Thyroid Hormone Substitution Research Articles

Diagnosing and management of thyroid nodules and goiter - current perspectives.

Due to the frequent diagnosis of benign thyroid nodules, it is necessary to deviate from the traditional paradigm based on frequent surgical treatment. This article highlights the evolution of diagnosis and treatment in recent years, beginning from standardization of ultrasound assessment of nodules and cytology results to minimally invasive techniques to reduce the size of symptomatic thyroid nodules. These achievements reduce the number of surgeries, enable more individualized care for patients with benign thyroid disease, reduce long-term complications, and promote cost-effectiveness within healthcare systems. Furthermore, although the use of minimally invasive techniques significantly decreases thyroid nodule volume, the thyroid nodule usually does not disappear and the challenges in this field are discussed (the efficacy of thermal ablation, a variable part of thyroid nodules that remains viable after thermal ablation, some of the nodules treated with thermal ablation may require a second treatment over time and the efficacy of thermal ablation in nodules with different phenotypes). However, although surgery still represents the "gold standard" for establishing the final histopathologic diagnosis, it is associated with lifelong thyroid hormone substitution need and serious complications in rare cases. Therefore, it should represent the ultima ratio only after a detailed diagnostic procedure. In the future, artificial intelligence-assisted programs for the evaluation and management of nodules are expected.

Is thyroid function testing necessary in all cases of new onset atrial fibrillation diagnosed in the emergency department? - a real-life study

Abstract Background Atrial fibrillation/flutter (AF) is the most frequent cardiac arrhythmia worldwide. It increases the risk for comorbidities and prompt management is thus important. One established risk factor for AF development is hyperthyroidism, and concomitant disease significantly impacts morbidity in these patients. Therefore, thyroid function testing is recommended in new-onset AF (NOAF) by the European Society of Cardiology. There are few studies examining the prevalence of previously undiagnosed hyperthyroidism in cases of NOAF, especially if diagnosed in the emergency department (ED). Furthermore, previous studies often relied upon thyroid stimulating hormone (TSH) levels to identify cases of hyperthyroidism, this approach is susceptible for diagnostic errors since TSH profiles can overlap in conditions like hyperthyroidism, non-thyroid illness, and central hypothyroidism (of which only the former is associated with AF). Because of this, it's essential to incorporate additional biomarkers for a more precise differentiation. Purpose We aim to evaluate the prevalence of previously undiagnosed hyperthyroidism in a real-life NOAF population admitted to and diagnosed in the ED with a 2.5-years follow-up. Furthermore, we aim to interpret thyroid dysfunctions in relation to TSH as well as free thyroid hormone levels and other relevant biomarkers. Methods This retrospective registry-based cohort study included all patients attending the ED at a medium-sized hospital in Sweden during 2018 and 2020. Inclusion criteria: main diagnosis of AF (ICD I48) and ≥18 years old. Exclusion criteria: multiple visits, previous AF, abnormal thyroid function within the previous 2 years, and current thyroid hormone substitution. Results Patients from a total of 1020 ED visits were screened for eligibility. After exclusion, 325 patients with NOAF were included in the analysis. Of those, 106 (33%) and 232 (71%) had undergone thyroid function testing in the ED and by the end of the 2.5-years follow-up, respectively. We found no cases of hyperthyroidism in the ED and only two cases (1% prevalence) during the 2.5-years follow-up. Conclusions In this real-life cohort we found modest thyroid testing rates in the ED, however, a majority of patients underwent testing during follow-up. Despite this, we found no cases of hyperthyroidism in the ED and only two cases during follow-up, this is considerably lower than previously reported and may raise a question whether all patients should undergo thyroid testing, or if thyroid testing should be directed towards those with a suspected thyroid disease.

Thyroidectomy for Euthyroid Patients with Hashimoto Disease and Persistent Symptoms: An Observational, Postrandomization Study.

