Measurement Of Thyroid-stimulating Hormone Research Articles

Considerations for Thyroidectomy as Treatment for Graves Disease.

Hyperthyroidism is a clinical state that results from abnormally elevated thyroid hormones. Thyroid gland affects many organ systems; therefore, patients usually present with multiple clinical manifestations that involve many organ systems such as the nervous, cardiovascular, muscular, and endocrine system as well as skin manifestations. Hyperthyroidism is most commonly caused by Graves disease, which is caused by autoantibodies to the thyrotropin receptor (TRAb). Other causes of hyperthyroidism include toxic multinodular goiter, toxic single adenoma, and thyroiditis. Diagnosis of hyperthyroidism can be established by measurement of thyroid-stimulating hormone (TSH), which will be suppressed with either elevated free T4 and/or T3 (overt hyperthyroidism) or normal free T3 and T4 (subclinical hyperthyroidism). Hyperthyroidism can be treated with antithyroid drugs (ATDs), radioactive iodine (RAI), or thyroidectomy. ATDs have a higher replacement rate when compared with RAI or thyroidectomy. Recent evidence has shown that thyroidectomy is a very effective, safe treatment modality for hyperthyroidism and can be performed as an outpatient procedure. This review article provides some of the most recent evidence on diagnosing and treating patients with hyperthyroidism.

Karakteristike nalaza na scintigramu štitaste žlezde sa 99mTc-pertehnetatom kod pacijenata sa diferenciranim tireoidnim karcinomom

Introduction: Differentiated thyroid carcinoma (DTC) derived from follicular cells is the most frequent endocrine malignancy, which most commonly occurs in patients with thyroid nodules. Aim: The aim of this retrospective analysis is to examine the type of scintigraphic finding of the thyroid gland obtained with 99mTc-pertechnetate in patients with DTC before tireoidectomy. Material and methods: Medical documentation comprised of 95 subjects with presurgical evaluation of thyroid nodules, including 18 men (51.5 ± 8.7 years old, range 43-68) and 77 women (48 ± 12, range 14-72 years). Other tests performed during the preoperative tests are the following: ultrasound examination of the thyroid gland, thyrotropin and thyroglobulin concentration measurement. Results: During the preoperative evaluation, thyroid ultrasound was performed in 20 (21%) out of 95 subjects with DTC, while 99mTc-pertechnetate scintigraphy was performed in 75 (79%) of patients, in addition to a clinical examination. What is the distribution of scintigraphic finding? Significantly, the highest incidence of DTC was found in the multinodular goiter: 61 (64%) subjects were diagnosed with this type of DTC, while 31 (33%) carcinomas were found in abnormal, solitary "cold" nodules. The most frequent histopathological finding amongst nodules and multinodular goiter detected by scintigraphy was papillary thyroid carcinoma. Thyroid carcinoma was found in two patients with Graves' disease and in one patient with a normal scintigraphic finding. The values of thyroid hormones were normal in 71% of DTC and elevated in fewer cases (21%). The ultrasound examination showed high-risk features in only 18 subjects (19%). Conclusion: Our results have shown that DTC is the most common finding in the multinodal goiter, and that it occurs much less often within the "cold" thyroid nodules. In a small percentage of subjects, thyroid neoplasm was found in patients with hyperthyroidism. The results of the study showed that thyroid gland scintigraphy with 99mTc-pertechnetate still has a significant diagnostic role in the examination of thyroid nodules.

Neonatal Thyroid-Stimulating Hormone Screening as an Indirect Method for the Assessment of Iodine Status in Central Siberia

