Peripheral Thyroid Hormone Metabolism Research Articles

SAT473 First Case Of Diffuse Thyroid Lipomatosis With Amyloid Deposits Presenting With Hyperthyroidism

Abstract Disclosure: A.M. Gonzalez Gil: None. M.A. Ruiz Santillan: None. H. Quadri: None. B.K. Force: None. R. Gaba: None. Background: Diffuse thyroid lipomatosis (DTL) is an exceedingly rare entity of unknown etiology which can be associated with amyloidosis. It generally presents with euthyroidism but very few cases with hyperthyroidism have been reported. Clinical Case: A 64-year-old woman from Pakistan with a several-year history of a non-tender goiter presented to the emergency department with an upper respiratory and gastrointestinal viral syndrome in the context of several weeks of progressively worsening fatigue. She also reported unintentional weight loss over several years. She denied other hyperthyroid or compressive symptoms. Her exam was notable for resting sinus tachycardia and an approximately 100 gm painless goiter. Laboratory evaluation was notable for a markedly elevated creatinine with nephrotic range proteinuria. She was declared to have end stage renal disease (ESRD) and hemodialysis was initiated. She was also found to have a suppressed TSH (<0.01 uIU/mL, NR=0.45-5.33) and elevated FT4 (2.17 ng/dl, NR=0.64-1.42). Total T3 was low (42 ng/dl, NR=87-178), which was attributed to hypoalbuminemia and altered peripheral thyroid hormone metabolism with underlying ESRD. Further evaluation revealed elevated ESR, CRP and thyroglobulin levels (625.9 ng/mL, NR=1.5-38.5), while thyroid stimulating immunoglobulin, thyroid receptor antibodies and thyroid peroxidase antibodies were undetectable. A thyroid ultrasound revealed an enlarged fatty thyroid consistent with DTL. A radioactive iodine uptake scan revealed normal 24-hour uptake (14.1%, NR=7-32%) in a slightly heterogeneous thyroid with no aberrant functioning thyroid tissue. She was started on atenolol, with significant improvement in her tachycardia, but her FT4 continued to increase. Methimazole was initiated. Dose uptitration and administration after dialysis resulted in near-normalization of FT4 levels. She subsequently underwent renal and thyroid biopsies, both of which showed apple green birefringence under polarized light with Congo Red stain, indicating amyloidosis. Core thyroid biopsy additionally showed benign adipose tissue with entrapped thyroid follicles, confirming concomitant DTL. Although other authors have found thyroid amyloid deposits in DTL, and yet others have reported hyperthyroidism in DTL without amyloidosis, this is the first reported case of hyperthyroidism in a patient with DTL with amyloid deposits. Interestingly, chronic hypoxia in amyloid goiters has been hypothesized to cause fibroblast-to-adipocyte metaplasia leading to DTL. We speculate that excess thyroid hormone release could also be mediated by follicular cells’ response to hypoxia induced by amyloid and fatty infiltration of the thyroid. Conclusion: To the best of our knowledge, this is the first reported case of diffuse thyroid lipomatosis with amyloid deposits to be associated with concurrent hyperthyroidism. Presentation Date: Saturday, June 17, 2023

Relationships of Chronic Kidney Disease and Thyroid Dysfunction in Patients with Stage 4 and 5 Chronic Kidney Disease: A Cross-Sectional Study

