Search Results (39)

Background: Hashimoto’s thyroiditis (HT), the most prevalent autoimmune thyroid disorder in reproductive-age women, has been linked to diminished ovarian reserve and subfertility. This study aimed to evaluate the relationship between HT and key fertility parameters, including hormonal markers and reproductive outcomes, while also exploring the potential impact of thyroid hormone replacement therapy. Methods: A retrospective observational study was conducted on 86 women undergoing fertility evaluation. Participants were divided into two groups based on anti-thyroid peroxidase antibodies (ATPO): the HT group (n = 49) and the control group (n = 37). Among women with HT, 57% were receiving levothyroxine (Euthyrox^®) at the time of assessment. Variables analyzed included serum levels of anti-Müllerian hormone (AMH), thyroid-stimulating hormone (TSH), insulin resistance index (HOMA-IR), number of oocytes retrieved, blastocysts formed, pregnancies achieved, and live births. Statistical methods included t-tests, Mann–Whitney U tests, Pearson/Spearman correlations, and linear regression models. Results: Women in the HT group had slightly lower AMH levels and oocyte counts compared to controls, though these differences did not reach statistical significance. TSH values were higher in the HT group and showed a significant negative correlation with blastocyst formation (p = 0.03). Although TSH also showed negative trends with oocyte count, pregnancies, and live births, these correlations did not reach statistical significance. A post-hoc subgroup analysis revealed that HT patients receiving levothyroxine tended to have higher numbers of oocytes retrieved and blastocysts formed compared to untreated HT patients, suggesting a possible beneficial effect of thyroid hormone replacement, although the differences were not statistically significant. Conclusions: HT is associated with subtle but clinically relevant impairments in ovarian reserve and reproductive potential. Thyroid hormone replacement may offer modest benefits and should be considered in the individualized management of fertility in women with thyroid autoimmunity. Full article

Cholestyramine, a bile acid sequestrant, has been used primarily for lipid-lowering purposes but has also shown potential in managing hyperthyroidism and thyrotoxicosis. The objective of this review is to assess the efficacy, safety, and clinical indications of cholestyramine in the treatment of hyperthyroidism, thyrotoxicosis, and associated conditions, particularly when conventional therapies fail or are contraindicated. A literature review of clinical guidelines, original research articles, and case reports was conducted, focusing on studies that explored cholestyramine’s use in the treatment of hyperthyroidism, thyrotoxicosis, and levothyroxine overdose. Cholestyramine has demonstrated effectiveness in rapidly reducing thyroid hormone levels in these conditions. Studies indicates that cholestyramine accelerates the reduction of T3 and T4 levels when used as adjunctive therapy alongside standard treatments, particularly in severe or refractory cases. Evidence from case reports also supports its utility in managing conditions such as amiodarone-induced thyrotoxicosis, thyroid storm, and preparation for thyroidectomy. However, the long-term effectiveness of cholestyramine remains uncertain, with potential challenges regarding gastrointestinal side effects and medication interactions. Further studies are needed to integrate it more widely into clinical guidelines for the management of thyroid disorders. Full article

