Direct Effect Of Thyroid Hormone Research Articles

SAT591 Abnormal Levels Of Thyroid Hormones During Development Alters The Migration And Activity Of GnRH Reproductive Neurons

Abstract Disclosure: C. Quignon: None. A. Backer: None. S. Wray: None. Clinical studies have shown that thyroid hormones disorders and alteration of thyroid hormone production by environmental endocrine disruptors, have deleterious effects on reproduction. By acting in the brain on the hypothalamic component of the reproductive axis, abnormal levels of thyroid hormones can disturb sex hormones production, oestrus cycles or puberty onset, possibly leading to subfertility. Moreover, in animal models, endocrine disruptors and thyroid hormones have been shown to have long-lasting transgenerational effects with the maternal hormones influencing the development of foetal reproductive functions. Despite clear evidence of an interaction between the thyroid and reproductive systems, the effect of T3, the active form of thyroid hormones, on the GnRH neurons controlling reproduction, have been poorly studied. In this work we investigated how T3 functionally interacts with GnRH neurons and how abnormal concentration of T3 alters the migration of these neurons during development. Calcium imaging was used to study the direct effect of T3 on GnRH neuronal activity in an ex vivo nasal explants model. Acute administration of T3 (30nM) was found to stimulate the activity of GnRH cells. Dual labelling of GnRH and thyroid hormone receptors (TR) showed that the GnRH neurons express both nuclear and membrane receptors. However, the use of an antagonist that specifically blocks the TR nuclear receptors (1-850), didn’t inhibit the T3 stimulatory effect. In contrast, blockage of integrin αV/β3 membrane receptors (with cilengitide), which have been shown to be activated by T3, prevented the T3-induced increase in GnRH neuronal activity. During development GnRH neurons migrate from the nasal placodes into the brain. Acute administration of T3 for 1hr significatively decreased the migration rate of the GnRH neurons in our ex vivo model. To assess the effect of thyroid disruption during pregnancy on the development of reproductive axis in utero, pregnant females mice have been treated with methimazole to induce hypothyroidism from gestational day 6 to 13. E13 embryos have been collected from treated and control dams and the distribution of migrating GnRH neurons will be compared between both groups. Together these studies are the first to report a direct effect of thyroid hormones on GnRH neuronal activity, through the integrin αV/β3 membrane receptors and show that T3 can modulate the migration of GnRH neurons during development. These results will bring new insights on how thyroid disruption by endocrine disruptor chemicals or thyroid diseases, especially during foetal development, can lead to long term reproductive defects. Presentation: Saturday, June 17, 2023

Hepatic Energy Metabolism under the Local Control of the Thyroid Hormone System.

The energy homeostasis of the organism is orchestrated by a complex interplay of energy substrate shuttling, breakdown, storage, and distribution. Many of these processes are interconnected via the liver. Thyroid hormones (TH) are well known to provide signals for the regulation of energy homeostasis through direct gene regulation via their nuclear receptors acting as transcription factors. In this comprehensive review, we summarize the effects of nutritional intervention like fasting and diets on the TH system. In parallel, we detail direct effects of TH in liver metabolic pathways with regards to glucose, lipid, and cholesterol metabolism. This overview on hepatic effects of TH provides the basis for understanding the complex regulatory network and its translational potential with regards to currently discussed treatment options of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) involving TH mimetics.

Effects of thyroid hormones on the functional state of bovine granulosa cells in vitro

