Serum Free T4 Research Articles

Investigation of the effect of hyperthyroidism on endoplasmic reticulum stress and tran- sient receptor potential canonical 1 channel in the kidney

Background/aim Hyperthyroidism is associated with results in increased glomerular filtration rate as well as increased renin-angiotensin-aldosterone activation. The disturbance of Ca2+ homeostasis in the endoplasmic reticulum (ER) is associated with many diseases, including diabetic nephropathy and hyperthyroidism. Transient receptor potential canonical 1 (TRPC1) channel is the first cloned TRPC family protein. Although it is expressed in many places in the kidney, its function is uncertain. TRPC1 is involved in regulating Ca2+ homeostasis, and its upregulation increases ER Ca2+ level, activates the unfolded protein response, which leads to cellular damage in the kidney. This study investigated the role of TRPC1 in the kidneys of hyperthyroid rats in terms of ER stress markers that are glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), (protein kinase R (PKR)-like endoplasmic reticulum kinase) (PERK), Inositol-requiring enzyme 1 (IRE1).Materials and methods Twenty male rats were assigned into control and hyperthyroid groups (n = 10). Hyperthyroidism was induced by adding 12 mg/L thyroxine into the drinking water of rats for 4 weeks. The serum-free T3 and T4 (fT3, fT4), TSH, blood urea nitrogen (BUN), and creatinine levels were measured. The histochemical analysis of kidney sections for morphological changes and also immunohistochemical and western blot analysis of kidney sections were performed for GRP78, ATF6, PERK, IRE1, TRPC1 antibodies.Results TSH, BUN, and creatinine levels decreased while fT3 and fT4 levels increased in the hyperthyroid rat. The morphologic analysis resulted in the capillary basal membrane thickening in glomeruli and also western blot, and immunohistochemical results showed an increase in TRPC1, GRP78, and ATF6 in the hyperthyroid rat (p < 0.05).Conclusion In conclusion, in our study, we showed for the first time that the relationship between ER stress and TRPC1, and their increased expression caused renal damage in hyperthyroid rats.

The Comparison between Free Thyroxine and Thyroid-Stimulating Hormone Levels on Melasma Severity: A Cross-Sectional Study

Background: Melasma has been suspected to be linked with levels of thyroid hormone. There is no study that explains the association between thyroid hormone level with melasma severity. Objective: This study aims to find the discrepancies in the levels of thyroid hormone in varying severity of melasma by using two different measurement techniques. Methods: Subjects were chosen consecutively from the dermatology clinic at RSUPN Dr. Cipto Mangunkusomo hospital. Forty-eight patients participated in this study were categorized into mild melasma and moderate-severe melasma based on modified melasma area and severity index (mMASI) and Janus II measurement. Results: Statistically, mMASI measurement showed no significant association between varying melasma severity with levels of thyroid stimulating hormone and free T4 (FT4), P 0.375 and P 0.208, respectively. The Janus II examination using polarized light modality has a weak positive correlation with the serum FT4 level (r=0.3; P 0.039). Weak correlation was also found between the two measurement strategies, Janus II and mMASI (r= 0.314; P 0.03). Conclusion: There are no significant differences observed in levels of thyroid hormone between subjects with varying degrees of melasma severity.

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.

Lyme Disease: An Autoimmunity-Based “Destructive Thyroiditis” or Just Another “Non-Thyroidal Illness”?

