Thyroid hormone analogues: Promising therapeutic avenues to improve the neurodevelopmental outcomes of intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is a pregnancy complication impairing fetal growth and development. The compromised development is often attributed to disruptions of oxygen and nutrient supply from the placenta, resulting in a number of unfavourable physiological outcomes with impaired brain and organ growth. IUGR is associated with compromised development of both grey and white matter, predisposing the infant to adverse neurodevelopmental outcomes, including long-lasting cognitive and motor difficulties. Cerebral thyroid hormone (TH) signalling, which plays a crucial role in regulating white and grey matter development, is dysregulated in IUGR, potentially contributing to the neurodevelopmental delays associated with this condition. Notably, one of the major TH transporters, monocarboxylate transporter-8 (MCT8), is deficient in the fetal IUGR brain. Currently, no effective treatment to prevent or reverse IUGR exists. Management strategies involve close antenatal monitoring, management of maternal risk factors if present and early delivery if IUGR is found to be severe or worsening in utero. The overall goal is to determine the most appropriate time for delivery, balancing the risks of preterm birth with further fetal compromise due to IUGR. Drug candidates have shown either adverse effects or little to no benefits in this vulnerable population, urging further preclinical and clinical investigation to establish effective therapies. In this review, we discuss the major neuropathology of IUGR driven by uteroplacental insufficiency and the concomitant long-term neurobehavioural impairments in individuals born IUGR. Importantly, we review the existing clinical and preclinical literature on cerebral TH signalling deficits, particularly the impaired expression of MCT8 and their correlation with IUGR. Lastly, we discuss the current evidence on MCT8-independent TH analogues which mimic the brain actions of THs by being metabolised in a similar manner as promising, albeit underappreciated approaches to promote grey and white matter development and improve the neurobehavioural outcomes following IUGR.

Use of thyroid hormones in hypothyroid and euthyroid patients: A survey of members of the Endocrine Society of Australia.

OBJECTIVE: Hypothyroidism is a common endocrine condition usually managed with levothyroxine (LT4). However, controversy remains around the use of liothyronine (LT3). We aimed to investigate the practices of Australian endocrinologists when managing patients with hypothyroidism, their use of LT3 + LT4 combination therapy and use of thyroid hormones in euthyroid patients. DESIGN AND PARTICIPANTS: Members of the Endocrine Society of Australia (ESA) were invited to participate in an online questionnaire. MEASUREMENTS: We analysed questionnaires that had complete demographic data. RESULTS: Eighty-seven questionnaires fulfilled the criteria. LT4 was used as first line treatment for hypothyroidism by all respondents. Only 45% reported that their patients were dispensed the brand of LT4 that they recommend. LT3 (alone or in combination) was prescribed by 44% in their clinical practice. Although 49% of respondents would consider LT3 + LT4 in patients with normal TSH who had ongoing symptoms of hypothyroidism, the inability of LT4 to restore normal physiology was ranked the least likely explanation for persistent symptoms and only 32% would consider it for themselves if they were diagnosed with hypothyroidism. The majority (55%), in accordance with evidence, would not prescribe thyroid hormone to euthyroid individuals but 39% would consider use in euthyroid female infertility with high levels of thyroid antibodies and 11% in euthyroid patients with a simple goitre growing over time. LT4 use in pregnancy was variable among members. CONCLUSIONS: Australian endocrinologists mostly follow international guidelines when prescribing thyroid hormone therapy and many prescribe combination LT3 and LT4 therapy, particularly for patients who remain symptomatic on LT4 monotherapy. Prescribing practices are largely similar to other countries who have completed similar questionnaires.

Cross-Talk Between Thyroid Disorders and Nonalcoholic Fatty Liver Disease: From Pathophysiology to Therapeutics.

