Resting Energy Expenditure and Cold Induced Thermogenesis in Patients with Overt Hyperthyroidism

Context Thyroid hormone is crucial for the adaptation to cold. Objective To evaluate the effect of hyperthyroidism on resting energy expenditure (REE), cold-induced thermogenesis (CIT) and changes in body composition and weight. Design Prospective cohort study. Setting Endocrine outpatient clinic at tertiary referral center. Patients Eighteen patients with overt hyperthyroidism. Main Outcome Measures We measured REE during hyperthyroidism, after restoring euthyroid TH levels and after 3 months of normal thyroid function. In fourteen patients energy expenditure (EE) was measured before and after a mild cold exposure of two hours and CIT was the difference between EEcold and EEwarm. Skin temperatures at eight positions were recorded during the study visits. Body composition was assessed by dual X-ray absorption. Results Free T4 (fT4) and free T3 (fT3) decreased significantly over time (fT4, p=0.0003; fT3, p=0.0001). REE corrected for lean body mass (LBM) decreased from 42 ± 6.7 kcal/24h/kg LBM in the hyperthyroid to 33±4.4 kcal/24h/kg LBM (-21%, p<0.0001 vs hyperthyroid) in the euthyroid state and three months later to 33 ± 5.2 kcal/24h/kg LBM (-21%, p=0.0022 vs. hyperthyroid, overall p<0.0001). Free T4 (p=0.0001) and free T3 (p<0.0001) were predictors of REE. CIT did not change from the hyperthyroid to the euthyroid state (p=0.96). Hyperthyroidism led to increased skin temperature at warm ambient conditions but did not alter core body temperature, nor skin temperature after cold exposure. Weight regain and body composition were not influenced by REE and CIT during the hyperthyroid state. Conclusions CIT is not increased in patients with overt hyperthyroidism.

A Discrete Ligand-Free T3 Supertetrahedral Cluster of Gallium Sulfide

Large discrete supertetrahedral clusters of metal chalcogenides are rare due to the difficulty of crystallizing solids in which the negative charge of the cluster is balanced by the positive charges of the countercations. Here, we describe a discrete ligand-free T3 supertetrahedral cluster, [Ga10S16(SH)4]6−, which was successfully synthesized in the presence of the superbase 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) using the neutral surfactant polyethyleneglycol (PEG)-400 as the reaction solvent. Protonated DBUH+ cations are incorporated into the crystal structure of the product, which can be formulated as [C9H17N2]6[Ga10S16(SH)4]. This compound, which represents the first example of a discrete ligand-free T3 cluster of gallium sulfide, was fully characterized by single-crystal and powder X-ray diffraction, elemental analysis, infrared spectroscopy, thermogravimetric analysis, and ultraviolet-visible diffuse reflectance. The results presented here indicate that the use of surfactants as solvents offers potential for the preparation of new compounds containing supertetrahedral clusters.

Effect of acute and chronic liver diseases on the thyroid function in children

Background Thyroid hormones modulate hepatic function through regulation of basal metabolic rate in addition; the liver metabolizes the thyroid hormones and regulates their endocrine effects. Objectives To assess thyroid functions in children with acute and chronic liver diseases. Methods 85 studied children were divided into 4 groups; group 1 (20 children) with acute hepatitis (AH), group 2 (20 children) chronic liver disease1 (CLD1; relatively preserved liver functions including Child-Pugh stage A), group 3 (20 children) chronic liver disease2 (CLD2; includes Child-Pugh stage B or C), group 4 (25 children) controls. All groups were subjected to detailed history, physical examination, Complete blood count, liver, renal function tests, viral markers, and thyroid functions (FT3, FT4, TSH). Results Free T3 levels were lower in children with AH, CLD1 and CLD2. There was significant increase in TSH serum levels in CLD2.In acute hepatitis a negative correlation between serum free T4 and AST (r = -0.991), positive correlation between serum TSH and AST, VLDL, and cholesterol levels (r= 0.503, 0.533 and 0.498). A positive correlation between free T3 levels and prothrombin concentration (r= 0.991). Negative correlations between free T3 levels and PT, serum bilirubin and LDL serum levels in children with CLD2 (r= -0.992) (r= -0.902) and (r= -0.946) Conclusion Acute and chronic liver diseases affect thyroid function in children and is correlated with the disease severity.

