Effects and Action Mode of Oleic Acid and Azone on Release and Penetration Process of Levothyroxine Sodium Patches.

In recent years, there has been a significant increase in the prevalence of thyroid diseases, particularly hypothyroidism. In this study, we investigated the impact and mechanisms of Chemical permeation enhancement(CPE) on transdermal permeation of levothyroxine sodium (L-T4) patches.We found that the combination of oleic acid (OA) and Azone (NZ) yielded the best transdermal permeation effect for L-T4.Subsequently, we also investigated the relevant propermeability mechanism.The results demonstrate that the combined application of OA and NZ significantly enhances the transdermal permeation of L-T4 compared to individual applications,it is attributed to two mechanisms: firstly, OA improves drug release by increasing the flowability of the pressure-sensitive adhesive (PSA) matrix; secondly, both OA and NZ act on the stratum corneum, especially facilitating L-T4 permeation through the hair follicle pathway. No skin irritation or cytotoxicity is observed with these final patches, which exhibit a remarkable therapeutic effect on hypothyroidism. this study contributes to the development of transdermal formulations of L-T4.

Is the acquired hypothyroidism a risk factor for developing psychiatric disorders?

Hypothyroidism is a prevalent thyroid condition in which the thyroid gland fails to secrete an adequate amount of thyroid hormone into the bloodstream. This condition may develop due to genetic or acquired factors. The most frequent cause of acquired hypothyroidism is chronic autoimmune thyroiditis, also known as Hashimoto's disease. Acquired hypothyroidism is diagnosed when patients present with overt hypothyroidism (also known as clinical hypothyroidism), as they exhibit increased TSH and decreased T3 and T4 serum levels. This article examines the prevalence of psychiatric disorders among patients diagnosed with acquired hypothyroidism with or without Levothyroxine treatment. We discuss the available evidence indicating that acquired hypothyroidism may be a risk factor for psychiatric disorders, and the effectiveness of thyroid treatment in relieving psychiatric symptoms. Additionally, we provide critical details on thyroid hormone cutoff values reported in the literature, their potential clinical importance, and their correlation with psychiatric symptoms. Finally, we examined the various mechanisms by which acquired hypothyroidism can lead to depression. The high rate of comorbidity between hypothyroidism and psychiatric disorders deserves special attention, indicating the importance of consistent monitoring and timely identification of psychiatric symptoms to prevent disease exacerbation and facilitate therapeutic management. On the other hand, several mechanisms underlie the strong association between depression and acquired hypothyroidism. Deeper research into these mechanisms will allow knowledge of the pathophysiology of depression in patients with acquired hypothyroidism and will provide clues to design more precise therapeutic strategies for these patients.

Adequate Dose of Levothyroxine for Thyroid-Stimulating Hormone Suppression after Total Thyroidectomy in Patients with Differentiated Thyroid Cancer.

Background: The adequate dose of levothyroxine (LT4) for patients who have undergone total thyroidectomy (TT) for differentiated thyroid cancer (DTC) is uncertain. We evaluated the LT4 dose required to achieve mild thyroid-stimulating hormone (TSH) suppression in DTC patients after TT. Methods: The electronic medical records of patients who underwent TT for DTC and received mild TSH suppression therapy were reviewed. Linear regression analysis was performed to evaluate the association between LT4 dose (µg/kg) and an ordinal group divided by body mass index (BMI). We also evaluated the trend in LT4 doses among groups divided by BMI and age. Results: In total, 123 patients achieved mild TSH suppression (0.1 to 0.5 mIU/L). The BMI variable was divided into three categories: <23 kg/m2 (n=46), ≥23 and <25 kg/m2 (n=30), and ≥25 kg/m2 (n=47). In the linear regression analysis, BMI was negatively associated with the LT4 dose after adjusting for age and sex (P<0.001). The LT4 doses required to achieve mild TSH suppression based on the BMI categories were 1.86, 1.71, and 1.71 µg/kg, respectively (P for trend <0.001). Further analysis with groups divided by age and BMI revealed that a higher BMI was related to a lower LT4 dose, especially in younger patients aged 20 to 39 (P for trend=0.011). Conclusion: The study results suggest an appropriate LT4 dose for mild TSH suppression after TT based on body weight in patients with DTC. Considering body weight, BMI, and age in estimating LT4 doses might help to achieve the target TSH level promptly.

