A study of the role of DIO1 and DIO2 polymorphism in thyroid cancer and drug response to therapy in the Saudi population.

BACKGROUND: Deiodinases comprise a group of selenoproteins that regulate the bioavailability of active thyroid hormones (TH) in a time and tissue specific fashion. They increase the hormonal activity by metabolizing their inactive precursors to active forms or terminate their activity by deactivating active hormones. The role of the deiodinase (DIO) gene polymorphisms in thyroid cancer is not fully understood yet. This study evaluated the potential association of the DIO1 and DIO2 genes with differentiated thyroid cancer and differential thyroxine dose requirement in thyroidectomized patients in a Saudi cohort. METHODS: We selected four variants (one DIO1 and three DIO2) for the association studies using Taqman assays in 507 DTC patients undergoing treatment with thyroxin against 560 disease-free individual, all of Saudi Arab origin. RESULTS: None of the studied variants was linked to differentiated thyroid cancer. The rs1388378_G > T was initially linked to thyroxine dose requirement (p = 0.035) when all patients were considered together, but this association was lost when the patients were classified into either near suppressed (0.1 ≤ TSH < 0.5) or suppressed (TSH < 0.1) TSH group. DISCUSSION: Although the results suggest only a weak relationship with differentiated thyroid cancer, they strongly indicate that the DIO2 polymorphism influences the hormonal dose requirement in patients undergoing treatment with thyroxine. This probably points to a distinction in the way this gene influences disease as compared to therapy thereof.

A review of select minerals influencing the haematopoietic process.

Micronutrients are indispensable for adequate metabolism, such as biochemical function and cell production. The production of blood cells is named haematopoiesis and this process is highly consuming due to the rapid turnover of the haematopoietic system and consequent demand for nutrients. It is well established that micronutrients are relevant to blood cell production, although some of the mechanisms of how micronutrients modulate haematopoiesis remain unknown. The aim of the present review is to summarise the effect of Fe, Mn, Ca, Mg, Na, K, Co, iodine, P, Se, Cu, Li and Zn on haematopoiesis. This review deals specifically with the physiological requirements of selected micronutrients to haematopoiesis, showing various studies related to the physiological requirements, deficiency or excess of these minerals on haematopoiesis. The literature selected includes studies in animal models and human subjects. In circumstances where these minerals have not been studied for a given condition, no information was used. All the selected minerals have an important role in haematopoiesis by influencing the quality and quantity of blood cell production. In addition, it is highly recommended that the established nutrition recommendations for these minerals be followed, because cases of excess or deficient mineral intake can affect the haematopoiesis process.

Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring.

Perinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes. We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development. Female rats received standard diet (9 % energy content from fat) or HF diet (29 % energy content from fat) before mating, during pregnancy and lactation. At weaning, male and female offspring were killed for tissue harvest. Maternal HF diet induced early obesity, white adipocyte hypertrophy and increased lipid accumulation in brown adipose tissue associated with sex-specific changes of the ECS's components in weanling rats. In male pups, maternal HF diet decreased CB1 and CB2 protein in subcutaneous adipose tissue. In female pups, maternal HF diet increased visceral and decreased subcutaneous CB1. In brown adipose tissue, maternal HF diet increased CB1 regardless of pup sex. In addition, maternal HF diet differentially changed oestrogen receptor across the adipose depots in male and female pups. The ECS and oestrogen signalling play an important role in lipogenesis, adipogenesis and thermogenesis, and we observed early changes in their targets in adipose depots of the offspring. The present findings provide insights into the involvement of the ECS in the developmental origins of metabolic disease induced by inadequate maternal nutrition in early life.

Nutrition, infection and stunting: the roles of deficiencies of individual nutrients and foods, and of inflammation, as determinants of reduced linear growth of children.