Hypopituitarism is a condition characterized by the deficiency of several hormones produced by the pituitary gland. Genetic factors play an important role. Variants in the POU1F1 gene are associated with combined pituitary hormone deficiency 1 (CPHD1), which manifests as deficiencies in growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin (PRL). This study aimed to analyze the phenotype, genotype, treatment, and outcomes of Vietnamese patients with deficiency. Six patients from five unrelated families, initially diagnosed with hypopituitarism, were enrolled in this study. Data on physical characteristics, biochemical tests, treatment, outcomes, and follow-up were collected. Exome sequencing and Sanger sequencing were conducted to identify disease-causing variants in five probands and their families. All six patients exhibited anterior pituitary hypoplasia on brain magnetic resonance imaging and presented with TSH, GH, and PRL deficiencies. Exome sequencing identified three variants in the POU1F1 gene: c.428G>A p.(Arg143Gln), c.557T>G p.(Leu186Arg), and c.811C>T p.(Arg271Trp). The c.811C>T p.(Arg271Trp) variant was found in three patients, while c.557T>G p.(Leu186Arg) is a novel variant. Based on the ACMG classification, these variants were categorized as likely pathogenic or pathogenic variants. All patients were definitively diagnosed with CPHD1 caused by POU1F1 variants. All patients received levothyroxine and recombinant human growth hormone (rhGH) replacement therapy, leading to considerable growth. During the first year of treatment, all patients showed excellent growth response, with height increases ranging from 11 to 24 cm. After three years of treatment, two patients achieved normal height. One of the six patients developed scoliosis during treatment, which resolved after a one-year pause in rhGH therapy. Upon resuming treatment, no recurrence of scoliosis was observed. Our findings reveal the importance of early hormone testing and genetic analysis in improving the care and outcomes for patients with combined pituitary hormone deficiency. Full article

Background: Hypothyroidism is the most common thyroid dysfunction in childhood, resulting from the decreased biological activity of thyroid hormones in tissues. Pediatric patients with hypothyroidism, when left untreated or when thyroid hormone levels fail to normalize despite treatment, may exhibit various complications such as growth retardation, obesity, and hypercholesterolemia. Aim: We conducted a monocentric retrospective study to evaluate potential differences in obesity rates and auxological parameters between healthy patients and children with hypothyroidism undergoing levothyroxine replacement therapy. Additionally, we examined possible differences in lipid and glucose metabolism between the two groups. Materials and Methods: We collected and analyzed data from the electronic medical records of 108 patients who were regularly followed up for thyroid dysfunction at the Pediatric Endocrinology Unit of the Fondazione Policlinico Universitario A. Gemelli IRCCS from January 2016 to June 2024. We also included 104 healthy controls who underwent thyroid function testing during the same period, followed up in the same department for regular auxological check-ups. Results: Our findings revealed that patients with acquired hypothyroidism had a lower height z-score compared to healthy controls (t(210) = −2.6; p = 0.01). Additionally, they exhibited higher blood glucose and triglyceride levels, although these values remained within the normal range. Conclusions: We highlight the critical importance of the early diagnosis of hypothyroidism to initiate levothyroxine replacement therapy promptly and mitigate the long-term effects of hypothyroidism on children’s growth. Full article

Houttuynia cordata Thunb. holds a longstanding reputation as a traditional folk remedy in East Asia, where it has been employed to treat a variety of inflammatory conditions, nephritis, hepatitis and cancer. Despite its extensive use, there exists a paucity of research examining its efficacy in managing thyroid disorders and diabetes. Moreover, the bioactive components responsible for modulating the molecular pathways remain elusive. Objectives: This research aimed to determine the key bioactive components in the ethanolic extract of H. cordata Thunb. (HCEE) responsible for its thyroid-modifying properties and examine its effects on rats with experimentally induced hypothyroidism and diabetes. Methods: Molecular docking was performed to investigate the possible mechanisms of thyroid regulation of HCEE constituents. Researchers induced hypothyroidism in rats by adding 6-propyl-2-thiouracil to their drinking water for a period of four weeks. To induce diabetes, the rats received an intraperitoneal injection of streptozotocin. The animals were then given daily oral doses of HCEE (500 mg/kg b.w.), levothyroxine (50 mg/kg b.w.), or glibenclamide (5 mg/kg b.w.) for 28 days. Following this treatment, standard methods were employed to measure biochemical parameters in the rats’ serum. Results: The results demonstrate that HCEE ameliorated hypothyroidism by increasing serum T3 (14.38%) and T4 (125.96%) levels and decreasing TSH (p < 0.01; −41.75%) levels. In diabetic rats with induced hypothyroidism, HCEE significantly (p < 0.001) increased T3 (149.51%) and T4 (73.54%) levels with reduced TSH (−64.39%) levels. In silico analysis demonstrated that the identified bioactive compounds from HCEE may enhance thyroid hormone function through interaction with the thyroid hormone receptor protein TRβ1 (PDB:3GWS), similar to the conventional pharmaceuticals levothyroxine and triiodothyronine (T3). Conclusions: HCEE exhibits potential as a natural alternative to synthetic medications in the prevention and treatment of thyroid dysfunctions. Full article

