Hypothalamic-pituitary-thyroid Research Articles

Stress and Molecular Drivers for Cancer Progression: A Longstanding Hypothesis.

Stress management is becoming very important part of cancer patient care. Chronic stressors lead to boost tumorigenesis and promote cancer development, recurrence, and drug resistant leading to poor health outcomes. The Hypothalamic-Pituitary-Adrenal (HPA) axis, which is activated by stress, also regulates Hypothalamic-Pituitary-Thyroid (HPT) axis. Stress related changes in immune function and inflammatory response also leads to reduced immune surveillance resulting in tumorigenesis. This article explores the hormonal axis impacted by stress and how chronic stress can lead to poor outcome of a cancer patient.

The impact of metformin on hypothalamic-pituitary-thyroid axis activity in postmenopausal women with untreated non-autoimmune subclinical hypothyroidism.

Metformin was found to reduce elevated thyrotropin levels in subjects with hypothyroidism. The impact on thyrotropin levels was stronger in women receiving oral contraceptive pills than in women not using any contraception. The aim of the present study was to determine whether physiological levels of oestradiol determine the effect of metformin on hypothalamic-pituitary-thyroid axis activity. The study population included 40 postmenopausal women with prediabetes and untreated non-autoimmune subclinical hypothyroidism, using (group A; n=18) or not using (group B; n=22) oestradiol replacement therapy. Over the entire study periods, all subjects were treated with metformin (2.55-3.00g daily). Plasma levels of glucose, lipids, insulin, thyrotropin, free thyroxine, free triiodothyronine, prolactin, gonadotropins and oestradiol were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at the beginning of the study and 6months later. At entry, both groups differed in gonadotropin and oestrogen levels. Despite improving insulin sensitivity, thyrotropin levels and Jostel's thyrotropin index in both study groups, these effects were stronger in group A than group B. Only in group A, metformin increased SPINA-GT, while only in group B the drug decreased FSH levels. Levels of the other variables remained at a similar level throughout the study. The effect of treatment on thyrotropin levels correlated with its baseline values, as well as with the improvement of insulin sensitivity. The results obtained suggest that the impact of metformin on hypothalamic-pituitary-thyroid axis activity depends on the oestrogen status of patients.

Clinical presentation and management of hypophysitis: An observational study of case series

Background: Hypophysitis is described as a rare chronic inflammatory affection of the pituitary gland. However, to date, its pathogenesis has not been completely cleared up. Clinical features are polymorphic, including symptoms related to inflammatory compression and/or hypopituitarism. Laboratory tests determine hormone deficiencies orientating replacement therapy’s protocol. MRI of the hypothalamic-pituitary region is crucial in exhibiting major radiological signs such as pituitary homogeneous enlargement and gland stalk’s thickening. The etiological diagnosis is still challenging without affecting the management strategy. Corticosteroids have widely been used but a close follow-up without any treatment has also been approved.Case Description: In this report, seven patients with hypophysitis have been collected over a period of 6 years. The average age of our patients was 32.1 years ± 11.8 with a female predominance (71.4%). Panhypopituitarism was objective in 42.9% of cases, a combined deficiency of the hypothalamic-pituitary thyroid, adrenal and gonadal axes in 28.6% of cases. A central diabetes insipidus was noted in 42.9% of the patients. Idiopathic hypophysitis was the most common etiology. The use of long course corticosteroids was required in 28.6% when compressive signs were reported.Conclusion: Hypophysitis remains a rare disease with nonspecific clinical and radiological patterns. Autoimmune origin seems to be the most frequent etiology. No guidelines have been established for hypophysitis management and the evolution is still unpredictable.

Insulin resistance attenuates the impact of levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in women with autoimmune subclinical hypothyroidism.

