Thyroid Hormone Replacement Therapy Research Articles

Impact of hormone replacement therapy on cardiovascular risk in patients with hypothyroidism: a systematic review

Hypothyroidism, which is developed in 4-10 % of the population, and subclinical hypothyroidism found in more than 10 % of people which are highly associated with cardiovascular pathophysiology at some level. Hypothyroidism, which is the most frequent endocrine disorder with a lack of enough thyroid hormones, presents a wide range of cardiovascular complications, including coronary artery disease, heart failure, and dyslipidemia. Thyroid hormone replacement therapy, particularly levothyroxine (LT4), continues to be the central management of hypothyroidism, which aims to restore euthyroidism and other cardiac comorbidities as well as relieving symptoms. Nonetheless, the complex interworking of thyroid function and cardiovascular health requires a detailed clarification of the processes associated with disease development and drug therapy. Hypothyroidism triggers a chain of cardiovascular alterations such as aberrant lipid metabolism, endothelial dysfunction, and lessened cardiac contractility primarily by lowering the thyroid hormone level. Besides, these modifications eventually lead to raised rates of atherosclerosis, myocardial infarction, and heart failure. LT4 replacement therapy achieves normalization of hyperthyroidism with the replacement of thyroid hormone deficiency, which restores the cardiovascular system to normal by doing so. LT4 modulates lipid metabolism, improves endothelial function, and stimulates myocardial contractility via several different mechanisms. LT4 therapy acts on systemic inflammation and oxidation to accentuate the protective effects of the cardiovascular system. Apart from this, there is an increasing awareness about the use of new thyroid hormone formulations, like LH4, in the therapy of hypothyroidism. LH4, the thyromimetic compound, demonstrated a similar binding affinity at the thyroid hormone receptor as T3 (triiodothyronine) but with better tissue selectivity and more metabolic stability. Clinical trials have proven the potency of LH4 in lowering symptoms of hypothyroidism, for example, fatigue, weight gain which are leading cause of cardiovascular disorders. LH4 administration has been safe for up to six months, and only mild adverse effects have been reported when it is used more than a year.

Patient-Reported Satisfaction with Thyroid Hormone Replacement Therapy for Subclinical Hypothyroidism in Older Adults: A Pooled Analysis of Individual Participant Data from Two Randomized Controlled Trials.

Background: The benefit of levothyroxine treatment of subclinical hypothyroidism (SCH) is subject to debate. This study compared treatment satisfaction between older adults with SCH using levothyroxine or placebo. Methods: We analyzed pooled individual participant data from two randomized, double-blind, placebo-controlled trials investigating the effects of levothyroxine treatment in older adults with SCH. Community-dwelling participants aged ≥65 years, with SCH (persistent thyrotropin levels 4.60-19.99 mIU/L for >3 months and normal free T4 level), were included. Intervention dose titration until thyrotropin levels normalized, with a mock dose adjustment of placebo. Treatment satisfaction was determined during the final study visit using the Treatment Satisfaction Questionnaire for Medication (TSQM), encompassing perceived effectiveness, side effects, convenience, and global satisfaction, along with the participants' desire to continue study medication after the trial. Results: We included 536 participants. At baseline, the median (interquartile range [IQR]) age was 74.9 (69.7-81.4) years, and 292 (55%) were women. The median (IQR) thyrotropin levels were 5.80 (5.10-7.00) mIU/L at baseline in both groups; at final visit, 4.97 (3.90-6.35) mIU/L in the placebo and 3.24 (2.49-4.41) mIU/L in the levothyroxine group. After treatment, the groups did not differ significantly in global satisfaction (mean difference [CI] -1.1 [-4.5 to 2.1], p = 0.48), nor in any other domain of treatment satisfaction. These results held true regardless of baseline thyrotropin levels or symptom burden. No major differences were found in the numbers of participants who wished to continue medication after the trial (levothyroxine 35% vs. placebo 27%), did not wish to continue (levothyroxine 27% vs. placebo 30%), or did not know (levothyroxine 37% vs. placebo 42%) (p = 0.14). In a subpopulation with high symptom burden from hypothyroid symptoms at baseline, those using levothyroxine more often desired to continue the medication after the trial than those using placebo (mean difference [CI]: -21.1% [-35.6% to -6.5%]). Conclusion: These pooled data from two RCTs showed no major differences in treatment satisfaction between older adults receiving levothyroxine or placebo. This finding has important implications for decision-making regarding initiating levothyroxine treatment for SCH. Our findings generally support refraining from routinely prescribing levothyroxine in older adults with SCH.