Despite adequate hormone substitution in Hashimoto disease, some patients may have persistent symptoms with a possible autoimmune pathophysiology. A recent randomized trial (RCT) using patient-reported outcome measures as the primary endpoint showed benefit in total thyroidectomy, but at a cost of high complication rates. To verify results from the RCT in an observational study including a wider range of patients and explore means of predicting who may benefit from such surgery. A total of 154 patients with Hashimoto disease, euthyroid with or without thyroid hormone substitution, and persistent Hashimoto-related symptoms were subjected to total thyroidectomy and followed for 18 months after surgery. The primary outcome was the General Health (GH) dimensional score in the Short Form-36 Health Survey (SF-36). Eighteen months after surgery, a clinically significant improvement in GH was seen, similar to the findings in the previous RCT. Anti-TPO antibody titers were markedly reduced after surgery, but preoperative titers or other preoperative parameters could not predict the outcome of surgery. Three (1.9%) of 154 patients experienced permanent unilateral recurrent nerve palsy and six (3.9%) experienced hypoparathyroidism after surgery. Thyroidectomy had a beneficial symptom-reducing effect in euthyroid patients with Hashimoto disease and persistent symptoms. The pathophysiology of residual symptoms remains unclear, and surgical complication rates are high. If thyroidectomy is considered as a treatment option, it should be performed in dedicated centers with experienced endocrine surgeons and as part of further studies on persistent symptoms. This trial is registered with NCT-02319538.

The dangerous trend of levothyroxine medicalization

Thyroid hormone replacement is paramount in overt hypothyroidism; recently, however, thyroid hormone substitution is increasingly prescribed to patients with normal thyroid hormone levels. This forum article discusses the complex causes and the possible negative effects of overusing thyroid hormone replacement drugs.

Intelligence quotient (IQ) outcome in children with early-treated congenital hypothyroidism: a systematic review and meta-analysis

Background Congenital hypothyroidism (CH) is the most common congenital endocrine disorder in childhood and is one of the most preventable causes of intellectual disability (ID). Late initiation of thyroid hormone substitution therapy has a negative impact on intellectual abilities in CH patients.
 Objective To compare Intelligence Quotient (IQ) between children with CH who underwent early treatment among the children without CH.
 Methods We performed online literature searches of ScienceDirect, Pubmed, Cochrane Library, and Google Scholar. We included clinical studies that examined IQ scores in patients with early-treated CH and without CH. Review Manager 5.4 was used to perform the meta-analysis.
 Results Twelve studies comparing pediatric patients with and without CH were included in this meta-analysis, for a total of 808 patients. Based on data analysis, IQ levels of verbal IQ [mean difference (MD) -9.05; (95%CI -14.51 to -3.59); (P<0.00001)], performance IQ [MD -11.70; (95%CI -17.41 to -5.99); (P<0.00001)], and total IQ [MD -10.78; (95%CI -14.03 to -7.54); (P<0.00001)]. While verbal, performance, total, of the early-treated CH group were within the normal range, they were each significantly lower than those in the non-CH group.
 Conclusion This meta-analysis reveals that IQ scores in early-treated CH subjects were within normal limits, but significantly lower than that of normal controls.

Einfluss der traumazentrierten Psychotherapie mit EMDR-Therapie auf somatische Komorbiditäten

Results of modern research show a relationship between emotional stress and the occurrence of autoimmune diseases as a comorbidity. The authors use EMDR therapy (Eye Movement Desensitization and Reprocessing) to treat trauma disorders. They wondered whether and to what extent this treatment also affects autoimmune processes. Parallel to the trauma-focused psychotherapy with EMDR, the thyroid hormone substitution dose was documented in patients with active Hashimoto's autoimmune thyroiditis requiring substitution. Hashimoto's autoimmune thyroiditis had already been diagnosed by a specialist and drug treatment had been initiated before starting outpatient psychotherapy. So far in five cases a decrease in autoimmune activity and a stability of the results in the follow-up between six months and one year could be observed. It is now necessary to examine whether these results can be confirmed in a larger number of patients and a diversity of therapists and whether these observations can be transferred to other somatic comorbidities.

Bone Turnover in Relation to Thyroid-Stimulating Hormone in Hypothyroid Patients on Thyroid Hormone Substitution Therapy.