Subjects with both subclinical hypothyroidism and autoimmune thyroiditis are frequently diagnosed with metabolic syndrome. The purpose of the current study was to investigate whether insulin sensitivity determines levothyroxine action on thyroid antibody titres and hypothalamic-pituitary-thyroid axis activity in young women with autoimmune subclinical hypothyroidism. The study population consisted of three age-, thyroid antibody- and thyrotropin-matched groups of women with autoimmune subclinical hypothyroidism: metformin-naive women with insulin resistance (group A, n=31), women receiving metformin treatment because of insulin resistance (group B, n=32), as well as metformin-naive women with normal insulin sensitivity (group C, n=35). Throughout the study, all subjects were treated with levothyroxine. Titres of thyroid peroxidase and thyroglobulin antibodies, as well as circulating levels of glucose, insulin, lipids, thyrotropin, free thyroid hormones, prolactin, high-sensitivity C-reactive protein (hsCRP) and 25-hydroxyvitamin D were determined at the beginning of the study and 6months later. Except for two individuals, all patients completed the study. At baseline, group A differed from groups B and C in circulating levels of glucose, HDL-cholesterol, triglycerides, hsCRP, 25-hydroxyvitamin D and the homeostatic model assessment 1 of insulin resistance (HOMA1-IR). Although levothyroxine reduced thyroid antibody titres, decreased thyrotropin levels and increased free thyroid hormone levels in all studied groups, the effect on antibody titres and thyrotropin levels was more pronounced in groups B and C than in group A. The impact of levothyroxine on thyroid antibody titres correlated with baseline and treatment-induced changes in HOMA1-IR, thyrotropin, hsCRP and 25-hydroxyvitamin D. The results of the current study suggest that the impact of exogenous levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity is determined by insulin sensitivity.

Thyroid Function in Preterm/Low Birth Weight Infants: Impact on Diagnosis and Management of Thyroid Dysfunction.

Maternal thyroid hormone crosses the placenta to the fetus beginning in the first trimester, likely playing an important role in fetal development. The fetal thyroid gland begins to produce thyroid hormone in the second trimester, with fetal serum T4 levels gradually rising to term. Full maturation of the hypothalamic-pituitary-thyroid (HPT) axis does not occur until term gestation or the early neonatal period. Postnatal thyroid function in preterm babies is qualitatively similar to term infants, but the TSH surge is reduced, with a corresponding decrease in the rise in T4 and T3 levels. Serum T4 levels are reduced in proportion to the degree of prematurity, representing both loss of the maternal contribution and immaturity of the HPT axis. Other factors, such as neonatal drugs, e.g., dopamine, and non-thyroidal illness syndrome (NTIS) related to co-morbidities contribute to the “hypothyroxinemia of prematurity”. Iodine, both deficiency and excess, may impact thyroid function in infants born preterm. Overall, the incidence of permanent congenital hypothyroidism in preterm infants appears to be similar to term infants. However, in newborn screening (NBS) that employ a total T4-reflex TSH test approach, a higher proportion of preterm babies will have a T4 below the cutoff, associated with a non-elevated TSH level. In NBS programs with a primary TSH test combined with serial testing, there is a relatively high incidence of “delayed TSH elevation” in preterm neonates. On follow-up, the majority of these cases have transient hypothyroidism. Preterm/LBW infants have many clinical manifestations that might be ascribed to hypothyroidism. The question then arises whether the hypothyroxinemia of prematurity, with thyroid function tests compatible with either non-thyroidal illness syndrome or central hypothyroidism, is a physiologic or pathologic process. In particular, does hypothyroxinemia contribute to the neurodevelopmental impairment common to preterm infants? Results from multiple studies are mixed, with some randomized controlled trials in the most preterm infants born <28 weeks gestation appearing to show benefit. This review will summarize fetal and neonatal thyroid physiology, thyroid disorders specific to preterm/LBW infants and their impact on NBS for congenital hypothyroidism, examine treatment studies, and finish with comments on unresolved questions and areas of controversy.

Diaphragma sellae sinking can predict the onset of hyponatremia after transsphenoidal surgery for pituitary adenomas.