Any dysfunction of the thyroid gland causes abnormal changes in the functioning of the reproductive system, primarily the ovaries. Therefore, the question of the possible direct effect of thyroid hormones on the bovine ovarian function by modulating the functional state or functional activity of granulosa cells seems relevantPurpose: to study in vitro the effect of thyroxine and triiodothyronine on the proliferative and steroidogenic activity, as well as apoptotic changes of bovine granulosa cells.Materials and methods. Granulosa cells were isolated from follicles with a diameter of 1-5 mm and precultured for two days in a medium containing 10 % serum. The cells were then placed in serum-free medium containing thyroxine (25-200 ng/mL) or triiodothyronine (0.5-4.0 ng/mL) and incubated for another 48 h. After culturing, the content of estradiol-17β and progesterone in the media was determined by ELISA. The proliferative activity and apoptotic changes in the cells were assessed by immunocytochemical assay, based on the expression level of proliferating cell nuclear antigen PCNA and pro-apoptotic protein Bax, respectively.Results. It was found that the proportion of cells with a positive reaction to PCNA increased 1.1 times (P<0.01) compared with that in the control at a triiodothyronine concentration of 1 ng/ml and did not change with its further increase to 4 ng/ml. In addition, the introduction of triiodothyronine at a concentration of 1 ng/ml into the medium led to a decrease in the relative number of Bax-positive cells from 25.6 ± 0.3% to 23.3 ± 0.6 % (P<0.01). A further increase in this concentration to 4 ng/ml enhanced the observed anti-apoptotic effect 1.1 times (P<0.05). The pattern of the effect of thyroxine on the proliferative activity and apoptotic changes of granulosa cells in culture was similar to that for triiodothyronine. Concurrently, the growth-stimulating and anti-apoptotic effects of thyroxine were achieved at a concentration of 50-200 ng/ml. At the same time, both thyroid hormones did not affect the secretion of estradiol-17β or progesterone by the cells.Conclusions. Thus, thyroxine and triiodothyronine can stimulate in vitro the proliferation of bovine granulosa cells, as well as inhibit the expression of the proapoptotic Bax protein in these cells, which is not associated with the regulation of the production of ovarian steroid hormones. Overall, these data suggest that thyroid hormones at physiological concentrations are able to exert a regulatory effect on the growth and atresia of bovine small antral follicles and, therefore, directly modulate the ovarian activity.

PSAT340 Thymic Hyperplasia in Graves’ Disease: A Case Report

Abstract Background Thymic hyperplasia (TH) can occur in Graves’ disease (GD) due to direct effect of thyroid hormone or thyrotropin receptor antibody stimulation. Recognition of this entity is important as treatment of GD can lead to reduction in TH and can prevent unnecessary intervention. This case highlights thymus enlargement likely due to TH in the setting of GD. Case A 44-year-old female with history of left-sided invasive breast cancer status post partial mastectomy and radiation therapy, was found to have an anterior mediastinal mass on surveillance breast MRI. Follow-up chest CT and MRI showed a homogenous anterior mediastinal mass (4.7×2.4×12.6 cm) and thyromegaly. She had a prior history of Hashimoto's thyroiditis diagnosed 20 years, not on treatment, as well as active tobacco use (0.5 PPD for 10 years). She had symptoms of weight loss, palpitations, heat intolerance and tremors. Physical examination revealed tachycardia, flushing, lid lag, diffusely enlarged thyroid and fine tremors. Laboratory investigation showed TSH < 0.01 uIU/mL (0.35-4.94 uIU/mL), free T4 2.84 ng/dL (0.5-1.39 ng/dL), total T3 479 ng/dL (48-178 ng/dL), positive TPO, TSI and thyroglobulin antibodies confirming GD. She was initially treated with methimazole and propranolol with plans for thymectomy. Treatment was complicated by methimazole induced agranulocytosis with absolute neutrophil count of 114 cells/uL (1500-7800 cells/uL) requiring hospitalization. Methimazole was discontinued, and she was treated with antibiotics, propranolol, prednisone, cholestyramine and potassium iodide before undergoing total thyroidectomy. Pathology was consistent with GD with an incidental 2 mm papillary thyroid microcarcinoma. Post-operatively she was started on levothyroxine. Follow up CT chest two weeks after surgery showed a decrease in size of the mediastinal mass supporting a diagnosis of TH secondary to GD. She is planned for repeat imaging in several months to determine if thymectomy is indicated. Discussion TH can occur in GD secondary to direct trophic effect from excess thyroid hormones or thyrotropin receptor antibody stimulation. Prevalence is unknown; however, studies have shown that approximately one-third of patients with GD have histological evidence of TH. In most documented cases, thymic enlargement is minimal; a 2014 study found 107 documented cases of GD related thymus enlargement, of which only 4 were malignant. Since anterior mediastinal masses can have a high malignancy potential, it is warranted to thoroughly evaluate the radiographic characteristics for malignancy including heterogeneous enhancement, invasion to surrounding structures, and presence of calcification. However, in the presence of untreated hyperthyroidism and absence of suspicious radiographic features, tissue biopsy or thymectomy should be avoided due to high risk of complications such as thyroid storm. TH in GD is often reversible with treatment of GD. Follow up chest imaging to look for decrease in size of thymus is recommended to reevaluate future need for biopsy or thymectomy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP507 PREVALENCE OF CARDIOVASCULAR DISEASE IN PATIENTS WITH SUBCLINICAL HYPOTHYROISIM

