Search Results (64)

Background/Objectives: Thyroid hormone (TH) deficiency during the pregnancy and lactation periods leads to enduring memory impairments in offspring. However, the mechanisms underlying the cognitive and memory deficits induced by developmental hypothyroidism remain largely unexplored. Methods: Mice were exposed to propylthiouracil (PTU) or purified water to detect changes in hippocampal neurogenesis and differentiation of their offspring to explain the pathogenesis of impaired learning and memory. In addition, HT22 cell line were used to investigate the regulation between Maf and Mef2c. Results: Our findings indicate that developmental exposure to PTU results in abnormalities of the preferential differentiation of GABAergic interneurons and a subsequent reduction in PV⁺ inhibitory interneurons in the hippocampus of mouse pups. More significantly, we also indicate that the downregulation of Maf and the consequent alteration of Mef2c are likely responsible for the mechanisms through which developmental hypothyroidism influences the differentiation and development of PV⁺ inhibitory interneurons in offspring. Conclusions: Consequently, the aberrant development of PV⁺ interneuron in the hippocampus of mice subjected to developmental hypothyroidism potentially contributes to memory deficits during adolescence and adulthood. Full article

Graves’ disease and hyperthyroidism in women with childbearing potential are a challenge in pre-conceptional counseling. The non-surgical alternatives are radioiodine therapy or antithyroid drugs. Here, we focus on the TSH receptor antibody (TRAb) level—without or after radioiodine therapy—and the probability of fetal or neonatal hyperthyroidism. This immunological effect should be weighed against the risk of congenital malformation taking propylthiouracil during pregnancy. For up to 2 years after radioiodine therapy for Graves’ disease, TRAb levels may remain above the pre-therapeutic level. The time of conception after radioiodine therapy and a high TRAb level are associated with the likelihood of neonatal hyperthyroidism: 8.8% probability if conception occurred 6–12 months after radioiodine therapy, with a 5.5% probability for 12–18 months, and 3.6% probability for 18–24 months. The TRAb value above 10 U/L in the third trimester is the main risk factor for neonatal hyperthyroidism. If a woman does not wish to postpone her family planning, the pre-conceptional counseling has to describe the risk of propylthiouracil, thiamazole, or of an uncontrolled hyperthyroidism. According to some national cohort studies (Danish, Swedish, Korean), the risk for fetal malformations (ear, urinary tract) under propylthiouracil is increased by 1.1–1.6%, in addition to the spontaneous risk for unexposed pregnant women. For thiamazole, the additional risk for fetal malformation was about 2–3%, depending on the dose of thiamazole. Propylthiouracil has posed a lower risk for congenital malformation than an uncontrolled hyperthyroidism. To minimize the risk for the newborn, women with Graves’ disease and hyperthyroidism should offer a definitive therapy strategy (e.g., radioiodine therapy) long before planning a pregnancy. Full article

Thyroid dysfunction may affect the intestinal microbiota through short-chain fatty acids (SCFAs) in marine fish. This study investigated the effects of triiodothyronine (T3, 20 ng/g) and thyroxine (T4, 20 ng/g), and propylthiouracil (PTU, 5000 ng/g) on growth performance, intestinal SCFA profiles, and microbiota composition in little yellow croakers Larimichthys polyactis. The results showed that dietary thyroid-active agent supplementation significantly decreased weight gain, and specific growth ratio. Moreover, dietary T3, T4, and PTU induced the states of hyperthyroidism, hyperthyroidism, and hypothyroidism, respectively, leading to differential alterations in intestinal SCFA profiles. Specifically, only dietary T4 supplementation significantly increased the diversity of intestinal microbiota. Our findings suggest that the genera Vibrio and Sediminibacterium play key roles in multiple metabolic pathways within the host intestine. Correlation analyses further indicated that intestinal acetic acid and isobutyric acid were characteristic metabolites involved in the alteration of the genus Vibrio abundance. These results provide a foundation for further investigation into the effects of thyroid-disrupting activities on growth, intestinal SCFA profiles, and microbiota composition in marine fish. Full article