Sinking of the diaphragma sellae (DS) may stretch the pituitary stalk, which in turn impairs neurohypophyseal function; thus, it may play a role in the development of postoperative hyponatremia. We aimed to assess the factors influencing the development of hyponatremia after transsphenoidal surgery (TSS) for pituitary adenomas and analyze the effect of DS sinking on hyponatremia. After applying the inclusion and exclusion criteria, we retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. The pituitary gland was scanned using a 3.0-T magnetic resonance imaging, and sagittal and coronal images were acquired. We evaluated the following: preoperative and postoperative hypothalamus‒pituitary‒thyroid axis function, hypothalamus‒pituitary‒adrenal axis function, intra-operative cerebrospinal fluid leaks, diabetes insipidus, hyponatremia, time from the day of surgery to the day of discharge, and time of hyponatremia onset. Of the 460 patients who had microscopic TSS for pituitary adenoma, 83 experienced postoperative hyponatremia. Hyponatremia occurred approximately 5.25days postoperatively and persisted for 5.54days. The lowest average blood sodium level was 123.9mEq/L, which occurred at 7.49days after surgery. Logistic regression analysis showed that the risk of hyponatremia was greater for patients with a significant DS sinking depth, a large pituitary stalk deviation angle difference, and a longer postoperative "measurable pituitary stalk". The difference in blood sodium levels between pre-TSS and 2days post-TSS was also an independent predictor of postoperative hyponatremia onset. DS sinking plays an important role in predicting hyponatremia onset after TSS for pituitary adenomas.

Evaluation of the hypothalamic-pituitary-thyroid axis function in a non-human primate animal model with chronic exposure to methamphetamine

Psychostimulants, such as amphetamine-type stimulants, induce alterations in hypothalamic-pituitary-thyroid (HPT) axis function. In this study, we sought to investigate the changes in the HPT axis using a wellcharacterized non-human primate model after chronic exposure to methamphetamine (MA). The data collected from 10 adult monkeys were retrospectively studied, assigning them into two groups—the control group (saline) and MA group. MA was injected for 4 weeks with gradually increasing dose, and later injected maintenance doses for 24 weeks. We collected and tested the blood samples on a weekly basis for T4, free T4, T3, free T3, TSH, TgAb, and TPOAb. We used western blotting and quantitative reverse transcription polymerase chain reaction techniques to test the protein and mRNA expression of bcl-2, Bax, and thyroid stimulating hormonereceptor. The MA group had significantly higher levels of T4, FT4, T3, and TSH than the control group. However, no significant difference was observed in FT3, TGAb, and TPOAb. Compared with the control group, most of the thyroid from the MA group consistently showed markedly disordered structure: varied size, lymphocytic infiltration, and local fibrosis. In the MA group, the protein and mRNA expression of Bax were significantly higher than the control group, whereas the protein and mRNA expression of Bcl-2 and TSH-R were significantly lower. These results indicate that chronic exposure to MA can lead to changes in the HPT axis function and induce apoptosis or other microdamage to the thyroid gland in a non-human primate model.

Thyroid Function Tests During Hospitalization for SARS-CoV-2 Infection Revisited

Thyroid Function Tests During Hospitalization for SARS-CoV-2 Infection Revisited

Sex Dimorphic Changes in Trh Gene Methylation and Thyroid-Axis Response to Energy Demands in Maternally Separated Rats.