Importance of right communication with healthcare providers and patients about the new levothyroxine formulation: an expert opinion from Asia Pacific Thyroid Advisory Board.

Levothyroxine (LT4), being "narrow therapeutic index" drug, may lead to significant fluctuations in thyroid stimulating hormone (TSH) levels. Such fluctuations can result in clinically noteworthy disruptions in thyroid function and give rise to adverse clinical consequences. Consequently, regulatory standards for LT4 potency have been tightened, with the most stringent specifications requiring maintenance of potency within the range of 95-105% of the labeled dose throughout the entire shelf-life of the product. The LT4 new formulation with tightened specification adheres to these rigorous standards, demonstrating established bioequivalence to its older formulation while upholding an equivalent standard of safety and efficacy. Furthermore, the novel formulation exhibits enhanced stability and an extended shelf-life. Of paramount significance is its capacity to provide patients with accurate and consistent dosing, thereby effectively catering to their medical requirements. The primary objective of the Asia-Pacific advisory board meeting (held in June 2022 with endocrinologists, experts from India, Indonesia, Philippines, Thailand, Malaysia and Singapore) was to establish the importance of appropriate communication to HCPs, patients and other stakeholders regarding the LT4 new formulation. The aim of this brief review is to highlight the importance of communication with healthcare professionals that should focus on providing accurate information on the LT4 new formulation, emphasizing efficacy, safety, and bioequivalence with clear guidance and ensure that patients and clinicians are fully informed about any changes to medications such as LT4 to reduce the risk of unrelated adverse events being incorrectly attributed to the newer formulation.

Epilepsy associated with Graves' disease: Report of two cases.

We present two cases of epilepsy associated with Graves' disease. Case 1 is a 22-year-old woman. She had three epileptic seizures and was diagnosed with idiopathic generalized epilepsy. She was treated with valproic acid (VPA). She was later diagnosed with Graves' disease, and treated with antithyroid medication (thiamazole). We added a thyroid medication (levothyroxine) because of a decrease in free thyroxine observed with antithyroid medication. Case 2 is an 18-year-old woman. She had three epileptic seizures and was diagnosed with juvenile myoclonic epilepsy and treated with VPA. Then, she was diagnosed with Graves' disease and was treated with thiamazole. Levothyroxine was added due to low fT4 induced by thiamazole. Due to poor compliance with antithyroid medication, the thyroid functional status was not stable. Both patients became seizure-free and euthyroid after VPA and thiamazole treatments.

Severe myxedema coma and pericardial effusion in a child with Down syndrome: the importance of adherence to levothyroxine therapy.

BACKGROUND: Myxedema coma is a rare, but life-threatening endocrinological emergency. Myxedema is characterized by altered mental status, and is accompanied by hypotension, bradycardia, hypothermia, bradypnea, hyporeflexia, hyponatremia, and hypoglycemia, all stemming from reduced metabolism due to severe hypothyroidism. Additionally, patients may exhibit signs of low cardiac output, edema in the extremities, peripheral circulatory disturbances, shock, and the development of pericardial and pleural effusions, ultimately leading to confusion and coma. We present a successfully treated case of severe myxedema coma with recurrent pericardial effusion and hypotensive shock. This case is characterized by an unusual clinical presentation and required a distinct treatment strategy highlighting its exceptional rarity. CASE: A 2-year-old boy with Down syndrome presented with recurrent pericardial effusion attributed to medication non-adherence. The critically-ill patient, experiencing a severe cardiogenic shock required mechanical ventilation and inotropic infusions in the pediatric intensive care unit. Elevated thyroid stimulating hormone (TSH), and low free T4 (fT4) and free T3 (fT3) levels prompted consideration of myxedema coma. Upon reviewing the patient's medical history, it was ascertained that he had an ongoing diagnosis of primary hypothyroidism, and exhibited non-adherence to the prescribed treatment regimen and failed to attend scheduled outpatient clinic appointments for follow-up assessments. The treatment plan, devised by the pediatric endocrinology team, included the peroral administration of L-thyroxine (L-T4) at a dose of 50 micrograms per day. After beginning regular oral L-T4 treatment, a gradual improvement in the patient's condition was observed. Notably, by the 15th day of oral therapy, the patient had made a full recovery. Contrary to the recommended intravenous treatment for myxedema coma, this patient was successfully treated with oral levothyroxine, due to the unavailability of the parenteral form in Türkiye. CONCLUSIONS: This case report presents an instance of non-adherence to L-T4 therapy, which subsequently progressed to severe myxedema coma. Changes in neurologic status and hemodynamic instability in a patient with a history of hypothyroidism should raise the concern of nonadherence and, though rare, myxedema coma should be in the differential diagnosis.