Hypothyroidism causes ovarian dysfunction and infertility in women and animals and impairs the hypothalamic expression of kisspeptin (Kp). However, kisspeptin is also expressed in the genital system, and the lack of the Kp receptor (Kiss1r) in the uterus is linked to reduced implantation rates. This study investigated the impact of hypothyroidism on the uterine expression of Kp and Kiss1r in female rats throughout the estrous cycle and the associated changes in uterine activity modulators. Hypothyroidism was induced through daily administration of propylthiouracil (PTU) over a period of 14 days. Plasma levels of LH, E₂, and P₄, cyclicity, body and uterine weight, uterine histomorphometry, and the gene and/or protein expression of Kiss1, Kiss1r, estrogen receptor α (ERα), progesterone receptor (PR), and thyroid hormone receptor α (TRα) were assessed. Additionally, proliferative activity (CDC-47) and the gene expression of uterine receptivity mediators (SMO, WNT4, BMP2, HAND2, MUC1, and LIF) were evaluated. Hypothyroidism prolonged the diestrus and increased progesterone levels during this phase, while decreasing luteinizing hormone and estradiol on proestrus. In the uterus, hypothyroidism reduced Kp immunostaining on diestrus and KISS1R mRNA levels on proestrus. These changes were accompanied by reduced endometrial glands, reduced uterine proliferative activity, and reduced ERα gene and protein expression. Additionally, hypothyroidism led to reduced uterine gene expression of LIF, BMP2, WNT4, and HAND2. On the other hand, thyroid hypofunction increased uterine PR and TRα immunostaining, while it reduced PGR gene expression on diestrus. These findings demonstrate that hypothyroidism reduces the expression of Kiss1/Kiss1r system in the uterus, which is associated with disrupted uterine estrogen and progesterone signaling and reduced expression of uterine receptivity mediators across the rat estrous cycle. Full article

Background: Hyperthyroidism, characterized by excessive thyroid hormone production, presents in diverse clinical forms, including overt and subclinical disease. Accurate and timely diagnosis is critical to prevent complications such as cardiac dysfunction, osteoporosis, and thyroid storm. Objective: To provide a comprehensive review of the clinical presentation, diagnostic methods, and management strategies for hyperthyroidism, focusing on current practices, advancements, and challenges in treatment. Methods: This review synthesizes findings from peer-reviewed literature on the diagnosis and management of hyperthyroidism. Results: Thyroid function tests (TFTs) are the cornerstone of hyperthyroidism diagnosis, with suppressed TSH levels and elevated T3 and/or T4 levels confirming overt disease. Thyroid receptor antibodies (TRAb) are critical for diagnosing autoimmune hyperthyroidism and predicting relapse risk. Iodine scintigraphy is utilized in specific cases, such as suspected toxic adenoma or multinodular goiter. Management strategies include beta-blockers for symptomatic relief, though side effects such as bradycardia and fatigue may occur. Antithyroid medications, including methimazole and propylthiouracil, inhibit hormone synthesis, with remission more likely in patients with low TRAb levels and small goiters. Definitive treatments include radioactive iodine therapy (RAI), which effectively reduces thyroid activity but often results in hypothyroidism, and thyroidectomy, a surgical option for large goiters or malignancy, with potential complications like hypocalcemia and recurrent laryngeal nerve injury. Conclusions: The management of hyperthyroidism necessitates a personalized approach integrating diagnostic precision, emerging innovations, and patient-centered care. Full article