The hypothalamus-pituitary-thyroid (HPT) axis regulates energy balance through the pleiotropic action of thyroid hormones. HPT basal activity and stimulation by cold or voluntary exercise are repressed by previous chronic stress in adults. Maternal separation (MS) modifies HPT basal activity; we thus studied the response of the axis to energy demands and analyzed possible epigenetic changes on Trh promoter. Nonhandled (NH) or MS male Wistar rats were cold exposed 1 h at adulthood; Trh expression in the hypothalamic paraventricular nucleus (PVN) and serum thyrotropin (TSH) concentration were increased only in NH rats. Two weeks of voluntary exercise decreased fat mass and increased Trh expression, and thyroid hormones concentration changed proportionally to running distance in NH male rats and MS male rats. Although NH females ran more than MS and much more than males, exercise decreased body weight and fat mass only in NH rats with no change on any parameter of the HPT axis but increased Pomc expression in arcuate-nucleus of NH and Npy in MS females. Overall, the methylation pattern of PVN Trh gene promoter was similar in NH males and females; MS modified methylation of specific CpG sites, a thyroid hormone receptor (THR)-binding site present after the initiation site was hypomethylated in MS males; in MS females, the THR binding site of the proximal promoter (site 4) and 2 sites in the first intron were hypermethylated. Our studies showed that, in a sex-dimorphic manner, MS blunted the responses of HPT axis to energy demands in adult animals and caused methylation changes on Trh promoter that could alter T3 feedback.

Lack of Evidence for a Relationship Between the Hypothalamus-Pituitary-Adrenal and the Hypothalamus-Pituitary-Thyroid Axis in Adolescent Depression.

In adults with major depressive disorder (MDD), a dysfunction between the hypothalamus-pituitary-adrenal (HPA) and the hypothalamus-pituitary-thyroid (HPT) axis has been shown, but the interaction of both axes has not yet been studied in adolescent major depressive disorder (MDD). Data from 273 adolescents diagnosed with MDD from two single center cross-sectional studies were used for analysis. Serum levels of thyrotropin (TSH), free levothyroxine (fT4), and cortisol were determined as indicators of basal HPT and HPA axis functioning and compared to that of adolescent controls by t-tests. Quantile regression was employed in the sample of adolescents with MDD to investigate the relationship between both axes in the normal as well as the pathological range of cortisol levels, considering confounders of both axes. In adolescent MDD, cortisol levels and TSH levels were significantly elevated in comparison to controls (p = <.001, d = 1.35, large effect size, and p = <.001, d = 0.79, moderate effect size, respectively). There was a positive linear relationship between TSH and cortisol (p = .003, d = 0.25, small effect size) at the median of cortisol levels (50th percentile). However, no relationship between TSH and cortisol was found in hypercortisolemia (cortisol levels at the 97.5th percentile). These findings imply that HPT and HPA axis dysfunction is common in adolescents with MDD and that function of both axes is only loosely related. Moreover, the regulation of the HPA and HPT axis are likely subjected to age-related maturational adjustments since findings of this study differ from those reported in adults.

Physiological and transcriptomic changes of zebrafish (Danio rerio) embryos-larvae in response to 2-MIB exposure

2-Methylisoborneol (2-MIB), a natural odorous substance, is widely distributed in water environment, but there is a paucity of information concerning its systemic toxicity. Herein, we investigated the effects of 2-MIB exposure on developmental parameters, locomotive behavior, oxidative stress, apoptosis and transcriptome of zebrafish. Zebrafish embryos exposed to different concentrations (0, 0.5, 5 and 42.8 μg/L) of 2-MIB showed no changes in mortality, hatchability, and malformation rate, but the body length of zebrafish larvae was significantly increased in a dose-dependent manner, and accompanied by the changes of growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis genes. Moreover, the swimming activity of zebrafish larvae increased, which may be due to the increase of acetylcholinesterase (AChE) activity. Meanwhile, 2-MIB caused oxidative stress and apoptosis in zebrafish larvae by altering the NF-E2-related factor 2 (Nrf2) and mitochondrial signaling pathways, respectively. Transcriptome sequencing assay showed that the phototransduction signaling pathway was significantly enriched, and most of the genes in this pathway exhibited enhanced expression after exposure to 2-MIB. These findings provide an important reference for risk assessment and early warning to 2-MIB exposure.