Background: Iodine deficiency is associated with goiter and impaired brain function. Neonatal thyroid-stimulating hormone (TSH) screening for congenital hypothyroidism used as an indicator of the degree of iodine deficiency and of its control. An increased frequency of thyroid-stimulating hormone (TSH) measurements above 5 mIU/L in newborn screening corresponds to the impaired iodine status of the population. The aim: to estimate the iodine deficiency and the effectiveness of iodine prophylaxis in Krasnoyarsk territory, Republics of Tuva and Khakassia according the results of neonatal TSH_screening. Methods: An 18-year analysis was performed in 34,980 newborns participating in the national thyroid newborn screening program. The TSH concentration was measured in dry blood spots collected by heel stick on filter paper, 96 hours after birth, using DELFIA method. Results: According to the data of the congenital hypothyroidism screening the rate of TSH < 5 mU/1 was 11.8% in Krasnoyarsk territory (23.9% in 2000) and corresponded to mild iodine deficiency. In different regions of Krasnoyarsk territory the rate of TSH < 5 mU/1 in the newborn varied from 3.5% to 23.7%. The highest values were marked in the Arctic peninsula Taimyr, in cities Zheleznogorsk (nuclear facility) and Sosnovoborsk, in Irbeysky, Suchobuzimsky, Eniseysky, Tuchtetsky, Novoselovsky regions (20.9–23.7%). In the Republic of Khakasia the rate of TSH < 5 mU/1 was 12.5%. In the Republic of Tyva the rate of TSH < 5 mU/1 was – 6.6% (38.6% in 1997; 11.5% in 2000). These results indicate mild iodine deficiency. Conclusion: Our investigations show mild iodine deficiency in Central Siberia demanding continuous adequate iodine prevention. Additional assessment of the iodine intake in the regions with mild iodine deficiency is needed to prevent suboptimal cognitive and psychomotor outcomes.

Assessment of iodine supplementation program on thyroid function in Sudan

The aim of this Study is to investigate whether the Iodine Supplementation Programme is successful or not. This Programme was implemented in Nyala to treat the Iodine deficiency. In this Study Nyala was selected to act as (a study area), due to the history of Iodine deficiency of this region, while Khartoum was selected to act as (a control area). 2000 samples were collected from Khartoum versus 450 samples from Nyala. Thyroxine (T4) and triiodothyronine (T3) levels in two regions were measured and performed by using radioimmunoassay (RIA), also the immunoradiometric assay (IRMA) used for measurement of thyroid stimulating hormone (TSH). The obtained results analyzed by using Statistical Package for Social Sciences (SPSS). (Coherent retrospective) used to determine differences between the study groups. The results of this study showed, there was no significant difference between the mean serum concentrations of T3 and TSH for Khartoum and Nyala. T4of Khartoum (117.93 ± 42.797) nmol/L and the mean serum T4 of Nyala (114.54 ± 45.526) nmol/L, the (P-value = 0.133).T3for Khartoum (1.8040 ± 0.99047) nmol/L and T3of Nyala (1.7307 ± 0.96508) nmol/L, the (P-value = 0.153). TSH for Khartoum (1.4480 ± 0.95807)mIU/Land the mean serum TSH of Nyala (1.4553 ± 1.0244) mIU/L, the (P-value = 0.885). The study showed a clear observation of improvement of hypothyroidism cases in Nyala while the ratio decreased from 64.09% to 0.6%. All the results were carried out according to normal range of Sudanese. The conclusion from this study the iodine supplementation programme is successful. The study recommends rising the health awareness among people by explain the severity of iodine deficiency, and continue in iodine supplementation programme, also establishment of monitoring system including monitoring the presence of iodized diets (sugar, salt, oils, and bread) in the markets. Finally, further studies are needed in other parts of Sudan to assess the size of iodine deficiency problem.

Commercially Bottled Purified Water as an Alternative Instrument Feed Water in Automated Time-Resolved Fluorescent Immunoassay for TSH, 17-OHP and IRT in Neonatal Screening

Objective. The study was undertaken to determine if commercially bottled purified water can be used as substitute instrument feed water for three (3) newborn screening immunoassays. Methdology. A total of 294 control samples and 300 patient samples were included in this study. Accuracy and precision studies using control samples, and parallel testing using patient samples, were done to compare the use of clinical laboratory reagent water (CLRW) and commercially bottled purified water (CBPW) in the performance of automated time-resolved fluorescent immunoassay of thyroid stimulating hormone (TSH), 17α-OH-progesterone (17-OHP) and immunoreactive trypsinogen (IRT). Results. The use of CBPW as instrument feed water for measurements of TSH, 17-OHP and IRT levels by automated time-resolved fluorescent immunoassay using AutoDELFIA (Perkin-Elmer) in NBS has an acceptable accuracy and precision compared to using CLRW. The parallel testing using patient samples showed that, overall, the performance of using CBPW in automated time-resolved fluorescent immunoassay for TSH, 17-OHP, and IRT is acceptable, compared with using CLRW as instrument feed water. Conclusion. Commercially bottled purified water can be used as substitute when setting up a laboratory water purification system is too expensive for a laboratory, or as back up to clinical laboratory reagent water when there is breakdown of the installed water purification system to be used as instrument feed water in automated time-resolved fluorescent immunoassay of TSH, 17-OHP and IRT in NBS using AutoDELFIA (Perkin-Elmer).