Background Bone turnover markers (BTMs) have emerged as a useful tool for monitoring bone remodeling activity in the skeleton, and their serum levels correlate with bone loss rates in osteoporotic and normal individuals. Whether the same holds for other metabolic bone diseases is still subject to discussion. Methods We analyzed the relation between levels of BTMs and TSH in 79 females on thyroid hormone substitution therapy for hypothyroidism. Based on the reference range for TSH (0.2–4.0 mU/L) in our lab, we assessed BTMs in five different groups of patients based on the following criteria: (1) hypothyroidism (TSH >4.0); (2) TSH in the high normal range (1.0–4.0); (3) TSH in the low normal range (0.2–1.0); (4) TSH below the normal range (0.01–0.2); (5) TSH undetectable (<0.01). We studied the relationship between TSH and four different bone markers: procollagen type 1 N-terminal propeptide (PINP), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin (OC), and bone specific alkaline phosphatase (BSAP). In a subgroup of patients, bone mineral density was assessed by a DXA scan. Results PINP emerged as the most sensitive and dynamic BTM for assessment of bone turnover in this patient group, achieving significant rho values on nonparametric correlation analysis for both TSH (rho −0.47; p=0.0001) and FT4 (rho 0.27; p=0.018). CTX and OC also revealed significant correlations to TSH, albeit with lower rho values (−0.37 and −0.24, respectively). Categorical analysis showed that bone turnover increased significantly, albeit with pronounced interindividual variability for TSH values below the lower limit of normal (0.2 mU/l), with the most severe affected being women exhibiting suppression of TSH. Further analysis of loss rates by DXA in a limited subgroup of patients showed that this was accompanied by accelerated bone loss. Conclusion PINP is the most sensitive marker of bone turnover in thyroid disorders. TSH values below the lower limit of normal are associated with increased bone turnover and accelerated bone loss, however, with pronounced interindividual variations. Assessment of PINP may be a valuable tool in cases where there is concern about possible adverse effects of thyroid hormone substitution therapy on bone.

Use of thyroid hormones in hypothyroid and euthyroid patients: a THESIS* survey of Belgian specialists *THESIS: treatment of hypothyroidism in Europe by specialists: an international survey

BackgroundHypothyroidism is a topic that continues to provoke debate and controversy with regards to specific indications, type of thyroid hormone substitution and efficacy. We investigated the use of thyroid hormones in clinical practice in Belgium, a country where currently only levothyroxine (LT4) tablet formulations are available.MethodMembers of the Belgian Endocrine Society were invited to respond to an online questionnaire. Results were compared with those from other THESIS surveys.ResultsEighty (50%) of the invited 160 individuals, completed the questionnaire. LT4 was the first treatment of choice for all respondents. As secondary choice, some also prescribed liothyronine (LT3) and LT4 + LT3 combinations (2 and 7 respondents, respectively). Besides hypothyroidism, 34 and 50% of respondents used thyroid hormones for infertile euthyroid TPOAb positive women and the treatment of a growing non-toxic goiter, respectively. Had alternative formulations of LT4 to tablets been available (soft gel or liquid L-T4), 2 out of 80 (2.5%) participants would consider them for patients achieving biochemical euthyroidism but remaining symptomatic. This proportion was higher in case of unexplained poor biochemical control of hypothyroidism (13.5%) and in patients with celiac disease or malabsorption or interfering drugs (10%). In symptomatic euthyroid patients, 20% of respondents would try combined LT4 + LT3 treatment. Psychosocial factors were highlighted as the main contributors to persistent symptoms.ConclusionsLT4 tablets is the preferred treatment for hypothyroidism in Belgium. A minority of the respondents would try combined LT4 + LT3 in symptomatic but biochemically euthyroid patients. Thyroid hormones are prescribed for euthyroid infertile women with thyroid autoimmunity and patients with non-toxic goiter, a tendency noted in other European countries, despite current evidence of lack of benefit.