Lambda-cyhalothrin and its common metabolite differentially modulate thyroid disruption effects in Chinese lizards (Eremias argus)

Although the thyroid effects of pyrethroids on non-target organisms have been well studied, research on the toxic effects of pyrethorid metabolites is still limited. In this study, a type of representative Chinese lizards was used as the model and exposed to environmentally relevant concentrations of lambda-cyhalothrin (LCT) and 3-phenoxybenzoic acid (PBA) through cultivation on 3 and 15 μg/g soil to evaluate and compare their disruption effects on lizard hypothalamus-pituitary-thyroid (HPT) axis. The alterations occurred in lizards were examined through histopathology analyses, hormone level and gene expression measurements, the molecular binding interactions were analyzed in silico as well. The results showed that LCT exposure increased the plasma triiodothyronine (T3), thyroxine (T4) levels and the follicular epithelium heights of thyroid glands, whereas PBA induced no or much less degree of alterations. The ugt and dio2 gene expression in lizard liver was significantly up-regulated by LCT, but PBA caused less or opposite effects. The in silico homology simulation illustrated that LCT binds to TRα in the similar way of T3, while PBA binds to TRβ in the same manner of T3. The results demonstrated that both LCT and its metabolite-PBA could disrupt lizard HPT axis but through distinct mechanisms. The information would facilitate the comprehensive environmental safety assessment of pyrethroids.

Sepsis as a Pan-Endocrine Illness-Endocrine Disorders in Septic Patients.

Sepsis is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. One of the elements of dysregulated host response is an endocrine system disorder. Changes in its functioning in the course of sepsis affect almost all hormonal axes. In sepsis, a function disturbance of the hypothalamic–pituitary–adrenal axis has been described, in the range of which the most important seems to be hypercortisolemia in the acute phase. Imbalance in the hypothalamic–pituitary–thyroid axis is also described. The most typical manifestation is a triiodothyronine concentration decrease and reverse triiodothyronine concentration increase. In the somatotropic axis, a change in the secretion pattern of growth hormone and peripheral resistance to this hormone has been described. In the hypothalamic–pituitary–gonadal axis, the reduction in testosterone concentration in men and the stress-induced “hypothalamic amenorrhea” in women have been described. Catecholamine and β-adrenergic stimulation disorders have also been reported. Disorders in the endocrine system are part of the “dysregulated host response to infection”. They may also affect other components of this dysregulated response, such as metabolism. Hormonal changes occurring in the course of sepsis require further research, not only in order to explore their potential significance in therapy, but also due to their promising prognostic value.

Hypothalamic-pituitary-thyroid axis function in female adolescent nonsuicidal self-injury and its association with comorbid borderline personality disorder and depression

ObjectivesBehavioral disturbances in adolescence are potentially linked to aberrant functioning of the thyroid gland. Accordingly, alterations of the hypothalamic-pituitary-thyroid (HPT) axis might impact psychopathological development. Yet corresponding research in adolescents with nonsuicidal self-injury (NSSI) and comorbid mental disorders is scarce. MethodsThe present study examined HPT axis functioning in adolescents with NSSI compared to healthy controls (HC) using blood-based assays of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and the ratio of these hormones (fT3/fT4 ratio). Cortisol was additionally examined to contrast HPT axis functioning with a well-established biomarker of stress responsivity. Moreover, associations between clinical characteristics, HPT axis and HPA axis functioning were investigated. Female adolescents meeting NSSI criteria according to DSM-5 criteria (n = 117) were compared to adolescent HC (n = 41). Standardized serum-based endocrinological assays and interview- and questionnaire-based psychiatric assessments were used. Smoking status was included as covariate for all analyses. ResultsNSSI patients displayed altered HPT axis functioning as fT3/fT4 ratio values were blunted in comparison to HC. Negative correlations were further present between fT3, fT3/fT4 ratio and severity of BPD symptoms, depression scores and symptomatic distress. TSH correlated negatively with severity of BPD symptoms and symptomatic distress exclusively. Cortisol values differed neither significantly between experimental groups nor correlated significantly with clinical characteristics. ConclusionsLongitudinal examinations, assessing links between psychopathology and endocrinological alterations, are warranted to address potential clinical implications of thyroid markers in child and adolescent psychiatry.

