypothyroidism, often defined as thyroid-stimulating hormone (TSH) greater than 2.5 mIU/L or greater than 4.0 mIU/L, is controversial. We determined the frequency and distribution of TSH testing by gestational age, as well as TSH values associated with treatment during pregnancy and the frequency of postpartum continuation of thyroid hormone therapy. METHODS: We performed a retrospective cohort study of pregnancies in Alberta, Canada. We included women without thyroid disease who delivered between October 2014 and September 2017. We used delivery records, physician billings, and pharmacy and laboratory administrative data. Our key outcomes were characteristics of TSH testing and the initiation and continuation of thyroid hormone therapy. We calculated the proportion of pregnancies with thyroid testing and the frequency of each specific thyroid test. RESULTS: Of the 188 490 pregnancies included, 111 522 (59.2%) had at least 1 TSH measurement. The most common time for testing was at gestational week 5 to 6. Thyroid hormone therapy was initiated at a median gestational age of 7 (interquartile range 5-12) weeks. Among women with first TSH measurements of 4.01 to 9.99 mIU/L who were not immediately treated, the repeat TSH measurement was 4.00 mIU/L or below in 67.9% of pregnancies. Thyroid hormone was continued post partum for 44.6% of the women who started therapy during their pregnancy. INTERPRETATION: The findings of our study suggest that current practice patterns may contribute to overdiagnosis of hypothyroidism and overtreatment during pregnancy and post partum.

Thyrotropin Causes Dose-dependent Biphasic Regulation of cAMP Production Mediated by Gs and Gi/o Proteins.

The thyrotropin (TSH) receptor (TSHR) signals via G proteins of all four classes and ß-arrestin 1. Stimulation of TSHR leads to increasing cAMP production that has been reported as a monotonic dose-response curve that plateaus at high TSH doses. In HEK 293 cells overexpressing TSHRs (HEK-TSHR cells), we found that TSHR activation exhibits an "inverted U-shaped dose-response curve" with increasing cAMP production at low doses of TSH and decreased cAMP production at high doses (>1 mU/ml). Since protein kinase A inhibition by H-89 and knockdown of ß-arrestin 1 or ß-arrestin 2 did not affect the decreased cAMP production at high TSH doses, we studied the roles of TSHR downregulation and of Gi/Go proteins. A high TSH dose (100 mU/ml) caused a 33% decrease in cell-surface TSHR. However, because inhibiting TSHR downregulation with combined expression of a dominant negative dynamin 1 and ß-arrestin 2 knockdown had no effect, we concluded that downregulation is not involved in the biphasic cAMP response. Pertussis toxin, which inhibits activation of Gi/Go, abolished the biphasic response with no statistically significant difference in cAMP levels at 1 and 100 mU/ml TSH. Concordantly, co-knockdown of Gi/Go proteins increased cAMP levels stimulated by 100 mU/ml TSH from 55% to 73% of the peak level. These data show that biphasic regulation of cAMP production is mediated by Gs and Gi/Go at low and high TSH doses, respectively, which may represent a mechanism to prevent overstimulation in TSHR-expressing cells. SIGNIFICANCE STATEMENT: We demonstrate biphasic regulation of TSH-mediated cAMP production involving coupling of the TSH receptor (TSHR) to Gs at low TSH doses and to Gi/o at high TSH doses. We suggest that this biphasic cAMP response allows the TSHR to mediate responses at lower levels of TSH and that decreased cAMP production at high doses may represent a mechanism to prevent overstimulation of TSHR-expressing cells. This mechanism could prevent chronic stimulation of thyroid gland function.

Evaluation of SNA001, a Novel Recombinant Human Thyroid Stimulating Hormone Injection, in Patients With Differentiated Thyroid Carcinoma.