Introduction: Chronic kidney disease (CKD) affects the pituitary-thyroid axis and peripheral metabolism of thyroid hormones, thereby causing dysfunction of thyroid hormones. This study aimed to highlight the correlation between thyroid dysfunction and the staging of chronic kidney disease. Methods: Fifty patients with CKD were studied between 2014–2017 in a tertiary care centre in Western India. These patients were split into a subgroup for Stage 4 and 5 CKD, based upon estimated glomerular filtration rate as per the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Thyroid function tests and lipid levels were compared in the different CKD subgroups by analysis of variance. Pearson’s correlation coefficient was used to evaluate the thyroid dysfunction with respect to degree of renal dysfunction in the study population. Results: Thyroid abnormalities were seen in 68% of the author’s patients. Euthyroid sick syndrome (ESS) was the most prevalent thyroid hormonal abnormality seen in 32% (n=16), followed by hypothyroidism category seen in the remaining 36% (n=18) of the study population. Of these, 18% (n=9) of the patients had subclinical hypothyroidism, while the remaining 18% (n=9) manifested overt hypothyroidism. Results showed that ESS had a positive correlation with estimated glomerular filtration rate (r=0.822; p<0.001). No significant differences were found between groups in thyroxine or thyroid-stimulating hormone (p>0.05). Linear regression in unadjusted analysis revealed that deranged low-density lipoprotein levels was found to be significantly associated negatively with hypothyroidism (p<0.001) in patients with CKD. Conclusion: Patients with Stage 4 and 5 CKD have many hormonal disturbances, of which ESS is a common occurrence, and has a significant association with dyslipidaemia, increasing morbidity in these patients. Hypothyroidism is more prevalent in patients with severe renal dysfunction, as a result of higher uremic milieu in these patients.

Vandetanib downregulates type 2 deiodinase in fibro/adipogenic progenitors.

Treatment with tyrosine kinase inhibitors (TKIs) has been associated with alterations in circulating thyroid hormone levels, possibly related to perturbations in peripheral thyroid hormone metabolism. In this study, we evaluated the effect of the multi-kinase inhibitor vandetanib on the expression of the three deiodinase selenoenzymes, responsible for the thyroid hormone activation (type 1 and type 2 deiodinases) or for its inactivation (type 3 deiodinase). Here, we show that the multi-kinase inhibitor vandetanib determines a strong cell-specific downregulation of type 2 deiodinase (D2) expression and a significant reduction in D2 enzymatic activity. This occurs in the diffused population of fibro/adipogenic progenitors, which reside in different tissues - including the muscles - and normally express D2. Given the widespread diffusion of mesenchymal cells within the body, our results may explain at least partially the alterations in thyroid hormone levels that occur in vandetanib-treated patients. Our findings represent a step forward into the understanding of the mechanisms by which TKIs induce hypothyroidism and identify a resident cell population in which such an effect takes place.

A Comprehensive Review of Thyroid Hormone Metabolism in the Gut and Its Clinical Implications.

Background: The gut is a target organ of thyroid hormone (TH) that exerts its action via the nuclear thyroid hormone receptor α1 (TRα1) expressed in intestinal epithelial cells. THs are partially metabolized via hepatic sulfation and glucuronidation, resulting in the production of conjugated iodothyronines. Gut microbiota play an important role in peripheral TH metabolism as they produce and secrete enzymes with deconjugation activity (β-glucuronidase and sulfatase), via which TH can re-enter the enterohepatic circulation. Summary: Intestinal epithelium homeostasis (the finely tuned balance between cell proliferation and differentiation) is controlled by the crosstalk between triiodothyronine and TRα1 and the presence of specific TH transporters and TH-activating and -inactivating enzymes. Patients and experimental murine models with a dominant-negative mutation in the TRα exhibit gross abnormalities in the morphology of the intestinal epithelium and suffer from severe symptoms of a dysfunctional gastrointestinal tract. Over the past decade, gut microbiota has been identified as an essential factor in health and disease, depending on its compositional and functional profile. This has led to a renewed interest in the so-called gut-thyroid axis. Disruption of gut microbial homeostasis (dysbiosis) is associated with autoimmune thyroid disease (AITD), including Hashimoto's thyroiditis, Graves' disease, and Graves' orbitopathy. These studies reviewed here provide new insights into the gut microbiota roles in thyroid disease pathogenesis and may be an initial step toward microbiota-based therapies in AITD. However, it should be noted that cause-effect mechanisms remain to be proven, for which prospective cohort studies, randomized clinical trials, and experimental studies are needed. Conclusion: This review aims at providing a comprehensive insight into the interplay between TH metabolism and gut homeostasis.

MRNA-miRNA sequencing reveals mechanisms of 2,2'-dipyridyl disulfide-induced thyroid disruption in Japanese flounder (Paralichthys olivaceus).