Abstract Introduction Thyroid hormones play an essential role in maintaining cardiovascular homeostasis. Experimental studies have revealed that subtle changes in thyroid hormone levels, as observed in subclinical hypothyroidism, have adverse effects on the cardiovascular system due to predisposition to endothelial dysfunction, dyslipidemia and direct effects of thyroid hormones on the myocardium. We conducted a retrospective cohort study to elicit the role of subclinical hypothyroidism as an independent risk factor for cardiovascular diseases. Methods We conducted a retrospective analysis of 3 years of the National Inpatient Sample (NIS) database, 2016 to 2018. Study populations were selected using ICD-10 diagnosis code. Discharge-level weight analysis was used to produce a national estimate. We conducted multivariate regression analysis to calculate odds ratio with STATA 17. Results During the study period, 106,970,745 study population met the inclusion criteria and 37,215 of subclinical hypothyroidism (SCH) patients were discharged. SCH patients tended to be more female (63.48% v 56.40%), older (mean age 58.22± 0.25 v 49.48 ± 0. 01), diabetic (24.84% v 21.47%) and obese (18.63% v 13.54%). Prevalence of hyperlipidemia and hypertension were similar in both SCH and non-SCH groups (3.75% v 3.24% and 29. 09% v 29.35% each). Caucasian patients were predominant in both groups with similar ethnicity distribution (62.26% v 64.96%). 3.56% of SCH patient had acute coronary artery syndromes (ACS), whereas 2.78% of non-SCH patients developed the ACS. For the patients without history of heart failure (HF), 2.54% of SCH patients developed new onset of HF, whereas 1.11% of non-SCH patients developed HF. After adjusting for age, sex, race and comorbid burden, SCH is not associated with ACS (p = 0.375) or Afib (p= 0.74) but associated with elevated risk for new onset of HF (OR 1.88, 1.62–2.18, p < 0. 0001). Conclusion Our study shows that subclinical hypothyroidism is not associated with higher rates of ACS or Atrial fibrillation, however it is associated with statistically significant higher risk of new onset HF. Further research needs to be done to determine subclinical hyperthyroidism as a potential risk factor for HF and assess the benefit of lower threshold for treating subclinical hypothyroidism in preventing or delaying the onset of HF in patients with associated cardiac risk factors. Presentation: No date and time listed

Hypothyroidism Presenting as Reversible Renal Impairment

Certain studies have shown pathophysiology of diminished renal function in hypothyroidism. Aetiology is due to direct effect of thyroid hormone on kidney, and also the hemodynamic effects play an important role.

Acute kidney injury secondary to hypothyroidism induced rhabdomyolysis: a case report

Renal impairment is occasionally reported in association with hypothyroidism. We report a case of a middle aged man, who presented with features of rhabdomyolysis and acute kidney injury which was ascribed to underlying undiagnosed hypothyroidism. The etiology is presumed to be multifactorial; hemodynamic effects and a direct effect of thyroid hormone on the kidney play important role. This case enlivens the necessity of assessing thyroid function in cases of unexplained renal failure. Awareness about this rare presentation of a common disease would alert the physician to effectively treat this dreaded yet reversible complication.
 Birdem Med J 2021; 11(1): 72-74

Maternal Thyroid Anomalies and Risk of Attention Deficit Hyperactivity Disorder in Progeny