The medical community acknowledges the presence of thyroid disorders and nonalcoholic fatty liver disease (NAFLD). Nevertheless, the interconnection between these two circumstances is complex. Thyroid hormones (THs), including triiodothyronine (T3) and thyroxine (T4), and thyroid-stimulating hormone (TSH), are essential for maintaining metabolic balance and controlling the metabolism of lipids and carbohydrates. The therapeutic potential of THs, especially those that target the TRß receptor isoform, is generating increasing interest. The review explores the pathophysiology of these disorders, specifically examining the impact of THs on the metabolism of lipids in the liver. The purpose of this review is to offer a thorough analysis of the correlation between thyroid disorders and NAFLD, as well as suggest potential therapeutic approaches for the future.

Impact of thyroid hormone replacement therapy on the course and functional outcome of aneurysmal subarachnoid hemorrhage.

BACKGROUND: Thyroid hormones were reported to exert neuroprotective effects after ischemic stroke by reducing the burden of brain injury and promoting post-ischemic brain remodeling. OBJECTIVE: We aimed to analyze the value of thyroid hormone replacement therapy (THRT) due to pre-existing hypothyroidism on the clinical course and outcome of aneurysmal subarachnoid hemorrhage (SAH). METHODS: SAH individuals treated between January 2003 and June 2016 were included. Data on baseline characteristics of patients and SAH, adverse events and functional outcome of SAH were recorded. Study endpoints were cerebral infarction, in-hospital mortality and unfavorable outcome at 6 months. Associations were adjusted for outcome-relevant confounders. RESULTS: 109 (11%) of 995 individuals had THRT before SAH. Risk of intracranial pressure- or vasospasm-related cerebrovascular events was inversely associated with presence of THRT (p = 0.047). In multivariate analysis, THRT was independently associated with lower risk of cerebral infarction (adjusted odds ratio [aOR] = 0.64, 95% confidence interval [CI] = 0.41-0.99, p = 0.045) and unfavorable outcome (aOR = 0.50, 95% CI = 0.28-0.89, p = 0.018), but not with in-hospital mortality (aOR = 0.69, 95% CI = 0.38-1.26, p = 0.227). CONCLUSION: SAH patients with THRT show lower burden of ischemia-relevant cerebrovascular events and more favorable outcome. Further experimental and clinical studies are required to confirm our results and elaborate the mechanistic background of the effect of THRT on course and outcome of SAH.

Thyroid hormone, gene expression, and Central Nervous System: Where we are.

Thyroid hormones (TH; T3 and T4) play a fundamental role in the fetal stage to the adult phase, controlling gene and protein expression in virtually all tissues. The endocrine and CNS systems have relevant interaction, and the TH are pivotal for the proper functioning of the CNS. A slight failure to regulate TH availability during pregnancy and/or childhood can lead to neurological disorders, for example, autism and cognitive impairment, or depression. In this review, we highlight how TH acts in controlling gene expression, its role in the CNS, and what substances widely found in the environment can cause in this tissue. We highlight the role of Endocrine Disruptors used on an everyday basis in the processing of mRNAs responsible for neurodevelopment. We conclude that TH, more precisely T3, acts mainly throughout its nuclear receptors, that the deficiency of this hormone, either due to the lack of its main substrate iodine, or by to incorrect organification of T4 and T3 in the gland, or by a mutation in transporters, receptors and deiodinases may cause mild (dysregulated mood in adulthood) to severe neurological impairment (Allan-Herndon-Dudley syndrome, presented as early as childhood); T3 is responsible for the expression of numerous CNS genes related to oxygen transport, growth factors, myelination, cell maturation. Substances present in the environment and widely used can interfere with the functioning of the thyroid gland, the action of TH, and the functioning of the CNS.

Use of thyroid hormones in hypothyroid and euthyroid patients: A THESIS questionnaire survey of UK endocrinologists.