Liquid L-T4 therapy in hypothyroid patients with gastric diseases, an observational study.

Introduction: This is an observational and retrospective study, in which we have analyzed data from patients affected by gastric diseases (p) who have been treated with liquid L-T4 (L-LT4;84 p), or tablet L-T4 (T-LT4;120 p), for the replacement therapy of hypothyroidism. The aim of the study is to compare the stability of TSH [normal range, 0.3-3.5 µIU/ml] in these patients. Methods: All p assumed L-T4 30 minutes before breakfast. The types of gastric disease were: a) T-LT4 group: 74 chronic gastritis (CG); 4 gastrectomy for gastric cancer (GTx); 42 gastro-plastics (GP); b) L-LT4 group: 60 CG; 3 GTx; 21 GP (p>0.05). 66% p in T-LT4 group were chronically treated with proton pump inhibitors (PPI), against 51% in L-LT4 group (p>0.05). The frequency of Helicobacter Pylori infection was 17% in both T-LT4 and L-LT4 groups. The gender distribution, mean age and body weight were similar in the 2 groups (p>0.05). The mean L-T4 dosage in T-LT4 group at the basal evaluation was 1.22+/-0.27 µg/kg/die, in the L-LT4 group 1.36+/-0.22 µg/kg/die (p>0.05). Results: At the basal evaluation the prevalence of patients with a TSH>3.5 µIU/mL in T-LT4 group was 36%, in L-LT4 group 46% (p<0.05). After adjustment of the dosage of the LT-4 therapy, the p were re-evaluated in an interval range of 5-9 months, for 4 times, during an overall period ranging from 23 to 31 months. At the first re-evaluation, the prevalence of p with a TSH>3.5 µIU/mL was 13% in both groups. At the second re-evaluation, the prevalence of p with a TSH>3.5 µIU/mL in T-LT4 group was 26%, in L-LT4 group 13% (p>0.05). At the third re-evaluation, the prevalence of p with TSH<3.5 µIU/mL in T-LT4 group was 19%, in L-LT4 group 9% (p=0.05). At the fourth and last re-evaluation, the prevalence of patients with a TSH>3.5 µIU/mL in T-LT4 group was 18%, in L-LT4 group 5% (p<0.05). Mean FT4 and FT3 circulating levels were not significantly different in the two group at each visit. Discussion: These data suggest that the liquid L-T4 formulation therapy can result in a more stable control of TSH levels in hypothyroid patients with gastric disorders in the long-term follow-up.

A Case Report of Myxedema Coma in the Setting of Normal Thyroid Stimulating Hormone.

Myxedema coma (MC) is a potentially fatal complication of hypothyroidism, with a high mortality rate. It is a clinically diagnosed condition, where the symptoms are related to decreased metabolic effects due to low active thyroid hormones. This case report highlights a severe case of MC, despite the thyroid stimulating hormone (TSH) being normal and the free thyroxine (FT4) being very mildly decreased.

Investigating the effect of levothyroxine replacement on cholesterol levels in hypothyroid patients.