SNA001 is a novel recombinant human thyroid stimulating hormone (rhTSH). rhTSH has long been approved in several countries to facilitate monitoring and ablation of thyroid carcinoma without hypothyroidism caused by thyroid hormone withdrawal (THW). To assess the safety, tolerance, pharmacokinetic and pharmacodynamic properties of SNA001, the two-period (SNA001 period and THW period), dose-ascending study in well-differentiated thyroid cancer (DTC) patients was designed. Three doses (0.45 mg, 0.9 mg, and 1.35 mg) of SNA001 were intramuscularly injected, twice in the SNA001 period to stimulate iodine-131 uptake and thyroglobulin (Tg) release. 24 h after the last dose of SNA001, iodine-131 (111-185 MBq) was administrated, followed by whole-body scan (WBS) 48 h later. THW period began just after SNA001 washout and lasted for about 3-6 weeks. When TSH level was above 30 mU/L, iodine-131 (111-185 MBq) was administrated, followed by a WBS and Tg detection 48 h later. Twenty-four DTC patients after thyroidectomy were enrolled; mean peak concentrations of SNA001 in 0.45, 0.9, and 1.35 mg groups were 18.5, 26.7, and 37.0 ng/ml (about 244.7, 354.2, and 489.6 mU/L) respectively, within 28-32 h after first dose of SNA001. SNA001 was metabolized in a dose-dependent manner. The results of WBS and Tg release in the SNA001 period were compared with those in the THW period. Compared to Tg level in baseline, the Tg levels in SNA001 and THW periods were increased, with 78% of subjects showing higher Tg levels in the THW period. 100% of the patients had concordant qualitative results of the scans within two periods in three groups. Symptoms of hypothyroidism were relieved in the SNA001 period compared with THW period, though there was no significant difference in most of the scale scores. There were no serious adverse events related to SNA001; the most common adverse events were gastrointestinal symptoms of mild and transient nature. Thus, SNA001 promises to be a safe and effective method to stimulate iodine-131 uptake and Tg secretion during monitoring and ablation for DTC without the disadvantages of incidental hypothyroidism.

Parálisis periódica hipopotasémica tirotóxica, a propósito de un caso / Hypokalemic thyrotoxic periodic paralysis. Report of one case

No disponible

Optimización del seguimiento de gestantes con enfermedad tiroidea autoinmune / Optimization of the follow-up of pregnant women with autoimmune thyroid disease

Objetivo: Determinar el riesgo de hipotiroidismo en gestantes con enfermedad tiroidea autoinmune y tirotropina (TSH) < 2,5 mUI/l al inicio del embarazo. Métodos: Estudio prospectivo longitudinal en gestantes de primer trimestre sin antecedentes de patología tiroidea y con TSH en primer trimestre < 2,5 mUI/l. Se determinaron TSH, tiroxina libre (T4l) y anticuerpos antiperoxidasa (TPO) y antitiroglobulina en los 3 trimestres. Se comparó la evolución de la función tiroidea y la aparición de hipotiroidismo gestacional (TSH > 4 mUI/l), entre las gestantes con autoinmunidad positiva y autoinmunidad negativa. Resultados: Se incluyeron 300 gestantes con TSH basal 1,3 ± 0,6 mUI/l (semana gestacional 9). El 17,7% (n = 53) tenían autoinmunidad positiva en el primer trimestre. Los títulos de anticuerpos TPO y antitiroglobulina disminuyeron entre el primer y el tercer trimestre un 76,8% y un 80,7% respectivamente. La evolución de la función tiroidea fue similar en el grupo con autoinmunidad positiva y el grupo con autoinmunidad negativa, y la aparición de hipotiroidismo fue del 1,9% (1/53) y del 2% (5/247) respectivamente. Las gestantes en las que la TSH aumentó por encima de 4 mUI/l (n = 6) tenían cifras superiores de TSH basal en comparación con las que mantuvieron TSH≤4 mUI/l a lo largo del embarazo (1,8 vs. 1,3 mUI/l; p = 0,047). Conclusión: En nuestra población, las mujeres con TSH < 2,5 mUI/l al inicio del embarazo tienen un riesgo mínimo de desarrollar hipotiroidismo durante la gestación, independientemente de la autoinmunidad tiroidea

Objective: To determine the risk of hypothyroidism in pregnant women with autoimmune thyroid disease and thyrotropin (TSH) < 2,5 mIU/l at the beginning of pregnancy. Methods: Prospective longitudinal study of pregnant women with no personal history of thyroid disease, and with TSH < 2.5 mIU/l in the first trimester. TSH, free thyroxine (FT4), anti peroxidase (TPO) and anti thyroglobulin antibodies were measured in the 3 trimesters of pregnancy. We compared thyroid function throughout pregnancy, and the development of gestational hypothyroidism (TSH >4 mIU/l) among pregnant women with positive thyroid autoimmunity and those with negative autoimmunity. Results: We included 300 pregnant women with mean baseline TSH 1.3 ± 0.6 mIU/l (9th gestational week). Positive thyroid autoinmunity was detected in 17.7% of women (n = 53) at the first trimester. Between the first and the third trimesters, TPO and anti thyroglobulin antibodies titers decreased 76.8% and 80.7% respectively. Thyroid function during pregnancy was similar among the group with positive autoimmunity and the group with negative autoimmunity, and the development of hypothyroidism was 1.9% (1/53) and 2% (5/247) respectively. Pregnant women in whom TSH increased above 4 mIU/l (n = 6), had higher baseline TSH levels compared to those who maintained TSH ≤4 mIU/l during pregnancy (1.8 vs. 1.3 mIU/l; p=.047). Conclusion: In our population, women with TSH levels <2.5 mIU/l at the beginning of pregnancy have a minimal risk of developing gestational hypothyroidism regardless of thyroid autoimmunity