This study was conducted to evaluate the thyroid-disrupting effects of 2,2'-dipyridyl disulfide using Japanese flounder (Paralichthys olivaceus) as an animal model and to reveal the underlying mechanisms from the perspective of miRNA-mRNA interactions. The results indicated that 2,2'-dipyridyl disulfide exposure decelerated the metamorphic progress of P. olivaceus, suggesting its thyroid-disrupting property as an antagonist. Furthermore, radioimmunoassays, thyroid histological observation, real-time polymerase chain reaction, and mRNA sequencing showed that 2,2'-dipyridyl disulfide exposure exerted its thyroid-disrupting effects on larval and juvenile P. olivaceus by targeting multiple processes and pathways involved in the thyroid system, including peripheral metabolism of thyroid hormones, the thyroid hormone synthesis pathway, and the thyroid hormone/thyroid hormone receptor signaling pathway. In particular, global upregulation of the gene expression of three deiodinases caused decreases in thyroid hormone levels after 2,2'-dipyridyl disulfide exposure that are believed to be responsible for the inhibition of metamorphosis in P. olivaceus. Finally, miRNA sequencing suggested that several evolutionarily conserved miRNAs play important roles in the mechanism of 2,2'-dipyridyl disulfide-induced thyroid disruption. Specifically, overexpression of pny-miR-723a and pny-miR-216a resulted in upregulation of deiodinase 1 mRNA levels in the 2,2'-dipyridyl disulfide exposure group. This study provides the first evidence that 2,2'-dipyridyl disulfide has thyroid-disrupting properties and is also the first study remarking on the roles of miRNA-mRNA interactions in the action mechanisms of thyroid disruptors.

Oxidized Pork Induces Hepatic Steatosis by Impairing Thyroid Hormone Function in Mice.

Recent studies have linked high consumption of red and processed meats to an increased risk of non-alcoholic fatty liver disease, and cooking-induced oxidation of proteins and amino acids might be contributing factors. Herein, this study investigates the influence of oxidized pork and the protein oxidation biomarker dityrosine (Dityr) on hepatic steatosis in mice. Low- and high-oxidative injury pork (LOP and HOP) are freeze-dried to prepare mouse diets. Mice are fed a diet of either the control, LOP, HOP, LOP+Dityr, or Dityr for 12 weeks. HOP and Dityr intake induced oxidative stress and inflammation that impaired thyroid function and peripheral metabolism (reduced type 1 deiodinase activity) of thyroid hormones (THs). These lead to a decrease in the circulating as well as liver THs and induced hepatic steatosis. This process might be regulated through reduced TH levels and altered TH target genes and proteins related to hepatic lipid metabolism that ultimately inhibited hepatic energy metabolism, as indicated by increased hepatic lipid synthesis, decreased hepatic lipid catabolism, and fatty acid oxidation. HOP intake could induce hepatic steatosis by impairing TH function. Dityr plays an important role in the HOP-induced harmful effects.

Evaluation of thyroid profile for renal dysfunction in dairy cows

Chronic pathological process in kidney saffect the hypothalamic-pituitary-thyroid system and peripheral metabolism of thyroid hormones. Pathological blood components, which accumulate due to intoxication of metabolic products, the uremic toxins, can affect the metabolism of T3 - and T4 -hormones. In cows on the Ukraine territory such thyroid diseases as hypothyroidism, less often hyperthyroidism, endemic and sporadic goiter, diffuse toxic goiter, tumors were detected, changes in the functional state of the thyroid gland with ketosis, osteodystrophy, hepatodystrophy, polymorbidic pathology were described. Metabolic diseases, which are based on impaired absorption of certain macro-and micronutrients, determine the functional activity of the thyroid gland. The data presented in the article indicate the develop of latent nephropathy in cows during the early milking period with the background of reduced energy supply, which was reflected in the disorders of filtration, excretory and concentration capacity of renal structures with a probable decrease the urea (p<0.001) and creatinine to 3982.4±414.4 μmol/l in urine, a decrease in the value of concentration indices – CI and FCU in 1.7 and 1.4 times, respectively, compared with animals in the control group, the development of hypostenuria with a decrease in relative urinary density to 1.022±0.004 kg/m3 (p<0,01) and selective proteinuria with a probable increase in the protein/creatinine ratio in 3.14 times compared with the cows of the control group. The disorders of the renal functional state was accompanied by changes in the thyroid profile in cows, which was characterized by a probable increase the T3 hormone level to 4.12±0.55 nmol/l (p<0.05) with a simultaneous decrease in thyroxine to 74.2±13,0 nmol/l (p<0,05) on the background of high values of TSH in blood serum (666.8±51.9 nMO/ml). Key words: nephropathy, highly productive cows, thyroid gland, thyroxine, triiodothyronine, thyroid-stimulating hormone.