Introduction: Effects of levothyroxine therapy on the lipid profile of hypothyroid patients lead to decrease in the risk of cardiovascular diseases and mortality. Objective: Overt or subclinical hypothyroid dysfunction has negative effects on lipid metabolism and leads to hypercholesterolemia that in turn increases the risk of cardiovascular diseases and mortality. In this matter, several interventional studies investigated the effects of levothyroxine therapy on the lipid profile of hypothyroid patients, and conflicting results have been obtained. The current research aims to investigate the effect of levothyroxine replacement on cholesterol levels in hypothyroid patients. Methods: The present prospective study examined 112 patients (mean age of 43.80 ± 14.36 years) with overt hypothyroidism. To do so, 72.3% of patients were females. Levothyroxine replacement therapy was prescribed for patients, and they were examined monthly to evaluate the effects of therapy on their lipid profiles. After reaching normal thyroid stimulating hormone (TSH), the patients' laboratory parameters, including TSH, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, were surveyed. Results: After Levothyroxine therapy, there was a significant reduction in mean TSH (62.03 vs. 2.33 ± 1.95; P < 0.0001), triglycerides (145.57 ± 88.65 vs. 121.91 ± 59.52, P = 0.002), cholesterol (203.90 ± 53.73 vs. 166.65 ± 40.07, P < 0.0001), and serum LDL (123.61 ± 45.03 vs. 95.99 ± 24.20, P < 0.0001), but the mean value of serum HDL did not show any significant change (54.18 ± 16.60 vs. 51.59 ± 18.38, P = 0.274). Conclusions: Levothyroxine therapy has beneficial effects on lipid profile in patients with overt hypothyroidism because it decreases serum triglyceride, total cholesterol, and LDL. However, levothyroxine therapy does not significantly change HDL levels.

The effect of high-dose Levothyroxine on hearing in patients operated for thyroid cancer.

OBJECTIVE: The aim of this study is to investigate the relationship between the use of high doses of levothyroxine (L-T4) and hearing loss in patients who have undergone surgery for thyroid cancer. MATERIAL METHOD: After total thyroidectomy for thyroid cancer, patients were divided into two groups according to L-T4 dose below 150 µg and above 150 µg. Demographic characteristics, postoperative duration, radioactive iodine treatment, bone densitometry scans with LDxa and FDxa, and right and left ear hearing levels were statistically compared in both groups. RESULTS: The study included 62 patients, 85.5% (n = 53) of whom were female, with a mean age of 48.8 ± 11.7 years. While 56.45% (n = 35) of the patients were taking L-T4 below 150 µg 43.55% (n = 27) were taking L-T4 above 150 µg. The mean postoperative duration of the participants was 4.1 ± 2.7 years, osteopenic 30.7% and osteoporotic 16.13% according to LDxa, osteopenic 29.0% and osteoporotic 1.6% according to FDxa. Hearing loss in both right and left ears was 41.9% and sensorineural hearing loss in both ears was 22.6%. Age, LDxa, FDxa, hearing loss in the right and left ear were found to be significantly different in the two groups above and below 150 µg according to the dose of L-T4 used (p < 0.05). However, no differences were found according to sex, height, weight, body mass index, postoperative period, or radioactive iodine treatment (p > 0.05). Both osteopenia and osteoporosis, as well as hearing loss in both the right and left ear, were significantly higher in the group taking L-T4 150 µg or more (p < 0.05). CONCLUSION: In our study, we found that patients taking 150 µg or more of L-T4 daily were more osteopenic and osteoporotic and had more hearing loss in both ears.

Subclinical Hypothyroidism and Thyroid Autoimmunity in Pregnancy: To Treat or Not to Treat.

Subclinical hypothyroidism and thyroid autoimmunity in pregnancy are common conditions. They are both associated with adverse maternal and offspring outcomes. Women with thyroid autoimmunity should be monitored with regular thyroid function tests preconception and during gestation to identify women who develop hypothyroidism. The effectiveness of thyroid hormone treatment in reducing adverse outcomes in pregnancy has been studied in a number of randomized controlled trials. Current evidence shows obstetrical benefits of levothyroxine treatment in pregnant women with a thyroid-stimulating hormone level greater than 4 mU/L.

Poly (hydroxyethylmethacrylate-co-methacryloyl glutamic acid) nanocarrier system for controlled release of levothyroxine.