Recombinant human thyrotropin (rhTSH) versus Levo-thyroxine withdrawal in radioiodine therapy of differentiated thyroid cancer patients: differences in abdominal absorbed dose.

PURPOSE: In DTC patients, 131-radioiodine therapy has routinely been used for many years for thyroid remnant ablation after thyroid surgery. To date, two different strategies can be used to achieve sufficient TSH stimulation on thyroid remnant: (I) Levo-thyroxine withdrawal or (II) rhTSH stimulation. The aim of our study was to compare the abdominal absorbed dose ratio between differentiated thyroid cancer patients who underwent thyroid remnant ablation after either L-T4 withdrawal or rhTSH stimulation. METHODS: We reviewed the records of 63 patients affected by differentiated thyroid cancer. All patients underwent thyroid remnant ablation after either L-T4 withdrawal or rhTSH stimulation. A post-therapy whole-body scan was obtained 5 days after 131-radioiodine therapy. Qualitative and quantitative image analysis was performed. Quantitative analysis was performed by drawing seven regions of interest on the abdomen (anterior and posterior views) to estimate both the activity ratio (AR) and absorbed dose ratio (DR) obtained in patients treated in hypothyroidism or after rhTSH stimulation. RESULTS: The values of the activity and absorbed dose ratios obtained on each abdomen region (liver, stomach, ascending colon, transverse colon, descending colon, rectum, and small intestine) were always higher in patients treated after L-T4 withdrawal than after rhTSH stimulation with p-values of 0.000, 0.000, 0.001, 0.000, 0.022, 0.007, and 0.002, respectively. CONCLUSIONS: DTC patients treated with 131-radioiodine after rhTSH stimulation have lower abdominal radioiodine activity than hypothyroid patients. Our data could be of practical relevance in terms of patient management. The potential impact on rare radioiodine-related gastrointestinal side effects is to be established in specifically designed prospective studies.

Evaluation and management of the child with hypothyroidism.

BACKGROUND: Thyroid hormones are critical for early neurocognitive development as well as growth and development throughout childhood. Prompt recognition and treatment of hypothyroidism is, therefore, of utmost importance to optimize physical and neurodevelopmental outcomes. DATA SOURCES: A PubMed search was completed in Clinical Queries using the key terms "hypothyroidism". RESULTS: Hypothyroidism may be present at birth (congenital hypothyroidism) or develop later in life (acquired hypothyroidism). Thyroid dysgenesis and dyshormonogenesis account for approximately 85% and 15% of permanent cases of congenital primary hypothyroidism, respectively. More than 95% of infants with congenital hypothyroidism have few, if any, clinical manifestations of hypothyroidism. Newborn screening programs allow early detection of congenital hypothyroidism. In developed countries, Hashimoto thyroiditis is the most common cause of goiter and acquired hypothyroidism in children and adolescents. Globally, iodine deficiency associated with goiter is the most common cause of hypothyroidism. Central hypothyroidism is uncommon and may be associated with other congenital syndromes and deficiencies of other pituitary hormones. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment. CONCLUSIONS: To optimize neurocognitive outcome in infants with congenital hypothyroidism, treatment with levothyroxine should be started as soon as possible, preferably within the first 2 weeks of life. Children with acquired hypothyroidism should also be treated early to ensure normal growth and development as well as cognitive outcome. The target is to keep serum TSH < 5 mIU/L and to maintain serum free T4 or total T4 within the upper half of the age-specific reference range, with elimination of all symptoms and signs of hypothyroidism.

Recombinant Thyrotropin vs Levothyroxine Withdrawal in 131I Therapy of N1 Thyroid Cancer: A Large Matched Cohort Study (ThyrNod).