Study of thyroid profile in pre and post-menopausal women: a case control study

Background:The prevalence and incidence of thyroid disorders is influenced primarily by sex and age are more common in women and in older adults. Thyroid disorders if left untreated will increase risk of cardiovascular diseases and osteoporosis. Hence, screening for thyroid dysfunction must be done as routine investigation in the women presenting with menopausal symptoms.Methods:This case control study includes 50 pre-menopausal women of age group 34-49 years and 50 post-menopausal women of age group 50-55 years, visiting General medicine department of Victoria hospital and hospital affiliated to Bangalore Medical College and Research Institute. All the subjects were subjected for serum triiodothyronine (T3), tetraiodothyronine or thyroxine (T4), thyroid stimulating hormone (TSH), free T3 and T4 levels.Results:Out of all subjects; 23 were hyperthyroid out of which 14 were post-menopausal women, 37 were hypothyroid out of which 19 were post-menopausal women. Chi-square test showed no significant association. Negative and weak correlation was seen between total T3 and age; total T4 and age; TSH and age; free T3 and age; free T4 and age in pre-menopausal women. Negative and moderate correlation was seen between total T3 and age; total T4 and age; free T3 and age. There was a positive and weak correlation seen between TSH and age; weak positive non-significant correlation seen between free T4 and age. Significant correlation was seen between total T3 and age in post-menopausal women.Conclusions:Post-menopausal women should be monitored for serum T3, T4, TSH levels for reducing risk of thyroid dysfunction.

Surgical treatment of patients with nodular toxic goiter

Nodular toxic goiter (NTG) accounts for 7.3 % to 10.0 % of the goiter population. There are difficulties in the preoperative differential diagnosis between NTG and other thyroid diseases. There is also controversy about the benefits of resection surgery over thyroidectomy in patients with NTG. The aim of the study: a comparative assessment of the diagnosis and treatment results of patients with NTG in the early and late postoperative periods after resection surgery and thyroidectomy. Materials and methods. The study enrolled 51 patients with NTG. The mean age of patients in the group was 51.7 ± 12.9 years. Results. Bilateral multinodular lesions prevailed – 34 (66.7 %) patients. Free T3 level was measured only in 15 (29.4 %) patients, 7 (46.7 %) of them had elevated T3 level. 15 (29.4 %) patients underwent hemithyroidectomy including the isthmus, 2 (3.9 %) had subtotal resection, 34 (66.7 %) patients underwent thyroidectomy. Conclusions. Multinodular bilateral thyroid lesions dominated the structure of NTG – 34 (66.7 %) patients who underwent thyroidectomy. Uninodular and multinodular unilateral pathology was diagnosed only in 17 (33.3 %) patients who underwent organ-preserving surgery. The measurements of free T3 level in patients with NTG allowed the diagnosis of T3-thyrotoxicosis in almost half of patients (46.7 %), which is a diagnostic criterion for detection of functional nodal autonomy. Following the organ-preserving surgery, 17 (33.3 %) patients with NTG required the use of hormone replacement therapy with levothyroxine at a mean dose of 25.0 (25.0; 50.0) mcg/day in the late postoperative period (>1 year).

A Study of Clinical Profile of Thyroid Disorders in Children in A Tertiary Care Hospital, Kurnool

Background: Thyroid hormone abnormalities are the commonest endocrine disorder in India and also the commonest preventable cause of mental retardation, so we want to determine the prevalence of thyroid dysfunction in children at kurnool district. Materials and Methods: A hospital based prospective observational study performed in new born and children below 18 years fulfilling the inclusion criteria visiting the pediatric OPD and IPD in Viswabharathi medical college, Kurnool if they had clinical suspicion of thyroid dysfunction. If suspicion of hypothyroidism, Free T4, Total T4, TSH levels and if suspicion of hyperthyroidism Free T3 and TSH were done. Results: Out of 70 case 3 cases (4.3%) are hyperthyroidism and 67 cases (95.7%) are hypothyroidism in these 3 (4.3%) cases had family history of thyroid disorders, male to female ratio was 1.3:6 and prevalence rate was high in the age group of 10 - 12 years 32.9% (23 cases). 13 (18.6%) cases had thyroid enlargement and 48 (68.57%) cases had anaemia. Treatment was started according to standard guidelines. Conclusion: The higher prevalence rate of thyroid disorders in childhood that to in female children and age group of 10 - 12 years in and around kurnool. Hence, screening of all new-borns and children should be mandatory as early diagnosis and treatment helps in prevention of complications of thyroid disorders. KEY WORDS: Free T3, Free T4, Goiter, Hyperthyroidism, Hypothyroidism, and Thyroid stimulating hormone.