There is considerable evidence that some Borrelial (Lyme spirochetal) proteins share significant antigenic properties with several thyroid-related proteins (e.g. TSH receptor, thyroglobulin, thyroid peroxidase) and can induce thyroid autoimmunity, sometimes associated with Hashimoto’s thyroiditis and perhaps also a “destructive thyroiditis” such as “silent” thyroiditis or “Hashitoxicosis.” As an acute illness, Lyme disease may also constitute a “non-thyroidal illness” capable of perturbing thyroid function tests without causing thyroid dysfunction. We report a 22-year old woman admitted with an acute paranoid schizophrenia, thyroid function tests consistent with autoimmunity, transient thyrotoxicosis (tachycardia, lid-lag, brisk DTR’s) and a greatly reduced radioiodine uptake. The thyroid was not palpably enlarged, nodular or tender. On screening assay, reactivity was demonstrated to 4 of 13 Borrelial proteins. Anti-Lyme IgM but not IgG, antibodies, were positive. This was consistent with recent Lyme disease infection. Serum TSH (NL: 0.358-3.74 mcU/ml), Free T4 (NL: 0.76-1.46 ng/dl), and Free T3 (NL: 2.18-3.98 pg/ml) were, respectively: Day1: 0.087 mcU/ml (suppressed), 1.52 ng/dl (slightly elevated), 2.07 pg/ml (slightly reduced); Day2: 0.148 (suppressed), 1.18 (normal), no FT3; Day4: 0.827 (normal), no FT4 or FT3; Day5: 1.66 (normal), 0.89 (normal), 1.77 (low). Anti-Tg and Anti-Peroxidase antibodies were both moderately elevated. Thyroid Stimulating Immunoglobulins were not elevated. The radioactive iodine uptake on Day4 was 2.8% (NL: 15-30% at 24 hr). Thyroid ultrasonogram was normal. An attractive explanation is that Lyme disease triggered a “destructive thyroiditis,” perhaps but not necessarily mediated by thyroid autoimmunity. This would account for the brief interval of thyrotoxicosis accompanied by a very low radioiodine uptake. Alternatively, Lyme disease, as an acute process, would expectedly be capable of eliciting the thyroid function abnormalities of “non-thyroidal illnesses” in general, as would acute psychosis, well-known to often resemble Graves’ disease at admission.

An Unusual Case of Hypopituitarism in a 68 Year Old Man With a Normal Appearing Pituitary Gland and a Remote History of Severe Headache Attributed to Possible Apoplexy

A 66-year-old previously healthy man was admitted to the hospital with severe hypotension and gastroenteritis symptoms, which were attributed to food poisoning. No one else who ate with him got sick. Random morning cortisol was found to be 0.6, which was followed by the Cortrosyn stimulation test. Baseline cortisol was 0.9, which went up to 2.0 mcg/dL in 30 minutes after Cortrosyn stimulation and 2.9 mcg per dl after an hour. He was treated with high dose steroids during his inpatient stay and sent home on physiologic steroid doses. He followed up in the Endocrinology clinic after hospital discharge. A review of old records showed he was prescribed testosterone about ten years prior for symptoms of hypogonadism, but he never took it. Detailed workup revealed hypopituitarism. Serum prolactin, growth hormone, IGF-1, LH, FSH, Testosterone, TSH, and free T4 were all decreased. Brain/pituitary MRI, however, showed no pituitary abnormalities. All pituitary hormones were checked multiple times and were found to be consistently low. He was given hormone replacement therapy with levothyroxine and testosterone in addition to continuing steroids resulting in marked improvement. He gave a remote history of the worst headache of his life about twenty years ago. He stayed awake all night but never went to the hospital for an evaluation. A possible pituitary apoplexy several years ago was suspected in this case. We have not found any such case in the medical literature with hypopituitarism with a completely normal-appearing pituitary gland. This case illustrates the importance of detailed history, physical examination, hormonal testing, and appropriate hormone replacement in patients where an obvious acute cause may not be ascertained.

Role of non-thyroidal illness syndrome in predicting adverse outcomes in COVID-19 patients predominantly of mild-to-moderate severity.

ObjectiveExisting studies reported the potential prognostic role of non‐thyroidal illness syndrome (NTIS), characterized by low triiodothyronine (T3) with normal/low thyroid‐stimulating hormone (TSH), mainly in severe COVID‐19. None considered the significant impact of SARS‐CoV‐2 viral load on adverse outcomes. We aimed to clarify the prognostic role of NTIS among predominantly mild‐to‐moderate COVID‐19 patients.DesignA prospective study of COVID‐19 patients.Patients and MeasurementsConsecutive adults admitted to Queen Mary Hospital for confirmed COVID‐19 from July to December 2020 were prospectively recruited. SARS‐CoV‐2 viral load was represented by cycle threshold (Ct) values from real‐time reverse transcription‐polymerase chain reaction of the respiratory specimen on admission. Serum TSH, free thyroxine and free T3 were measured on admission. The outcome was deterioration in clinical severity, defined as worsening in ≥1 category of clinical severity according to the Chinese National Health Commission guideline.ResultsWe recruited 367 patients. At baseline, 75.2% had mild disease, and 27 patients (7.4%) had NTIS. Fifty‐three patients (14.4%) had clinical deterioration. Patients with NTIS were older, had more comorbidities, worse symptomatology, higher SARS‐CoV‐2 viral loads and worse profiles of inflammatory and tissue injury markers. They were more likely to have clinical deterioration (p < .001). In multivariable stepwise logistic regression analysis, NTIS independently predicted clinical deterioration (adjusted odds ratio 3.19, p = .017), in addition to Ct value <25 (p < .001), elevated C‐reactive protein (p = .004), age >50 years (p = .011) and elevated creatine kinase (p = .017).ConclusionsNon‐thyroidal illness syndrome was not uncommon even in mild‐to‐moderate COVID‐19 patients. NTIS on admission could predict clinical deterioration in COVID‐19, independent of SARS‐CoV‐2 viral load, age and markers of inflammation and tissue injury.