In mammals, the maintenance of energy homeostasis relies on complex mechanisms requiring tight synchronization between peripheral organs and the brain. Thyroid hormones (THs), through their pleiotropic actions, play a central role in these regulations. Hypothyroidism, which is characterized by low circulating TH levels, slows down the metabolism, which leads to a reduction in energy expenditure as well as in lipid and glucose metabolism. The objective of this study was to evaluate whether the metabolic deregulations induced by hypothyroidism could be avoided through regulatory mechanisms involved in metabolic flexibility. To this end, the response to induced hypothyroidism was compared in males from two mouse strains, the wild-derived WSB/EiJ mouse strain characterized by a diet-induced obesity (DIO) resistance due to its high metabolic flexibility phenotype and C57BL/6J mice, which are prone to DIO. The results show that propylthiouracil (PTU)-induced hypothyroidism led to metabolic deregulations, particularly a reduction in hepatic lipid synthesis in both strains. Furthermore, in contrast to the C57BL/6J mice, the WSB/EiJ mice were resistant to the metabolic dysregulations induced by hypothyroidism, mainly through enhanced lipid metabolism in their adipose tissue. Indeed, WSB/EiJ mice compensated for the decrease in hepatic lipid synthesis by mobilizing lipid reserves from white adipose tissue. Gene expression analysis revealed that hypothyroidism stimulated the hypothalamic orexigenic circuit in both strains, but there was unchanged melanocortin 4 receptor (Mc4r) and leptin receptor (LepR) expression in the hypothyroid WSB/EiJ mice strain, which reflects their adaptability to maintain their body weight, in contrast to C57BL/6J mice. Thus, this study showed that WSB/EiJ male mice displayed a resistance to the metabolic dysregulations induced by hypothyroidism through compensatory mechanisms. This highlights the importance of metabolic flexibility in the ability to adapt to disturbed circulating TH levels. Full article

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing, affecting up to 30% of the population, with approximately 20% of cases occurring in non-obese individuals. The recent shift to the term metabolic dysfunction-associated steatosis liver disease (MASLD) highlights the disease’s heterogeneity. However, there are no well-established animal models replicating non-obese NAFLD (NO-NAFLD). This study aimed to evaluate the relevance of the high-fat diet (HFD) combined with the propylthiouracil (PTU)-induced rat model in mimicking the histopathology and pathophysiology of NO-NAFLD. We first analyzed metabolic and clinical parameters between NO-NAFLD patients (Average BMI = 21.96 kg/m²) and obese NAFLD patients (Average BMI = 29.7 kg/m²). NO-NAFLD patients exhibited significantly higher levels of carnitines, phospholipids, and triglycerides. In the animal model, we examined serum lipid profiles, liver inflammation, histology, and transcriptomics. Hepatic steatosis in the HFD+PTU model at week 4 was comparable to that of the HFD model at week 8. The HFD+PTU model showed higher levels of carnitines, phospholipids, and triglycerides, supporting its relevance for NO-NAFLD. Additionally, the downregulation of lipid synthesis-related genes indicated differences in lipid accumulation between the two models. Overall, the HFD+PTU-induced rat model is a promising tool for studying the molecular mechanisms of NO-NAFLD. Full article

Bitterness from phenylthiocarbamide and 6-n-propylthiouracil (PROP) varies with polymorphisms in the TAS2R38 gene. Three SNPs form two common (AVI, PAV) and four rare haplotypes (AAI, AAV, PVI, and PAI). AVI homozygotes exhibit higher detection thresholds and lower suprathreshold bitterness for PROP compared to PAV homozygotes and heterozygotes, and these differences may influence alcohol and vegetable intake. Within a diplotype, substantial variation in suprathreshold bitterness persists, and some AVI homozygotes report moderate bitterness at high concentrations. A second receptor encoded by a gene containing a functional polymorphism may explain this. Early work has suggested that PROP might activate TAS2R4 in vitro, but later work did not replicate this. Here, we identify three TAS2R4 SNPs that result in three diplotypes—SLN/SLN, FVS/SLN, and FVS/FVS—which make up 25.1%, 44.9%, and 23.9% of our sample. These TAS2R4 haplotypes show minimal linkage disequilibrium with TAS2R38, so we examined the suprathreshold bitterness as a function of both. The participants (n = 243) rated five PROP concentrations in duplicate, interleaved with other stimuli. As expected, the TAS2R38 haplotypes explained ~29% (p < 0.0001) of the variation in the bitterness ratings, with substantial variation within the haplotypes (AVI/AVI, PAV/AVI, and PAV/PAV). Notably, the TAS2R4 diplotypes (independent of the TAS2R38 haplotypes) explained ~7–8% of the variation in the bitterness ratings (p = 0.0001). Given this, we revisited if PROP could activate heterologously expressed TAS2R4 in HEK293T cells, and calcium imaging indicated 3 mM PROP is a weak TAS2R4 agonist. In sum, our data are consistent with the second receptor hypothesis and may explain the recovery of the PROP tasting phenotype in some AVI homozygotes; further, this finding may potentially help explain the conflicting results on the TAS2R38 diplotype and food intake. Full article