OBJECTIVE: Management of hypothyroidism is controversial because of medication cost pressures and scientific uncertainty on how to address treatment dissatisfaction experienced by some patients. The objective was to investigate the experience and preferences of UK endocrinologists in use of thyroid hormones. DESIGN: Web-based survey. PATIENTS: UK endocrinologists were invited to participate. MEASUREMENTS: Responses to questionnaire. RESULTS: The response rate was 21% (272/1295). While levothyroxine monotherapy is regarded as the treatment of choice for hypothyroidism, 51% of respondents stated that combined treatment with levothyroxine and liothyronine could be considered for levothyroxine-treated patients whose symptoms persist despite normalisation of serum thyroid stimulating hormone (TSH) concentration. However, only 40% are currently prescribing such treatment, and just 23% would consider taking it themselves. A small minority prescribe desiccated thyroid extract, and those most likely to do so are aged over 60 years. Most respondents stated that they have no influence over brand or formulation of levothyroxine dispensed to their patients and expect no major differences in efficacy between different formulations. A total of 9% would prescribe levothyroxine for euthyroid enlarging goitre, and 29% for euthyroid female infertility with high titre thyroid peroxidase antibodies, despite recent trials finding no benefit. CONCLUSIONS: UK endocrine practice in management of hypothyroidism is broadly in line with international guidance. However, a minority of respondents would consider thyroid hormone supplementation in euthyroid individuals for female infertility, enlarging goitre, and other indications in which evidence of efficacy is lacking. Willingness to consider prescribing combined levothyroxine and liothyronine, for hypothyroid symptoms which persist despite normalised TSH, has increased in comparison to previous international surveys, despite inconsistent evidence of benefit.

The effect of thyroid hormone therapy on muscle function, strength and mass in older adults with subclinical hypothyroidism-an ancillary study within two randomized placebo controlled trials.

BACKGROUND: loss of skeletal muscle function, strength and mass is common in older adults, with important socioeconomic impacts. Subclinical hypothyroidism is common with increasing age and has been associated with reduced muscle strength. Yet, no randomized placebo-controlled trial (RCT) has investigated whether treatment of subclinical hypothyroidism affects muscle function and mass. METHODS: this is an ancillary study within two RCTs conducted among adults aged ≥65 years with persistent subclinical hypothyroidism (thyrotropin (TSH) 4.60-19.99 mIU/l, normal free thyroxine). Participants received daily levothyroxine with TSH-guided dose adjustment or placebo and mock titration. Primary outcome was gait speed at final visit (median 18 months). Secondary outcomes were handgrip strength at 1-year follow-up and yearly change in muscle mass. RESULTS: we included 267 participants from Switzerland and the Netherlands. Mean age was 77.5 years (range 65.1-97.1), 129 (48.3%) were women, and their mean baseline TSH was 6.36 mIU/l (standard deviation [SD] 1.9). At final visit, mean TSH was 3.8 mIU/l (SD 2.3) in the levothyroxine group and 5.1 mIU/l (SD 1.8, P < 0.05) in the placebo group. Compared to placebo, participants in the levothyroxine group had similar gait speed at final visit (adjusted between-group mean difference [MD] 0.01 m/s, 95% confidence interval [CI] -0.06 to 0.09), similar handgrip strength at one year (MD -1.22 kg, 95% CI -2.60 to 0.15) and similar yearly change in muscle mass (MD -0.15 m2, 95% CI -0.49 to 0.18). CONCLUSIONS: in this ancillary analysis of two RCTs, treatment of subclinical hypothyroidism did not affect muscle function, strength and mass in individuals 65 years and older.

Are We Restoring Thyroid Hormone Signaling in Levothyroxine-Treated Patients With Residual Symptoms of Hypothyroidism?