Effects of sex, age, sampling time, and season on thyroid-stimulating hormone concentrations: A retrospective study

BackgroundMeasuring thyroid-stimulating hormone (TSH) is essential for diagnosing and monitoring thyroid diseases. The aim of this study was to evaluate the effect of sex, age, sampling time and season on TSH in a large Chinese population and to determine which factor had the greatest impact on TSH measurement results. MethodsData were obtained from the laboratory information system from September 1, 2013 to August 31, 2016. A total of 80150 TSH measurements of outpatients were enrolled in this study. TSH was measured using a Siemens ADVIA Centaur XP automatic chemiluminescence immunoassay analyzer. Linear regression models were used to assess the association between log-transformed TSH concentrations and sex, age, sampling time and season. ResultsThe serum TSH concentrations in women were significantly higher than in men. In all subjects, serum TSH concentrations increased by 0.005 μIU/mL for each year of age. TSH concentrations showed circannual variation during the 3 consecutive years of data collection and decreased during the summer while increased during the winter. The serum TSH concentrations decreased from 7 a.m. to 1 p.m. while increased from 1 p.m. to 4 p.m. The same trend was observed in TSH concentrations for sampling time stratified by sex. Linear regression revealed that sampling time might be the major factor affecting serum TSH concentrations. ConclusionSex, age, season, and sampling time significantly affected serum TSH concentrations. Age-related alteration in serum TSH concentrations was observed in this study. Sampling time was the major factor affecting serum TSH concentrations.

Incidence of Congenital Hypothyroidism Over 37 Years in Ireland.

Congenital hypothyroidism (CHT) is one of the most common preventable causes of learning disability. Newborn screening with whole-blood thyroid-stimulating hormone measurements was introduced in the Republic of Ireland in 1979 and is coordinated from a single center with an unchanged protocol since its inception. Our objective in this study was to describe the incidence of CHT in the Republic of Ireland over the past 37 years in the context of a complete national population and an unchanged screening protocol. The newborn screening records of all individuals who were diagnosed with CHT between 1979 and 2016 were reviewed. Infants with positive screening results had a whole-blood thyroid-stimulating hormone value of ≥15 mU/L at 72 to 120 hours of life; values of 8 to 15 mU/L required a repeat whole-blood screening test. Of 2 361 174 infants who were screened between July 1979 and December 2016, 1063 (662 girls) were diagnosed with CHT (incidence: 0.45 cases per 1000 live births). The number of detected cases increased from 0.27 cases per 1000 live births treated between 1979 and 1991 to 0.41 cases per 1000 live births treated between 1992 and 2004 to 0.65 cases per 1000 live births treated between 2005 and 2016. The increase in detected cases of CHT was predominantly in the normal or hyperplastic gland category. The incidence of CHT has increased significantly in the Republic of Ireland over the past 37 years despite a consistent screening cutoff. The increased rate was not explained by an increased survival rate of preterm infants or a changing population heterogeneity.

Does TSH Reliably Detect Hypothyroid Patients?

To evaluate the reliability of normal Thyroid Stimulating Hormone (TSH) as a thyroid function test and assess the effect of Adrenocorticotropic Hormone (ACTH) on serum TSH concentration. Patients presenting to the National Institutes of Health Department of Endocrinology outpatient clinic with symptoms consistent with hypothyroidism were identified. Thyroid hormone concentrations were measured by liquid chromatography/tandem mass spectrometry and immunoassay. Patients with normal TSH concentrations were assessed for both clinical and biochemical hypothyroidism.We evaluated the effect of ACTH stimulation (performed on patients for assessment of adrenal function) on TSH concentration. Patients with symptoms consistent with hypothyroidism but with normal TSH values in the range of 1-4 IU/mL and normal free T4 (FT4) values by immunoassay measurements were confirmed to be biochemically hypothyroid following measurements of thyroid hormones by mass spectrometry. We present case studies of two patients, a 76-year-old male and a 58-year-old female. Improvement in the male patient's hypothyroid symptoms, including afternoon fatigue, constipation, alopecia, dry skin and high cholesterol, was documented after initiating thyroid hormone replacement.ACTH stimulation resulted in an average decrease of 17% in TSH between time 0 and 60 minutes post stimulation. Although measurement of TSH is a convenient screen for thyroid function, it is influenced by many factors which may affect its overall reliability. We believe thyroid function should be assessed by more than a single test. We recommend measurement of thyroid hormone concentrations by mass spectrometry if the patient's clinical presentation is discordant with their TSH levels.