Response of preterm infants with transient hypothyroxinaemia of prematurity to the thyrotropin-releasing hormone stimulation test is characterized by a delayed decrease in thyroid-stimulating hormone after the peak.

We evaluated the response to the thyrotropin-releasing hormone (TRH) stimulation test in very low-birth weight (VLBW) infants to elucidate the aetiology of transient hypothyroxinaemia of prematurity (THOP). We performed TRH stimulation tests on 43 VLBW infants. Subjects were divided into two groups; a THOP group (N=11; basal TSH<15mU/L and basal FT4≤0.8ng/dL) and a non-THOP group (N=32; basal TSH<15mU/L and basal FT4>0.8ng/dL). Basal FT4 and FT3 were measured before, and TSH (0, 30, 60, 90, 120 and 180minutes) was measured after, the administration of TRH (7µg/kg). We calculated the ratio of TSH 180minutes to THS 0minute as the primary outcome. We also collected data on T3 and rT3 in this study. In both groups, TSH 30minutes values were the highest. However, the ratios of TSH 180minutes to THS 0minutes in the non-THOP group and the THOP group were (median [IQR]) 1.3 [1.0-1.7] and 3.0 [1.5-5.3] (P<.01). No significant differences were observed in T3 (1.0 [0.8-1.3] and 0.7 [0.4-0.7] ng/mL, P=.06). However, in the THOP group, rT3 was significantly lower than that of the non-THOP group (168.0 [148.1-197.0] and 92.9 [74.7-101.6] pg/mL, P<.01). The delayed decrease in the TSH concentration after the peak for the TRH tests and decreased levels of rT3 suggest that the main aetiology for THOP is suppression at the level of the hypothalamus, but not inactivation of peripheral thyroid hormone metabolism.

Regulation of type 3 deiodinase in rodent liver and adipose tissue during fasting.

Fasting induces profound changes in the hypothalamus-pituitary-thyroid axis and peripheral thyroid hormone (TH) metabolism, ultimately leading to lower serum thyroid hormone (TH) concentrations. In the present study, we aimed to investigate the regulation of type 3 deiodinase (D3) during fasting in two metabolic tissues: liver and white adipose tissue (WAT). To this end, we studied the effect of modulation of the mammalian target of rapamycin (mTOR) and hypoxia inducible factor 1α (HIF1α) on D3 expression in primary rat hepatocytes and in 3T3-L1 adipocytes. In addition, we studied the role of the constitutive androstane receptor (CAR) on liver TH metabolism using primary hepatocytes and CAR-/- mice. Twenty-four-hour fasting increased liver Dio3 expression in mice. Inhibition of mTOR using mTOR inhibitors markedly induced Dio3 mRNA expression in primary hepatocytes; this increase was accompanied by a small increase in D3 activity. Stimulation of these cells with a CAR agonist induced both Dio3 mRNA expression and activity. Fasting increased hepatic D3 expression in WT but not in CAR-/- mice. In WAT, Dio3 mRNA expression increased five-fold after 48-h fasting. Treatment of 3T3-L1 adipocytes with mTOR inhibitors induced Dio3 mRNA expression, whereas stimulation of these cells with cobalt chloride, a compound that mimics hypoxia and stabilizes HIF1α, did not induce Dio3 mRNA expression. In conclusion, our results indicate an important role of mTOR in the upregulation of D3 in WAT and liver during fasting. Furthermore, CAR plays a role in the fasting induced D3 increase in the liver.

Inhibition of Type 1 Iodothyronine Deiodinase by Bisphenol A.