INTRODUCTION: Levothyroxine (LT4) at doses that maintain the serum thyroid-stimulating hormone levels within the normal range constitutes the standard of care for the treatment of hypothyroidism. After a few months, this eliminates the signs and symptoms of overt hypothyroidism in the majority of patients, owing to the endogenous activation of thyroxine to triiodothyronine, the biologically active thyroid hormone. Still, a small percentage of the patients (10%-20%) exhibit residual symptoms, despite having normal serum thyroid-stimulating hormone levels. These symptoms include cognitive, mood, and metabolic deficits, with a significant impairment in psychological well-being and quality of life. OBJECTIVE: To provide a summary of progress in the approach of patients with hypothyroidism that exhibit residual symptoms despite treatment. METHODS: We reviewed the current literature and here we focused on the mechanisms leading to a deficiency of T3 in some LT4-treated patients, the role of residual thyroid tissue and the rationale for combination therapy with LT4 + liothyronine (LT3). RESULTS: A score of clinical trials comparing therapy with LT4 versus LT4 + LT3 concluded that both are safe and equally effective (neither is superior); however, these trials failed to recruit a sufficiently large number of patients with residual symptoms. New clinical trials that considered LT4-treated symptomatic patients revealed that such patients benefit from and prefer therapy containing LT4 + LT3; desiccated thyroid extract has also been used with similar results. A practical approach to patients with residual symptoms and on initiation of combination therapy with LT4 + LT3 is provided. CONCLUSION: A recent joint statement of the American, British, and European Thyroid Associations recommends that a trial with combination therapy be offered to patients with hypothyroidism that do not fully benefit from therapy with LT4.

Changes in quality of life after thyroidectomy in subjects with thyroid cancer in relation to the dose of levothyroxine.

PURPOSE: Previous studies demonstrated decreased quality of life (QoL) in differentiated thyroid cancer (DTC) survivors and suggested QoL variability related to time from thyroidectomy and levothyroxine dosage. The aims of this study were to evaluate QoL in thyroidectomized subjects in different levothyroxine states and to evaluate the association between TSH and thyroid hormones and QoL. METHODS: Prospective 5-year study enrolling 208 patients thyroidectomized for DTC, studied in one to four times according to levothyroxine dosage: withdrawal (WITHD), complete (C-SUPP) and mild TSH-suppression (M-SUPP), replacement (REPL). Each patient was allowed to participate into the study more than one time. A total of 300 evaluations were collected, consisting of detailed thyroid hormone profile and QoL assessment through the ThyPRO questionnaire. RESULTS: Comparing the four groups, significant differences were found for anxiety, impaired social and daily life and item 12 (overall impact of thyroid disease) domains (p < 0.05). Interestingly, C-SUPP subjects reported the best scores in almost all ThyPRO scales. Significant correlations were found between QoL and pituitary-thyroid axis function, as well as between QoL and gender, being females more affected. At multiple regression analyses fT3 demonstrated to be the best explanatory factor for overall impact of thyroid disease on the patient's life, followed by gender. CONCLUSIONS: TSH-suppressive doses of levothyroxine are more effective in improving QoL in DTC patients after thyroidectomy. These results confirm the urgent need of further studies aimed to define the best treatment of hypothyroidism, effective on well-being and harmless for patients.

Triac Treatment Prevents Neurodevelopmental and Locomotor Impairments in Thyroid Hormone Transporter Mct8/Oatp1c1 Deficient Mice.

Patients with inactive thyroid hormone (TH) transporter MCT8 display intellectual disability due to compromised central TH transport and action. As a therapeutic strategy, application of thyromimetic, MCT8-independent compounds Triac (3,5,3'-triiodothyroacetic acid), and Ditpa (3,5-diiodo-thyropropionic acid) was proposed. Here, we directly compared their thyromimetic potential in Mct8/Oatp1c1 double knock-out mice (Dko) modeling human MCT8 deficiency. Dko mice received either Triac (50 ng/g or 400 ng/g) or Ditpa (400 ng/g or 4000 ng/g) daily during the first three postnatal weeks. Saline-injected Wt and Dko mice served as controls. A second cohort of Dko mice received Triac (400 ng/g) daily between postnatal weeks 3 and 6. Thyromimetic effects were assessed at different postnatal stages by immunofluorescence, ISH, qPCR, electrophysiological recordings, and behavior tests. Triac treatment (400 ng/g) induced normalized myelination, cortical GABAergic interneuron differentiation, electrophysiological parameters, and locomotor performance only when administered during the first three postnatal weeks. Ditpa (4000 ng/g) application to Dko mice during the first three postnatal weeks resulted in normal myelination and cerebellar development but only mildly improved neuronal parameters and locomotor function. Together, Triac is highly-effective and more efficient than Ditpa in promoting CNS maturation and function in Dko mice yet needs to be initiated directly after birth for the most beneficial effects.

Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy.

The majority of patients with hypothyroidism feel better when levothyroxine treatment restores thyroid-stimulating hormone (TSH) concentrations to normal. Increasingly, a significant minority of patients remain symptomatic and are dissatisfied with their treatment. Overzealous treatment of symptomatic patients with subclinical hypothyroidism may contribute to dissatisfaction among hypothyroidism patients, as potential hypothyroid symptoms in patients with minimal hypothyroidism rarely respond to treatment. Thyroid hormone prescriptions have increased by 30% in the United States in the last decade. The diagnosis of subclinical hypothyroidism should be confirmed by repeat thyroid function tests ideally obtained at least 2 months later, as 62% of elevated TSH levels may revert to normal spontaneously. Generally, treatment is not necessary unless the TSH exceeds 7.0-10 mIU/L. In double-blinded randomized controlled trials, treatment does not improve symptoms or cognitive function if the TSH is less than 10 mIU/L. While cardiovascular events may be reduced in patients under age 65 with subclinical hypothyroidism who are treated with levothyroxine, treatment may be harmful in elderly patients with subclinical hypothyroidism. TSH goals are age dependent, with a 97.5 percentile (upper limit of normal) of 3.6 mIU/L for patients under age 40, and 7.5 mIU/L for patients over age 80. In some hypothyroid patients who are dissatisfied with treatment, especially those with a polymorphism in type 2 deiodinase, combined treatment with levothyroxine and liothyronine may be preferred.

Is thyroid hormone supplementation avoidable for patients with low-risk papillary thyroid cancer after thyroid lobectomy? A two-center observational study.

OBJECTIVE: Changing insights regarding the extent of surgery for low-risk papillary thyroid cancer (PTC) stir up discussions on the benefits and harms of thyroid lobectomy versus total thyroidectomy. The chance of needing postoperative thyroid hormone supplementation after thyroid lobectomy is still unclear. The purpose of this retrospective two-center study was to identify the incidence and risk factors of postoperative thyroid-stimulating hormone (TSH) elevation (>2.0 µIU/ml) after thyroid lobectomy for low-risk PTC. DESIGN AND METHODS: Medical records of 201 consecutive patients with low-risk PTC from two tertiary centers who underwent thyroid lobectomy between 2015 and 2019 were retrospectively reviewed. Postoperative thyroid function tests were measured regularly and patients were prescribed levothyroxine if the TSH level was higher than 2.0 µIU/ml. Multivariable regression models were used to evaluate potential risk factors associated with postoperative TSH elevation after thyroid lobectomy. RESULTS: At 6 weeks postoperatively, 85% had TSH level of >2 µIU/ml; this increased to 88% by 3-6 months. Receiver operating characteristic analysis identified preoperative TSH cut-off (>1.7 µIU/ml) to predict postoperative TSH elevation. Multivariate analysis revealed that only a high preoperative TSH level (>1.7 µIU/ml) was an independent risk factor for a postoperative TSH level of >2 µIU/ml (odds ratio = 7.71; p < .001). CONCLUSION: Nearly 90% of the patients who underwent thyroid lobectomy for low-risk PTC had a postoperative TSH level of >2 µIU/ml, necessitating thyroid hormone supplementation in accordance with current guidelines. This finding highlights that preoperative patient counseling should also focus on raising awareness about postoperative thyroid hormone supplementation for low-risk PTC patients seeking thyroid lobectomy.