Background. The fetus is dependent on adequate maternal supply of thyroid hormones, which have important neurodevelopmental roles. Impaired thyroid function was linked with exposure to several environmental toxicants, and these thyroid-related effects may be a mechanism through which environmental toxicants affect neurodevelopment. Extreme maternal thyroid dyshomeostasis causes adverse neurodevelopmental effects, but impacts of subtler thyroid disruption remain unclear. We evaluated the risk of Attention Deficit Hyperactivity Disorder (ADHD) in children of mothers with thyroid anomalies, and the relation between gestational maternal thyroid hormone levels and child ADHD risk. Methods. The study included 445,477 singletons born in 1999-2012 in a large Israeli health fund, with data on ADHD diagnoses retrieved through 2019. Maternal thyroid conditions were ascertained through ICD-9 codes with subsequent validation through review of drug dispensing and laboratory data. ADHD cases were identified through ICD-9 codes, with additional information on dispensing of stimulants and nonstimulants medications. Analyses were performed using Cox proportional hazard and additive Poisson regression models employing a robust variance estimator. Results. Children of mothers who experienced hypothyroidism had a higher ADHD risk compared to children of mothers without thyroid conditions (HR=1.11, 95% C.I:1.07-1.15), with more robust results in the subgroup of ADHD children who also received pharmaceutical ADHD treatments. Hyperthyroidism results were less consistent. Results were materially unchanged when restricting to mothers gestationally treated with levothyroxine. Analysis of maternal gestational thyrotropin and free-thyroxine levels did not show consistent associations with ADHD risk. Conclusions. Maternal hypothyroidism was associated with increased child ADHD risk, but seemingly not due to direct effects of thyroid hormones. Instead, factors that influence maternal thyroid function may have etiologic roles in ADHD through pathways independent of maternal gestational thyroid hormones, and thus be unaffected by medication treatment. Environmental factors known to disrupt thyroid function should be examined for possible involvement in ADHD etiology.

Maternal Thyroid Disorders and Risk of Autism Spectrum Disorder in Progeny.

Maternal thyroid dysfunction is suspected of causing adverse neurodevelopmental effects, but current evidence is inconclusive. Epidemiologic investigations generally suggest an association between maternal thyroid dysfunction and neurodevelopment impairments in progeny, but clinical trials of thyroid treatment during pregnancy reported null effects. To better understand these discrepant findings, we evaluated the association between maternal thyroid conditions and autism spectrum disorder (ASD), including examining the role of gestational thyroid-related hormone concentrations and thyroid medications use. Analyses considered 437,222 singleton live births occurring in a large Israeli health fund in 1999-2013, followed through 2016. Thyroid conditions and ASD cases were identified through International Classification of Diseases-9 codes with subsequent validation through review of medical records. Laboratory gestational thyroid hormone measurements were also considered. Children of mothers who ever experienced hypothyroidism had a higher risk of ASD compared with children of mothers without hypothyroidism (adjusted odds ratio [aOR] = 1.26, 95% confidence interval [CI] = 1.12, 1.42). The association with hyperthyroidism was less consistent, but elevated in main analyses (aOR = 1.42, 95% CI = 1.04, 1.94). These associations were not explained by maternal gestational thyroid hormones levels nor mitigated by gestational use of thyroid medications. Results indicate that maternal thyroid conditions are associated with increased ASD risk in progeny, but suggestively not due to direct effects of thyroid hormones. Instead, factors that influence maternal thyroid function could have etiologic roles in ASD through pathways independent of maternal gestational thyroid hormones and thus be unaffected by medication treatment. Factors known to disrupt thyroid function should be examined for possible involvement in ASD etiology.

Direct effects of thyroid hormones on hepatic lipid metabolism.

It has been known for a long time that thyroid hormones have prominent effects on hepatic fatty acid and cholesterol synthesis and metabolism. Indeed, hypothyroidism has been associated with increased serum levels of triglycerides and cholesterol as well as non-alcoholic fatty liver disease (NAFLD). Advances in areas such as cell imaging, autophagy and metabolomics have generated a more detailed and comprehensive picture of thyroid-hormone-mediated regulation of hepatic lipid metabolism at the molecular level. In this Review, we describe and summarize the key features of direct thyroid hormone regulation of lipogenesis, fatty acid β-oxidation, cholesterol synthesis and the reverse cholesterol transport pathway in normal and altered thyroid hormone states. Thyroid hormone mediates these effects at the transcriptional and post-translational levels and via autophagy. Given these potentially beneficial effects on lipid metabolism, it is possible that thyroid hormone analogues and/or mimetics might be useful for the treatment of metabolic diseases involving the liver, such as hypercholesterolaemia and NAFLD.