Roxadustat and transfusional iron overload induced hypothyroidism in a hemodialysis patient: a case report with a literature review

BackgroundAlthough roxadustat has been reported to cause central hypothyroidism, the details of the mechanisms and clinical characteristics of patients who are prone to developing hypothyroidism with roxadustat are uncertain.Case presentationA 53-year-old man with a 3-year history of hemodialysis due to diabetic kidney disease who had been treated with roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, for 2 years was admitted to the hospital because of worsening gait disturbance and impaired consciousness. He had also acquired pure red cell aplasia associated with T-cell large granular lymphocytic leukemia and received multiple blood transfusions. Because his serum concentration of thyroid hormones was low, we diagnosed him with hypothyroidism, and his consciousness level recovered to normal with thyroid hormone replacement therapy. Computed tomography revealed a high-intensity atrophic thyroid gland, and magnetic resonance imaging showed diffusely reduced T2 and T1 signals of the pituitary anterior gland. These findings confirmed the accumulation of iron in the pituitary and thyroid glands. Combined pituitary stimulation tests with thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, and corticotropin-releasing hormone revealed that the patient had pan-hypopituitarism. After discontinuation of roxadustat, the patient was treated with another hypoxia-inducible factor prolyl hydroxylase inhibitor, vadadustat. One month after switching medication, a stimulation test with thyrotropin-releasing hormone showed normal responses to thyroid-stimulating hormone. The patient was treated with levothyroxine 50 μg daily without any significant symptoms and is currently under follow-up observation as an outpatient.ConclusionsWe encountered a dialysis patient with roxadustat-induced hypothyroidism associated with transfusion iron overload. To our knowledge, this is the first case to clearly show that roxadustat can impair thyroid-stimulating hormone secretion in repeated thyrotropin-releasing hormone stimulation tests. Because the present patient had received roxadustat for more than 2 years before hypothyroidism became apparent, regular monitoring of the thyroid function may be needed in patients with renal anemia who have been treated with roxadustat, especially those at high risk of thyroid dysfunction.

Renal dysfunction caused by severe hypothyroidism diagnosed by renal biopsy: a case report.

There is a close relationship between thyroid dysfunction and renal dysfunction. However, thyroid dysfunction can unfortunately result in inaccurate measurements of serum creatinine and cystatin C levels. The chronic decrease in cardiac output due to hypothyroidism can reduce renal plasma flow (RPF) resulting in renal dysfunction. We report the case of a 36-year-old male in whom renal dysfunction detected during a company health check-up was found to be caused by severe hypothyroidism. His serum creatinine levels showed poor results, but serum cystatin C levels were within the normal range. The physician thus prioritized serum cystatin C for assessing the patient's renal function, and concluded that his renal function was normal. He subsequently visited our hospital, aged 36years, for a comprehensive examination. His serum creatinine level was 1.88mg/dL and his serum cystatin C level was 0.75mg/dL, indicating an unusual discrepancy between the two measurements. The patient also presented with fatigue, suggesting hypothyroidism, and we therefore evaluated his thyroid function. His free thyroxine level was below the sensitivity of the assay, while his thyroid-stimulating hormone level was > 100 μIU/mL. A renal biopsy was performed to further explore the underlying cause of his renal dysfunction, which suggested that reduced RPF could be the leading cause of his renal ischemia, with no indications of chronic glomerulonephritis or other abnormalities. His hypothyroidism and renal function improved after thyroid hormone replacement therapy. Given the limited reports of renal biopsy tissue examination during the acute phase of hypothyroidism, the current case provides important information regarding the diagnosis of renal dysfunction in patients with hypothyroidism.

Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone synthesis and exerts antioxidant effects. Therefore, it may be of relevance in the management of HT. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on thyroid function (thyrotropin [TSH], free and total thyroxine [fT4, T4], free and total triiodothyronine [fT3, T3]), thyroid antibodies (thyroid peroxidase antibodies [TPOAb], thyroglobulin antibodies [TGAb], thyrotropin receptor antibody [TRAb]), ultrasound findings (echogenicity, thyroid volume), immune markers, patient-reported outcomes, and adverse events in HT. The study protocol was registered on PROSPERO (CRD42022308377). We systematically searched MEDLINE, Embase, CINHAL, Web of Science, Google Scholar, and the Cochrane CENTRAL Register of Trials from inception to January 2023 and searched citations of eligible studies. Two independent authors reviewed and coded the identified literature. The primary outcome was TSH in patients without thyroid hormone replacement therapy (THRT); the others were considered secondary outcomes. We synthesized the results as standardized mean differences (SMD) or odds ratio (OR), assessed risk of bias using the Cochrane RoB 2 tool, and rated the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We screened 687 records and included 35 unique studies. Our meta-analysis found that selenium supplementation decreased TSH in patients without THRT (SMD -0.21 [confidence interval, CI -0.43 to -0.02]; 7 cohorts, 869 participants; I2 = 0%). In addition, TPOAb (SMD -0.96 [CI -1.36 to -0.56]; 29 cohorts; 2358 participants; I2 = 90%) and malondialdehyde (MDA; SMD -1.16 [CI -2.29 to -0.02]; 3 cohorts; 248 participants; I2 = 85%) decreased in patients with and without THRT. Adverse effects were comparable between the intervention and control groups (OR 0.89 [CI 0.46 to 1.75]; 16 cohorts; 1339 participants; I2 = 0%). No significant changes were observed in fT4, T4, fT3, T3, TGAb, thyroid volume, interleukin (IL)-2, and IL-10. Overall, certainty of evidence was moderate. Conclusions: In people with HT without THRT, selenium was effective and safe in lowering TSH, TPOAb, and MDA levels. Indications for lowering TPOAb were found independent of THRT.

Study of patient satisfaction with thyroid hormone replacement therapy in patients with hypothyroidism

Study of patient satisfaction with thyroid hormone replacement therapy in patients with hypothyroidism

Effects of laparoscopic sleeve gastrectomy on thyroid hormones and relationship between metabolic parameters and long-term total weight loss.

Bariatric surgery has significant effects on metabolic parameters and hormone levels. However, the specific impact of laparoscopic sleeve gastrectomy (LSG) on thyroid hormones and other metabolic parameters remains unclear. This study aimed to investigate the short and long-term effects of LSG on thyroid hormone levels, HbA1c, and other metabolic parameters. A total of 619 euthyroid patients without a history of thyroid disease or thyroid hormone replacement therapy were included in the study. Patients with diabetes were excluded from the study. Preoperative, 1-year postoperative, and 5-year postoperative levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), HbA1c, and other metabolic parameters were recorded and analyzed. LSG resulted in significant weight loss and improvements in metabolic parameters. At 1year postoperatively, there were significant reductions in BMI, HbA1c, TSH, fT3, and triglyceride levels, while fT4 levels increased. A statistically significant negative correlation was found between preoperative HbA1c level and percentage of total weight loss (%TWL) value at the fifth postoperative year. Additionally, a statistically significant negative correlation was found between the 5-year change in TSH and %TWL. Being the first study to predict long-term total weight loss based on preoperative HbA1c, it is significant. This finding has important implications for personalized patient management and could aid clinicians in identifying individuals who may benefit most from sleeve gastrectomy as a treatment modality. This is valuable in that it emphasizes multidisciplinary work, including the endocrinologist and dietician.

The course of subacute thyroiditis from COVID-19 infection

The aim of this literature review is the analysis of the new data on subacute thyroiditis that emerged due to studying of potential effect SARS-CoV-2 has on disease’s manifestation and clinical course. The pandemic affected hundreds of millions of people, and thyroiditis as a consequence of viral infection has become more frequently observed in scientific research and case reports. Many academic works indicate that the virus directly impacts both the thyroid gland and the immune system, and some new pathogenic mechanisms were discovered during the course of the pandemic. Despite the fact that subacute thyroiditis is a self-limiting disease, its possible outcome is a permanent primary hypothyroidism with a need of a lifelong thyroid hormone replacement therapy. It also has a tendency to be relapsing. Certain characteristics has been found which show how modern de Quervain thyroiditis is different from the one several years ago. The scale of the pandemic made it evident for scientific community that there is a need for a rapid design of a vaccine as a specific preventive measure. Millions of people received COVID-19 vaccines and reports about subacute thyroiditis following the vaccination started to emerge, the systemic reviews on the issue were written, all this is also highlighted in this review article. Despite the fact that the World Health Organization declared an end to the pandemic in May 2023, the virus itself is likely to still be circulating in the population and it will continue to be one of the etiological factors behind de Quervain thyroiditis, also, coronaviral evolution did not come to an end.