More Live Births in Primary Subfertile Intracytoplasmic Sperm Injection-Treated Women with High Normal TSH Levels

Objectives: The aim of this study was to analyze the fertility outcome in intracytoplasmic sperm injection (ICSI)-treated women across normal range thyroid-stimulating hormone (TSH) levels. Published results are inconclusive about optimal TSH levels and fertility. Design: This is a retrospective cohort study in 752 ICSI-treated women with predominantly severe male factor subfertility, starting treatment between the first of January 2008 and the first of March 2012 with a follow-up until 2014. Participants/Materials, Setting, Methods: Women aged 22–45 years with TSH 0.3–4.5 mIU/L without thyroid hormone substitution were included in Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands, an iodine-sufficient area. Demographic and baseline characteristics were compared between groups of patients based on TSH, using one-way ANOVA, Kruskal-Wallis ANOVA, and χ² test. The patient was the unit of analysis: all cumulative cycles per patient were analyzed up to and including the first ongoing pregnancy. The primary outcome was a cumulative live birth rate. Clinical pregnancy rate, pregnancy loss, and ongoing pregnancy rate were secondary outcomes. The χ² test and logistic regression were used to compare interquartile groups while adjusting for confounders. Logistic regression was used with the natural logarithm of TSH as a continuous predictor. Primary and secondary subfertile women were analyzed separately. Results: Analysis of the total cohort (n = 752) showed no difference in fertility outcomes across the normal TSH range. The cumulative live birth rate for the 4 groups of primary subfertile women (n = 455) was 76% in the upper TSH quartile compared to 56%, 60%, and 59% in the lower TSH quartiles. Limitations: Levels of thyroxine and presence of thyroid autoimmunity were not measured in this retrospective cohort study. Conclusions: The observation that a higher live birth rate was found in primary subfertile ICSI-treated women with high but allegedly normal TSH levels contributes to the hypothesis that in certain subfertile women in addition to a male factor, female factors such as subtle hypothyroidism and/or thyroid autoimmunity may play a role in keeping them from conception, which can be overcome by the process of ICSI.

Management of adenomas and toxic multinodular goiters with Iodine 131

In accordance with all the guidelines of the various international scientific societies, treatment using radioiodine (RAI) of autonomous toxic adenomas and toxic multinodular goiters is highly recommended and its effectiveness its efficacy has now been widely demonstrated and established. RAI treatment is effective to normalise thyroid function, remove functional autonomy and reduce thyroid volume. According to published data on several thousand patients treated with RAI, the success rates ranges between 85% and 100%. Moreover, with more than 70 years of experience, this treatment does not present any particular risk for patients. However, as regards pregnancy, there are no absolute contra-indications to radioiodine treatment. To date, these results include a relatively high rate of hypothyroidism in the long term and approximately one patient out of five treated, will require thyroid hormone substitution. It would be more effective to harmonise and work up on dosimetric personalized models allowing the calculation of the effective dose to be delivered to the autonomous nodule to be treated while preserving the normal thyroid parenchyma in order to optimise the patient's outcome and to favor extensive euthyroidism.

Thyroid hormone therapy in old age

There is evidence that the treatment of overt hyperthyroidism with thyroid hormones is able to reduce mortality as well as cardiovascular and musculoskeletal morbidity. It remains unclear whether these data can be extrapolated to the mildest form of hypothyroidism, subclinical hypothyroidism. Furthermore, it is uncertain whether and to what extent the threshold for therapeutic intervention needs to be modified in the elderly, in whom hypothalamo-pituitary regulation is increasingly insensitive to the negative feedback by thyroid hormones and the patients' response to thyroid hormones changes. The aim of this review is to evaluate the current evidence on the treatment of hypothyroidism in old age with regard to the initiation of therapy and the therapeutic goals. According to new original data and meta-analyses, therapy with thyroid hormones does not alter morbidity and mortality in patients with subclinical hypothyroidism with thyroid stimulating hormone (TSH) below the range of 7-10 mU/l. These data support the TSH threshold of 10 mU/l recommended in guidelines, particularly in elderly patients over the age of 65years, in whom TSH serum levels increase with age. In contrast to the recommendations, the prescription of thyroxine more than doubled in alarge study from Denmark and TSH levels decreased from 10 mU/l to under 7 mU/l between 2001 and 2015. As (the primarily unspecific) symptoms and quality of life are not altered by thyroxine replacement in studies on subclinical hypothyroidism and elderly patients are more susceptible to side effects, thyroid hormone substitution should generally not be started at TSH levels <10 mU/l.