A decrease in peripheral thyroid hormone conversion efficiency in patients treated with immune checkpoint inhibitors and L-T3 as a possible alternative therapeutic escape option.

Hypothyroidism is a frequently occurring side effect in patients under treatment with immune checkpoint inhibitors (ICIs). Actually, the origin of hypothyroidism with ICI use is classified as a primary (thyroid) or as secondary/tertiary hypothyroidism (hypothalamus-pituitary). Treatment consists of levothyroxine (L-T4) substitution. Recently, we were rarely confronted with a clinically overt hypothyroidism in three patients under treatment with ICIs who were non-responsive to T4 therapy. As a therapeutical escape, liothyronine (L-T3) was started with a significant clinical and/or biochemical improvement suggesting an underlying functional defect in the peripheral free T4 (fT4) to free T3 (fT3) conversion (as supported by calculation of SPINA-GD). Against this background, we discussed our three patients along an extended review of this clinical topic.

Antiseizure medications and thyroid hormone homeostasis: Literature review and practical recommendations.

Thyroid hormones play an essential role in central nervous system development, normal physiological brain function, and repair mechanisms. On one hand, thyroid hormone alterations influence cortical excitability, and on the other hand antiseizure medications (ASMs) are associated with alterations in thyroid hormone metabolism. Although this interaction has long been described, and epilepsy is a common and chronic neurological disease, studies describing the interplay are often small and retrospective. We performed a systematic review of the current literature on epilepsy, ASMs, and thyroid hormone metabolism according to PRISMA guidelines. Forty-seven studies were included. Most studies were retrospective cross-sectional studies (n = 25) and investigated thyroid function alterations in patients on older ASMs such as phenobarbital, phenytoin, carbamazepine, and valproate. Overall, almost one third of patients with epilepsy had thyroid hormone alterations, especially patients on valproate (25%) and carbamazepine (10%-25%). Studies with patients receiving polytherapy are scarce, but reported a higher risk for hypothyroidism in patients with older age (p = .004), female sex (p = .014), longer duration of epilepsy (p = .001), intractable epilepsy (p = .009), and polytherapy. Studies on newer ASMs are also limited, and further studies on an interplay with thyroid hormone homeostasis are essential to improve the care for epilepsy patients. ASMs are associated with alterations in thyroid hormone metabolism. Thyroid function monitoring is indicated in patients on ASMs, especially those with refractory epilepsy and those on polytherapy. We provide a practical guidance for thyroid function monitoring for the clinician taking care of patients on ASMs.

Effect of radioiodine therapy under thyroid hormone withdrawal on health-related quality of life in patients with differentiated thyroid cancer.

OBJECTIVE: To investigate the effect of radioactive iodine therapy under thyroid hormone withdrawal in differentiated thyroid cancer patients on health-related quality of life. METHODS: Patients who were diagnosed with differentiated thyroid cancer after thyroidectomy were involved in this study. All of them were managed with thyroid hormone withdrawal. Health-related quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and its thyroid cancer module at three different time points. Changes in health-related quality of life were evaluated by Wilcoxon and Kruskal-Wallis tests. Univariable logistic regression analysis was used to determine social-demographic and clinical factors associated with worse health-related quality of life. RESULTS: A total of 99 differentiated thyroid cancer patients were involved in this study. Changes in health-related quality of life at different time points showed that 1 month post-radioactive iodine treatment, an improvement in nausea and vomiting, insomnia and appetite loss was observed. Impairments of global health, role, cognitive and social function and problems of discomfort in the head and neck, voice concerns, dry mouth, fatigue, pain, dyspnea, thyroid fatigue, fear, tingling or numbness, joint pain and shoulder function increased after radioactive iodine treatment. Univariable logistic regression analysis demonstrated potential factors associated with worse health-related quality of life. Thyroid stimulating hormone and parathyroid hormone levels were more sensible to changes in functional domain. Patients aged ≥55-year-old, with annual income under ¥50 000, low parathyroid hormone and pT4 tumour stage experienced higher changes in symptom scales after radioactive iodine treatment. CONCLUSION: After radioactive iodine treatment, differentiated thyroid cancer patients experienced negative health-related quality of life, and most of these impairments might not recover in the short term. Thyroid stimulating hormone and parathyroid hormone levels, annual income and pT tumours stage were independent risk factors for decreased health-related quality of life.