Background: Autoimmune thyroiditis (AIT) is a common thyroid disorder in children, linked to an increased risk of papillary thyroid carcinoma (PTC). Characteristic ultrasonographic features of AIT can obscure PTC, delaying diagnosis. Case Presentation: An 11-year-old girl with a two-year history of AIT presented with persistently elevated thyroid-stimulating hormone (TSH) levels despite levothyroxine therapy. Examination revealed a firm, slightly enlarged right thyroid lobe. Serial thyroid ultrasounds showed typical AIT features, with no apparent tumor. However, a cervical lymph node ultrasound detected a suspicious lymph node with pathological vascularization. Fine-needle aspiration suggested possible PTC metastasis. The patient underwent total thyroidectomy with central and right lateral neck dissection. Histopathology confirmed multifocal PTC with cervical lymph node metastases (pT3aN1bM0). Postoperative radioactive iodine therapy resulted in undetectable thyroglobulin levels, indicating a biochemical response. Conclusions: Children with AIT may harbor occult PTC even without thyroid gland abnormalities suggestive of malignancy. Comprehensive ultrasound evaluation, including cervical lymph nodes, is vital for early detection and timely treatment. Full article

The approaches to correct thyroid deficiency include replacement therapy with thyroid hormones (THs), but such therapy causes a number of side effects. A possible alternative is thyroid-stimulating hormone (TSH) receptor activators, including allosteric agonists. The aim of this work was to study the effect of ethyl-2-(4-(4-(5-amino-6-(tert-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]pyrimidin-4-yl)phenyl)-1H-1,2,3-triazol-1-yl) acetate (TPY3m), a TSH receptor allosteric agonist developed by us, on basal and thyroliberin (TRH)-stimulated TH levels and the hypothalamic-pituitary-thyroid (HPT) axis in male rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes mellitus (T2DM). Single and three-day administration of TPY3m (i.p., 20 mg/kg) was studied, and the effect of TPY3m on the HPT axis was compared with that of levothyroxine. TPY3m increased TH levels when administered to both healthy and diabetic rats, normalizing thyroxine and triiodothyronine levels in T2DM and, unlike levothyroxine, without negatively affecting TSH levels or the expression of hypothalamic and pituitary genes responsible for TSH production. TPY3m pretreatment preserved the stimulatory effects of TRH on TH levels and thyroid gene expression. This indicates the absence of competition between TPY3m and endogenous TSH for TSH receptor activation and is supported by our in vitro results on TPY3m- and TSH-stimulated adenylate cyclase activity in rat thyroid membranes. Morphological analysis of thyroid glands in diabetic rats after three-day TPY3m administration shows an increase in its functional activity without destructive changes. To summarize, TPY3m, with the activity of a partial allosteric agonist of the TSH receptor, was created as a prototype of drugs to correct thyroid insufficiency in T2DM. Full article