Hypothyroidism in Clinical Practice

Hypothyroidism in Clinical Practice

HINT: a novel prognostic model for patients with hepatitis B virus-related acute-on-chronic liver failure.

HBV-related acute-on-chronic liver failure (HBV-ACLF) deteriorates rapidly in the short term, which necessitates accurate initial clinical decision making. To develop a novel prognostic score for patients with HBV-ACLF and clarify the role of thyroid hormones in HBV-ACLF. A retrospective cohort of 635 HBV-ACLF patients was enrolled to develop and validate a novel prognostic score for HBV-ACLF. Additionally, a cross-sectional cohort (n=199) and a prospective longitudinal HBV-ACLF cohort (n=56) were recruited to clarify the association between thyroid hormone status and the 30-day mortality of HBV-ACLF. HINT, a novel prognostic score based on hepatic encephalopathy, INR, neutrophil count, and thyroid-stimulating hormone (TSH) using the deriving cohort (n=426), was significantly higher in non-survivors than survivors (1.17±2.38 vs -1.87±1.26, P<0.0001). The AUROC of HINT for 30-day mortality was 0.889, which was significantly higher than that of the Child-Pugh, MELD, CLIF-SOFA, CLIF-C ACLF, and COSSH-ACLF scores (all P<0.05). These results were confirmed in the validation cohort (n=209), except that the AUROC of HINT was comparable to that of COSSH-ACLF (P=0.357). Among thyroid hormones, only the TSH level on admission was significantly lower in non-survivors than in survivors (P=0.01). During the 14-day longitudinal observation, TSH levels increased significantly in the improvement group (P<0.001) but did not change in the deterioration or fluctuation groups, and gradually increased in survivors (P<0.001) but not in non-survivors. HINT, as a prognostic score for HBV-ACLF, is simpler than and superior to the Child-Pugh, MELD, CLIF-SOFA, and CLIF-C ACLF scores and at least comparable with the COSSH-ACLF score. Sequential TSH measurements may facilitate prediction of the clinical course of ACLF.

The effect of 17 years of increased salt iodization on the prevalence and nature of goiter in Croatian schoolchildren.

Background High goiter prevalence caused by iodine deficiency (medium content 5.6 mg potassium iodide [KI]/kg of salt, median urine iodine concentration [UIC] 68 μg/L) in Croatia was observed in 1991 and 1995 when salt was iodized with 10 mg KI/kg. A new regulation introduced in 1996, specified 25 mg KI/kg of salt resulting in an increase of median UIC to 248 μg/L. Afterwards, goiter prevalence was only assessed in two small studies. Methods In this study, we investigated the prevalence and etiology of goiter in 3594 schoolchildren 17 years after an increase in salt iodization in Croatia. Thyroid size was determined by palpation in 1777 girls and 1817 boys aged 10-18 years. In goitrous children, a thyroid ultrasound and thyroid-stimulating hormone, free thyroxine (fT4), free triiodothyronine (fT3), thyroid peroxidase (TPO) and thyroglobulin (TG) antibody measurements were performed. Results Goiter was found in 32 children (0.89% vs. 2.8% in 1991, p<0.00001 and 27% in 1995, p<0.00001), simple goiter (SG) in 18/32 (56%) goitrous children vs. 126/152 (82.8%) in 1991 p<0.00001, autoimmune thyroiditis (AT) in 13/32 (40.6%) vs. 19/152 (12.5%) in 1991 p<0.0009, nodules in four: two cysts, toxic adenoma and carcinoma (in 1991 two adenomas and one cyst), Graves' disease was not found (four in 1991). Subclinical hypothyroidism was found in three children. Thyroid disease was diagnosed in four of 32 children before the investigation. Increased iodine supply decreased goiter prevalence and SG/AT ratio in goitrous patients. Conclusions As thyroid abnormalities were found in 0.89% of children and some required treatment, thyroid examination is important in apparently healthy children regardless of sufficient iodization.