P-69 Beneficial outcomes of hypothyroidism treatment in atrial fibrillation patient

Abstract Introduction It is well established that hyperthyroidism is a strong independent risk factor for atrial fibrillation (AF). However, the relationship between hypothyroidism and AF is complex and not fully understood. The abnormal thyroid hormone levels can disrupt the electrical signals that regulate heart rhythm, potentially leading to AF. Some symptoms of hypothyroidism, such as fatigue, weakness, and shortness of breath, can mimic the symptoms of AF. This can make it challenging to diagnose AF in individuals with underlying thyroid issues. Meanwhile the treatment of hypothyroidism in A patient with AF can significantly improve the symptoms. Clinical Case A 54 years old female was referred to the Therapy department with fatigue and palpitations. She was diagnosed one year ago with paroxysmal tachysystolic atrial fibrillation. CHADSVASK-1, EHRA-3. She experienced paroxysmal episodes four to five times a month for which she took propafenone. At presentation echocardiography (ECHO) showed LVEDD-50, LVEDS-35, IVS-12, LVPW-11, LA-42, EF-57%. The blood sample revealed TSH-8.41 (reference range 0.3-4 mIU/l), free T4-1.15 (reference range 10-25 pmol/l), free T3-3.76 (reference range 2.5-5.8 pmol/l), AbTPO-1040 (reference range 2.5-30 IU/ml). On thyroid ultrasound examination dimensions of right lobe were 18 *23 * 39 mm, left lobe were 22*20*38 mm, isthmus 3.8 mm, and no nodules were present. Total thyroid volume was 19.5 mL. The gland had heterogeneous echotexture and normal vascularity. Treatment with levothyroxine 50 mcg was started. After 6 weeks of treatment with levothyroxine TSH improved to 3.8 mIU/l and patient's fatigue and palpitation symptoms significantly improved, and no new paroxysms were detected. Conclusion: Managing hypothyroidism through thyroid hormone replacement therapy can often help control and sometimes even reverse AF if the arrhythmia was related to thyroid dysfunction. However, some individuals, as in this case, may continue to have AF even after their thyroid levels are normalized. In this case we emphasize the importance of understanding the effect of hypothyroidism on AF.

Development and In Vivo Evaluation of Sustained Release Microparticles Loaded with Levothyroxine for Hypothyroidism Treatment

Hypothyroidism is a chronic condition combated by a daily oral supplementation of levothyroxine. In addition to the need for frequent dosing, oral administration may result in variable absorption of the drug leading to a failure in achieving normal thyroid function. Therefore, the development of a long-acting injectable system capable of delivering the drug is necessary. This work was aimed at developing sustained release microparticles loaded with levothyroxine. The microparticles were produced through the emulsification-solvent evaporation method using 2 grades of biocompatible and biodegradable polyesters: poly(ᴅ,ʟ-lactide-co-glycolide) (PLGA) and poly(ᴅ,ʟ-lactide) (PLA). Both polymers produced microparticles with very similar sizes (1.9 µm) and zeta potential values (around -22.0 mV). However, PLA microparticles had a significantly higher drug loading (6.1% vs. 4.4%, respectively) and encapsulation efficiency (36.8%, vs. 26.1%, respectively) when compared to PLGA counterparts. While both types of microparticles displayed a biphasic release pattern in vitro, a slower rate of release was observed with PLA microparticles. Moreover, a similar biphasic release pattern was found in vivo, with an initial phase of rapid release followed by a slower phase in the subsequent 10 days. These results indicate the possibility of developing levothyroxine loaded polyester microparticles as a potential long-acting thyroid hormone replacement therapy.

Supraglottic myxoedema successfully treated orally.