Effect of delayed diagnosis and treatment of congenital hypothyroidism on intelligence and quality of life: an observational study

BACKGROUND Congenital hypothyroidism is one of the most prevalent, albeit preventable causes of intellectual disability. This study determined the intellectual outcome and health-related quality of life (QoL) in children and adolescents clinically diagnosed with congenital hypothyroidism and the associations among age of starting thyroid hormone treatment, current free thyroxine (FT4) level, intelligence quotient (IQ), and QoL.METHODS Intelligence (Wechsler scales) and QoL (PedsQLTM 4.0 parent proxy-report) tests were administered to 25 patients with congenital hypothyroidism in the pediatric clinic of Cipto Mangunkusumo Hospital, Jakarta. Nineteen patients underwent thyroid ultrasonography or scintigraphy to determine the etiology of congenital hypothyroidism.RESULTS A total of 25 patients with the median age of 9 (5.5–12.5) years were recruited. Eighteen patients had a total IQ of &lt;70. The age of treatment initiation did not correlate with full scale IQ (FSIQ) (r = −0.261, p = 0.071) and verbal IQ (VIQ) (r = −0.232, p = 0.265). The late initiation of treatment was correlated with lower performance IQ (PIQ) (r = −0.325, p = 0.025). The higher current FT4 levels was correlated with higher scores ofFSIQ (r = 0.314, p = 0.046) and PIQ (r = 0.320, p = 0.043). The late initiation of treatment (r = 0.006, p = 0.980) and higher current FT4 levels (r = 0.246, p = 0.310) were not correlated with QoL. Hemiagenesis of thyroid gland was the most common etiology.CONCLUSIONS The late initiation of thyroid hormone substitution in patients with congenital hypothyroidism negatively affects intellectual abilities.

Review shows that thyroid hormone substitution could benefit transient hypothyroxinaemia of prematurity but treatment strategies need to be clarified.

Thyroid hormones are crucial for foetal and neonatal brain development. This paper provides an overview of the normal role of thyroid hormones in foetal brain development and the pathophysiology of transient hypothyroxinaemia of prematurity (THOP). It also discusses the diagnostic and therapeutic controversies around THOP and looks at directions for future research. We used the PubMed and Embase databases to identify papers published in English from 1969 to June 2018. This identified 20 papers about the impact of THOP on neurodevelopment and seven randomised controlled trials about therapeutic approaches from 1981-2016. THOP has been researched for more than three decades. The impact of temporarily low thyroxine levels, without any increase in pituitary-secreted thyroid-stimulating hormone at a critical timeframe in an infant's brain development, is still debated. Heterogeneity in THOP definitions, difficulties with thyroid hormone assessment, identifying patients at risk and a clear lack of sufficiently powered studies add to the current controversy. There are indications that thyroid hormone substitution might be useful in extremely low gestational age neonates with THOP. Some preterm infants could benefit from THOP treatment, but more studies are needed to clarify further treatment strategies, including the optimal timing of initiation and duration.

Live birth rate after intrauterine insemination is not different between women with lower quartile versus higher quartile normal range thyroid stimulating hormone levels.