The Effectiveness of Thyroid Hormone Replacement Therapy on Heart Failure and Low-Triiodothyronine Syndrome: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: The purpose of this study was to conduct a systematic review and meta-analysis evaluating the role of thyroid hormone therapy in patients with heart failure and low-triiodothyronine syndrome. METHODS: The electronic databases PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and China Biology Medicine disc were systematically searched to identify eligible studies published before November 27, 2021. The mean difference was pooled for randomized controlled trials using a random-effects model. RESULTS: The meta-analysis showed that thyroid hormone treatment improved the left ventricular ejection fraction (weighted mean difference [WMD] 5.61, 95% confidence interval [CI]: 4.38 to 6.85, I2 = 63.12%, P < 0.01). The cardiac output improved with thyroid hormone therapy (WMD 0.65, 95% CI: 0.42 to 0.89, I2 = 84.28%, P < 0.01). The early-to-late diastolic transmitral flow velocity in the thyroid hormone group was also improved compared to the control group (WMD 0.29, 95% CI: 0.15 to 0.42, I2 = 95.08%, P < 0.01). The left ventricular diastolic dysfunction was decreased with thyroid hormone treatment (WMD -5.17, 95% CI: -7.47 to -2.88, I2 = 90.18%, P < 0.01). The brain natriuretic peptide decreased with thyroid hormone treatment (standardized mean difference -1.49, 95% CI: -2.15 to -0.84, I2 = 90.18%, P < 0.01). Noradrenaline decreased with thyroid hormone therapy (WMD -349.86, 95% CI: -401.05 to -298.67, I2 = 0%, P < 0.01). Free triiodothyronine increased with thyroid hormone treatment (standardized mean difference 2.18, 95% CI: 0.75 to 2.60, I2 = 98.20%, P < 0.01). CONCLUSION: This meta-analysis showed that thyroid hormone replacement therapy was effective in patients with heart failure and low-triiodothyronine syndrome.

Presence or severity of Hashimoto's thyroiditis does not influence basal calcitonin levels: observations from CROHT biobank.

PURPOSE: The influence of Hashimoto's thyroiditis (HT) on calcitonin (Ct) production is unresolved question. The aim of this study was to explore if basal Ct levels are influenced by the presence/severity of HT or correlated with clinical phenotypes of HT patients. METHODS: We included 467 HT patients and 184 control participants, from Croatian Biobank of HT patients (CROHT), in this retrospective study. Calcitonin levels between HT patients and controls were compared using Mann-Whitney test. Ct levels between two subgroups of HT patients, divided by intake of levothyroxine (LT4) therapy, were additionally tested to take into account the illness severity. Spearman rank correlation test was used to analyze correlations between Ct levels and 14 relevant phenotypes. RESULTS: We have not detected significant differences in median Ct levels between HT patients and controls (2.2 vs 2.35 pg/mL, respectively, P = 0.717) nor in-between two subgroups of HT patients (P = 0.347). We have not detected statistically significant correlations between Ct levels and clinical phenotypes, although we identified three weak nominal correlations: negative correlation of Ct with TgAb in all HT patients (r = - 0.1, P = 0.04); negative correlation of Ct with age in subgroup of HT patients without LT4 therapy (r = - 0.13, P = 0.04); positive correlation of Ct with BSA in subgroup of HT patients on LT4 therapy (r = 0.16, P = 0.042). CONCLUSION: Our results suggest that HT patients of all disease stages preserve Ct production as healthy individuals and there is no need for Ct measurements in the absence of a nodule. Additional confirmation and clarification of observed nominal correlations are needed due to potential clinical relevance of TgAb and age-dependent Ct decrease in HT women.