Proteinuria Associated with Thyroid Disorders - Cases Report and Literature Review

Background: The interactions between thyroid and kidney have been reported mainly in the patients with proteinuria coexistent with autoimmune thyroiditis. The proposed mechanisms focus on direct effects of thyroid hormone on the hemodynamics and morphology of kidney and indirect effects through deposition of immune complexes consisting of thyroid component. Case presentation: Herein we describe two cases presenting with proteinuria associated with thyroid disorder. Both patients presented with nephrotic-range proteinuria and hematuria but were not responsive to immunosuppression therapy. Immunopathology demonstrated the deposits of multiple immunoglobulins and complements along glomerular basement membrane and mesangium. One case presented with mesangial proliferative glomerulonephritis (MsPGN) in the context of thyroid papillary carcinoma. After removal of tumor, the urine protein disappeared. This is the first report about the MsPGN related to thyroid tumor. The other case was diagnosed as MN secondary to Hashimoto’s thyroiditis. More interestingly, both patients suffered relapse of the proteinuria accompanied by opposed disturbance of thyroid hormone at the follow-up. Once the thyroid hormone was corrected, the renal function improved. Conclusion: This study proposes a possibility that a hormone-cytokine axis connecting these two organs mediates the changes of microenvironment in kidney with the thyroid hormone change, and then influence the renal function.

Thyroid hormones and cardiovascular disease.

Myocardial and vascular endothelial tissues have receptors for thyroid hormones and are sensitive to changes in the concentrations of circulating thyroid hormones. The importance of thyroid hormones in maintaining cardiovascular homeostasis can be deduced from clinical and experimental data showing that even subtle changes in thyroid hormone concentrations - such as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome - adversely influence the cardiovascular system. Some potential mechanisms linking the two conditions are dyslipidaemia, endothelial dysfunction, blood pressure changes, and direct effects of thyroid hormones on the myocardium. Several interventional trials showed that treatment of subclinical thyroid diseases improves cardiovascular risk factors, which implies potential benefits for reducing cardiovascular events. Over the past 2 decades, accumulating evidence supports the association between abnormal thyroid function at the time of an acute myocardial infarction (MI) and subsequent adverse cardiovascular outcomes. Furthermore, experimental studies showed that thyroid hormones can have an important therapeutic role in reducing infarct size and improving myocardial function after acute MI. In this Review, we summarize the literature on thyroid function in cardiovascular diseases, both as a risk factor as well as in the setting of cardiovascular diseases such as heart failure or acute MI, and outline the effect of thyroid hormone replacement therapy for reducing the risk of cardiovascular disease.

A model for chronic, intrahypothalamic thyroid hormone administration in rats.

In addition to the direct effects of thyroid hormone (TH) on peripheral organs, recent work showed metabolic effects of TH on the liver and brown adipose tissue via neural pathways originating in the hypothalamic paraventricular and ventromedial nucleus (PVN and VMH). So far, these experiments focused on short-term administration of TH. The aim of this study is to develop a technique for chronic and nucleus-specific intrahypothalamic administration of the biologically active TH tri-iodothyronine (T3). We used beeswax pellets loaded with an amount of T3 based on in vitro experiments showing stable T3 release (∼5 nmol l(-1)) for 32 days. Upon stereotactic bilateral implantation, T3 concentrations were increased 90-fold in the PVN region and 50-fold in the VMH region after placing T3-containing pellets in the rat PVN or VMH for 28 days respectively. Increased local T3 concentrations were reflected by selectively increased mRNA expression of the T3-responsive genes Dio3 and Hr in the PVN or in the VMH. After placement of T3-containing pellets in the PVN, Tshb mRNA was significantly decreased in the pituitary, without altered Trh mRNA in the PVN region. Plasma T3 and T4 concentrations decreased without altered plasma TSH. We observed no changes in pituitary Tshb mRNA, plasma TSH, or plasma TH in rats after placement of T3-containing pellets in the VMH. We developed a method to selectively and chronically deliver T3 to specific hypothalamic nuclei. This will enable future studies on the chronic effects of intrahypothalamic T3 on energy metabolism via the PVN or VMH.