The regulation of linear growth by nutritional and inflammatory influences is examined in terms of growth-plate endochondral ossification, in order to better understand stunted growth in children. Linear growth is controlled by complex genetic, physiological, and nutrient-sensitive endocrine/paracrine/autocrine mediated molecular signalling mechanisms, possibly including sleep adequacy through its influence on growth hormone secretion. Inflammation, which accompanies most infections and environmental enteric dysfunction, inhibits endochondral ossification through the action of mediators including proinflammatory cytokines, the activin A-follistatin system, glucocorticoids and fibroblast growth factor 21 (FGF21). In animal models linear growth is particularly sensitive to dietary protein as well as Zn intake, which act through insulin, insulin-like growth factor-1 (IGF-1) and its binding proteins, triiodothyronine, amino acids and Zn2+ to stimulate growth-plate protein and proteoglycan synthesis and cell cycle progression, actions which are blocked by corticosteroids and inflammatory cytokines. Observational human studies indicate stunting to be associated with nutritionally poor, mainly plant-based diets. Intervention studies provide some support for deficiencies of energy, protein, Zn and iodine and for multiple micronutrient deficiencies, at least during pregnancy. Of the animal-source foods, only milk has been specifically and repeatedly shown to exert an important influence on linear growth in both undernourished and well-nourished children. However, inflammation, caused by infections, environmental enteric dysfunction, which may be widespread in the absence of clean water, adequate sanitation and hygiene (WASH), and endogenous inflammation associated with excess adiposity, in each case contributes to stunting, and may explain why nutritional interventions are often unsuccessful. Current interventions to reduce stunting are targeting WASH as well as nutrition.

Normal cortisol response to cold pressor test, but lower free thyroxine, after recovery from undernutrition.

Undernutrition is a stressor with long-term consequences, and the effect of nutritional recovery on cortisol and thyroid hormone status is unknown. To investigate basal thyroid hormones and the cortisol response to a cold pressor test in children recovered from undernutrition, a cross-sectional study was undertaken on children (6-16 years) separated into four groups: control (n 41), stunted (n 31), underweight (n 27) and recovered (n 31). Salivary cortisol was collected over the course of 10 h: upon awakening, before and after an unpleasant and a pleasant stimulus. Cortisol upon awakening was highest in the stunted and lowest in the underweight groups: control=5·05 (95% CI 3·71, 6·89) nmol/l, stunted=6·62 (95% CI 3·97, 11·02) nmol/l, underweight=2·51 (95% CI 1·75, 3·63) nmol/l and recovered=3·46 (95% CI 2·46, 4·90) nmol/l (P=0·005). Girls had higher cortisol concentrations upon awakening compared with boys (P=0·021). The undernourished groups showed an elevated cortisol response both to the unpleasant stimulus and at the last measurement (16.00 hours) compared with that of the recovered group: AUC, control=2·07 (95% CI 1·69, 2·45) nmol/l×30 min, stunted=2·48 (95% CI 1·91, 3·06) nmol/l×30 min, underweight=2·52 (95% CI 2·07, 2·97) nmol/l×30 min, recovered=1·68 (95% CI 1·26, 2·11) nmol/l×30 min (P=0·042); and control=2·03 (95% CI 1·75, 2·39) nmol/l×30 min, stunted=2·51 (95% CI 1·97, 3·19) nmol/l×30 min, underweight=2·61 (95% CI 2·16, 3·16) nmol/l×30 min, recovered=1·70 (95% CI 1·42, 2·03) nmol/l×30 min (P=0·009). Lower free thyroxine (T4) was found in the recovered and stunted groups: control=1·28 (95% CI 1·18, 1·39) pmol/l, stunted=0·98 (95% CI 0·87, 1·10) pmol/l, underweight=1·10 (95% CI 1·01, 1·21) pmol/l and recovered=0·90 (95% CI 0·83, 0·99) pmol/l (P<0·001). Multivariate analysis showed a lower cortisol concentration along 10 h (06.00-16.00 hours) in the recovered compared with the other groups (P=0·017), and similar concentrations between the recovered and control group. In conclusion, the children with recovery in weight and height had a cortisol stress response similar to control but a lower basal free T4. Longitudinal studies are warranted to determine the extent of these endocrine changes after recovery of undernutrition and in adulthood.