Growth hormone replacement may influence the biological action of thyroid hormone on liver and bone tissue

ObjectiveGrowth hormone (GH) replacement alters the peripheral interconversion of thyroxine (T4) and triiodothyronine (T3). However, little is known about the clinical impact of these alterations. We aimed to compare changes observed in the serum T3:T4 ratio with known biological markers of thyroid hormone action derived from different peripheral tissues. DesignWe prospectively studied twenty GH deficient men before and after GH replacement in a tertiary referral endocrine center. Serum biochemical measurements included insulin like growth factor-1 (IGF-1), thyroid hormones (free & total T3, free & total T4 and reverse T3) and TSH. Changes in thyroid hormone concentration were compared to alterations in hepatic and bone biomarkers of thyroid hormone action. ResultsGH replacement provoked a decline in serum free T4 concentration (−1.09 ± 1.99 pmol/L; p = 0.02) and an increase in free T3 (+0.34 ± 0.15 pmol/L; p = 0.03); therefore, the free T3:free T4 ratio increased from 0.40 ± 0.02 to 0.47 ± 0.02 (p = 0.002). Sex hormone binding globulin (SHBG) level was unchanged. However, a decline in serum ferritin (−26.6 ± 8.5 ng/mL; p = 0.005) correlated with a fall in freeT4. Alterations in lipid profile, including a rise in large HDL sub-fractions and Lp (a) (+2.1 ± 21.1 nmol/L; p = 0.002) did not correlate with thyroid hormone levels. Significant increases were recorded in serum bone turnover markers - procollagen type 1 amino-terminal propeptide +57.4%; p = 0.0009, osteocalcin +48.6%; p = 0.0007; c-terminal telopeptides of type 1 collagen +73.7%; p = 0.002. Changes in bone formation markers occurred in parallel with fluctuations in thyroid hormone. ConclusionGH-induced alterations in the thyroid axis are associated with complex, tissue specific effects on thyroid hormone action. Modulation of bone turnover markers suggests that GH may improve the biological action of thyroid hormone on bone.

English

BACKGROUND Subclinical hypothyroidism is the term used to describe a condition where there is isolated elevated serum thyroid stimulating hormone level in the setting of normal serum free thyroxin levels in the absence or presence of symptoms. There is no uniformity in various studies regarding association between subclinical hypothyroidism and type 2 diabetes mellitus with regard to prevalence and change in metabolic profile. METHODS After enrolment of patients, a detailed relevant history of patients was taken and detailed clinical examination was done. All information obtained from patients was recorded in predesigned proforma. After 8 hours of fasting, serum levels of glucose, HbA1c, total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) by fully automated clinical biochemistry analyser EM 200 were checked. Serum free T3, free T4 and thyroid stimulating hormone (TSH) were measured using standard assay. RESULTS Fasting glucose was significantly higher (P = .00001) in diabetes mellitus plus subclinical hypothyroidism group than patients with diabetes mellitus (DM) and euthyroid group (156.3 + 15.77 mg / dl vs. 128.1 + 21.44 mg / dl). Fasting insulin was significantly higher (P = .00001) in diabetes mellitus plus subclinical hypothyroidism group than patients with DM and euthyroid group (3.69 + 0.82 mu / L vs. 2.36 + 0.75 mu / L). There was no significant difference between two groups regarding HbA1c. CONCLUSIONS From our study we conclude that prevalence of subclinical hypothyroidism was higher in type 2 diabetes patients than normal population and there was female predominance. Body mass index was significantly higher in subclinical hypothyroidism group and there was no significant difference between the two groups regarding duration of diabetes mellitus. Patients with subclinical hypothyroidism have poor glycaemic control. KEYWORDS Subclinical Hypothyroidism, Diabetes Mellitus, Metabolic Profile

Corneal Tomographic Analysis Among Patients With Thyroid Gland Dysfunction.