STUDY QUESTIONDoes lower quartile normal range thyroid stimulating hormone (TSH) compared to higher quartile normal range in women without thyroid hormone substitution affect live birth rate after a complete IUI treatment series?SUMMARY ANSWERLower quartile normal range TSH, in women without thyroid hormone substitution, does not affect live birth rate after a complete intrauterine insemination treatment series compared to higher quartile normal range TSH.WHAT IS KNOWN ALREADYTSH is historically seen as the most sensitive test for thyroid function. Its distribution is right-skewed. Whether the preconceptional upper reference TSH values in subfertile women should be 2.5 or 4.5 mIU/L is under debate. Studies have shown that IUI patients treated with levothyroxine for TSH levels above 2.5 mIU/L show higher pregnancy rates. However, no adverse outcome is associated with untreated high normal TSH levels studied in first IUI cycles. Thyroid peroxidase antibodies have also impaired outcomes in some studies whereas others have shown an effect only in combination with high normal TSH levels. As a subgroup, patients with unexplained infertility showed increased levels of TSH. This article adds to the value of TSH evaluation and fertility outcome in four quartiles and in the context of a completed IUI treatment modus of a maximum of six inseminations.STUDY DESIGN, SIZE, DURATIONThis is a retrospective cohort study in 909 women undergoing 3588 IUI cycles starting treatment between the first of January 2008 and the first of March 2012.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen aged 22–45 years with TSH 0.3–4.5 mIU/L without thyroid hormone substitution were included at Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands, an Iodine-sufficient area. The primary endpoint was live birth. Clinical pregnancy, pregnancy loss and ongoing pregnancy were secondary endpoints. Logistic regression was used with the natural logarithm of TSH as a continuous predictor. Chi-square tests and logistic regression were used to compare groups of patients based on TSH values in four quartile TSH groups (0.3–1.21 mIU/L; 1.22–1.75 mIU/L; 1.76–2.34 mIU/L; 2.35–4.5 mIU/L) on basic characteristics and on the endpoints while adjusting for confounders.MAIN RESULTS AND THE ROLE OF CHANCEAnalysis with the natural logarithm of TSH as a continuous variable showed no association with live birth, pregnancy chance or pregnancy loss. There were no differences in any of the outcomes across the quartile TSH level ranges after regression analysis before and after adjusting for age, BMI, use of alcohol, tobacco, use or gonadotrophins, sperm count, diminished ovarian reserve, unexplained infertility and primary or secondary subfertility.The distribution of primary and secondary subfertility and smoking characteristics were remarkably different across the four groups, with proportionally the lowest prevalence of primary subfertility and the highest rate of smoking in the lowest TSH group (0.3–1.20 mIU/L).LIMITATIONS, REASONS FOR CAUTIONUnknown values of free thyroxine and thyroid peroxidase antibodies, as well as the retrospective character of the study, limit the clinical interpretability.WIDER IMPLICATIONS OF THE FINDINGSTSH in the highest quartile range (2.35–4.5 mIU/L) in subfertile women preceding IUI is not associated with a lower live birth rate or rate of clinical and ongoing pregnancy, or with loss of pregnancies, compared to subfertile women with TSH in the lower three quartile groups after complete intrauterine insemination treatment.STUDY FUNDING/COMPETING INTEREST(s)The department of Obstetrics and Gynaecology, division of Reproductive Medicine, and of Internal Medicine, division of Endocrinology provided support. There are no competing interests.TRIAL REGISTRATION NUMBERN/A.

Interactions between hypothalamic pituitary thyroid axis and other pituitary dysfunctions.

Central hypothyroidism is defined as low circulating free thyroxine (free T4) with inappropriately low circulating thyrotropin (TSH), in context of a hypothalamic pituitary pathology. Rare cases of idiopathic central hypothyroidism caused by a functional defect may occur, and the condition is often overlooked due to difficulty in achieving the correct diagnosis, sparse symptomatology of the condition and a high risk of misinterpretion of the biochemical changes in central hypothyroidism. Central hypothyroidism is mainly seen in patients with hypothalamic-pituitary pathology due to one of many possible aetiologies, where other hormone deficiencies often co-exist, and both the presence of other deficiencies and their replacement have a strong influence on the measurement of the thyroid-related hormones and thereby interpretation of the thyroid function variables in relation to the clinical impact of thyroid hormone substitution therapy. Conversely, lack of thyroid hormone has a similar strong influence on the interpretation of other pituitary hormone axes, as well as their replacement. Undertreating patients with central hypothyroidism may have serious metabolic consequences with a potentially increased risk of cardiovascular morbidity. The present review thus aims at describing central hypothyroidism, by an overview of interactions of hypothyroidism with other pituitary hormones, diagnosing/testing for central hypothyroidism, and focusing on consequences of undertreatment. Finally, it is mentioned how to deal with new diagnostic settings with lower a priori likelihood of hypopituitarism, particularly in view of the importance of stringent diagnostic testing in order to avoid overdiagnosing central hypothyroidism.