A "Grave" Case of Mitral Regurgitation: Cardio-Obstetric Approach to Severe Mitral Regurgitation With Cardiogenic Shock.

A 26-year-old woman presented at 26 weeks of pregnancy with severe mitral regurgitation (MR) and cardiogenic shock in the setting of profound hyperthyroidism. An intra-aortic balloon pump was placed, and surgical intervention was considered. However, with management of thyrotoxicosis and delivery, complete resolution of MR and cardiogenic shock was achieved. (Level of Difficulty: Intermediate.).

Two Cases of Methimazole-Induced Agranulocytosis With Their Risk Factors.

Background: Antithyroid drugs, such as methimazole (MMI), are standard therapies for the medical management of thyrotoxicosis. Agranulocytosis is a rare but lethal adverse effect of antithyroid medications. We have reported 2 cases of MMI-induced agranulocytosis with similar risk factors that likely predisposed them to this adverse reaction. Case Report: Case 1 involved a 71-year-old woman, with a history of Graves disease, who presented with an altered mental status. She was recently discharged on 40 mg of MMI twice daily, and she continued this dose for 2 months. She was readmitted and found to have neutropenic fever in the setting of MMI-induced agranulocytosis. MMI was discontinued, and she was started on filgrastim. Her cell counts gradually improved, and she was subsequently discharged.Case 2 involved a 68-year-old woman, with a history of Graves disease, who presented with severe back pain, nausea, and vomiting. She was recently discharged on 10 mg of MMI twice daily, which was increased to 10 mg 3 times a day. She was readmitted to the hospital because of a septic shock in the setting of pneumonia, colitis, bacteremia, and MMI-induced agranulocytosis. A bone marrow biopsy showed a polyclonal infiltrate with up to 85% plasma cells. Despite treatment with antibiotics, filgrastim, and continuous renal replacement therapy, she ultimately passed away. Discussion: Although these cases had differing outcomes, they shared similar features and risk factors, including older age, female sex, and relatively higher doses of MMI. Conclusion: Close follow up and awareness of risk factors, such as age, female sex, and higher doses of MMI, may decrease the risk of MMI-induced agranulocytosis and fatal outcomes.

High Prevalence of Hormonal Changes and Hepatic Osteodystrophy in Frail Patients with Cirrhosis-An Observational Study.

Background/Aim: Hormonal changes and hepatic osteodystrophy are less often studied complications of cirrhosis. This study describes the variance in hormones and osteodystrophy between Frail and Not frail patients with cirrhosis. Methods: 116 outpatients with cirrhosis were prospectively enrolled in this study. Frailty assessment was done using Liver Frailty Index (LFI). Sociodemographic assessment, anthropometry, nutritional assessment, hormone profile, and dual-energy X-ray absorptiometry scan were done in all patients. Results: 116 patients, predominantly males (100 (86.2%) with mean age of 50.16 years (95% CI, 48.43-51.89) were included. Malnutrition was more common in Frail group as compared to Not frail group. Subjective global assessment (SGA) class-B patients were significantly more in Frail group (37 (74%) vs 3 (4.5%), P = 0.001). The prevalence of lower parathyroid hormone (PTH) (14 (28%) vs 2 (3%)), testosterone (33 (66%) vs 15 (22.7%)), vitamin D3 (44 (88%) vs 39 (59.1%)), and cortisol (37 (74%) vs 37 (56.1) levels was higher in Frail group (P < 0.05). The number of patients diagnosed with osteodystrophy (34 (68%) vs 21 (31.8%), P = 0.001) was significantly higher in Frail group. The marker of osteoclastic activity, ß-cross laps, was significantly elevated in the Frail group both in males (736 (655-818) vs 380 (329-432), P = 0.001) and (females 619 (479-758) vs 313 (83-543), P = 0.02). Bone mineral density (BMD) at lumbar spine (LS) and neck of femur (NF) had significant correlation with LFI (ρ = 0.60, P = 0.001 for LS and ρ = 0.59, P = 0.001 for NF), serum testosterone (ρ = 0.58, P = 0.001 for LS and ρ = 0.53, P = 0.001 for NF), ß-cross laps (ρ = 0.38, P = 0.001for LS and ρ = 0.35, P = 0.000 for NF), vitamin D3 (ρ = 0.23, P = 0.04 for LS and ρ = 0.25, P = 0.01 for NF), PTH (ρ = 0.52, P = 0.001 for LS and ρ = 0.48. P = 0.001 for NF), and cortisol (ρ = 0.50, P = 0.001 for LS and ρ = 0.45, P = 0.001 for NF) levels. Conclusion: This is the first study that highlights the high prevalence of hormonal changes and hepatic osteodystrophy in frail patients with cirrhosis and opens a new dimension for research and target of therapy in this field.