Objective: This study aimed to explore whether subclinical hypothyroidism (SCH) treated with levothyroxine in pregnancy complicated by gestational diabetes mellitus (GDM) is associated with an increased risk of gestational hypertensive disorders (GHDs) (gestational hypertension and preeclampsia). Methods: 96 pregnant women with GDM were enrolled in this study and grouped as per the European Thyroid Association criteria into the SCH (n = 21) and euthyroid groups (n = 75). All subjects were tested for anthropometric parameters, maternal glucose homeostasis parameters, lipid levels, thyroid function tests, and blood pressure. All GDM pregnant women received nutritional and insulin therapy where needed, and the SCH group received levothyroxine treatment. Then, the maternal and newborn outcomes were compared. Data were analyzed using Student’s t-test, Mann–Whitney U, and Chi-square tests wherever applicable. p values of <0.05 were considered significant. Results: Patients with GDM and SCH had a pre-pregnancy BMI and BMI at inclusion in the study smaller than those of the euthyroid group (p = 0.0004, p = 0.0009). There were no significant differences between groups regarding the incidence of GHD, preterm prelabor rupture of membranes (PPROMs), macrosomia, low birth weight, and fetal distress (p > 0.05). Patients with GDM and SCH treated with levothyroxine had more premature delivery than the euthyroid group (p = 0.03). Conclusions: Subclinical hypothyroidism treated with levothyroxine in women with GDM does not increase the risk of gestational hypertensive disorders, but is associated with increased risk for prematurity. Full article

Hashimoto’s thyroiditis (HT) is a prevalent autoimmune disorder marked by chronic inflammation of the thyroid gland, predominantly affecting children and adolescents. In a previous study, we developed a “maximal” mathematical model of thyroid physiology to simulate the complex interactions within the thyroid gland. The present research introduces an enhanced version of the “maximal” model, integrating the pathophysiological impacts of HT. It specifically models the adverse effects of thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies (TPOAb and TgAb) on TPO, Tg, sodium iodide symporter (NIS), albeit indirectly, and thyroid volume. Additionally, we present a new “minimal” model offering a streamlined interpretation of thyroid physiology and pathophysiology, designed for faster computational analysis while maintaining essential physiological interactions. Both models were fitted against longitudinal clinical data from patients with HT, assessing the concentrations of Thyroid Stimulating Hormone (TSH), Thyroxine (T4), and thyroid volume over 36 months, in both untreated patients and those receiving levothyroxine (LT4) treatment. The adaptation of the models to data shows that both of them accurately reproduce the available observed clinical outcomes, with the “maximal” model providing more detailed physiological insights but requiring extensive data and longer computation times. In contrast, the “minimal” model, despite exhibiting less realistic TSH oscillations, offers rapid parameter estimation and may be more feasible in clinical settings. These models hold significant potential as tools for detailed study and management of HT, enabling simulations of disease progression and therapeutic responses, thus paving the way for personalized treatment strategies. Full article

Background/Objectives: The management of differentiated thyroid cancer (DTC) patients has undergone a major paradigm shift in past years, especially regarding the role of a careful postoperative disease assessment both in deciding for or against the use of iodine-131 therapy (i.e., patients’ selection) and in selecting the correct goal of the treatment: ablative, adjuvant or therapeutic. Furthermore, diagnostic and risk-oriented uses of iodine isotopes (i.e., ^123/124/131I) should always be considered during both postoperative assessment and follow-up of DTC patients to improve early staging and response assessment to initial treatments, respectively. The present review summarizes current (and real-life-related) evidence and the emerging perspectives on the therapeutic, diagnostic, and theragnostic use of radioiodine isotopes. Methods: A review of the pertinent literature was performed in PubMed, Web of Science, and Scopus without language restrictions or time limits and using one or more fitting search criteria and terms. Results: According to the literature evidence and real-life clinical practice, a risk-oriented postoperative iodine-131 therapy remains pivotal for most DTC patients and improves early disease staging through post-therapy functional imaging (i.e., theragnostic aim). Accordingly, the goal of iodine-131 therapy, the optimal strategy (empiric vs. dosimetric approach), the appropriate stimulation method [i.e., levothyroxine (L-T4) withdrawal vs. recombinant human thyrotropin (rhTSH) administration] and, finally, the suggested radioiodine activity to deliver for iodine-131 therapy (RIT) should be personalized, especially in metastatic DTC patients. Conclusions: The evidence related to the diagnostic and theragnostic use of iodine isotopes leads to a significant improvement in the postoperative risk stratification and staging of DTC patients in addition to a more accurate assessment of the response to initial treatments. In conclusion, radioiodine is really an oldie but goldie radiotracer. It has both a current fundamental role and a future perspective for the more careful management of DTC patients. Full article