A multicenter study for the evaluation of the reference interval for TSH in Italy (ELAS TSH Italian Study)

Background The aims of this study were: (1) to calculate reliable thyroid stimulating hormone (TSH) reference intervals using laboratory databases; (2) to evaluate the relationship between TSH, sex and age values in different large Italian populations. Methods The TSH values stored in the laboratory information system of clinical laboratories of four Italian city hospitals, including 146,801 TSH measurements (with the respective age and sex data of individuals) were taken in consideration. Assuming a log-normal distribution, to log-transformed TSH values were applied the Dixon's iterative principle in order to exclude the outliers. At the end of this iterative process 142,821 log-transformed TSH results remained. The four clinical laboratories measured serum TSH concentrations using the same TSH immunoassay method (Access TSH 3rd IS, using UniCel DxI platform). Results The TSH reference interval calculated in the present study (0.362-5.280 mIU/L) is similar to that suggested by the manufacturer for the Access TSH 3rd IS assay (0.45-5.33 mIU/L). TSH values in females were significantly higher than in males (females: mean=2.06 mIU/L; standard deviation [SD]=1.26 mIU/L; n=101,243; males: mean=1.92 mIU/L; SD=1.19 mIU/L; n=41,578; p<0.0001). Moreover, a negative linear relationship was observed between TSH throughout all interval age values (from 0 to 105 years). Conclusions The results of the present multicenter study confirm that data mining techniques can be used to calculate clinically useful reference intervals for TSH. From a pathophysiological point of view, our results suggest that some Northern populations of Italy might still suffer some harmful effects on the thyroid gland due to mild to moderate iodine intake deficiency. Specific clinical trials are needed to confirm these results.

Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm.

Automated immunoassays used to evaluate thyroid function are vulnerable to different types of interference that can affect clinical decisions. This review provides a detailed overview of the six main types of interference known to affect measurements of thyroid stimulating hormone (TSH), free thyroxine (T4) and free triiodothyronine (T3): macro-TSH, biotin, antistreptavidin antibodies, anti-ruthenium antibodies, thyroid hormone autoantibodies, and heterophilic antibodies. Because the prevalence of some of these conditions has been reported to approach 1% and the frequency of testing for thyroid dysfunction is important, the scale of the problem might be tremendous. Potential interferences in thyroid function testing should always be suspected whenever clinical or biochemical discrepancies arise. Their identification usually relies on additional laboratory tests, including assay method comparison, dilution procedures, blocking reagents studies, and polyethylene glycol precipitation. Based on the pattern of thyroid function test alterations, to screen for the six aforementioned types of interference, we propose a detection algorithm, which should facilitate their identification in clinical practice. The review also evaluates the clinical impact of thyroid interference on immunoassays. On review of reported data from more than 150 patients, we found that ≥50% of documented thyroid interferences led to misdiagnosis and/or inappropriate management, including prescription of an unnecessary treatment (with adverse effects in some situations), inappropriate suppression or modification of an ongoing treatment, or use of unnecessary complementary tests such as an I123 thyroid scan. Strong interaction between the clinician and the laboratory is necessary to avoid such pitfalls.

Thyroid nodules: diagnosis and management.

Thyroid nodules are common. Their importance lies in the need to assess thyroid function, degree of and future risk of mass effect, and exclude thyroid cancer, which occurs in 7-15% of thyroid nodules. There are four key components to thyroid nodule assessment: clinical history and examination, serum thyroid stimulating hormone (TSH) measurement, ultrasound and, if indicated, fine-needle aspiration (FNA). If the serum TSH is suppressed, a thyroid scan with 99Tc can distinguish between a solitary hot nodule, a toxic multinodular goitre or, less commonly, thyroiditis or Graves' disease within a coexisting nodular thyroid. Scintigraphically cold nodules are evaluated in the same way as in the setting of normal or elevated serum TSH levels. Thyroid ultrasonography should be performed only for palpable goitre and thyroid nodules and by specialists with expertise in thyroid sonography. Routine thyroid cancer screening is not recommended, except in high risk individuals, as the detection of early thyroid cancer has not been shown to improve survival. FNA may be performed for nodules ≥ 1.0 cm depending on clinical and sonographic risk factors for thyroid cancer. FNA specimens should be read by an experienced cytopathologist and be reported according to the Bethesda Classification System. Molecular analysis of indeterminate FNA samples has potential to better discriminate benign from malignant nodules and thus guide management. Surgery is indicated for FNA findings of malignancy or indeterminate cytology when there is a high risk clinical context. Surgery may also be indicated for suspicion of malignancy; larger nodules, especially with symptoms of mass effect; and in some patients with thyrotoxicosis.