Ninety-day repeated oral toxicity study of saponified Capsicum annum fruit extract with 50% capsanthin in Sprague-Dawley Rats with a 28-day recovery period.

A ninety-day oral toxicity study of saponified Capsicum annum fruit extract with 50% (w/w) capsanthin (SCFE-50 C) was performed by oral gavage administration to male and female Sprague-Dawley (SD) rats at doses of 0, 500, 1000 and 2000 mg/kg BW/day for a period of ninety consecutive days. To assess the reversal of toxicity, the treatment phase was followed with a twenty-eight-day recovery period. The treatment with SCFE-50 C in both male and female SD rats showed no mortality, and no treatment-related toxicologically significant changes were observed in any groups. No significant differences between treated and control groups were found in feed consumption, body weight gain, individual organ weights, ocular examination, clinical chemistry or blood biochemistry. The necroscopy and histopathology examination did not reveal any clinically significant changes in male and female rats from the 2000 mg/kg BW/day group. According to this study, the no observable adverse effect level (NOAEL) for saponified Capsicum annum fruit extract with 50% (w/w) capsanthin (SCFE-50 C) administered by oral gavage for 90-days is > 2000 mg/kg BW/day in SD rats.

Thyroid Storm in a Patient With COVID-19.

OBJECTIVE: A thyroid storm is a severe exacerbation of thyrotoxicosis that can cause significant morbidity and mortality. The emergence of the novel coronavirus (SARS-CoV-2) that originated in Wuhan, China, has become a worldwide pandemic. We present the first documented case of thyroid storm (as defined by the Burch-Wartofsky criteria) in a patient with COVID-19. METHODS: Laboratory and diagnostic studies, including thyroid function tests, thyroid antibody testing, SARS-CoV-2 nasopharyngeal polymerase chain reaction testing, and thyroid ultrasound were performed. RESULTS: A 25-year-old woman presented to the hospital with dry cough, dyspnea, palpitations, weight loss, diarrhea, and anxiety. Physical examination revealed exophthalmos with proptosis and chemosis, tachycardia, diffusely enlarged goiter with bruit, and fine tremor. Laboratory results demonstrated a thyroid-stimulating hormone level of <0.01 mIU/L (normal range [NR], 0.44-5.3 mIU/L), free thyroxine level of 5.34 ng/dL (NR, 0.64-1.42 ng/dL), total triiodothyronine level of 654 ng/dL (NR, 87-178 ng/dL), and thyroid-stimulating immunoglobulin level of 7.18 IU/L (NR, 0.00-0.55 IU/L). Thyroid ultrasound revealed heterogeneous echotexture with increased vascularity. Nasopharyngeal COVID-19 testing was positive. She was treated promptly with propranolol, propylthiouracil, and hydrocortisone with improvement in symptoms, and later switched to methimazole. Her COVID-19 course was uncomplicated, and she left the hospital with minimal respiratory symptoms. CONCLUSION: Thyroid storms are one of the more prevalent endocrine emergencies and are often precipitated by acute events including infections. Patients with thyroid storms may have concomitant SARS-CoV-2 infection that could influence the clinical course and severity of the disease. In patients with symptoms of thyrotoxicosis and respiratory symptoms, clinicians should consider performing a COVID-19 test.

Clinical Case Report: Dissociation of Clinical Course of Coexisting Autoimmune Hepatitis and Graves Disease.