The deterioration in the structure of thyroid hormones causes many thyroid-related disorders, which leads to a negative effect on the quality of life, as well as the change in metabolic rate. For the treatment of thyroid disorders, daily use of levothyroxine-based medication is essential. In the study, it is aimed to develop a polymeric nanocarrier that can provide controlled drug release of levothyroxine. In this respect, the p(HEMA-MAGA) nanopolymer was synthesized and then characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Zeta size analysis. The specific surface area of the nanopolymer was calculated as 587.68 m2/g. The pH, temperature, concentration, and time parameters were determined for levothyroxine binding to p(HEMA-MAGA) and optimum binding was determined as pH 7.4, 25 °C, 25 µg/mL concentration, and 30 min adsorption time. As a result of the release performed at pH 7.4, a release profile was observed which increased for the first 3 days and continued for 14 days. According to the results of MTT cell viability analysis, it was determined that the p(HEMA-MAGA) nanopolymeric carrier system had no cytotoxic effect. This developed polymer-based nanocarrier system is suitable for long-term and controlled release of levothyroxine. This is a unique and novel study in terms of developing poly hydroxyethylmethacrylate-co-methacryloyl glutamic acid-based polymeric nanoparticles for levothyroxine release.

Affinity-based nanoparticles were developed for long-term and controlled release of levothyroxine.p(HEMA-MAGA) nanopolymer was synthesized and characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Zeta size analysis.Optimization studies of levothyroxine binding into p(HEMA-MAGA) nanopolymers were carried out and controlled release studies were made with loading in optimum parameters.MTT cell viability analysis were performed for determining that the p(HEMA-MAGA) nanopolymeric carrier system had no cytotoxic effect.

Mild exercise plus levothyroxine ameliorate deficits of spatial navigation, anxiety profile, and hippocampal BDNF in hypothyroid male offspring rats.

PURPOSE: Levothyroxine (LEV) monotherapy cannot completely improve cognitive and behavioral impairments induced by hypothyroidism, whereas a combination therapy of exercise and LEV may ameliorate these deficits. This study aimed to determine the effects of mild-intensity forced exercise and LEV treatment on the anxiety profile and cognitive functions in male offspring of hypothyroid dams. METHOD: Twenty-four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6-propyl-2-thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty-four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 µg/kg, i.p.) with or without forced mild-intensity exercise. After 14 days of interventions, anxiety-like behaviors, spatial learning and memory, and hippocampal brain-derived neurotrophic factor (BDNF) levels were evaluated. FINDING: A pre and postnatal PTU-induced model of hypothyroidism increased anxiety-like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety-like behaviors. Exercise plus LEV more effectively improved anxiety-like behaviors and spatial learning than exercise or LEV alone. CONCLUSION: Practically, these pre-clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism.

Does the use of double hormone replacement therapy for trauma patient organ donors improve organ recovery for transplant.

BACKGROUND: With an ongoing demand for transplantable organs, optimization of donor management protocols, specifically in trauma populations, is important for obtaining a high yield of viable organs per patient. Endocrine management of brain-dead potential organ donors (BPODs) is controversial, leading to heterogeneous clinical management approaches. Previous studies have shown that when levothyroxine was combined with other treatments, including steroids, vasopressin, and insulin, BPODs had better organ recovery and survival outcomes were increased for transplant recipients. AIM: To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients. METHODS: A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed. Exclusion criteria included patients who were not solid organ donors, patients who were not declared brain dead (donation after circulatory death), and patients who did not receive steroids in their hospital course. Levothyroxine and steroid administration, the number of organs donated, the types of organs donated, and demographic information were recorded. Univariate analyses were performed with P < 0.05 considered to be statistically significant. RESULTS: A total of 88 patients met inclusion criteria, 69 (78%) of whom received levothyroxine and steroids (ST/LT group) vs 19 (22%) receiving steroids without levothyroxine (ST group). No differences were observed between the groups for gender, race, pertinent injury factors, age, or other hormone therapies used (P > 0.05). In the ST/LT group, 68.1% (n = 47) donated a high yield (3-5) of organ types per donor compared to 42.1% (n = 8) in the ST group (P = 0.038). There was no difference in the total number of organ types donated between the groups (P = 0.068). CONCLUSION: This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population. Limitations to this study include the retrospective design and the relatively small number of organ donors who met inclusion criteria. This study is unique in that it mitigates steroid administration as a confounding variable and focuses specifically on the adjunctive use of levothyroxine.