Myxoedema coma is a severe form of hypothyroidism with multiple organ dysfunction, characterised by an altered state of consciousness and hypothermia. Intravenous thyroid hormone replacement therapy is the preferred treatment for myxoedema. The mortality rate associated with this disease is high, and early detection and intervention are essential. Supraglottal myxoedema is a rare form of periglottic oedema and can be fatal. A previously healthy 66-year-old man presented with impaired consciousness, hypothermia, and nonpitting oedema. Blood tests revealed the presence of hypothyroidism and respiratory acidosis. He was intubated for type 2 respiratory failure; however, severe laryngeal oedema made the procedure difficult to perform. Oral thyroid hormone therapy was initiated under the diagnosis of myxoedema coma. Tracheostomy was performed because of prolonged type 2 respiratory failure and laryngeal oedema. Three weeks after admission, the patient was weaned off the ventilator. Approximately a week later, laryngeal oedema improved, and the tracheostomy tube was removed. The patient was discharged and remained stable for 3 months. This case report describes a patient with comatose myxoedema and supraglottic oedema who was successfully treated with oral medication alone. This case shows that supraglottic oedema should be considered even in the absence of wheezing or other signs of upper airway obstruction. Myxoedema coma is a differential diagnosis of respiratory acidosis. In myxoedematous coma, the possibility of difficult intubation due to supraglottic oedema should be considered. Tracheostomy should be considered for supraglottic myxoedema, which often results in prolonged ventilator use. Supraglottic myxoedema can be treated with oral medications.

Evaluation of cortical and trabecular bone structure of the mandible in patients using L-Thyroxine

BackgroundLong-term use of L-Thyroxine (LT4), the synthetic thyroxine hormone used for thyroid hormone replacement therapy, is an important risk factor for osteoporosis. The aim of this study was to investigate the differences between mandibular cortical index (MCI) and trabecular bone fractal dimension (FD) values on panoramic radiographs of patients using LT4 and control subjects.MethodsA total of 142 female patients, 71 cases and 71 controls, were analyzed in the study. Ages were matched in case and control groups and the mean age was 36.6 ± 8.2 (18 to 50) years. MCI consisting of C1 (Normal Mandibular Cortex), C2 (Moderately Resorbed Mandibular Cortex) and, C3 (Severely Resorbed Cortex) scores was determined for case and control groups. Fractal analysis was performed using ImageJ on selected regions of interest from the gonial and interdental regions. The box-count method was used to calculate FD values. Wilcoxon signed-rank test, Mann-Whitney U test, and Spearman correlation analysis were applied to compare the measurements. Statistical significance of differences was established at P < 0.05 level.ResultsFD values did not show statistically significant differences between case and control groups (p > 0.05). The mean FD in the right gonial region was 1.38 ± 0.07 in the case group and 1.38 ± 0.08 in the control group (p = 0.715). The mean FD in the right interdental region was 1.37 ± 0.06 in the cases and 1.36 ± 0.06 in the control group (p = 0.373). The mean FD in the left gonial region was 1.39 ± 0.07 in the cases and 1.39 ± 0.07 in the control group (p = 0.865). The mean FD in the left interdental region is 1.37 ± 0.06 in the cases and 1.38 ± 0.05 in the control group (p = 0.369). The most common MCI score was C1, with 62% in the cases and 83.1% in the control group. MCI scores showed a statistically significant difference between cases and controls (p = 0.016, p < 0.05). While the C2 score was higher in the cases, the C1 score was higher in the controls.ConclusionsLT4 use was not associated with the FD of mandibular trabecular bone, but was associated with MCI values of cortical bone. Further studies on larger samples with different imaging modalities and image processing methods are needed.

Thyroid medications and patient adherence: understanding prescription patterns and factors influencing treatment compliance

Thyroid problems are common in India affecting around 42 million people. Early diagnosis and therapy play an important role in managing this endocrine disorder. Hypothyroidism and hyperthyroidism are the most common thyroid disorders and are treated with thyroid hormone replacement therapy and antithyroid drugs. However, medication adherence, side effects, and misunderstanding of the importance of medication lead to inconsistent intake. This study aimed to evaluate the pattern of prescribing and adherence to thyroid medication. This cross-sectional study was conducted over 6 months in a tertiary care hospital, involving 188 patients with thyroid disorders. Data was collected using a validated form and medication adherence rationing scale. The collected data, including MARS scores, were entered into Microsoft Excel and analyzed using IBM SPSS Version 25. Quantitative data were analyzed using the mean and standard deviation, while categorical data were summarized using frequencies and percentages. The Chi-square test was used to evaluate associations, with a significance level of p &lt; 0.05. In our study, 163 participants diagnosed with hypothyroidism exhibited a notable adherence rate of 89.57%. The 25 hyperthyroid patients showed strong adherence to the recommended drugs, with those provided methimazole having the highest adherence rate (52.0%). No statistically significant connections were found when examining the variables affecting drug adherence. Levothyroxine and methimazole were the preferred medications for managing hypothyroidism and hyperthyroidism, respectively. A high adherence rate among patients indicates heightened awareness and understanding of their condition, as well as consistent adherence to the medication schedule. These findings emphasize the importance of early diagnosis, appropriate prescription patterns, and patient adherence in effectively managing thyroid disorders.