OBJECTIVE: Concurrent autoimmune disorders, including autoimmune hepatitis (AIH), with Graves disease have been reported. Glucocorticoids can simultaneously lower thyroid hormone levels and treat AIH. Recurrence of hyperthyroidism is associated with recurrence of hepatitis. We present a case of coexisting AIH and Graves thyrotoxicosis, which improved with prednisone, but the thyrotoxicosis recurred during a prednisone taper while the hepatitis stayed in remission. METHODS: Evaluation included measurements of liver enzyme levels, thyroid function tests, and thyroid-stimulating antibodies as well as abdominal ultrasound, magnetic resonance imaging, and liver biopsy. RESULTS: A 47-year-old woman presented with nausea and jaundice. Workup showed an aspartate aminotransferase level of 1956 (reference, 10-42) U/L and alanine aminotransferase level of 1634 (reference, 14-54) IU/L. The liver biopsy was consistent with AIH. Nine months later, she reported palpitations, heat intolerance, and weight loss and was diagnosed with Graves disease. The patient received prednisone at 60 mg daily, and the liver and thyroid functions normalized after 1 month. Prednisone was tapered to 5 mg daily. Seven months later, she presented with a thyroid-stimulating hormone level of 0.049 (reference, 0.340-5.6) µIU/mL) and free thyroxine level of 3.96 (reference, 0.58-1.64) ng/dL. Liver enzymes remained at normal levels. Prednisone was increased from 5 to 20 mg to treat hyperthyroidism. The patient was referred for thyroidectomy for a diagnosis of Graves disease with thyrotoxicosis. CONCLUSION: This case is an example of coexisting autoimmune diseases, Graves disease and AIH, with different clinical courses. Despite initial resolution with glucocorticoid therapy, Graves disease recurred, while AIH stayed in remission.

Ventricular Fibrillation: A Rare Initial Presentation of Thyrotoxic Periodic Paralysis.

Thyrotoxic periodic paralysis is a life-threatening complication of hyperthyroidism characterized by transient episodes of muscle paralysis and hypokalemia, commonly seen in Asian men. We present a rare case of ventricular fibrillation as the initial presentation of thyrotoxic periodic paralysis. (Level of Difficulty: Intermediate.).

Increased Thyroid-Hormone Requirements Consistent With Type 3 Deiodinase Induction Related to Ibrutinib in a Thyroidectomized Woman.

OBJECTIVE: Tyrosine-kinase inhibitors (TKIs) are chemotherapeutic agents associated with increased thyroid-hormone requirements and altered deiodinase activity. We present the first case to link these findings to the TKI ibrutinib. METHODS: Serial thyroid-stimulating hormone (TSH), free-thyroxine (FT4), free-triiodothyronine (FT3), and reverse-triiodothyronine (rT3) levels were assessed. RESULTS: An 80-year-old, 62-kg woman with hypothyroidism secondary to total thyroidectomy for stage I papillary thyroid cancer, on maintenance levothyroxine (LT4) 137 µg daily, presented for follow-up. Compared to one year prior, the patient's weight had increased by 2 kg and TSH from 2.58 to 27.60 µIU/mL (normal: 0.45-4.50 µIU/mL) while on pantoprazole. Ibrutinib, her other medication, had been started seven months prior for chronic lymphocytic leukemia. Despite sequential confirmation of proper LT4 adherence and self-administration, adjustment of LT4 to 150 µg, and discontinuation of pantoprazole, the patient's hypothyroid symptoms worsened, and the TSH was 73.90 µIU/mL six months later. LT4 was increased to 175 µg six days a week and 262.5 µg once weekly. Two months later, the TSH was 3.92 µIU/mL (steady-state condition), FT4 2.32 ng/dL (normal: 0.82-1.77 ng/dL), FT3 1.6 pg/mL (normal: 2.0-4.4 pg/mL), and rT3 69.6 ng/dL (normal: 9.2-24.1 ng/dL). Ibrutinib was discontinued the next month due to gastrointestinal side effects and elevated blood pressure. Four months later, LT4 had been reduced to 150 µg, and the FT4 reached 1.92 ng/dL, FT3 2.0 pg/mL, and rT3 26.6 ng/dL. CONCLUSION: This report links ibrutinib to increased thyroid-hormone requirements in a thyroidectomized woman whose decreased T3:T4, T3:rT3, and T4:rT3 ratios suggested type 3 deiodinase induction and type 2 deiodinase inhibition.