Leptin Decreases Energy Expenditure but Increases Thyroid Hormone in Patients With Lipodystrophy

Leptin is an adipokine that signals energy sufficiency. In rodents, leptin deficiency is associated with decreased body temperature and energy expenditure (EE), which is reversed with leptin replacement. Leptin’s role in EE in humans is unclear; however, one study of 10% weight-reduced healthy subjects suggested that leptin replacement to pre-weight loss levels restored the decline in EE, thyroid hormone, and catecholamines associated with weight loss. Patients with lipodystrophy (LD) are characterized by deficiency of adipose tissue and can serve as models to study effects of leptin deficiency and replacement in humans. We hypothesized that treatment with recombinant leptin (metreleptin) in patients with LD would increase EE, thyroid hormone, and catecholamines. We conducted a non-randomized crossover study of 25 patients with LD who were hospitalized for 19 days on an iso-caloric diet. The initiation cohort consisted of 17 patients with no prior exposure to metreleptin, who were first studied for 5 days without metreleptin (period 1), then were treated with metreleptin for 14 days (period 2). The withdrawal cohort consisted of 8 previously metreleptin-treated patients who were continued on metreleptin for the first 5 days of the study (period 1), then were taken off metreleptin for 14 days (period 2). At the end of each period, we measured 24-hour EE (TEE) and resting EE (REE) using indirect calorimetry and free T3, T4, epinephrine, norepinephrine and dopamine after an 8–12 hour fast. In the leptin initiation cohort, TEE and REE decreased from 2402±383 kcal/day and 1805±332 kcal/day to 2272±396 kcal/day (p=0.003) and 1688±318 kcal/day (p=0.03), respectively. Free T3 increased from median (IQR) 248 (200, 270) pg/mL to 295 (259, 315) (p=0.006). No changes in catecholamines were observed in the initiation cohort. In the withdrawal cohort, free T3 decreased from 295 (267, 331) pg/mL to 265 (237, 323) (p=0.008), free T4 decreased from 1.2 ±0.2 ng/dL to 1.0±0.2 (p=0.002), and norepinephrine decreased from 191±70 pg/mL to 112±47 (p=0.03) after metreleptin withdrawal. No changes in EE, epinephrine or dopamine were observed in the withdrawal cohort. Contrary to previous studies in rodents and healthy humans, we found that introduction of metreleptin reduced EE in patients with LD. Consistent with rodent and prior human data, patients with LD had increased thyroid hormone on metreleptin, which would be expected to increase EE. The discrepancy in EE compared to other models may be due to metreleptin-induced correction of severe metabolic derangements in LD, including reduction in energy-requiring processes such as de novo lipogenesis and gluconeogenesis. These changes may offset increases in leptin-induced mediators of increased EE, such as thyroid hormone.

Growth Hormone (GH) and Thyroid Stimulating Hormone (TSH) Co-Secreting Pituitary Macroadenoma

Background: TSH secreting pituitary adenomas are rare and accounts for 0.5-3% of all pituitary adenomas. Only 20-25% of those adenomas co-secrete other hormones like growth hormone or prolactin. Mixed GH and TSH secreting adenomas present with symptoms from tumor growth and features of both acromegaly and hyperthyroidism. Clinical Case: A 57 years old woman with a past medical history of chronic joint pains and bilateral knee swelling presented to her PCP with complaints of chronic fatigue. Evaluation revealed a normal TSH level and MNG and patient did not have any further work-up. She reported undergoing periodic knee arthrocentesis which gave her only temporary pain relief. Two years later, patient presented with complaints of unintentional weight loss, tremors and palpitations. She also reported enlargement in the size of hands, feet and forehead and no improvement in the knee swelling after multiple arthrocentesis. Lab evaluation revealed high free T4 2.31ng/dl (0.58-1.64), high free T3 6.44pg/ml (2.50-4.30), non-suppressed TSH 1.32mU/L (0.34-5.00), elevated IGF-1 415ng/ml (47-236), GH 7.76ng/ml (0.01-3.61) and prolactin 6.69ng/mL (2.74-26.72). Neck USG showed multiple nodules and 24hr radioactive iodine uptake scan showed increased uptake at 43%. 75gm OGTT showed non-suppression of GH level. MRI of brain showed 1.8 cm pituitary macroadenoma. Patient underwent transsphenoidal pituitary resection in January 2018 and the final pathology showed positive tumor staining for GH and TSH. Following surgery, patient reported improvement in symptoms. Lab work-up from October 2018 showed normal IGF 189 ng/ml (47-236), normal GH 0.35(0.01-3.61), Free T4 0.80(0.58-1.64), Free T3 2.41(2.50-4.30), TSH 0.06(0.34-5.00) and MRI from August 2020 showed no evidence of residual pituitary tumor. Conclusion: This is a rare case of a GH and TSH co-secreting pituitary macroadenoma. This case highlights the importance of considering acromegaly early in the differential diagnosis of patients presenting with chronic musculoskeletal symptoms and to pursue work up for central hyperthyroidism in a hyperthyroid patient presenting with a non-suppressed TSH level.