To analyze the corneal tomographic parameters of patients with thyroid gland dysfunction. This case-control study included 100 eyes of 50 patients with thyroid gland dysfunction and 100 eyes of 50 healthy controls. All eyes were examined by Pentacam (Oculus Optikgeräte GmbH). Pentacam parameters were compared between patients with thyroid gland dysfunction and controls. Spearman's correlation coefficient between different Pentacam parameters and the serum level of free thyroxin (T4) and thyroid-stimulating hormone (TSH) was calculated. Patients with hypothyroidism had significantly higher median values of steep and maximum simulated keratometric readings, central corneal thickness (CCT), and thinnest pachymetry (CTmin) than both patients with hyperthyroidism and controls (P⩽ .05). The median values of the average and maximum pachymetric progression index (PPI), posterior elevation, and back difference elevation were significantly higher in patients with hyperthyroidism than in patients with hypothyroidism and controls (P ⩽ .05). The Ambrósio Relational Thickness (ARTmax) was significantly reduced in patients with hyperthyroidism (P ⩽ .001). Both CCT and CTmin showed a moderately positive correlation with serum TSH level and a moderately negative correlation with serum free T4 level. Patients with non-autoimmune thyroid gland dysfunction had significantly thinner CCT, CTmin, and inferior vertical deviation than the autoimmune group (P ⩽ .05). Thyroid gland dysfunction is associated with significant corneal tomographic changes. Patients with hyperthyroidism tend to have thinner corneas and more abnormal tomographic parameters correlating with keratoconus. No significant tomographic changes were found in association with autoimmune thyroid gland dysfunction. The authors recommend screening and regular follow-up of patients with thyroid gland dysfunction for early detection and management of keratoconus. [J Refract Surg. 2021;37(3):192-197.].

Acetylcholinesterase activity and thyroid hormone levels in Ecuadorian adolescents living in agricultural settings where organophosphate pesticides are used.

Organophosphates are frequently applied insecticides that inhibit acetylcholinesterase (AChE) activity resulting in cholinergic overstimulation. Limited evidence suggests that organophosphates may alter thyroid hormone levels, although studies have yielded inconsistent findings. We aimed to test the associations between AChE activity, a physiological marker of organophosphate exposure, and thyroid function in adolescents. We included information of 80 adolescent participants (ages 12-17y in 2016, 53% male) growing up in agricultural settings in Ecuador. We measured fingerstick erythrocytic AChE activity and hemoglobin concentration, and concurrent serum thyroid stimulating hormone (TSH) and free-T4 (fT4) concentrations. General linear models were used to test associations which adjusted for demographic and anthropometric variables. TSH associations were further adjusted for fT4. The mean (SD) AChE, TSH and fT4 levels were 3.77 U/mL (0.55), 2.82 μIU/ml (1.49) and 1.11ng/dl (0.13), respectively. Lower AChE activity, indicating greater organophosphate exposure, was marginally associated with greater fT4 concentrations (difference per SD decrease in AChE activity (β)=0.03ng/dL, [90% CI: 0.00, 0.06]) but not with TSH (β=-0.01 μIU/ml, [-0.38, 0.36]). Gender modified the AChE-TSH association (p=0.03). In girls, lower AChE activity was associated with higher fT4 levels (β=0.05ng/dL [0.01, 0.10]) and lower TSH concentrations (β=-0.51 μIU/ml, [-1.00, -0.023]). No associations were observed in boys. These cross-sectional findings suggest that alterations in the cholinergic system from organophosphate exposures can increase fT4 levels coupled with a beyond-compensatory downregulation of TSH in female adolescents. This is the first study to characterize these associations in adolescents.