Differentiated thyroid cancer: a focus on post-operative thyroid hormone replacement and thyrotropin suppression therapy.

This review focuses on post-operative thyroid hormone replacement and thyrotropin suppression therapy in patients with differentiated thyroid cancer. A clinical review. Differentiated thyroid cancers (DTC), including papillary and follicular thyroid cancers, have an excellent prognosis and their management leverages a unique set of clinical tools arising from homology to the normal thyroid follicular cell. Surgery is the cornerstone of initial management, and post-operative care often requires thyroid hormone replacement therapy, which may be approached with the intent of physiologic normalization or used pharmacologically to suppress TSH as part of a DTC treatment. Management of DTC and approaches to TSH suppression are tailored to an individual's risk of DTC recurrence and are adjusted to a patient's clinical status and comorbidities over time with the goal of mitigating risk and maximizing benefit.

FRI332 Check Point Inhibitor Induced Hypophysitis/Hypopituitarism

Abstract Disclosure: R.S. Chandpuri: None. Introduction: A case of Renal cell cancer with metastasis to contralateral kidney, which was treated with nivolumab/ Ipilimumab leading to hypophysitis/hypopituitarism. Case: 42-year-old female with past medical history of Left renal mass who underwent left radical nephrectomy. On surveillance imaging she was found to have evidence of new paraspinal mass suspicious for metastatic spread involving retroperitoneal lymph nodes and contralateral kidney. She would be referred to her oncologist for observation versus chemotherapy. Her oncologist ordered nivolumab and ipilimumab. Patient tolerated chemotherapy well. A surveillance brain MRI was ordered to check for any metastatic involvement and it showed enlargement of the pituitary gland with focal hypo-enhancing area concerning for immune check point inhibitor therapy induced hypophysitis. Labs showed- cortisol-0.8, ACTH &amp;lt;5, TSH-0.6, Free T4-0.60, Prolactin-57.9, FSH-3.7, LH-5.0. Clinically she would complain of fatigue, generalized weakness, hypotension and amenorrhea. The patient was reluctant to start thyroid hormone replacement therapy, and she appeared clinically euthyroid. A dedicated Pituitary MRI showed partially empty sella turcica, sella measuring approximately 0.2 cm in maximal height. There was no abnormal thickening or nodular enhancement of the pituitary stalk. No suprasellar mass effect or chiasmatic compression. She was placed on Prednisone/ Hydrocortisone with improvement in her fatigue and blood pressure. Conclusion: Immune checkpoint inhibitors are a new form of immunotherapy used in the treatment of various cancers (melanoma, RCC, colorectal). These agents can cause immune-mediated pituitary lesions (hypopituitarism/hypothyroidism). These drugs can cause a spectrum of issues ranging from single hormone deficiency to pan-hypopituitarism. Due to the new advances in chemo/immune therapy, providers need to be aware of such conditions to quickly recognize and treat them. Symptoms of this condition can be masked and can be attributed to other diseases processes ie(depression, anxiety, chronic fatigue syndrome). It would be best to come up with a screening process/order set for such patients with close communication between primary care, endocrinologists, oncologists in order to identify and treat the patients. Presentation: Friday, June 16, 2023

Effect of thyroid hormone replacement treatment on cardiac diastolic function in adult patients with subclinical hypothyroidism: a meta-analysis.