Increased frequency of microalbuminuria in patients with type 3 autoimmune polyglandular syndrome (APS) compared to isolated autoimmune type 1 diabetes mellitus: A real-life study.

AIM OF THE STUDY: The primary aim of the study was to evaluate the differences in metabolic control and chronic microvascular complications in patients with type 3 autoimmune polyglandular syndrome (APS3), compared to type 1 diabetes mellitus (T1DM) alone. Secondary aims were to evaluate the age of autoimmune thyroid disease (AIT) onset and the effects of levothyroxine treatment on metabolic control in patients with APS3. MATERIAL AND METHODS: We retrospectively reviewed 276 patients with T1DM alone and 214 patients with APS3 and evaluated clinical and metabolic parameters and microvascular complications. RESULTS: Patients with T1DM showed a longer duration of diabetes (p = 0.001) and lower age of diabetes onset (p = 0.020) compared to patients with APS3. Female gender (p = 0.001) and microalbuminuria (p = 0.006) were significantly more frequent in patients with APS3 compared to T1DM. In addition, patients with APS3 showed higher AIT onset frequency in the 16-30 quartile age-range. Furthermore, APS3 patients treated with levothyroxine showed significantly better HbA1c values than non-treated patients (p = 0.001). CONCLUSIONS: We found that patients with APS3 showed positive microalbuminuria, earlier than T1DM. Patients with APS3 showed higher frequency of AIT age of onset in the 16-30 age-range and those treated with levothyroxine had better metabolic control, than untreated ones.

Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey).

OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.

Evaluating the effectiveness of combined T4 and T3 therapy or desiccated thyroid versus T4 monotherapy in hypothyroidism: a systematic review and meta-analysis.

BACKGROUND: Persistent symptoms in hypothyroid patients despite normalized TSH levels suggest the need for alternative treatments. This study aims to evaluate the effectiveness of combined T4 and T3 therapy or desiccated thyroid (DTE) compared to T4 monotherapy, with a focus on thyroid profile, lipid profile, and quality of life metrics. METHODS: We conducted a systematic review in Embase, Medline/PubMed, and Web of Science up to 11/23/2023. We used the following keywords: "Armour Thyroid," OR "Thyroid extract," OR "Natural desiccated thyroid," OR "Nature-Throid," "desiccated thyroid," OR "np thyroid," OR "Synthroid," OR "levothyroxine," OR "Liothyronine," "Cytomel," OR "Thyroid USP," OR "Unithroid." AND "hypothyroidism. " We only included RCTs and excluded non-RCT, case-control studies, and non-English articles. RESULTS: From 6,394 identified records, 16 studies qualified after screening and eligibility checks. We included two studies on desiccated thyroid and 15 studies on combined therapy. In this meta-analysis, combination therapy with T4 + T3 revealed significantly lower Free T4 levels (mean difference (MD): -0.34; 95% CI: -0.47, -0.20), Total T4 levels (mean difference: -2.20; 95% CI: -3.03, -1.37), and GHQ-28 scores (MD: -2.89; 95% CI: -3.16, -2.63), compared to T4 monotherapy. Total T3 levels were significantly higher in combined therapy (MD: 29.82; 95% CI: 22.40, 37.25). The analyses demonstrated moderate to high heterogeneity. There was no significant difference in Heart Rate, SHBG, TSH, Lipid profile, TSQ-36, and BDI Score. Subjects on DTE had significantly higher serum Total T3 levels (MD: 50.90; 95% CI: 42.39, 59.42) and significantly lower serum Total T4 (MD: -3.11; 95% CI: -3.64, -2.58) and Free T4 levels (MD: -0.50; 95% CI: -0.57, -0.43) compared to T4 monotherapy. Moreover, DTE treatment showed modestly higher TSH levels (MD: 0.49; 95% CI: 0.17, 0.80). The analyses indicated low heterogeneity. There was no significant difference in Heart Rate, SHBG, Lipid profile, TSQ-36, GHQ-28, and BDI Score. CONCLUSIONS: Our study revealed that combined therapy and DTE lead to higher T3 and lower T4 levels, compared to T4 monotherapy in hypothyroidism. However, no significant effects on heart rate, lipid profile, or quality of life were noted. Given the heterogeneity of results, personalized treatment approaches are recommended.