Prospective study of thyroid functions in multiple sclerosis patients treated with interferon beta in Alexandria University MS clinic

BackgroundThe incidence of thyroid dysfunction in multiple sclerosis (MS) patients on interferon (as a disease-modifying line) has been reported in many studies performed on patients already on interferon therapy. Our study adopted a prospective follow-up of the thyroid profile in those patients newly starting interferon beta therapy over 1 year trying to find a correlation between the start of therapy and the occurrence of this dysfunction.ObjectivesTo evaluate the incidence of thyroid dysfunction in MS patients before and 1 year after of interferon beta.MethodsA prospective cohort study on 48 MS patients newly receiving interferon beta therapy through MS clinic were subjected to assessment of thyroid profile including serum TSH, free T3, and T4 at the start of treatment; they were followed-up at 6- and 12-month intervals after the start of therapy.Results and conclusionThere was a statistically significant increase in serum-free T3 levels in those treated with interferon beta therapy in a follow-up of 1 year. Our work also showed a decrease in serum-free T4 levels without statistical significance. TSH levels showed a tendency towards increase without statistical significance.

English

BACKGROUND Thyroid disease is more common in people with diabetes mellitus than in general population. Among thyroid disorders, subclinical hypothyroidism is more common than the overt form. Hypothyroidism is associated with dyslipidaemia, hypertension and cardiac disease. Subclinical hypothyroidism has also been reported to have these features. With this background, we aimed to determine the prevalence of subclinical thyroid disorder and its influence on the metabolic profile of patients with type 2 diabetes mellitus (DM). METHODS 234 type 2 diabetes patients, 117 males and 117 females, who were previously not known to have thyroid disease, were screened for thyroid dysfunction using serum free T3, free T4, and thyroid stimulating hormone (TSH) levels. Patients were evaluated for clinical features of thyroid disease and investigated for microvascular complications of DM, dyslipidaemia and cardiac disease. Individuals with subclinical hypothyroidism were further screened for anti-thyroid peroxidase (TPO) antibodies. RESULTS In this study, subclinical hypothyroidism was present in 29 (12.4 %) of 234 type 2 diabetics; no case of subclinical hyperthyroidism was detected. 25 of these 29 patients with subclinical hypothyroidism were females. Elevated TPO antibody levels were present in 82.8 % (24 out of 29) subclinical hypothyroidism (SCH) patients. SCH was found to be associated with higher body mass index (BMI) and patients aged more than 50 years. No significant difference was found in glycaemic profile or lipid profile between patients with SCH and euthyroid subjects. There was no significant difference among SCH patients with and without microvascular complications. Left Ventricle (LV) diastolic dysfunction was present in 34.4 % of SCH patients. CONCLUSIONS SCH is common among type 2 diabetics, especially in females and most commonly due to autoimmune thyroid disease. SCH in type 2 DM is associated with a higher BMI and an older age group, but it does not seem to have an influence on glycaemic profile, lipid profile or microvascular complications of diabetes. KEYWORDS Thyroid Stimulating Hormone (TSH), Type 2 Diabetes Mellitus (T2DM), Subclinical Hypothyroidism (SCH), BMI, Anti–TPO (Thyroid Peroxidase) Antibody

Modulation of the serum leptin by thyroid hormones: Observations in newly diagnosed thyrotoxic patients

Background: Leptin and thyroid hormones both are involved in regulation of energy metabolism. Many studies were conducted for studying the relationship and the interaction between the thyrostat and the lipostat which till present is incompletely understood. The aim of this work was to study serum leptin levels in patients suffering from thyrotoxicosis who are newly diagnosed treatment naive patients, thus the association between leptin and thyroid hormones can be purified as much as possible. Methods: a case control study conducted at Port-Said General hospital endocrine out-patient clinic. The study included 15 patients with thyrotoxicosis and 30 control euthyroid subjects (15 lean, 15 obese). All of the included patients are analyzed for thyroid profile and serum leptin. Results: The results revealed a statistically significant difference regarding serum leptin between the Thyrotoxic group and control obese. No correlation was found between serum leptin and either BMI, TSH, Free T3 or Free T4 in each of the studied group, but a significant negative correlation was found between leptin and either free T3 and free T4 in the combined groups. Conclusion: Serum leptin level is lower in treatment naive thyrotoxic patients when compared to euthyroid control. The serum leptin showed no correlation with either BMI or TSH, also no correlation was found between serum leptin and free T3 or free T4 in each of the studied group suggesting presence of other factors that indirectly affect and interconnect these two major endocrinal systems involving energy metabolism.

Effect of sleeve gastrectomy on thyroid-stimulating hormone levels in morbidly obese patients with normal thyroid function.