Acrylamide induces a thyroid allostasis-adaptive response in prepubertal exposed rats.

Some endocrine-disrupting chemicals (EDCs) can affect the endocrine system through covalent interactions with specific sites, leading to deregulation of physiological homeostasis. The acrylamide (AA) present in some fried or baked foods is an example of an electrophile molecule that is able to form adducts with nucleophilic regions of nervous system proteins leading to neurological defects. A positive correlation between increased urinary AA metabolite concentration and reduced levels of thyroid hormones (TH) was described in adolescents and young adults. Thus, this study aimed to evaluate whether AA affects the physiology of the hypothalamus-pituitary-thyroid (HPT) axis and the possible repercussions in peripheral TH-target systems. For this, male Wistar rats were exposed to doses of 2.5 or 5.0 mg AA/Kg/day, based on the LOAEL (Lowest Observed Adverse Effect Level) during prepubertal development. The expression of molecular markers of HPT functionality was investigated in the hypothalamus, pituitary, thyroid, heart and liver, as well as the hormonal and lipid profiles in blood samples. Herein, we showed that AA acts as EDCs for thyroid gland function, increasing the transcript expression of several proteins related to TH synthesis and altering hypothalamus-pituitary-thyroid axis homeostasis, an effect evidenced by the higher levels of THs in the serum. Compensatory mechanisms were observed in TH-target tissues, such as an increase in Dio3 mRNA expression in the liver and a reduction in Mct8 transcript content in the hearts of AA-treated rats. Together, these results pointed out an allostatic regulation of the HPT axis induced by AA and suggest that chronic exposure to it, mainly associated with food consumption, might be related to the higher prevalence of thyroid dysfunctions.

Protective effect of a polyherbal bioactive fraction in propylthiouracil-induced thyroid toxicity in ratsby modulation of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes.

Hypothyroidism is the most frequent consequence of the interaction of a large variety of drugs, environmental pollutants and industrial chemicals with the thyroid gland. It is associated with diminished endocrine function which may lead to hyperlipidemia, diabetes, Alzheimer's disease, weight gain, and other metabolic disorders. The present study evaluates the pro-thyroid activity of a bioactive fraction from a polyherbal teabag in rats with hypothyroidism induced by propylthiouracil. The teabag was formulated to stimulate synthesis and/or release of T4 and affectthe conversion of T4 to T3. Phytoconstituents of the polyherbal teabag are potent antioxidants that may be responsible for the pro-thyroid activity. The tea-extract (1000 mg) was found to contain 1076 µg of gallic acid and 1131 µg of rutin from HPTLC analysis. Rats received propylthiouracil (8 mg/kg) for the first 15days followed by the polyherbal tea-extract (500, 1000 and 1500 mg/kg), the standard drug levothyroxine (0.1 mg/kg), aerobic exercise, and a combination of tea-extract (1000 mg/kg) and aerobic exercise daily along with propylthiouracil for the next 30 days. Finally, rats received their respective treatments alone without propylthiouracil for 15 more days. Lipid profile and levels of glucose, insulin, T3, T4, TSH, cortisol, homocysteine, creatinine, uric acid, malondialdehyde, glucose-6 phosphatase, and endogenous antioxidants were determined. All treatments attenuated significantly the propylthiouracil-elevated TSH, homocysteine, creatinine, uric acid, glucose-6-phosphatase, insulin, and malondialdehyde levels, and restored favorably the propylthiouracil-altered lipid profile, T3, T4, and endogenous antioxidant levels. The polyherbal tea-extract (1000 and 1500 mg/kg) treatment and thecombination treatment of tea-extract (1000 mg/kg) with aerobic exercise displayed significant restoration of the suboptimalthyroid function. This may be due to a favorablemodulation ofthe hypothalamic-pituitary-thyroid and the hypothalamic-pituitary-adrenal axes.