Background/Objectives: Levothyroxine (L-T4) is available for use in congenital hypothyroidism (CH) in three formulations: tablets, drops, and oral solution. This study aims to compare the efficacy and safety of all three L-T4 formulations. Methods: We enrolled 63 children born between January 2019 and April 2023 in the Emilia-Romagna Region (Italy) and diagnosed with CH by newborn screening. They were divided according to the L-T4 formulation used: drops (Group D), oral solution (Group S), and tablets (Group T). Clinical and laboratory data were collected up to 3 years after the start of replacement therapy. Results: Serum-free thyroxine (sFT4) and thyroid stimulating hormone (sTSH) normalization occurred within the first month of treatment in most patients of all groups. No negative effects on growth and cognitive development were observed. At 7–15 days we found higher median sTSH levels (p = 0.031) and a greater percentage of patients with sTSH > 5 µU/mL (p = 0.011) in Group S than in Group T, but comparable sFT4 levels. At 12 months, a greater percentage of patients of Group D showed sFT4 values below the normal range than Group S (p = 0.011) and Group T (p = 0.038); Conclusions: Overall, our study reported an equal efficacy of the L-T4 oral solution compared to drops and tablets in CH treatment. A larger series of patients and a long-term follow-up are needed. Full article

Background/Objectives: Women with subclinical hypothyroidism (SCH) were reported to be at an increased perinatal risk. We aimed to investigate the relationship between SCH and perinatal outcomes in singleton pregnancies resulting from assisted reproduction technology (ART). Methods: We retrospectively examined the perinatal outcomes of ART singleton pregnancies in women who underwent thyroid function screening before conception and delivered at our hospital from January 2020 to July 2023. We defined SCH as thyroid-stimulating hormone (TSH) levels > 2.5 mU/L and normal free T₄ levels. The patients were categorized into three groups: normal thyroid function (group A), SCH without levothyroxine therapy (group B), and SCH with levothyroxine therapy (group C). The risks of preterm birth, preeclampsia, fetal growth restriction, manual placental removal, and blood loss at delivery were compared among the three groups. Results: Out of the 650 ART singleton deliveries, 581 were assigned to group A, 34 to group B, and 35 to group C. The preterm birth rate at <34 weeks was significantly higher in group B and significantly lower in group C than in group A. The rate of preterm delivery at <34 weeks increased in correlation with TSH levels. Levothyroxine therapy was the significant preventive factor for preterm birth at <34 weeks. Conclusions: The preterm birth rate before 34 weeks was significantly higher in the SCH group. Levothyroxine therapy is a significant protective factor against preterm birth before 34 weeks. Universal screening for thyroid function and appropriate hormone therapy in pregnant women may help reduce perinatal risks, including preterm birth. Full article

Primary hyperthyroidism is a rarely diagnosed endocrinopathy in equids and there have been no previous reports of structural and functional cardiac changes associated with hyperthyroidism in these species. This case report investigates a 20-year-old mule gelding that presented for a three-month history of thin body condition despite polyphagia, with a heart murmur and elevated free and total thyroid hormone concentrations. On presentation, physical exam revealed a body condition score of two out of nine, persistent tachycardia, pansystolic heart murmur and firm bilateral ventral proximal cervical masses. Bloodwork confirmed markedly elevated free T4, total T4 and T3 concentrations. Echocardiogram demonstrated left ventricular concentric hypertrophy with increased ventricular and atrial systolic function. Bilateral thyroidectomy was performed under standing sedation without complications. Histopathology demonstrated adenocarcinoma of the left thyroid gland and multiple adenomas with osseous metaplasia within the right thyroid. The mule was supplemented with levothyroxine sodium two weeks post-op after a thyroid panel demonstrated undetectable concentrations. Polyphagia resolved following surgery and the mule began gaining weight. Echocardiographic changes improved but did not resolve at two years post-operative. Continued bi-annual follow up and monitoring of thyroid levels was recommended. This case represents the first documentation of hemodynamically relevant cardiac remodeling in an equid associated with primary hyperthyroidism. Full article