Plastics are ubiquitously present in our daily life and some components of plastics are endocrine-disrupting chemicals, such as bisphenol A and phthalates. Herein, we aimed to evaluate the effect of plastic endocrine disruptors on type 1 and type 2 deiodinase activities, enzymes responsible for the conversion of the pro-hormone T4 into the biologically active thyroid hormone T3, both in vitro and in vivo. Initially, we incubated rat liver type 1 deiodinase and brown adipose tissue type 2 deiodinase samples with 0.5 mM of the plasticizers, and the deiodinase activity was measured. Among them, only BPA was capable to inhibit both type 1 and type 2 deiodinases. Then, adult male Wistar rats were treated orally with bisphenol A (40 mg/kg b.w.) for 15 days and hepatic type 1 deiodinase and brown adipose tissue type 2 deiodinase activities and serum thyroid hormone concentrations were measured. In vivo bisphenol A treatment significantly reduced hepatic type 1 deiodinase activity but did not affect brown adipose tissue type 2 deiodinase activity. Serum T4 levels were higher in bisphenol A group, while T3 remained unchanged. T3/T4 ratio was decreased in rats treated with bisphenol A, reinforcing the idea that peripheral metabolism of thyroid hormone was affected by bisphenol A exposure. Therefore, our results suggest that bisphenol A can affect the metabolism of thyroid hormone thus disrupting thyroid signaling.

SUN-575 Anabolic Steroids Induced Hyperthyroidism

Anabolic steroid injections widely used by athletes during strength training period, all studies were done in this field showed transient effect of androgenic anabolic steroids on thyroid which were mainly causing hypothyroidism, However hyperthyroidism cases were never reported up to our knowledge. We present a 25-year-old Emarati male previously healthy, who is referred to endocrine service for hyperthyroidism management. He presented with thyrotoxicosis manifestations. Medical history revealed that he was using anabolic steroids, testosterone, and gonadotropin injection which were prescribed in private gym by trainer. Anabolic steroids were taken twice for few months over 2years prior to his current presentation with hyperthyroidism. Autoimmune profile was negative for thyroid disorder. Radioiodine uptake scan was normal initially then after a year showed diffuse uptake. No evidence of clear cause of his hyperthyroidism. He remained in thyrotoxic state for more than a year post stopping the anabolic steroids. He was treated with radioactive iodine ablation (RAI) according to his preference. Develop post-RAI thyroiditis treated with beta blockers and analgesia. Symptoms completely resolved after 6 weeks and thyroid function returned to normal. The patient has remained asymptomatic on continued follow up care. This case points to the effect of anabolic steroids on thyroid function. Hence all published studies showed that it could cause hypothyroidism not hyperthyroidism. few Literatures are showing that anabolic steroid’s prominent effect on human thyroid function is reduction of TBG with consequent reduction of Total T3 and T4. In rats, anabolic steroids also act in the peripheral metabolism of thyroid hormones and seem to exert an important proliferative effect on thyroid cells. By this effect we believe that, anabolic steroid might cause hyperthyroidism in our patient. To our knowledge, this is the first case report addressing anabolic steroids causing permanent hyperthyroidism. Our patient proved that the effect of anabolic steroid was not transient as he remained in thyrotoxic state for more than a year after stopping steroids and uptake scan showed diffuse high uptake which goes with thyroid cells proliferation hypothesis.

Thyroid Hormone Profile in Children with Sepsis: Does Euthyroid Sick Syndrome Exist?

BACKGROUND:Alterations in peripheral thyroid hormone metabolism play an eminent role in the development of the euthyroid sick syndrome. Altered solvation may also lead to changes in peripheral thyroid hormones. Data on thyroid hormones in critically ill children remain unclear.AIM:This study was aimed to evaluate thyroid hormone profile in children with sepsis as well as to assess the association between thyroid level and sepsis outcome.METHODS:An observational cohort study was conducted in 80 children with sepsis from October 2015 to January 2016 in Haji Adam Malik General Hospital. T3 and T4 level were measured on day 1 and after > 72 hours of sepsis diagnosed.RESULTS:We recorded length of stay in PICU, patient outcome and analysed the relationship with the chi-square test. Level of T3 and T4 were decreased on day 1 in pediatric sepsis. Of 80 subjects, 57 (71.2%) with low-level T3 and 41 (51.2%) with low T4 were found. The relationship between T3 and T4 level on day 1 with the length of stay were not found (P = 0.500; P = 0.987). There were a significant relationship between level of T3 and T4 with outcome (P = 0.0001; OR 24.706; P = 0.014; OR 3.086). Subject with normal T3 and T4 level had 24 and 3 times life chances compare to lower level.CONCLUSION:The Euthyroid Sick Syndrome in children with sepsis does exist. There was a significant relationship between T3 and T4 level on day 1 with patient outcome.