Analysis of Hypothalamic TRH Neurons in Regulating Thyroid Hormone Levels

Thyroid hormone (TH) is a major regulator of development and metabolism. An important mechanism controlling TH production is the negative feedback at the hypothalamic and pituitary level and it has been suggested that thyroid hormone receptor β (TRβ) is the main mediator of TH actions in the hypothalamic paraventricular nucleus (PVN). Nevertheless, the direct actions of TH and TRβ in the negative regulation of TRH have yet to be demonstrated in vivo. Here we used two approaches to investigate the TRH neuron. First, we used a chemogenetic tool to directly investigate the role of TRH neurons on the regulation of thyroid hormone levels. Mice expressing Cre-recombinase in TRH neurons received bilateral injections of the activating designer receptors exclusively activated by designer drugs (DREADD) directly into the PVN. Activation of TRH neurons produced a rapid and sustained increase in circulating TSH levels in both males and females. TSH levels increased approximately 10-fold from baseline within 15 minutes of injection of CNO, returning to baseline within 2.5 hours. TH levels were increased approximately 2-fold in males and females. Therefore, using a chemogenetic approach, we were able to directly evaluated the role of PVN TRH neurons on the control of thyroid activity, for the first time. Next, we generated mice deficient in TRβ specifically in neurons expressing melanocortin 4 receptor (MC4R), which overlaps with TRH expression in the PVN. Knockout mice (KO) developed normally and showed no change in TH and TSH levels. TRH mRNA levels in the PVN of KO mice were similar to control mice. To investigate if the deletion of TRβ in the PVN changes the sensitivity of the HPT axis to T3, mice were rendered hypothyroid and given increasing doses of T3 for 2 weeks. Results show no difference in TRH mRNA or serum TSH between controls and KO. Surprisingly, despite the presence of detectable genomic recombination on the TRβ gene in the PVN, there was no difference in TRβ mRNA expression between control and KO mice, suggesting that either MC4R-positive neurons do not express TRβ or they represent a very small population of TRβ-positive cells in the PVN. Present data show that TRH neuron activation rapidly stimulates TSH release and increases TH levels, demonstrating a major role of these neurons in the regulation of the hypothalamic-pituitary-thyroid (HPT) axis. Nevertheless, deletion of TRβ from MC4R neurons had no major effect on either TRH or TH levels in in mice. Additionally, TRβ in MC4R-positive TRH neurons in the PVN is not necessary for TH-induced suppression of TRH mRNA. Although further studies are necessary, these data suggest that there are distinct populations of hypophysiotropic TRH neurons in the PVN, some of which are not regulated by thyroid hormone and TRβ.

Leptin Regulates Hypothalamus-Pituitary-Thyroid Axis via TRH in Energy Expenditure During Fasting: The Study on TRH Deficient Mouse