CONTEXT: Recombinant human thyrotropin (rhTSH) has been shown to be an effective stimulation method for radioactive iodine (RAI) therapy in differentiated thyroid cancer, including in those with nodal metastases (N1 DTC). OBJECTIVES: To demonstrate the noninferiority of rhTSH vs thyroid hormone withdrawal (THW) in preparation to RAI regarding disease status at the first evaluation in the real-life setting in patients with N1 DTC. DESIGN: This was a French multicenter retrospective study. Groups were matched according to age (<45/≥45 years), number of N1 nodes (≤5/>5 lymph nodes), and stage (pT1-T2/pT3). RESULTS: The cohort consisted of 404 patients pT1-T3/N1/M0 DTC treated with rhTSH (n = 205) or THW (n = 199). Pathological characteristics and initially administrated RAI activities (3.27 ± 1.00 GBq) were similar between the two groups. At first evaluation (6 to 18 months post-RAI), disease-free status was defined by thyroglobulin levels below threshold and a normal ultrasound. Disease-free rate was not inferior in the rhTSH group (75.1%) compared with the THW group (71.9%). The observed difference between the success rates was 3.3% (-6.6 to 13.0); rhTSH was therefore considered noninferior to THW because the upper limit of this interval was <15%. At the last evaluation (29.7 ± 20.7 months for rhTSH; 36.7 ± 23.8 months for THW), 83.5% (rhTSH) and 81.5% (THW) of patients achieved a complete response. This result was not influenced by any of the known prognostic factors. CONCLUSIONS: A preparation for initial RAI treatment with rhTSH was noninferior to that with THW in our series of pT1-T3/N1/M0-DTC on disease-free status outcomes at the first evaluation and after 3 years.

Could short thyroid hormone withdrawal be an effective strategy for radioiodine remnant ablation in differentiated thyroid cancer patients?

PURPOSE: Current guidelines recommend thyroid hormone withdrawal (THW) of 3-4 weeks before radioiodine remnant ablation (RRA) of differentiated thyroid carcinoma (DTC). We aimed to evaluate (1) the reliability of a shorter THW (i.e., 14 days) to achieve adequate TSH levels (i.e., 30 mU/l), (2) the association between length of THW and response to therapy, and (3) the potential association between pre-ablation TSH levels and patients' outcome. METHODS: After thyroidectomy, all patients started LT4 therapy, which was subsequently discontinued in order to perform RRA. Patients were broken down into two groups according to the length of THW: group A, 2 weeks of THW, and group B, 3-4 weeks of THW. We used clinical, biochemical, and imaging data to evaluate patients' outcome. By means of univariate and multivariate analysis, including main DTC prognostic factors, we assessed the impact of THW length and TSH levels on patients' outcome. RESULTS: We evaluated 222 patients, 85 of whom were treated with RRA after a THW period of 2 weeks (group A). All other 137 patients underwent RRA after 3-4 weeks THW (group B). At the time of RRA all patients presented TSH levels ≥30 mU/l. After a median follow-up time of 3.4 years, we found 183 patients (82%) with excellent response to treatment and 39 patients (18%) showing incomplete response. Kaplan-Meier response to therapy curves showed that ablation-Tg, tumor size, and lymph node status were significantly associated with prognosis; no associations were found between THW length, TSH levels, and prognosis. Multivariate Cox model showed that only ablation-Tg was significantly associated with treatment response. CONCLUSIONS: Prior to RRA, a short 2-week THW is an effective method to stimulate TSH levels. No difference in terms of incomplete response to treatment was observed between DTC patients prepared for RRA with a short THW and those with the long THW.

Thyrotrophic status in patients with pituitary stalk interruption syndrome.

Pituitary stalk interruption syndrome (PSIS) is associated with simultaneous or subsequent pituitary hormone deficiencies (PHDs). Although the clinical features of multiple PHDs are well known, the status of the thyrotrophic axis in PSIS has not been thoroughly investigated.The clinical data of 89 PSIS patients and 34 Sheehan syndrome (SS) patients were retrospectively analyzed.The prevalence of central hypothyroidism in the PSIS patients and the SS patients was 79.8% and 70.6%, respectively. The thyroid-stimulating hormone (TSH) levels in the PSIS patients were significantly higher in comparison with the SS patients (5.13 ±â€Š3.40 vs 1.67 ±â€Š1.20 mU/L, P < .05). TSH elevation (8.79 ±â€Š3.17 mU/L) was noticed in 29 of 71 (40.85%) hypothyroid PSIS patients but not in the 24 hypothyroid SS patients. The TSH levels in the hypothyroid PSIS patients were significantly higher in comparison with the euthyroid PSIS patients (5.42 ±â€Š3.67 vs 3.66 ±â€Š1.50 mU/L). Thyroid hormone replacement significantly reduced the TSH levels in the PSIS patients with elevated TSH levels from 7.24 ±â€Š0.98 to 1.67 ±â€Š1.51 mU/L (P < .05). The logistic regression analysis suggested that TSH level was not significantly associated with pituitary stalk status and height of the anterior pituitary gland.PSIS is a newly recognized cause of central hypothyroidism. The proportion and amplitude of TSH elevations are higher in PSIS than in other causes of central hypothyroidism.