Taste sensitivity can have a significant impact on consumers’ food choices. Consumers’ taster status and emotions can be guided by sensory information of sugared products. This paper aimed to develop emotional lexicons for sugar-free chocolates based on consumers’ taster status applying the check-all-that-apply (CATA) methodology. South African respondents’ (n = 153) bitter perception was evaluated with n-propylthiouracil (PROP) paper strips. Respondents received one sugar-free dark chocolate and one sugar-free milk chocolate and completed an electronic questionnaire. Respondents mainly purchased chocolate for its flavour, and enjoyed the taste of the sugar-free dark chocolate more than sugar-free milk chocolate. The non-tasters (>50%) chose positive emotions for sugar-free milk chocolate, while the medium tasters, selected more positive emotions for dark chocolate. The supertasters selected the most negative emotions for the sugar-free dark chocolate. Practical significant associations were found between the non-tasters and the emotion guilty, as well as between the supertasters and the emotions, discontented and disgust. Each taster status requires the development of a distinctive lexicon to be emotionally satisfied by sugar-free products. Full article

Background: Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism. Methodology: Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves’ disease (n = 21), amiodarone-induced thyrotoxicosis (n = 7), and hyperfunctioning multinodular goiter (n = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil. Results: The median (IQR) time to development of agranulocytosis was 6.0 (4.0–11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves’ disease), and two patients died of septic shock secondary to AIA. Conclusions: AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously. Full article

Due to the limited scientific knowledge on the impact of commercial oenological additives on flavour perception, the aim of this work was to evaluate the effect of different types of oenological additives on the long-lasting flavour perception (flavour persistence) during wine tasting, also considering the effect of the individual PROP (6-n-propylthiouracil) taster status (PTS). To do so, white and red wines with two oenotannins (ellagitannin and gallotannin) and a commercial yeast mannoprotein were prepared. A control wine of each type was also made without additives. All the wines were spiked with a mixture of aromatic compounds responsible for the “fruity” and “woody” notes. Retronasal aroma and astringency were evaluated at the same time using time–intensity (TI) methodology and a trained panel (n = 40), including PROP non-tasters (NTs) and tasters (Ts). The results showed a significant effect of PTS on the long-lasting perception of astringency, being Ts who showed higher values than NTs for most TI parameters. However, PTS did not affect aroma persistence. In addition, the three oenological additives had an effect on astringency and retronasal aroma perception. They significantly increased the long-lasting perception of astringency compared to the control, while gallotannin also increased the persistence of the woody aroma. Full article

The thyroid hormones (THs) regulate various physiological mechanisms in mammals, such as cellular metabolism, cell structure, and membrane transport. The therapeutic drugs propylthiouracil (PTU) and phenytoin are known to induce hypothyroidism and decrease blood thyroid hormone levels. To analyze the impact of these two drugs on systemic metabolism, we focused on metabolic changes after treatment. Therefore, in a rat model, the metabolome of thyroid and liver tissue as well as from the blood plasma, after 2-week and 4-week administration of the drugs and after a following 2-week recovery phase, was investigated using targeted LC-MS/MS and GC-MS. Both drugs were tested at a low dose and a high dose. We observed decreases in THs plasma levels, and higher doses of the drugs were associated with a high decrease in TH levels. PTU administration had a more pronounced effect on TH levels than phenytoin. Both drugs had little or no influence on the metabolomes at low doses. Only PTU exhibited apparent metabolome alterations at high doses, especially concerning lipids. In plasma, acylcarnitines and triglycerides were detected at decreased levels than in the controls after 2- and 4-week exposure to the drug, while sphingomyelins and phosphatidylcholines were observed at increased levels. Interestingly, in the thyroid tissue, triglycerides were observed at increased concentrations in the 2-week exposure group to PTU, which was not observed in the 4-week exposure group and in the 4-week exposure group followed by the 2-week recovery group, suggesting an adaptation by the thyroid tissue. In the liver, no metabolites were found to have significantly changed. After the recovery phase, the thyroid, liver, and plasma metabolomic profiles showed little or no differences from the controls. In conclusion, although there were significant changes observed in several plasma metabolites in PTU/Phenytoin exposure groups, this study found that only PTU exposure led to adaptation-dependent changes in thyroid metabolites but did not affect hepatic metabolites. Full article