Thyroid cancer management: from a suspicious nodule to targeted therapy.

Thyroid nodules are very common, and their frequency is four to five times higher in women than in men. Most of them are benign, with only a very little percentage revealing a malignant neoplasm. About 50% of thyroid nodules are detected by self-palpation of neck, whereas the other 50% are diagnosed by neck ultrasonography and following fine-needle aspiration. Management of thyroid nodules is very difficult, because benign nodules are prevalent, whereas thyroid carcinoma is uncommon, representing only 1% of all malignancies. A standard diagnostic approach is represented by 'first-level' exams, consisting in neck ultrasonography and serum thyroid-stimulating hormone measurement, followed, only for nodules that are suspicious of malignancy, by 'second-level' exams, consisting of fine-needle aspiration and mutational test, which does detect particular DNA mutations present only in malignant cells. In this review, we will analyze the genetics of thyroid cancer and its heterogeneity, and we will briefly describe the current available diagnostic and therapeutic approaches.

Smoking Is Positively Associated with Antithyroperoxidase Antibodies and Antithyroglobulin Antibodies in Populations with Mildly Deficient Iodine Intake.

To evaluate the relationship between smoking and both antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) positivity in subjects from Panshan, Zhangwu, and Huanghua with mildly deficient, more than adequate, and excessive iodine intake, respectively. Smoking-related data were collected by questionnaire, and laboratory measurements of TPOAb, TgAb, and thyrotropin (TSH) were determined at baseline and follow-up. (1) A 1.48-fold increased risk of TPOAb positivity was found in smokers than in non-smokers after adjusting for confounders (age, sex, and areas) (OR[95% CI] = 1.48[1.12-1.95], p = 0.01). (2) Among female subjects, the prevalence of thyroid autoantibodies in smokers was increased than that in non-smokers in Panshan, Zhangwu, and Huanghua (TPOAb): 16.79 vs. 8.89%, 14.14 vs. 11.09%, 19.53 vs. 9.57%; TgAb 15.32 vs. 9.29%, 12.79 vs. 11.94%, 17.19 vs. 10.55%, respectively). The difference was significant in Panshan after adjusting for age. (3) Female long-term smokers (> 20years) had an increased frequency of thyroid autoantibody positivity than non-smokers after adjusting for confounders (TPOAb OR[95% CI] = 1.60[1.10-2.34]; TgAb OR[95% CI] = 1.31[0.88-1.94]). (4) There was no difference in the incidence of thyroid autoantibodies among non-smokers, new smokers, and long-term smokers at follow-up. (5) TSH was greater in TPOAb-positive subjects than in seronegative smokers (1.56 vs. 1.20mU/L, p < 0.001) and non-smokers (1.97 vs. 1.58mU/L, p < 0.001). However, TSH was also greater in non-smokers than in smokers, regardless of whether subjects were positive (1.97 vs. 1.56mU/L, p = 0.04) or negative (1.58 vs. 1.20mU/L, p < 0.001) for TPOAb. Long-term smoking could increase the prevalence of thyroid autoantibodies in a population with mildly deficient iodine intake. TSH levels were lesser in smokers than in non-smokers and greater in subjects with thyroid autoantibody positivity than in seronegative subjects. The influence of smoking on TSH levels was independent of thyroid autoantibody levels.

Prognostic Value of Thyroid Hormone Ratios in Patients With Advanced Metastatic Colorectal Cancer Treated With Regorafenib: The TOREADOR Study