Preeclampsia and Thyrotoxicosis: A Case of Impending Storm

Introduction: Preeclampsia is a complication of pregnancy defined by new onset hypertension after 20 weeks with proteinuria or new onset thrombocytopenia, renal or liver dysfunction, pulmonary edema or cerebral/visual symptoms. Hyperthyroidism in pregnancy is usually due to Graves’ disease, and if poorly controlled can increase the risk of preeclampsia and thyroid storm. In this case report we present a case of preeclampsia with impending thyroid storm treated successfully with medical therapy, delivery, and plasmapheresis. Case Description: A 40-year-old female who is 31 6/7 weeks pregnant presents with cough and dyspnea. She has no known thyroid disease. Her systolic blood pressure at presentation is >160 mmHg. She is diagnosed with preeclampsia based on elevated spot protein/creatinine ratio (1.4 g/g) and persistent hypertension. A brain natriuretic peptide is elevated to 847 (reference range <= 100 pg/ml). Complete blood count and comprehensive metabolic panel are normal, with exception of mild alkaline phosphatase elevation. A CT pulmonary angiogram is negative for pulmonary embolism but shows bilateral pleural effusions. She is started on intravenous antihypertensive medications and furosemide. Due to persistent tachycardia, thyroid function is checked and is notable for a thyroid stimulating hormone level of 0.05 (non-pregnant reference range 0.35 – 4.94 mIU/L), an elevated free T3 of 13.7 (non-pregnancy reference range 1.7 – 3.7 pg/ml), and an elevated free T4 > 4 (non-pregnancy reference range 0.70-1.48 ng/dL). She is started on therapy for impending thyroid storm, including maximum doses of propranolol, propylthiouracil, hydrocortisone and saturated solution of potassium iodide. Her thyroid stimulating immunoglobulin is > 500 (reference range <= 122%) and TSH receptor antibody is > 40 (reference range <= 1.75 iU/L) leading to a new diagnosis of Graves’ disease. On hospital day three, she develops altered mental status and fetal bradycardia, warranting emergency cesarean section. On hospital day five she develops worsening confusion, abnormal liver function tests and increasing levels of free T4 and free T3. At this time, she is started on plasmapheresis therapy. Free T4 and free T3 values normalize after two rounds. Her medications are slowly weaned, and she is discharged from the hospital on methimazole 20 mg daily. Her baby is discharged after a brief hospital stay for sequela of prematurity. Discussion: While far less common than preeclampsia, thyrotoxicosis may present with similar symptomatology and can pose significant morbidity and mortality risk for pregnant patients. However, with prompt diagnosis and appropriate therapies, the disorder can be treated successfully and without lasting harm to the mother or fetus. For these reasons, it should remain on the differential for patients with symptoms of preeclampsia, and thyroid studies should be considered.

Quality of Life in Patients With Hypothyroidism

Introduction: The quality of life (QoL) of thyroid diseases has been less studied than other chronic diseases. There is however evidence suggesting long lasting physical and psychological symptomatology related to thyroid diseases. Objective: To analyze the QoL in patients with hypothyroidism. Methods: We evaluated 274 patients with a mean age of 56.2 ± 14.2 years, 89.1 % female and divided them by diagnosis: autoimmune thyroiditis (AIT, n = 145), multinodular goiter (MG, n = 31), total thyroidectomy (TT) for thyroid cancer (n = 46), total thyroidectomy for MG (n = 36), TT for Graves disease (GD, n = 9) and radioactive iodine therapy (RAI) for GD (n = 7), and assessed thyroid function tests, thyroid antibodies, lipid profile, high-sensitivity C-reactive protein, vitamin B12, folic acid and applied the Thyroid Dependent Quality of Life questionnaire (ThyDQoL). Statistical analysis was performed with the One-way ANOVA test and Pearson’s correlation test. P values ≤ 0.05 were considered as statistically significant. Results: In this sample, the subgroups who reported worse QoL were the TT for thyroid cancer (-2.47 points) followed by the RAI for GD (-2.14 points) and the AIT (-2.11 points), although these differences were not statistically significant. Regarding the internal domains of the ThyDQoL, we found a significant difference between the subgroup TT for thyroid cancer and MG in bodily discomfort (-4.03 ± 3.61 vs -1.47 ± 1.66; p = 0.04) and household tasks (-2.95 ± 2.92 vs -0.90 vs 1.61; p = 0.02). Within the subgroups, we observed significant correlations involving QoL and vitamin B12 in the AIT subgroup (r = 0.16; p = 0.05), between QoL and lipoprotein(a) (r = -0.50; p = 0.03) in the MG subgroup, between QoL and free T3 (r = -0.31; p = 0.03) in the TT for thyroid cancer subgroup and between QoL and free T3 (r = -0.76; p = 0.04) in the RAI for GD subgroup. Conclusions: In this study we found that patients submitted to TT for thyroid cancer had the worse QoL among patients with hypothyroidism. This may be related to the use of thyroid hormone suppressive therapy. We also observed that certain domains of QoL are more affected by some causes of hypothyroidism. Further studies are needed to analyze more deeply the symptomatology that contributes to worsening of QoL in these patients.