THYROID DYSFUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE

It is known that patients with chronic kidney disease (CKD) often have hypothyroidism. In patients with CKD, iodine excretion in the urine is disrupted. The high content of iodine in the thyroid gland and tissues leads to a disruption in the synthesis and peripheral metabolism of thyroid hormones. In hypothyroidism, there is a disruption of sodium and water reabsorption in the proximal tubule, the volume of the filtrate increases, the volume of the tubular apparatus overloads, and the eGFR decreases.THЕAIM:to study the occurrence of hypothyroidism in patients with different stages of CKD, to evaluate the parameters of thyroid status and antithyroid antibodies in patients with CKD.PATIENTS AND METHODS.953 patients from I.P. Pavlov SPbSMU clinics (screening group) were examined. TSH, free T4, serum creatinine were defined and eGFR was calculated using the formula CKD-EPI in all patients. A group of patients with hypothyroidism accounted for 466 patients. Patients with a normal TSH of 0.4-2.5 mIU / L (comparison group) were selected from the screening group.RESULTS.eGFR in the screening group and in the group of hypothyroid patients correlated with age. Hypothyroidism was associated with female sex and older age. In the group of patients with advanced stage CKD (3B-5), the incidence of subclinical and manifest hypothyroidism was 3 times higher than in the group with normal GFR (GFR&gt; 90 ml / min, p = 0.007). In the group of patients with hypothyroidism, the frequency of advanced stages of CKD (3B-5) was 2 times higher than in the comparison group (p = 0.02). In patients with CKD, a direct correlation was found between GFR and free T3 (r = 0.34, p = 0.02). Thyroid peroxidase antibodies were revealed in 64% of patients with CKD with hypothyroidism.CONCLUSION.Hypothyroidism is associated with chronic kidney disease. For patients with CKD, there is a syndrome of euthyroid pathology ("low T3" syndrome). Hypothyroidism in patients with CKD is not always the outcome of autoimmune thyroiditis.

Diagnosis and treatment of intra-abdominal infection complicated with hypothyroidism

Intra-abdominal infection complicated with hypothyroidism is very common. It mostly featured decreased T3, with or without decreased T4, and without elevated thyroid stimulating hormone(TSH). This particular type of hypothyroidism was called "low T3 syndrome" or "thyroid illness syndrome", and is called "non-thyroid illness syndrome" increasingly in recent years. Its pathogenesis has not been fully understood, and probably is associated with abnormality of hypothalamic-pituitary-thyroid axis, disorder of peripheral thyroid hormone metabolism, change in thyroid hormone binding protein, regulation of triiodothyronine receptors, effect of cytokines, and lack of trace element selenium. Intra-abdominal infection complicated with hypothyroidism should be differentiated from primary hypothyroidism, which may be one cause of mental depression, insufficient anabolism, and poor tissue healing. Therefore, the changes of T3 and T4 levels should be actively monitored in patients with severe or prolonged intra-abdominal infection. Whether treatment is needed for intra-abdominal infection complicated with hypothyroidism remains controversial. T3 replacement therapy may improve prognosis. When low T3 syndrome presents as a disease-mediated hypothyroidism, we recommend the use of levothyroxine(L-T4) or liothyronine (L-T3) treatment to improve the prognosis of critical patients. Enteral nutrition can improve hypothyroidism and has good efficacy for enterocutaneous fistula patients with intra-abdominal infection.