Maternal thyroid hormone is required for parvalbumin neurone development in the anterior hypothalamic area.

Thyroid hormone (TH) is crucial for brain development and function. This becomes most evident in untreated congenital hypothyroidism, leading to irreversible mental retardation. Likewise, maternal hypothyroxinaemia, a lack of TH during pregnancy, is associated with neurological dysfunction in the offspring, such as autism and reduced intellectual capacity. In the brain, TH acts mainly through TH receptor α1 (TRα1). Consequently, mice heterozygous for a dominant-negative mutation in TRα1 display profound neuroanatomical abnormalities including deranged development of parvalbumin neurones. However, the exact timing and orchestration of TH signalling during parvalbumin neurone development remains elusive. In the present study, we dissect the development of parvalbumin neurones in the anterior hypothalamic area (AHA) in male mice using different mouse models with impaired pre- and postnatal TH signalling in combination with bromodeoxyuridine birth dating and immunohistochemistry. Our data reveal that hypothalamic parvalbumin neurones are born at embryonic day 12 and are first detected in the AHA at postnatal day 8, reaching their full population number at P13. Interestingly, they do not require TH postnatally because their development is not impaired in mice with impaired TH signalling after birth. By contrast, however, these neurones crucially depend on TH through TRα1 signalling in the second half of pregnancy, when the hormone is almost exclusively provided by the mother. For the first time, our findings directly link a maternal hormone to a neuroanatomical substrate in the foetal brain, and underline the importance of proper TH signalling during pregnancy for offspring mental health. Given the role of hypothalamic parvalbumin neurones in the central control of blood pressure, the present study advocates the inclusion of cardiovascular parameters in the current discussion on possible TH substitution in maternal hypothyroxinaemia.

The Role of Thyroid Dysfunction and The Importance of Conducting Regular Thyroid Function Tests in patients with PCOS: A Narrative Review

Polycystic Ovary Syndrome (PCOS) and thyroid pathology, the two endocrine abnormalities have been connected to each other since quite a long while, however, the majority of the scientists have researched the relationship amongst hypothyroidism and PCOS, a backward relationship of PCOS prompting thyroid brokenness is presently being tested into. Consequently this investigation went for investigating the likelihood of improvement of thyroid brokenness in ladies with PCOS. Thyroid hormones effectively affect the regenerative arrangement of the human female. Modification in thyroid capacity, especially hypothyroidism, can cause ovulatory brokenness and prompt impeded female richness. Hypothyroidism and PCOS are frequently joined by expanded serum free testosterone, luteinizing hormone (LH) and elevated cholesterol. At the point when the ovaries of hypothyroid women with PCOS have seen with an ultrasound, an expansion in ovarian volume and the presence of reciprocal multicystic ovaries are frequently obvious. At the point when thyroid hormone substitution treatment is started, notwithstanding settling thyroid hormone levels, ovarian sores relapse and ovarian volume are diminished. In this way ladies with PCOS could be at a hazard for the advancement of thyroid issue and biochemical screening of all the thyroid parameters including that of thyroid autoantibodies is of most extreme significance in such people.