Fourth ventricular thyrotropin induces satiety and increases body temperature in rats.

Besides its well-known action to stimulate thyroid hormone release, thyrotropin mRNA is expressed within the brain, and thyrotropin and its receptor have been shown to be present in brain areas that control feeding and gastrointestinal function. Here, the hypothesis that thyrotropin acts on receptors in the hindbrain to alter food intake and/or gastric function was tested. Fourth ventricular injections of thyrotropin (0.06, 0.60, and 6.00 µg) were given to rats with chronic intracerebroventricular cannulas aimed at the fourth ventricle. Thyrotropin produced an acute reduction of sucrose intake (30 min). The highest dose of thyrotropin caused inhibition of overnight solid food intake (22 h). In contrast, subcutaneous administration of corresponding thyrotropin doses had no effect on nutrient intake. The highest effective dose of fourth ventricular thyrotropin (6 µg) did not produce a conditioned flavor avoidance in a standardized two-bottle test, nor did it affect water intake or gastric emptying of glucose. Thyrotropin injected in the fourth ventricle produced a small but significant increase in rectal temperature and lowered plasma levels of tri-iodothyronin but did not affect plasma levels of thyroxine. In addition, there was a tendency toward a reduction in blood glucose 2 h after fourth ventricular thyrotropin injection ( P = 0.056). In conclusion, fourth ventricular thyrotropin specifically inhibits food intake, increases core temperature, and lowers plasma levels of tri-iodothyronin but does not affect gastromotor function.

[Key minerals significant for hypothyroidism including Hashimoto's thyroiditis - function and presence in food].

Thyroid diseases belong to the most common disorders of the ductless glands. Particular attention is paid to the growing morbidity of autoimmune affliction of the thyroid gland, including Hashimoto's thyroiditis. The main method of treatment is an oral substitution of thyroid hormones. However, the literature pays particular attention to supporting therapy with a diet rich in components essential for the proper functioning of this organ.

Recombinant human TSH stimulated thyroglobulin levels at remnant ablation predict structural incomplete response to treatment in patients with differentiated thyroid cancer.

In patients with differentiated thyroid cancer, stimulated thyroglobulin (sTg) levels after thyroid hormone withdrawal (THW) at remnant ablation (RA) and at 6 to 12 months are known to have good prognostic value. This study aimed to evaluate the prognostic impacts and best cutoff values of sTg levels under recombinant human thyroid stimulating hormone (rhTSH) treatment at RA and at follow-up. A total of 151 patients were enrolled, of whom 77 were followed up with rhTSH-stimulated Tg (rhTSH-sTg) and 74 with THW-stimulated Tg (THW-sTg) at 6 to 12 months after rhTSH-aided RA. Risk stratification, response to treatment (excellent, indeterminate, biochemical incomplete, and structural incomplete response [SIR]), and clinical outcome were accessed by revised American Thyroid Association (ATA) guideline criteria. Seven out of 151 (4.6%) patients were confirmed to have SIR during the median follow-up of 79.0 months; 3 in the rhTSH group and 4 in the THW group. One hundred thirty-two out of 151 (87.4%) patients were confirmed to have excellent response; 68 (51.5%) in the rhTSH group and 64 (48.5%) in the THW group. The cutoff values of sTg for predicting SIR to treatment at rhTSH-aided RA, THW-sTg, and rhTSH-sTg were 4.64 ng/mL (sensitivity 85.7%, specificity 76.4%, negative predictive value [NPV] 99.2%), 2.41 ng/mL (sensitivity 100%, specificity 94.3%, NPV 100%), and 1.02 ng/mL (sensitivity 66.7%, specificity 94.6%, NPV 98.6%), respectively. sTg levels using rhTSH at both RA and follow-up has a high NPV and are as effective as using THW for predicting SIR. The risk classification according to the revised ATA guidelines can be used effectively to supplement rhTSH-aided sTg levels to predict better clinical outcomes.