The Thyroid and the Kidney: A Complex Interplay in Health and Disease

Thyroid hormones may directly affect the kidney and altered kidney function may also contribute to thyroid disorders. The renal manifestations of thyroid disorders are based on hemodynamic alterations or/and to direct effects of thyroid hormones. The renin-angiotensin system plays a crucial role in the cross-talk between the thyroid and the kidney. Hypothyroidism may be accompanied by an increase of serum creatinine and reduction of glomerular filtration rate (GFR), whereas hyperthyroidism may increase GFR. Treatment of thyroid disorders may lead to normalization of GFR. Primary and subclinical hypothyroidism and low triiodothyronine (T3) syndrome are common features in patients with chronic kidney disease (CKD). In addition low levels of thyroid hormones may predict a higher risk of cardiovascular and overall mortality in patients with end-stage renal disease. The causal nature of this correlation remains uncertain. In this review, special emphasis is given to the thyroid pathophysiology, its impact on kidney function and CKD and the interpretation of laboratorial findings of thyroid dysfunction in CKD.

Expression of the Skeletal Calsequestrin Isoform in Normal and Regenerated Skeletal Muscles and in the Hearts of Rats With Altered Thyroid Status

We have investigated expression of skeletal calsequestrin (CSQ1) and fiber type composition in normal and regenerated fast and slow skeletal muscles and in the left heart ventricles of euthyroid (EU), hypothyroid (HY) and hyperthyroid (TH) adult inbred Lewis strain rats. The CSQ1 level was determined by SDS-PAGE followed by Western blot analysis. CSQ1 gene expression was assessed using reverse transcription and subsequent real time polymerase chain reaction. Muscle regeneration was achieved by intramuscular grafting of either soleus or extensor digitorum longus (EDL) from 3- to 4-week-old rats to either EDL or soleus muscle of 2-month-old rats. The fiber type composition was assessed by a stereological method applied to stained muscle cross sections. We found that the protein and mRNA levels for CSQ1 were highest in the EDL muscle, the relative CSQ1 protein levels in the soleus muscle were two times lower and the transcript levels more than 5 times lower compared to the EDL. In the left heart ventricle, protein isoform and CSQ1 transcript were also present, although at protein level, CSQ1 was hardly detectable. TH status increased and HY status decreased the expression of CSQ1 in the EDL, but its relative levels in the soleus and in the heart did not change. The regenerated soleus transplanted into EDL, as well as EDL transplanted into soleus exhibited protein and mRNA levels of CSQ1 corresponding to the host muscle and not to the graft source. TH status increased the percentages of the fastest 2X/D and 2B fibers at the expense of slow type 1 and fast 2A fibers in the EDL and that of fast 2A fibers in the soleus at the expense of slow type 1 fibers. HY status led to converse fiber type changes. We suggest that the observed changes in CSQ1 levels in TH and HY compared to EU rats can be related to fiber type changes caused by alteration of the thyroid status rather than to the direct effect of thyroid hormones on CSQ1 gene expression.

Thyroid Hormone Accelerates the Differentiation of Adult Hippocampal Progenitors

Disrupted thyroid hormone function evokes severe physiological consequences in the immature brain. In adulthood, although clinical reports document an effect of thyroid hormone status on mood and cognition, the molecular and cellular changes underlying these behavioural effects are poorly understood. More recently, the subtle effects of thyroid hormone on structural plasticity in the mature brain, in particular on adult hippocampal neurogenesis, have come to be appreciated. However, the specific stages of adult hippocampal progenitor development that are sensitive to thyroid hormone are not defined. Using nestin-green fluorescent protein reporter mice, we demonstrate that thyroid hormone mediates its effects on hippocampal neurogenesis by influencing Type 2b and Type 3 progenitors, although it does not alter proliferation of either the Type 1 quiescent progenitor or the Type 2a amplifying neural progenitor. Thyroid hormone increases the number of doublecortin (DCX)-positive Type 3 progenitors, and accelerates neuronal differentiation into both DCX-positive immature neurones and neuronal nuclei-positive granule cell neurones. Furthermore, we show that this increase in neuronal differentiation is accompanied by a significant induction of specific transcription factors involved in hippocampal progenitor differentiation. In vitro studies using the neurosphere assay support a direct effect of thyroid hormone on progenitor development because neurospheres treated with thyroid hormone are shifted to a more differentiated state. Taken together, our results indicate that thyroid hormone mediates its neurogenic effects via targeting Type 2b and Type 3 hippocampal progenitors, and suggests a role for proneural transcription factors in contributing to the effects of thyroid hormone on neuronal differentiation of adult hippocampal progenitors.