There are many studies, which demonstrate that morbid obesity is associated with an increase in Thyroid Stimulating Hormone (TSH) levels. However, the effect of Laparoscopic Sleeve Gastrectomy (LSG) procedure on postoperative TSH levels is not clear. This study aims to evaluate the effect of weight loss after LSG procedure on TSH levels in euthyroid patients with morbid obesity. 159 Euthyroid patients who applied for an LSG procedure (93.7% female, with a mean age of 34.18±10.01 years, BMI 43.2±6.82 kg/m2) were retrospectively analyzed for the study. The parameters used in the analysis were their serum free T3 levels (fT3), free T4 levels (fT4), and TSH levels preoperatively and at 6 months after surgery. The postoperative correlation between TSH and BMI (Body Mass Index), % EWL (Percent Excess Weight Loss), and % TWL (Total Weight Loss) levels were evaluated. Mean BMI change from 43.2±6.82 kg/m2 to 30.48±5.63 kg/m2 (p<0.001), 6 months after LSG, was associated with a mean reduction in the TSH from 2.27±1.09 µU/dL to 1.61±0.99 µU/dL; p<0.001). Serum fT3 levels (3.23±0.42 ng/dL at baseline and 3.21±0.48 ng/dL at 6 months after surgery; p=0.409) remained steady. Serum fT4 levels (1.21±0.18 µU/dL at baseline and 1.43±0.20 µU/dL at 6 months after LSG; p<0.001) increased. Change in TSH was significantly correlated with change in BMI at 6 months after surgery (r=0.200, p=0.015). However, the decrease in TSH following LSG procedure did not correlate with % EWL (r=-0.114, p=0.159) and % TWL (r=-0.100, p=0.209). After the LSG procedure, there was a significant decrease in TSH levels and a significant increase in fT4 levels, but no change was seen in fT3 levels. While this decrease in TSH levels showed a positive correlation with BMI, no statistically significant correlation was found with % EWL and % TWL.

STUDY OF ASSOCIATION OF RESISTIN AND LEPTIN WITH THYROID HORMONES IN HYPOTHYROID PATIENTS

Objective:The present study was aimed to evaluate the levels of resistin and leptin in hypothyroid patients and to find a possible association of thyroid hormones with resistin and leptin. Material and Methods:The present study was conducted on 100 previously diagnosed hypothyroid (PDH) patients (38 Males &amp; 62 Females) and 100 newly diagnosed hypothyroid (NDH) patients (44 Males &amp; 56 Females) attending the outpatient clinics or admitted in wards of J.L.N. Hospitals, Ajmer. 100 healthy control subjects of same age group of either gender were selected for the study. Blood samples were drawn from patients and controls, after overnight fast of at least 8 hours. Estimation of Serum Leptin, Resistin, free T3, free T4, and TSH was done by using Enzyme- Linked Immunosorbant Assay (ELISA) technique. Differences in the parameters among the groups were analyzed by ANOVA test followed by its Tukey HSD post hoc analysis. Correlations between variables were tested using the Pearson rho (r: Correlation coefficient) correlation test. Results:Findings of the present study shows that the levels of serum fT3 (1.79 ± 0.29 pg/mL) and serum fT4 (0.34 ± 0.11 ng/dL) were significantly lower in NDH group compared to PDH group (fT3 = 3.00 ± 0.32 pg/mL &amp; fT4 = 0.81 ± 0.15 ng/dL) and control group (fT3 = 3.12 ± 0.31 pg/mL &amp; fT4 = 0.85 ± 0.11ng/dL) whereas serum TSH levels were significantly higher in NDH group (40.59 ± 13.55 μIU/mL) compared to PDH group (5.34 ± 1.47 μIU/mL) and control group (3.23 ± 1.04 μIU/mL) [Table 1 Figure 1]. Serum leptin levels were significantly higher in NDH group (21.37 ± 6.44 ng/mL) compared to PDH group (16.51 ± 4.47 ng/mL) and control group (11.15 ± 5.29 ng/mL) [Table 2]. A highly significant variation (p&lt;0.0001) in the levels of serum leptin was found between the groups. Serum resistin levels were significantly higher in NDH group (14.50 ± 2.72 ng/mL) compared to PDH group (11.33 ± 1.59 ng/mL) and control group (7.78 ± 1.19 ng/mL) [Table 2]. Highly Significant difference (p&lt;0.0001) in resistin levels was found between the groups. Conclusion: It was suggested that thyroid dysfunction does not affect the leptin levels and also thyroid hormones were not involved in the synthesis and secretion of leptin. Further studies are required to gain more insight into the relationship between leptin and thyroid dysfunction. Resistin shows a significant correlation with thyroid hormones which indicate that serum resistin might be considered as a confirmation extra test for the early detection of atherosclerosis and atherosclerosis induced conditions in hypothyroid patients.