Abstract Objectives: The hypothalamic-pituitary-thyroid (HPT) axis plays a significant role in the regulation of energy expenditure. Previous reports demonstrated that thyroid hormones are critically involved in metabolic process, and hypothyroidism was induced by fasting. The mechanism by which TRH neurons sense alterations in peripheral energy stores is supposed to be regulated by leptin, an adipose tissue-derived hormone. Leptin was initially considered as a hormone to prevent obesity, it was later showed that the major role of leptin is to signal the switch from the fed to the starved state at the hypothalamic level. Recently, we generated TRH-deficient mice (TRH-/-). The mice exhibit tertiary/central hypothyroidism with characteristic elevation of serum TSH level and diminished TSH biological activity. In this study, we used TRH-/- to investigate the physiological role of TRH in fasting energy expenditure, including the mechanism regulated by leptin. Methods: Twelve-week-old male F2 hybrid ICR mice were used in this study. (1) Wild-type mice (WT) and TRH-/- were fasted up to 50 hrs. Blood samples were collected from tail veins at various points. Anterior pituitary samples were obtained from euthanized mice before and after 16 hrs fasting. (2) Serum free T4 (FT4) and TSH levels assessed. (3) The expression level of TSHβ mRNA in anterior pituitary were detected using qPCR assays. (4) We repeated these experiments using mice with leptin administration; leptin (0.5μg/g•BW) was administrated every 6 hours starting at after 2 hours fasting. Results: In WT, the level of FT4 was decreased chronologically during fasting to approximately 50% at 50 hrs after fasting. Serum TSH decreased to 70% and the expression level of TSHβ mRNA in anterior pituitary also decreased to 30% compared to before fasting. Administration of leptin recovered the level of FT4 to basal level. However, the level of serum TSH and TSHβ mRNA in pituitary were not recovered to basal levels. By contrast, in TRH-/-, the level of FT4 were also decreased after fasting indicating that the decrease of FT4 by fasting was independent of TRH. However, the level of FT4 was not recovered by leptin suggesting that the recovery of FT4 by leptin was TRH dependent. Serum TSH level decreased to 75% after fasting, and no recovery to basal level with leptin administration was observed in TRH-/- same as WT. In TRH-/-, the pituitary TSHβ mRNA expression level was about 50% of WT before fasting. It did not correlate with the serum TSH level. In addition, no increase in TSHβ mRNA expression level by leptin administration was observed in TRH-/-. These findings suggested that the TSHβ mRNA expression level in the pituitary is completely TRH-dependent in TRH-/-. Conclusion: Fasting-induced hypothyroxinemia was independent of TRH. Leptin regulates H-P-T axis via TRH during fasting-induced energy expenditure. Leptin may modulate the biological activity of TSHβ.

Transient hypothyroxinemia of prematurity and its risk factors in an extramural neonatal intensive care unit.

Thyroid functions in preterm newborns may be altered in the first week of life. Hypothyroxinemia has been commonly reported in these babies, which could be due to the immaturity of the hypothalamic pituitary thyroid axis or acute illness. It could have a long-term impact on the developing brain of these babies. We conducted this study to estimate the incidence of transient hypothyroxinemia of prematurity (THOP) and to determine its risk factors. We analyzed thyroid stimulating hormone (TSH) and free T4 levels of 64 preterm neonates admitted in the neonatal intensive care unit. TSH and free T4 levels were measured in the first week and then at 14-21 days of life to estimate the incidence of THOP and determine its risk factors. We also estimated the incidence of congenital hypothyroidism (CH) and delayed TSH elevation in CH. Risk analysis was conducted using simple and multiple logistic regression, and numerical data was compared using the Mann Whitney U test and t test. THOP was seen in 25% of the preterm babies. Caesarean delivery, presence of one or more morbidities, mechanical ventilation, birth weight ≥ 1,500 g, and gestational age ≥ 32 weeks were identified as risk factors for THOP based on simple logistic regression. In multiple regression, mechanical ventilation and gestational age ≥ 32 weeks were significantly associated with THOP. CH was seen in 2 (3.1%) babies, and 1 of these cases had delayed TSH elevation. Thyroid abnormalities are common in preterm admitted neonates. Mechanical ventilation is an independent risk factor for development of THOP.

Thyroid function and dysfunction in preterm infants-Challenges in evaluation, diagnosis and therapy.