Treatment of Obesity with Thyroid hormones in Europe. Data from the THESIS* Collaboration.

PURPOSE: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. METHODS: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions". RESULTS: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91). CONCLUSIONS: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.

The Effect of Apalutamide on Thyroid Function in Prostate Cancer Patients.

Context: Apalutamide (APT) is a nonsteroidal antiandrogen medication used to treat metastatic castrate-sensitive and nonmetastatic castrate-resistant prostate cancer. Early clinical trials of APT identified thyroid dysfunction as a common adverse effect of therapy, but the clinical presentation and management of APT-induced hypothyroidism has not been studied. Objective: The objective of our study is to elucidate the clinical presentation and treatment approach of APT-associated thyroid dysfunction in prostate cancer patients. Methods: We report a case series of 16 patients with APT-associated thyroid dysfunction during prostate cancer treatment at 2 academic medical centers. Patient clinical parameters, thyroid function laboratory data, and thyroid hormone requirements over the course of APT treatment were analyzed. Results: Among the 16 patients in our case series with APT-associated hypothyroidism, 3 had no prior thyroid disease and 13 had preexisting hypothyroidism. The patterns of thyroid dysfunction included overt and subclinical hypothyroidism. The median time from APT initiation to thyroid function test abnormality was 19 weeks, but occurred in some cases as early as 2 to 4 weeks. Hypothyroidism was effectively managed with thyroid hormone replacement using levothyroxine (LT4), though some patients with preexisting hypothyroidism required a 2- to 3-fold dose increase while on APT to achieve a euthyroid state. In the subset of patients who completed or stopped APT therapy, thyrotropin levels fell at a median of 11 weeks post APT therapy and thyroid hormone requirements decreased to near pre-APT levels. Conclusion: APT-associated thyroid dysfunction presents as new or worsening hypothyroidism and should prompt initiation or increase in thyroid hormone replacement. Monitoring of thyroid function tests is recommended every 1 to 2 months for all patients on APT and 2 to 3 months after completion of APT.

Levothyroxine may not adequately prepare hypothyroid women for controlled ovarian hyperstimulation.

BACKGROUND: Thyroid axis dysregulation during controlled ovarian hyperstimulation (COH) is more pronounced in hypothyroid-treated women. Whether or not this leads to compromised thyroid hormone levels within the ovarian follicular fluid is not known. AIMS: To determine whether ovarian follicular thyroid hormone levels are compromised in adequately replaced hypothyroid women undergoing controlled ovarian hyperstimulation (COH), and/or influence cycle/pregnancy outcomes. MATERIALS AND METHODS: Prospective cohort study involving 46 euthyroid (anti-thyroid peroxidase antibody negative) and 16 levothyroxine-replaced women with baseline thyroid-stimulating hormone (TSH) <2.5 mIU/L attending their first COH cycle. Follicular fluid TSH, free triiodothyronine (T3) and free thyroxine (T4) were recorded at oocyte pick-up. Serum levels were measured at: (i) baseline; (ii) human chorionic gonadotropin trigger day; and (iii) cycle conclusion. The number of mature oocytes retrieved, fertilisation, early pregnancy loss and live birth rates were compared. RESULTS: Median serum TSH levels were similar at baseline (1.76 vs 1.24 mIU/L, P = 0.053), but free T3 levels were lower (4.5 vs 4.8 pmol/L, P = 0.029) in levothyroxine-replaced compared to euthyroid women, with serum TSH levels increasing across ovarian stimulation (P = 0.006) into pregnancy testing (P = 0.030). Follicular fluid free T3 levels were lower in levothyroxine-replaced women (median 4.3 vs 4.6 pmol/L, P = 0.032). Fertilisation rates were lower (52% vs 71%, P = 0.043) in women requiring levothyroxine replacement, but numbers of mature oocytes retrieved, early pregnancy loss and live births did not differ. CONCLUSION: Adequately replaced hypothyroid women achieve lower ovarian follicular fluid free T3 levels and poorer fertilisation rates compared to euthyroid women undergoing COH. Optimising T3 levels may be pivotal in improving COH outcomes in hypothyroid women.