THYROID DYSFUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE: THE STATE OF THE PROBLEM AND THE WAYS OF SOLVING

Disturbance of the thyroid function is often detected in patients with different profiles. A special feature of patients with chronic kidney disease is the higher incidence of various thyroid function disturbances, especially hypothyroidism. It is known that in patients with chronic kidney disease (CKD) iodine excretion from the body is violated, since normally 90% of iodine is excreted in urine. Accumulation of high concentrations of inorganic iodine leads to the formation of the Wolf-Chaikoff effect: suppression of iodine organization in the thyroid gland and disruption of the thyroid hormones synthesis. Peripheral metabolism of thyroid hormones is also disturbed, namely, deiodinase type I activity is suppressed and peripheral conversion of T4 into T3 is inhibited (so-called low T3 syndrome). Therefore, patients with CKD are often diagnosed with hypothyroidism, and the origin of hypothyroidism is not always associated with the outcome of autoimmune thyroiditis. The article presents an overview of a large number of population studies of thyroid gland dysfunction in patients with CKD, as well as experimental data specifying the pathogenetic mechanisms of thyroid dysfunction in patients with CKD. Therapeutic tactics are still not regulated. However, in a number of studies, replacement therapy with thyroid hormones in patients with CKD had some advantages.

TSH Has Effects on Peripheral Thyroid Hormone Metabolism That Are Mild but Run Counter to Its Direct Effects on Thyroid Hormone Secretion

Clinical ThyroidologyVol. 30, No. 3 SummariesTSH Has Effects on Peripheral Thyroid Hormone Metabolism That Are Mild but Run Counter to Its Direct Effects on Thyroid Hormone SecretionCharles H. EmersonCharles H. EmersonSearch for more papers by this authorPublished Online:1 Mar 2018https://doi.org/10.1089/ct.2018;30.138-141AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 30Issue 3Mar 2018 InformationCopyright 2018 American Thyroid Association, Inc.To cite this article:Charles H. Emerson.TSH Has Effects on Peripheral Thyroid Hormone Metabolism That Are Mild but Run Counter to Its Direct Effects on Thyroid Hormone Secretion.Clinical Thyroidology.Mar 2018.138-141.http://doi.org/10.1089/ct.2018;30.138-141Published in Volume: 30 Issue 3: March 1, 2018PDF download

Effects of Thyrotropin on Peripheral Thyroid Hormone Metabolism and Serum Lipids.

Subclinical hypothyroidism is associated with dyslipidemia and atherosclerosis. Whether these effects are in part mediated via direct effects of thyrotropin (TSH) on peripheral thyroid hormone (TH) metabolism and/or concentrations of serum lipids is not clear. This study examined whether TSH has direct effects on peripheral TH metabolism and serum lipids. Eighty-two patients with differentiated thyroid cancer were retrospectively analyzed. All patients had undergone total thyroidectomy and 131I remnant ablation. During follow-up, two successive injections of recombinant human TSH (rhTSH) were administered to patients on a stable dose of levothyroxine. In all patients, TSH, thyroxine (T4), free T4 (fT4), triiodothyronine (T3), reverse T3 (rT3), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, lipoprotein(a), and triglyceride levels were measured immediately before the first and approximately 72 hours after the second injection of rhTSH. After rhTSH stimulation, T3 values decreased (from 1.91 to 1.81 nmol/L; p < 0.001). T4, fT4, and rT3 did not change. After rhTSH, median apolipoprotein B increased from 0.90 to 0.92 g/L (p = 0.03), lipoprotein(a) from 0.21 to 0.24 g/L (p < 0.001), and triglycerides from 1.98 to 2.50 mmol/L (p < 0.001). Serum high-density lipoprotein cholesterol decreased from 0.98 to 0.81 mmol/L (p < 0.001). Multiple regression analysis showed that the changes in lipids were most closely associated with the decrease in T3 levels. TSH has direct effects on peripheral TH metabolism by decreasing T3 levels in levothyroxine-treated thyroidectomized patients. This decrease in T3 levels is accompanied by unfavorable changes in serum lipids.