Thyroid dysfunction on the heart: clinical effects, prognostic impact and management strategies.

Thyroid hormones have a considerable influence on cardiac function and structure. There are direct and indirect effects of thyroid hormone on the cardiovascular system, which are prominent in both hypothyroidism and hyperthyroidism. In this review, we discuss how thyroid dysfunction impacts cardiovascular pathophysiology and the underlying molecular mechanisms.

Impact of pharmacist-managed immune checkpoint inhibitor toxicities.

BACKGROUND: Immune checkpoint inhibitors are associated with unique autoimmune side effects that differ from traditional cytotoxic chemotherapy. Pharmacists may play an important role in providing key supportive care measures necessary to aid patients and oncologists through immune-related adverse events (irAEs). This study aims to evaluate the impact of a pharmacist-managed irAE protocol in an oncology clinic. METHODS: This study is a retrospective chart review of the implementation of a pilot irAE pharmacy protocol. Patients treated with an immune checkpoint inhibitor and subsequently identified to have dermatologic, gastrointestinal, hepatic, or thyroid toxicities and managed under the pilot irAE pharmacy protocol from 1 October 2018 to 28 February 2019 were enrolled. Study endpoints included number of pharmacist interventions and physician satisfaction. Additional endpoints included pharmacotherapy initiated, dose adjustments, and patient follow-ups. RESULTS: From 1 October 2018, to 28 February 2019, 17 patients were referred and approved by their primary oncologists for pharmacy management under the pilot irAE protocol. During the pilot period, pharmacists initiated 21 new medications for the treatment of irAEs, including thyroid hormone replacement in 7 patients (41%) and oral corticosteroids in 6 patients (35%) with a total of 28 dose adjustments. In addition, the pilot protocol included an assessment of physician satisfaction, which showed a reduced number of physician hours per month managing irAEs, increased physician confidence in irAE management, and a desire for continued pharmacist-management of irAEs. CONCLUSIONS: Oncology pharmacists had an impact on management of toxicities in our oncology clinic as indicated by the pharmacist interventions and physician satisfaction.

Physical activity, sports participation and exercise-related constraints in adult women with primary hypothyroidism treated with thyroid hormone replacement therapy.

Awareness of physical activity (PA) constraints in patients with primary hypothyroidism on thyroid hormone replacement therapy (THR) is important. Hence, this cross-sectional matched case-control study aimed to determine PA and sports participation (SP) in patients with hypothyroidism on THR in comparison to control subjects. Accordingly, survey questions were selected from the National Survey on Injuries and Physical Activity in the Netherlands (IPAN), supplemented with questions related to self-reported clinical characteristics and exercise-related constraints (ERC) of patients. In total, 1,724 female patients (mean age 53.0 years ±11.6) and 1,802 controls (mean age 52.6 ± 13.2) were included. Compared to controls, patients were less likely to comply with the moderate-intensity PA guideline (OR 0.70; 95% CI: 0.611-0.803), although patients were more actively participating in sports (OR 1.40; 95% CI: 1.156-1.706). Two-thirds of patients reported that hypothyroidism was limiting their PA performance. These limitations were more pronounced in patients with autoimmune thyroiditis (AIT) than in patients with hypothyroidism from other aetiology (OR 1.93; 95% CI: 1.518-2.457), representing disease-specific exercise intolerance. In order to establish effective intervention programmes to encourage regular PA in hypothyroid patients on THR with exercise intolerance, further research is warranted to better understand PA barriers.