Thyroid hormone levels have a crucial role for optimal brain development from gestation through the first 2 postnatal years. However, thyroid hormones vary with gestational age, and their levels vary between term and preterm infants. Preterm newborns are prone to thyroid dysfunction which is now more frequently observed with the advances of neonatal care and improved survival of extremely premature infants. Thus, hypothyroxinaemia of prematurity associated with delayed TSH elevation is very common in low birth weight premature infants most likely due to the immaturity of the hypothalamic-pituitary thyroid axis. Furthermore, postnatal illness, medications and iodine status may contribute to the thyroid dysfunction or affect the interpretation of the thyroid function tests. Despite available guidelines, timing of screening and optimal treatment of thyroid dysfunction in premature infants remains controversial. Furthermore, it is unknown whether untreated thyroid dysfunction in premature babies affects neurodevelopmental outcome. In the vast majority of preterm infants, hypothyroxinaemia is transient; however, permanent hypothyroidism due to thyroid dysgenesis or enzyme defects might also occur. Therefore, careful monitoring of thyroid function and long-term follow-up is needed to assess an appropriate therapeutic approach. This article reviews thyroid physiology in preterm infants, the influences of gestation and other neonatal conditions on thyroid function tests, optimal timing of screening and possible predictors to differentiate transient hypothyroxinaemia from permanent hypothyroidism.

Study of thyroid profile in relation to glycemic control in type 2 diabetes mellitus patients

Diabetes mellitus is an endocrine metabolic disorder that causes significant morbidity and mortality around the world. Thyroid gland dysfunction is a significant problem in diabetic patients. In diabetics, hypothyroidism is the most common thyroid abnormality. When compared to healthy people, diabetic patients have a higher incidence of thyroid abnormalities. Diabetes mellitus treatment can be complicated due to irregular thyroid activity. A total of 120 people were studied, with 60 patients with type 2 diabetes mellitus (Cases group) and 60 healthy people (Control group). Patients with and without strong diabetic control are represented in 60 cases. Both subjects had their fasting venous blood samples taken. In both the cases and control groups, fasting blood sugar, HbA1c, serum T3 (Triiodothyronine), serum T4 (Thyroxine), and serum TSH (Thyroid-stimulating hormone) were measured.The thyroid abnormality was significantly seen in diabetic patients when compared to healthy individuals. The abnormality was more significant in patients with poor glycemic control. When comparing cases to controls, mean serum TSH levels were significantly higher, whereas mean serum T3 and T4 levels were significantly lower. Thyroid hormone levels in type 2 diabetics are abnormal due to a change in the hypothalamic–pituitary–thyroid axis. This in turn produces significant metabolic disturbances. This is more significant in diabetics with poor glycemic control. Routine screening for thyroid function should be done in diabetics, which helps in preventing complications. This contributes to improved treatment by lowering morbidity and improving quality of life.

Thyroid axis activity and dopamine function in depression

BackgroundSeveral lines of evidence suggest alterations in both hypothalamic-pituitary-thyroid (HPT) axis and dopamine (DA) function in depressed patients. However, the functional relationships between HPT and DA systems have not been well defined. MethodsWe examined thyrotropin (TSH) response to 0800 h and 2300 h protirelin (TRH) challenges, and adrenocorticotropic hormone (ACTH), cortisol and growth hormone (GH) responses to apomorphine (APO, a DA receptor agonist), in 58 drug-free DSM-IV major depressed inpatients without a suicidal behavior, and 22 healthy hospitalized controls. ResultsCompared with controls, patients showed 1) lower basal serum 2300 h-TSH, 2300 h-∆TSH, and ∆∆TSH (difference between 2300 h-∆TSH and 0800 h-∆TSH) levels, and 2) lower cortisol response to APO (∆COR). A negative relationship between ∆∆TSH values and hormonal responses to APO was observed in the depressed group, but not in the control group. When patients were classified on the basis of their ∆∆TSH status, patients with reduced ∆∆TSH values (< 2.5 mU/L) showed hormonal APO responses comparable to those of controls. Patients with normal ∆∆TSH values exhibited lower ∆ACTH, ∆COR, and ∆GH values than patients with reduced ∆∆TSH values and controls. ConclusionTaken together, these results suggest that hypothalamic DA function is unaltered in depressed patients with HPT dysregulation (i.e., increased hypothalamic TRH drive leading to altered TRH receptor chronesthesy on pituitary thyrotrophs). Conversely, hypothalamic DA-receptor function is decreased in patients with normal HPT axis activity. These findings are discussed in the context of the role of TRH as a homeostatic neuromodulator in depression.