Thyroid profile in nondialysis-dependent patients with chronic kidney disease in a tertiary hospital in southern Nigeria

Background: Chronic kidney disease (CKD) affects the hypothalamus–pituitary–thyroid axis and peripheral metabolism of thyroid hormones, which affects the concentration and activity of the hormones. Subclinical hypothyroidism (SCH) is the most common thyroid abnormality reported among patients with CKD and it has been associated with increased cardiovascular risk. The objective of this study was to determine thyroid hormone levels and thyroid disorders among Nigerian nondialysis-dependent patients with CKD. Materials and Methods: A cross-sectional, observational study was conducted in a tertiary hospital in southern Nigeria. Nondialysis-dependent patients with CKD attending the renal outpatient clinic of the hospital were recruited over a period of 3 months. Control participants were recruited from healthy consenting hospital staff. Patients with known thyroid disease were excluded. Serum thyroxine (T4), triiodothyronine (T3), and thyroid stimulating hormone (TSH) levels were assayed using the enzyme-linked immunosorbent assay method. Results: Forty patients with CKD (26 men and 14 women) and 20 healthy adults (10 men and 10 women) were studied. The mean age of patients and controls were 54.9 ± 13 years and 44.7 ± 7.3 years, respectively. The mean T4 levels for patients and controls were 4.98 ± 1.23 μg/ml and 5.49 ± 1.06 μg/ml, respectively. The median (interquartile range) values of T3 and TSH for patients were 0.8 (0.7) ηg/ml and 2.6 (3.1) μIU/ml, while that of the controls were 1.85 (2.1) ηg/ml and 1.4 (3.1) μIU/ml. Overt biochemical hypothyroidism was seen in 22% of patients while 10% of patients had SCH. Conclusion: Overt biochemical hypothyroidism was more prevalent among nondialysis-dependent patients with CKD compared to SCH in this study. A larger population study should be performed to confirm this finding among Nigerian patients with CKD.

Thyroid dysfunction in patients of chronic kidney disease

Background: Thyroid hormones play a very important role in regulating metabolism, development, protein synthesis, and influencing other hormone functions. CKD has been known to affect the pituitary-thyroid axis and the peripheral metabolism of thyroid hormones. We aimed to study the thyroid dysfunction in patients of chronic kidney disease for the prevalence of subclinical hypothyroidism.Methods: This cross-sectional study was conducted at Chhatrapati Shivaji Subharti Hospital and Medical College, Meerut, Uttar Pradesh, India, over a 2 year period. The study group comprised 100 patients with Chronic kidney disease. Free thyroxine (fT3, fT4) and thyroid-stimulating hormone (TSH) were measured. Patients with family history of thyroid disorder or past history of any medication for thyroid disease or history of any surgery or any radiological intervention to thyroid gland were excluded from the study.Results: Of 100 CKD patients, 25 were found to have subclinical hypothyroidism (SCH) and 75 were euthyroid. The mean age in patients with SCH was 47.72±10.09 and in euthyroid patients was 46.11±14.332. 12 males (48%) and 13 females (52%) patients were found to have subclinical hypothyroidism and 49 male (65%), 26 female (35%) patients were euthyroid. Prevalence of SCH was 25% with a mean TSH level of 8.68± 1.84.Conclusions: We observed a high prevalence of SCH in our CKD patients. SCH is an additional risk factor in CKD patients and the present study finds thyroid dysfunction being SCH to be very common in CKD patients and reveals significant association between CKD progression and thyroid dysfunction.

Tissue thyroid hormone metabolism is differentially regulated during illness in mice.

Illness induces major modifications in central and peripheral thyroid hormone (TH) metabolism, so-called nonthyroidal illness syndrome (NTIS). As a result, organ-specific changes in local TH availability occur depending on the type and severity of illness. Local TH availability is of importance for the regulation of the tissue-specific TH target genes and determined by the interplay between deiodinating enzymes, TH transport and TH receptor (TR) expression. In the present study, we evaluated changes in TH transport, deiodination and TR expression, the resulting tissue TH concentrations and the expression of TH target genes in liver and muscle in three animal models of illness. We induced (1) acute systemic inflammation by intraperitoneal injection of bacterial endotoxin (LPS), (2) chronic local inflammation by a turpentine injection in the hind limb and (3) severe pneumonia and sepsis by intranasal inoculation with Streptococcus pneumoniae We found that all aspects of peripheral TH metabolism are differentially regulated during illness, depending on the organ studied and severity of illness. In addition, tissue TH concentrations are not equally affected by the decrease in serum TH concentrations. For example, the decrease in muscle TH concentrations is less severe than the decrease observed in liver. In addition, despite lower TH concentrations in muscle in all three models, muscle T3 action is differentially affected. These observations help to understand the complex nature of the nonthyroidal illness syndrome.