A study of levothyroxine substitution therapy on subclinical hypothyroid patients and its effects on lipid profile in the department of medicine at tertiary care hospital

Background: Subclinical hypothyroidism is represented by high serum thyroid stimulating hormone (TSH) and normal serum free T4 and T3, Recent studies on subclinical hypothyroidism and lipid profile indicates that the serum total cholesterol, LDL-C, and total triglycerides were significantly increased. Clinical evidence suggests that thyroid replacement therapy with levothyroxine has beneficial effect.&#x0D; Methods: It is a hospital based prospective observational study involving 122 patients based on non probability sampling conducted in the Department of Internal Medicine. The study involved patients who have been diagnosed with subclinical hypothyroidism with normal level of free T4, T3 and elevated levels of TSH with positive Thyroperoxidase (TPO) antibodies. Patients were advised to investigate lipid profile before and after prescribing levothyroxine. Follow up was done after 6-9 wks.&#x0D; Results: In this study 122 patients diagnosed with Subclinical hypothyroidism were prescribed with levothyroxine in which 112 came for follow up. The mean age of the patient was 46.81. There was significant reduction in mean TSH from 12.09 (±1.89)mIU/L to 7.97(±1.59)mIU/L,TC from 217.12( ±20.87)mg/dl to 198.47( ±17.34)mg/dl and LDL from 137.16(±14.57)mg/dl to 124.62( ±12.89)mg/dl was found along with significant reduction in VLDL was found after levothyroxine therapy, There was slight reduction in serum triglyceride was found with no significant alteration in HDL and BMI levels.&#x0D; Conclusion: The study showed significant reduction in the lipid profile including TC, LDL and VLDL after levothyroxine therapy. There was significant reduction in the level of TSH was also found whereas the level of free T4 and T3 were not much altered. There was no significant change found in the level of HDL and BMI.

Analysis of the Relationships between Multiple Endocrine Hormones and Return of Spontaneous Circulation (ROSC) in Cardiac Arrest Patients: Possible Association of the Serum Free T4 Level with ROSC.

Background Endocrine hormones are closely associated with homeostasis, so it is important to clarify hormone secretion dynamics in shock. Few reports, however, have examined the dynamics of endogenous hormone secretion relative to prognosis in cardiac arrest patients. Therefore, to clarify the roles of endocrine hormones in out-of-hospital cardiac arrest (OHCA) patients, the concentrations of anterior pituitary, thyroid, and adrenocortical hormones were measured, and their associations with return of spontaneous circulation (ROSC) were examined. Methods The subjects were OHCA patients transported to our Emergency Department. In addition to conventional clinical laboratory tests, the following were measured: serum TSH, serum free T3, serum free T4 (F-T4), plasma ACTH, serum cortisol, serum GH, serum IGF-1, plasma aldosterone concentration (PAC), and plasma renin activity. The primary endpoint was the presence or absence of ROSC, and the secondary endpoint was 24-hour survival. Results A total of 29 patients, 17 in the ROSC group and 12 in the non-ROSC group, were studied. There were associations between ROSC and low serum potassium, high F-T4, low cortisol, and low PAC on bivariate analyses. There were associations between ROSC and serum potassium, F-T4, and GH using the step-wise method. On multiple logistic regression analysis, a relationship between ROSC and high serum F-T4 level was identified by both methods. There were also associations between 24-hour survival and both low serum potassium and elevated blood glucose levels. Conclusions The present findings suggest a possible relationship between the serum F-T4 level and ROSC in OHCA patients. A higher serum F-T4 level might cause an increase in the β-adrenergic response in cardiomyocytes and increased responsiveness to catecholamines and was possibly associated with ROSC.

Defining Normative Sonographic Measurements of Neonatal Thyroid Volumes: Results of 165 Healthy Neonates from a Single Center in Northwest Malaysia.