Thyroid emergencies : Thyroid storm and myxedema coma

Thyroid emergencies are rare life-threatening endocrine conditions resulting from either decompensated thyrotoxicosis (thyroid storm) or severe thyroid hormone deficiency (myxedema coma). Both conditions develop out of along-standing undiagnosed or untreated hyper- or hypothyroidism, respectively, precipitated by an acute stress-associated event, such as infection, trauma, or surgery. Cardinal features of thyroid storm are myasthenia, cardiovascular symptoms, in particular tachycardia, as well as hyperthermia and central nervous system dysfunction. The diagnosis is made based on clinical criteria only as thyroid hormone measurements do not differentiate between thyroid storm and uncomplicated hyperthyroidism. In addition to critical care measures therapy focusses on inhibition of thyroid hormone synthesis and secretion (antithyroid drugs, perchlorate, Lugol's solution, cholestyramine, thyroidectomy) as well as inhibition of thyroid hormone effects in the periphery (β-blocker, glucocorticoids).Cardinal symptoms of myxedema coma are hypothermia, decreased mental status, and hypoventilation with risk of pneumonia and hyponatremia. The diagnosis is also purely based on clinical criteria as measurements of thyroid hormone levels do not differ between uncomplicated severe hypothyroidism and myxedema coma. In addition to substitution of thyroid hormones and glucocorticoids, therapy focusses on critical care measures to treat hypoventilation and hypercapnia, correction of hyponatremia and hypothermia.Survival of both thyroid emergencies can only be optimized by early diagnosis based on clinical criteria and prompt initiation of multimodal therapy including supportive measures and treatment of the precipitating event.

Does thyroid dysfunction increase the risk of breast cancer? A systematic review and meta-analysis.

To investigate the relationship between hypothyroidism, hyperthyroidism, thyroid hormone replacement, and the risk of breast cancer. We searched the PubMed, Cochrane Library, EMbase, Web of Science, and China Biology Medicine (CBM) databases through June 2016 to identify researches that assessed the relationship between thyroid dysfunction and the risk of breast cancer together with the impact of thyroid hormone substitution treatment on incidence of breast cancer. Quality of evidence was assessed per outcome, using GRADE. A total of 13 population-based studies including 24,808 participants were identified as eligible for this meta-analysis. A meta-analysis of 12 researches illustrated that hypothyroidism was not related to the risk for breast cancer [odds ratio (OR)=0.83, 95% confidence interval (CI) 0.64-1.08, P=0.162]. 10 researches illustrated that hyperthyroidism was also not related to the risk of breast cancer (OR=1.03, 95% CI 0.83-1.30, P=0.767). The impact of therapy was evaluated in six researches; there was no proof of a relationship between thyroid hormone substitution treatment and breast cancer with an overall OR of 0.83 (95% CI 0.57-1.21, P=0.965). Our meta-analysis illustrated that thyroid dysfunction may not be related to increased risk of breast cancer as well as the thyroid hormone substitution treatment did not reduce the incidence of breast cancer; while this study has some confounders that might weaken the results of this meta-analysis, we believe that the findings provide valuable information for stakeholders concerned with outcomes in patients with thyroid dysfunction.

Thyroid disorders are associated with impaired response to psychopharmacological treatment of major depression

Introduction: The association of thyroid disorders (TDs) and mood disorders is a well-investigated empirical finding. Although TDs are highly prevalent in patients with major depression (MD), the impact of TDs on treatment outcome has been sparsely investigated. Methods: Treatment Response was analyzed in 704 in-patients with MD participating in the Munich Antidepressant Response Signature (MARS) project, a large observational naturalistic psychopharmacological treatment study. TD was defined by thyroid hormone substitution, morphological thyroid gland abnormalities, or thyroid autoimmunity. Treatment response was measured by weekly Hamilton Depression Rating Scale (HDRS) assessments during 6 weeks. All patients were euthyroid at baseline. TSH levels were analyzed for potential prediction of treatment outcome. Results: MD patients with TD (n = 172) displayed a significantly impaired treatment outcome compared to MD patients without TD (n = 532) in response rates after 6 weeks (p = 7.4E-04), remission rate at discharge (p = 0.018) as well as in mean HDRS change after 6 weeks (p = 0.019). These differences were most pronounced under treatment with Serotonin Reuptake Inhibitors (SSRIs). TSH levels were not associated with treatment outcome. Discussion: Our results suggest that MD patients with comorbid TD may be at risk for impaired treatment outcome. Replication and substantiation of these findings could inform differential antidepressant therapy for these patients.