BackgroundThe impact of free triiodothyronine (FT3)/free thyroxine (FT4) ratio on survival in hospitalized geriatric patients was recently described. Up today, there are no data regarding the prognostic role of FT3/FT4 ratio in patients with advanced cancer. We evaluated the impact of FT3/FT4 ratio on survival in patients with refractory colorectal cancer (CRC) treated with regorafenib. MethodsPatients with metastatic CRC treated with regorafenib with available clinical data and baseline measurement of FT3, FT4, and thyroid-stimulating hormone (TSH) were considered eligible. Exploratory analyses included subjects treated at Istituto Oncologico Veneto. A confirmatory analysis was planned based on FT3/FT4 ratio tertile results, and a validation cohort was built on data retrieved from University of Cagliari. ResultsIn an exploratory cohort, the median overall survival in patients with low, intermediate, and high FT3/FT4 ratios, according to tertiles' value, was 4.8, 5.0, and 7.6 months, respectively (P = .003). The differences were significant in the multivariate model (hazard ratio, 0.43; 95% confidence interval, 0.28-0.68; P = .0003). Confirmatory results were obtained in a validation cohort, both in univariate (P = .0002) and in multivariate (hazard ratio, 0.56; 95% confidence interval, 0.36-0.88; P = .0118) models. ConclusionsHigh baseline FT3/FT4 ratio is strongly associated to better outcome in patients with progressive metastatic CRC treated with regorafenib. Further investigations are ongoing to draw definitive conclusions regarding a potential predictive effect.

Hypothyroidism-when and how to treat?

The diagnosis of hypothyroidism is primarily based on clinical signs and symptoms as well as measurement of thyroid-stimulating hormone (TSH) concentration. Subclinical hypothyroidism is characterized by elevated TSH with normal serum free thyroxine (fT4) and triiodothyronine (fT3) levels, while in manifest hypothyroidism serum fT4 and fT3 levels are reduced. Common causes of primary hypothyroidism are autoimmune thyroiditis as well as therapeutic interventions, such as thyroid surgery or radioiodine therapy. Signs and symptoms of hypothyroidism include fatigue, bradycardia, constipation and cold intolerance. In subclinical hypothyroidism, symptoms may be absent. Initiation of levothyroxine (T4) therapy not only depends on the level of TSH elevation, but also on other factors, such as patient age, presence of pregnancy or comorbidities. Treatment of patients with subclinical hypothyroidism is still acontroversial topic. In general, thyroid hormone replacement therapy in non-pregnant adults ≤ 70years is clearly indicated if the TSH concentration is >10 mU/l. Standard of care for treatment of hypothyroidism is T4 monotherapy. The biochemical treatment goal for T4 replacement in primary hypothyroidism is aTSH level within the reference range (0.4-4.0 mU/l). In contrast, in secondary hypothyroidism, serum fT4 levels are the basis for adjusting thyroid hormone dosage. Inadequate replacementofT4 resulting in subclinical or even manifest hyperthyroidism should urgently be avoided. T4/liothyronine (T3) combination therapy is still amatter of debate and not recommended as standard therapy, but may be considered in patients with persistence of symptoms, despite optimal T4 treatment, based on expert opinion.

Neural and Endocrinal Pathobiochemistry of Vitiligo: Comparative Study for a Hypothesized Mechanism.

The etiology of vitiligo is still unclear. The aim is to investigate a neural and hormonal etio-pathology of vitiligo. Sixty acrofacial vitiligo patients were divided into two subgroups as active vitiligo patients group (AVPs; n = 35) and stable vitiligo patients group (SVP; n = 25). Forty healthy subjects without any systemic or dermatological disease were used as controls. Blood samples were collected, and the samples were used for measurement of free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), cortisol, estrogen, testosterone, melatonin, and prolactin levels by ELISA, while norepinephrine (NE), epinephrine (Epi), dopamine (DA), homo-vanillic acid (HVA), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) by high-pressure liquid chromatography. The current results showed a significant increase in plasma levels of Epi, NE, DA, HVA, serotonin, 5-HIAA, melatonin, and in serum level of TSH and prolactin either in SVP or AVP groups than the control group and in AVP than SVP group. The serum levels of fT3 and fT4 were significantly decreased either in SVP or AVP groups than the control group. A significant increase in estradiol levels was observed in females within AVP than females in either SVP or control groups. There was a significant increase in serum level of cortisol in AVP than either SVP or control group. There was a significant decrease in serum level of ACTH in either AVP or SVP than control and in AVP than SVP group. In conclusion, there are some neural and endocrine markers that play a pivotal role in pathogenesis and/or consequences of vitiligo. The abnormally disturbed levels of theses markers lead to melanocyte destruction and/or depigmentation.

Low thyroid function is not associated with an accelerated deterioration in renal function.

Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups. Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models. A total of 72856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function. Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.