Background:Congenital hypothyroidism is the most common cause of treatable mental impairment and growth retardation in newborns. Early diagnosis requires measurement of serum thyroid-stimulating hormone (TSH) and free T4 coupled with an ultrasound of the thyroid gland. However, detailed sonographic evaluation of the thyroid gland requires comparison to the local thyroid normative volumetric values, which is currently lacking.Methods:A cross-sectional study was conducted from November 10, 2015, to April 18, 2018, recruiting 165 healthy neonates with normal TSH in their 1st week of life, from a single center in Northwest Malaysia. Ultrasound thyroid was done by a single ultrasonographer (κ = 0.86, percent agreement = 92.4), and the thyroid volume (TV) was calculated using the Brunn formula.Results:All measurements showed skewed distribution with no significant difference between the right and left lobes. The local normative values for neonatal total TV was 0.61 (interquartile range [IQR] = 0.230) cm3, 0.31 (IQR = 0.150) cm3 for right TV, and 0.28 (IQR = 0.110) cm3 for left TV. There was a strong correlation between the right and left TVs, r = 0.767, P < 0.001. There were also no differences in the total TV across different genders and races.Conclusion:The normative values for TV determined in our study may be used accordingly in clinical practice to evaluate thyroid hypoplasia or goiter by other Asian countries due to the similarly shared biodemography.

Thyroid hormone disorders: a predictor of mortality in patients with septic shock defined by Sepsis-3?

Decreased serum thyroid hormone levels and their prediction of mortality in septic patients are still controversial, especially with the evolution of the definition of sepsis. This study aimed to assess the ability of thyroid hormone disorders to predict the early mortality of patients with septic shock defined by Sepsis-3. Sixty-three adult patients with septic shock admitted to a university hospital emergency intensive care unit (EICU) were studied. Serum free T3 (FT3), free T4 (FT4), thyroid stimulating hormone (TSH), C-reactive protein (CRP), procalcitonin (PCT), and lactate levels were determined and compared with survival status and organ dysfunction. Among the 63 patients studied, lower serum FT3 and FT4 levels were significantly associated with higher sequential organ failure assessment (SOFA) scores. Patients with septic shock with lower levels of FT3 (≤ 1.70pmol/L) and FT4 (≤ 9.99pmol/L) had significantly increased 28-day mortality. There was no significant difference in the serum TSH level between the survivor and nonsurvivor groups. The areas under the receiver operating characteristic curves for FT3 and FT4 levels were associated with 28-day mortality (0.92 and 0.89, respectively) and were higher than that for SOFA (0.82), CRP (0.65) and lactate (0.59). The decrease in serum levels of FT3 and FT4 in patients with septic shock is associated with the severity of organ dysfunction and 28-day mortality. Early detection of serum FT3 and FT4 levels could help clinicians to identify patients at high risk of clinical deterioration.

Clinical features and thyroid dysfunction in adverse events involving the pituitary gland during PD-1 blockade therapy.

Programmed cell death-1 (PD-1) blockade therapy, an immune checkpoint treatment, can induce hypophysitis or hypopituitarism as an immune-related adverse event (pituitary irAE). We aimed to clarify the clinical features of pituitary irAEs during PD-1 blockade therapy. This retrospective study investigated consecutive patients treated with nivolumab, an anti-PD-1 antibody, at Kyoto University Hospital between 1 September 2014 and 31 August 2019. We examined patients' baseline characteristics and analysed the clinical data of those who developed pituitary irAEs. Of the 374 recruited patients, 7 (1.9%) developed pituitary irAEs, and each presented with isolated secondary adrenal insufficiency. In 4 patients, changes in ACTH were delayed relative to those in cortisol: when serum cortisol levels fell below the reference range, plasma ACTH levels were still normal. Pituitary irAEs were accompanied by elevated serum-free T3 (fT3) levels, which resolved with glucocorticoid replacement. Serum TSH levels were not suppressed despite elevated serum fT3 levels and 1 patient even presented with high fT3 level above the reference range (fT3, 7.1pmol/L; free T4 (fT4), 13.9pmol/L; and TSH, 5.1mIU/L). Isolated secondary adrenal insufficiency was a common pituitary irAE during PD-1 blockade therapy. This condition was accompanied by thyroid dysfunction, including elevation of fT3 without TSH suppression.