Plasma C‐type natriuretic peptide forms and thyroid status in prepubertal children with acquired thyroid disease

C-type natriuretic peptide (CNP) and thyroid hormone (TH) are essential for normal skeletal growth. Plasma CNP peptides correlate with growth velocity, but the relationship between thyroid status and CNP production is unknown. This study examined the impact of restoring normal TH levels on CNP and height velocity (HV) in children with acquired hypo- and hyperthyroidism. We performed a prospective, observational study in prepubertal children with acquired hypothyroidism (n = 15) and hyperthyroidism (n = 12). Blood levels of CNP, amino-terminal proCNP (NTproCNP), bone-specific alkaline phosphatase (BSAP), IGF-I and TH levels were measured before and during the first 6 months of standard treatment for hypo- and hyperthyroidism, and correlations were determined. At baseline, HV, CNP, NTproCNP and BSAP were significantly higher in hyper- than in hypothyroid subjects. Changes in TH after treatment were closely coupled to change in CNP and NTproCNP in hyperthyroid, but not in hypothyroid, children. In addition, a positive association of HV with CNP peptides was found during treatment of hyperthyroidism. Normalizing TH did not correlate with changes in BSAP or IGF-I in either group. Plasma CNP peptides are higher in children with hyperthyroidism than in those with hypothyroidism at diagnosis and, in hyperthyroid children, change concordantly with TH and HV during treatment. Differential responses of CNP in the two groups suggest CNP production is dependent on growth plate activity and not a direct effect of TH on CNP gene expression. Our findings suggest novel mechanisms underlying changes in skeletal response during treatment in children with acquired thyroid disease.

Thyroid bone disease

Thyroid bone disease

Distribution of subpopulations of dendritic cells in peripheral blood of patients treated with exogenous thyrotropin

BackgroundDendritic cells (DCs) play a major role as regulators of inflammatory events associated with thyroid pathology. The immunoregulatory function of DCs depends strongly on their subtype, as well as maturation and activation status. Numerous hormonal factors modulate the immune properties of DCs, however, little is known about effects exerted by the hypothalamus-pituitary-thyroid-axis. Recently, we have shown a direct regulatory influence of thyroid hormones (TH) on human DCs function. The aim of the present study was to analyze the effect of systemically administered thyrotropin (TSH) on human blood DCs ex vivo.MethodsBlood samples for the cytometric analysis of peripheral blood plasmacytoid and myeloid DCs subtypes were collected from patients subjected to total thyroidectomy because of differentiated thyroid carcinoma at 2 time points: (i) directly before the commencement of TSH administration and (ii) 5 days after first TSH injection. The whole blood quantitative and phenotypic analysis of plasmacytoid and myeloid DCs subtypes was performed by flow cytometry.ResultsAdministration of TSH did not influence the percentage of plasmacytoid DCs in peripheral blood of study participants. Also the percentage of the two main myeloid DCs subpopulations – CD1c/BDCA1+ DCs and CD141/BDCA3+ DCs did not change significantly. TSH administration had no effect on the surface expression of CD86 – one of the major costimulatory molecules – neither in the whole peripheral blood mononuclear cell (PBMC) fraction nor in particular DCs subtypes.ConclusionsIn the present study, we demonstrated no influence of systemic TSH administration on human peripheral blood DCs subtypes. These results are in accordance with our previous work suggesting the direct effect of TH on human DCs ex vivo.

Thyroid Disorders and Hypocoagulability

This review focuses attention on some practical aspects of the relationship between thyroid disorders and hypocoagulability, as related to an impairment of hemostasis and fibrinolysis. An understanding of this topic in daily clinical practice is important given that the interaction between hemostatic abnormalities and thyroid disorders is still poorly recognized by the medical community. Even if the bleeding tendency is in general mild and may be reversed by restoration of an euthyroid state, severe hemorrhagic events may complicate the course of both hyper- and hypothyroidism, as precipitated by such conditions as thrombocytopenia, acquired von Willebrand syndrome, and acquired hemophilia. The pathogenesis of the hemostatic abnormalities resides in either the direct effect of thyroid hormones or some conditions in an autoimmune mechanism. Physicians and endocrinologists should pay close attention to both clinical hemorrhagic events in their patients as well as to any laboratory abnormalities identified by blood coagulation testing.