Although subclinical hypothyroidism (SCH) is related to abnormalities in left ventricular diastolic function, the use of levothyroxine as a regular treatment remains debatable. This meta-analysis aimed to determine whether thyroid hormone replacement therapy affects cardiac diastolic function in patients with SCH as measured by echocardiography. This meta-analysis included a search of the EMBASE, PubMed, Web of Science, and Cochrane Library databases from their inception to May 18, 2023, for studies analyzing cardiac morphology and functional changes in patients with SCH before and after thyroid hormone replacement. The outcome measures were cardiac morphology and diastolic and overall cardiac function, as assessed using ultrasound parameters (including ventricular wall thickness, chamber size, mitral wave flow, tissue Doppler, and speckle tracking). The quality of the studies was assessed using the Newcastle-Ottawa Scale. The standard mean differences (MDs) and 95% confidence intervals (CI) were calculated using fixed- or random-effects models. Seventeen studies met the inclusion criteria. A total of 568 patients participated and completed the follow-up. All studies specifically stated that serum thyrotropin levels returned to normal by the end of the study period. Compared with baseline levels, no significant morphological changes were observed in the heart. In terms of diastolic function, we discovered that the ratios of E-velocity to A-velocity (E/A) had greatly improved after thyroid hormone replacement therapy, whereas the ratios of the mitral inflow E wave to the tissue Doppler e' wave (E/e') had not. Global longitudinal strain (GLS) increased significantly after treatment with levothyroxine. In adult patients with SCH, thyroid hormone supplementation can partially but not completely improve parameters of diastolic function during the observation period. This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement, an updated guideline for reporting systematic reviews (11) and was registered with INPLASY (INPLASY202320083). https://inplasy.com/inplasy-2023-2-0083.

Systematic Review to Gauge the Effect of Levothyroxine Substitution on Progression of Diabetic Nephropathy in Patients With Hypothyroidism and Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) and thyroid dysfunction are two disorders that are closely related. This systematic review aimed to investigate the effect of levothyroxine supplementation on diabetic nephropathy in type 2 diabetic patients with co-existing thyroid dysfunction. We explored medical databases such as PubMed, Medline, Multidisciplinary Digital Publishing Institute (MDPI), and Cochrane Library for relevant medical literature. The papers were screened, and 12 research papers involving 10,371 patients were identified after applying eligibility criteria and quality assessment using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The included papers analyzed the effect of aberrant thyroid profile on kidney disease in diabetic individuals and the role that achieving euthyroid status with levothyroxine supplementation could play in diabetic nephropathy. Reduced free triiodothyronine (FT3) was the most common independent factor associated with diabetic microvascular and macrovascular complications. Levothyroxine (LT4) regimen was more effective than the placebo in lowering urinary albumin excretion rate (UAER), low-density lipoprotein cholesterol, and uric acid and decreasing oxidative stress overall. However, replacement therapy's effect may differ in the short and long terms. Thyroid hormone replacement therapy (THRT) may reduce the risk of diabetic nephropathy and cardiovascular disease (CVD) development in hypothyroid patients, but more randomized trials are needed to confirm the effect of THRT.

Factors related to bone mineral density in female patients receiving TSH-suppressive doses of levothyroxine for thyroid cancer

Background: Patients with thyroid cancer receive a high-dose thyroid hormone therapy after total thyroidectomy for suppression of thyroid stimulating hormone (TSH); this may affect bone mineral density (BMD). Identifying the common factors that affect BMD (including the duration of a high dose of thyroid hormone treatment) may, therefore, aid the delivery of appropriate and comprehensive care in such cases. Objective: To identify the factors related to BMD in female patients with thyroid cancer. Materials and Methods: This cross-sectional study evaluated data pertaining to the BMD and demographic characteristics of female patients with thyroid cancer. The patients were aged at least 40 years and received a high-dose thyroid hormone replacement therapy after total thyroidectomy at the Rajavithi Hospital between January 2004 and December 2019. The relationships between BMD and associated factors were analyzed using Pearson’s correlation and multiple linear regression. A p-value of less than 0.05 was considered statistically significant. Results: A total of 100 female patients with a mean age of 55.37 ± 11.36 (40-82) years and mean body mass index (BMI) of 24.8 ± 4.96 (15-40) were included; 60 and 56 of them were postmenopausal and coffee drinkers, respectively. High-dose thyroid hormone replacement therapy was received for a mean duration of 94.59±50.36 (3-210) months and 13 patients had a history of fractures; 60%, 30%, and 10% had normal BMD, osteopenia, and osteoporosis, respectively. The factors affecting BMD included the BMI (p-value &lt;0.001) and postmenopausal status(p-value &lt;0.001). Subgroup analyses showed the BMI to be the factor affecting BMD in the premenopausal group (p-value &lt;0.001). Age, BMI, and calcium supplement intake were found to have an effect on the BMD in the postmenopausal group (p-value= 0.003, 0.002, and 0.020, respectively). The duration of high-dose thyroid hormone intake had no effect on the BMD in both the overall population (p-value= 0.558) and the subgroups based on the menopausal status (p-value = 0.437 and 0.380 in premenopausal and postmenopausal groups, respectively). Conclusion: In female patients who were treated for thyroid cancer, the factors affecting the BMD included the BMI in the premenopausal group and the age, BMI, and calcium supplementation in the postmenopausal group.