Individual taste sensitivity influences food preferences, nutritional control, and health, and differs greatly between individuals. The purpose of this study was to establish a method of measuring and quantifying an individual’s taste sensitivity and to evaluate the relationship between taste variation and genetic polymorphisms in humans using agonist specificities of the bitter taste receptor gene, TAS2R38, with the bitter compound 6-n-propylthiouracil (PROP). We precisely detected the threshold of PROP bitter perception by conducting the modified two-alternative forced-choice (2AFC) procedure with the Bayesian staircase procedure of the QUEST method and examined genetic variation in TAS2R38 in a Japanese population. There were significant differences in PROP threshold between the three TAS2R38 genotype pairs for 79 subjects: PAV/PAV vs AVI/AVI, p < 0.001; PAV/AVI vs AVI/AVI, p < 0.001; and PAV/PAV vs PAV/AVI, p < 0.01. Our results quantified individual bitter perception as QUEST threshold values: the PROP bitter perception of individuals with the PAV/PAV or PAV/AVI genotypes was tens to fifty times more sensitive than that of an individual with the AVI/AVI genotype. Our analyses provide a basic model for the accurate estimation of taste thresholds using the modified 2AFC with the QUEST approach. Full article

We evaluated sex differences in the perception of bitter compounds and an aromatic bitter herbal liqueur (Mirtamaro) obtained by the infusion of myrtle leaves/berries together with a mixture of Mediterranean herbs/plants as flavoring/bittering ingredients. In a healthy population (n = 231 participants), using bivariate correlations and multivariate linear regression analyses, significant sex differences emerged in quinine bitterness perception, with women showing a higher bitter taste intensity rating than men. Among all participants, 40 subjects (subpopulation) were randomly selected for the evaluation of sex differences in Mirtamaro gustatory and olfactory perception using a hedonic Likert-type scale. Women showed higher ratings in Mirtamaro aroma (odor intensity) and bitterness (taste intensity) perception than men, with a superior capacity to perceive/describe its sensory attributes. 1,8-Cineole and methyl chavicol were the main contributors to the bitter liqueur aroma. A significant correlation (r = 0.564, p < 0.01) between Mirtamaro odor pleasantness/taste pleasantness was observed in women, indicating a positive contribution of aromatic herbs to bitter taste acceptability. Moreover, a higher bitter intensity rating of 6-n-propylthiouracil was evidenced in women than men. Our results highlighted sex differences in bitter taste acuity and the role of aromatic herbs/plants in modulating bitter taste acceptance, which is useful information in the field of precision nutrition and medicine. Full article

Sugar-sweetened beverages are known promotors of adverse health outcomes. This study aimed to find a relation between taste perception, preferences for beverages, anthropometric parameters, and frequency of beverage consumption. Taste perception of sweetness was tested using an adopted sensitivity test with sucrose and different concentrations of sugar-sweetened apple juice. Furthermore, bitter-compound 6-n-propylthiouracil (PROP) and salty perception were tested and accompanied by a questionnaire on beverage intake. We did not find a clear relationship between taste perception, anthropometrics, and beverage intake. Nevertheless, in males, the bitter intensity perception of PROP was positively correlated with the BMI percentiles (CDC, r = 0.306, p ≤ 0.043) and the waist circumference (r = 0.326, p = 0.031). Furthermore, the liking of sweet taste (p < 0.05) and sweet intensity rating (p < 0.05) of apple juice increased with intensity, and adolescents with overweight or obesity had a higher intake of free sugars from beverages (p < 0.001). The role of taste perception on anthropometric measures and beverage intake remains unclear and requires further investigation. Full article