Objectives: To investigate quality of life using the SF-12 scale in euthyroid Hashimoto’s thyroiditis patients on levothyroxine therapy for at least three years. Methods: This prospective case–control study included 44 euthyroid Hashimoto’s thyroiditis patients and 44 matched controls, conducted at a university hospital’s endocrinology clinic from 6 November to 30 December 2023. Participants completed the SF-12 questionnaire; data were analyzed using Shapiro–Wilk, Student’s t-test, Mann–Whitney U, Yates chi-squared, and Spearman’s tests. Results: The study involved 88 participants (Hashimoto’s group: 35 females, 9 males; control group: 31 females, 13 males), with average ages of 49.50 and 47.43 years old, respectively. Significant differences were observed in TSH, T4 levels, and family history (p < 0.05). The Hashimoto’s thyroiditis group showed higher thyroid peroxidase antibodies (95.69 IU/mL) and lower scores on both physical and mental sub-dimensions of SF-12, with a significant difference in physical scores (p < 0.05). Significant correlations were found between age and Anti-TG; Anti-TPO and Anti-TG; BMI and T3; TSH and T4; HDL and triglycerides; MCS-12 and PCS-12; Anti-TPO and T3; cholesterol and T3; and LDL and cholesterol (p < 0.05). Other variables showed no significant correlations (p > 0.05). Conclusions: Our study shows that effective control of hypothyroidism is not sufficient to reduce the negative effects of Hashimoto’s thyroiditis on patients’ health-related quality of life. Beyond the normalization of hormone levels, comprehensive therapeutic strategies targeting the autoimmune aspects of the disease are essential for the management of Hashimoto’s thyroiditis. This study provides a foundation for developing effective therapies that can enhance quality of life for patients with Hashimoto’s thyroiditis. Full article

Gestational hypothyroidism may lead to preeclampsia development. However, this pathophysiological is unknown. We expect to find a shared mechanism by comparing hypothyroidism and preeclampsia. From our transcriptome data, we recognized olfactory receptors as that fingerprint. The reduction of taste and smell in hypothyroid patients has been known for a long time. Therefore, we decided to look to the olfactory receptors and aimed to identify genes capable of predicting preeclampsia (PEC). Methods: An Ion Proton Sequencer (Thermo Fisher Scientific, Waltham, MA, USA) was used to construct the transcriptome databases. RStudio with packages Limma v.3.50.0, GEOquery v.2.62.2, and umap v.0.2.8.8 were used to analyze the differentially expressed genes in GSE149440 from the Gene Expression Omnibus (GEO). The 7500 Real-Time PCR System (Applied Biosystems, Foster City, CA, USA) was used for RT-qPCR amplification of OR6X1 and OR4E2. Results: Our transcriptomic datasets analysis revealed 25.08% and 26.75% downregulated olfactory receptor (ORs) in mild nontreated gestational hypothyroidism (GHT) and PEC, respectively. In the GSE149440 GEO dataset, we found OR5H1, OR5T3, OR51A7, OR51B6, OR10J5, OR6C6, and OR2AG2 as predictors of early-onset PEC. We also evaluate two chosen biomarkers’ responses to levothyroxine. The RT-qPCR demonstrated a difference in OR6X1 and OR4E2 expression between GHT and healthy pregnancy (p < 0.05). Those genes presented a negative correlation with TSH (r: −0.51, p < 0.05; and r: −0.44, p < 0.05), a strong positive correlation with each other (r: 0.89; p < 0.01) and the levothyroxine-treated group had no difference from the healthy one. We conclude that ORs could be used as biomarkers at the beginning of gestation, and the downregulated ORs found in GHT may be improved with levothyroxine treatment. Full article