Treating subclinical hypothyroidism in individuals with or without mental health problems -A Delphi based expert consensus study in two countries.

Subclinical hypothyroidism (SCH) is a common endocrine problem with prevalence estimates between 4% and 20%. Symptoms are often non-specific but can substantially affect well-being leading to repeated medical consultations. The effect of thyroid hormone replacement therapy (THRT) in patients with SCH remains uncertain. Current guidelines, limited by the lack of high-quality evidence, have been controversial with limited adherence in clinical practice. Three-round modified Delphi method to establish consensus regarding diagnosis and treatment of individuals with SCH with and without affective disorder or anxiety, conducted with clinicians from three specialties, general practice, endocrinology and psychiatry, and two countries, Sweden and the United Kingdom. Sixty clinicians, 20 per specialty, were recruited. Fifty-three (88%) participants completed all three rounds. The participants reached consensus on five of the 26 practice statements that (a) repeated testing was required for the diagnosis of subclinical hypothyroidism, (b) antibody screening should usually occur, and (c and d) antibody screening would strengthen the indication for thyroid hormone replacement therapy in both individuals with or without affective disorder or anxiety. The participants disagreed with (e) a requirement of a TSH threshold ≥ 20 mIU/L for thyroid hormone replacement therapy start. Psychiatrists and GPs but not endocrinologists, agreed that there was a frequent discrepancy between laboratory results and clinical symptoms, and disagreed that testing for thyroid dysfunction was overused in patients presenting with depression or anxiety, or fatigue. In many aspects, attitudes toward diagnosing and treating SCH remain diverse. The inability of our Delphi panel to achieve consensus on most items and the disagreement with a TSH ≥ 20 mIU/L threshold for treatment suggest that the concept of SCH may need rethinking with a better understanding of the hypothalamic-pituitary-thyroid physiology. Given that the scientific evidence is currently not conclusive, guidelines in this area should not be taken as definitive.

#4846 ROXADUSTAT-INDUCED HYPOTHYROIDISM: THE EFFECT OF ROXADUSTAT ON SUPPRESSION OF THYROID FUNCTION

Abstract Background and Aims There have been only two case reports of hypothyroidism in patients treated with roxadustat, a HIF-PH inhibitor as new renal anemia drug. However, there has yet been no studies to examine the effect of roxadustat on thyroid function. Method In this study, we retrospectively examined the effects of roxadustat on thyroid-stimulating hormone (TSH) in hemodialysis patients by two blood examinations, before and during treatment with roxadustat. We included patients who had TSH levels measured after at least two consecutive weeks of roxadustat treatment and before. We excluded patients with a history of taking other HIF-PH inhibitors before roxadustat. The period was from September 2021 to November 2022 in this interim analysis. A p value of&amp;lt;0.05 was considered statistically significant. Analyses were performed using SPSS. Results 93 patients were included in this analysis. TSH levels significantly decreased after treatment with roxadustat. A total of 58.1% of patients had decreased TSH levels (2.23 ± 1.18 v.s. 1.81 ± 1.35, μIU/mL, p value = 0.040, Wilcoxon signed-rank test), and 18.3% of patients had a significant decrease below the normal range. Additionally, patients treated with thyroid hormone replacement therapy in primary hypothyroidism had a higher frequency (81.0%) of TSH decrease compared to patients without (p value = 0.013, Pearson's chi-square test). Conclusion This is the first study to examine that roxadustat has a suppressive effect on TSH secretion in hemodialysis patients. We also found that roxadustat-induced hypothyroidism is prevalent in the high frequency of TSH suppression, especially in primary hypothyroidism patients treated with thyroid hormone replacement therapy. Thyroid hormone receptor beta (THRβ), which is expressed in the hypothalamus and pituitary gland, plays an important role in regulating thyroid hormone through feedback mechanisms. Yao et al. have reported that roxadustat has a similar structure to T3 and acts as a THRβ-selective ligand, particularly activating THRβ. Therefore, it is possible that roxadustat suppresses TSH secretion through negative feedback via THRβ. It is important to monitor thyroid function in patients receiving roxadustat. Roxadustat should be avoided in patients with primary hypothyroidism, since it is inferred that roxadustat-induced hypothyroidism cannot be improved by enhancement of thyroid hormone replacement therapy.