Low CSF/serum ratio of free T4 is associated with decreased quality of life in mild hypothyroidism - A pilot study.

BACKGROUND & OBJECTIVE: Patients with mild hypothyroidism often are depressed and have impaired quality of life despite serum free-T4 and T3 within reference values. Therefore, we investigated whether their symptoms were dependent on the concentrations of free -T4 and T3 in the circulation and cerebrospinal fluid (CSF). METHODS: Twenty-five newly diagnosed, untreated hypothyroid subjects and as many age- and sex-matched healthy controls were investigated. Blood and CSF sampling was performed in the morning after an overnight fast. Quality of life (QoL) was assessed by a Likert scale. In the hypothyroid subjects, the MADRS rating scale was also used to evaluate symptoms of depression. Furthermore, the results obtained by the questionnaires were related to serum and CSF levels of free- T4 and T3 as well as the ratios between them in CSF and in serum. RESULTS: Self-reported health was considerably lower in hypothyroid subjects. MADRS was considerably higher than the normal range for healthy individuals. Low CSF/serum free-T4 ratio was correlated with an increased depressed state according to MADRS (p < 0.01), and in addition, CSF/serum free-T4 ratio correlated positively with the self-reported general health Likert scale (p < 0.05). Concentrations of TSH, or free-T3 in serum or CSF, were not associated with an increased depressed state or self-reported general health. CONCLUSIONS: Low CSF/serum ratio of free-T4 was correlated with impaired general health and mood, in contrast to serum measurements not showing any correlations. These findings might partly explain why some patients with hypothyroidism suffer from mental symptoms, despite adequate serum levels of free-T4. However, the findings need to be confirmed in further and larger studies.

Hormonal Contribution to Liver Regeneration.

An understanding of the molecular basis of liver regeneration will open new horizons for the development of novel therapies for chronic liver failure. Such therapies would solve the drawbacks associated with liver transplant, including the shortage of donor organs, long waitlist time, high medical costs, and lifelong use of immunosuppressive agents. Regeneration after partial hepatectomy has been studied in animal models, particularly fumarylacetoacetate hydrolase-deficient (FAH -/-) mice and pigs. The process of regeneration is distinctive, complex, and well coordinated, and it depends on the interplay among several signaling pathways (eg, nuclear factor κß, Notch, Hippo), cytokines (eg, tumor necrosis factor α, interleukin 6), and growth factors (eg, hepatocyte growth factor, epidermal growth factor, vascular endothelial growth factor), and other components. Furthermore, endocrinal hormones (eg, norepinephrine, growth hormone, insulin, thyroid hormones) also can influence the aforementioned pathways and factors. We believe that these endocrinal hormones are important hepatic mitogens that strongly induce and accelerate hepatocyte proliferation (regeneration) by directly and indirectly triggering the activity of the involved signaling pathways, cytokines, growth factors, and transcription factors. The subsequent induction of cyclins and associated cyclin-dependent kinase complexes allow hepatocytes to enter the cell cycle. In this review article, we comprehensively summarize the current knowledge regarding the roles and mechanisms of these hormones in liver regeneration. Articles used for this review were identified by searching MEDLINE and EMBASE databases from inception through June 1, 2019.

Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are examples of autoimmune thyroid disease (AITD), the commonest autoimmune condition. Antibodies to thyroid peroxidase (TPO), the enzyme that catalyses thyroid-hormone production and antibodies to the receptor for the thyroid-stimulating hormone, are characteristic of HT and GD, respectively. It is presently accepted that genetic susceptibility, environmental factors, including nutritional factors and immune disorders contribute to the development of AITD. Aiming to investigate the effect of iodine, iron and selenium in the risk, pathogenesis and treatment of thyroid disease, PubMed and the Cochrane Library were searched for relevant publications to provide a narrative review. Iodine: chronic exposure to excess iodine intake induces autoimmune thyroiditis, partly because highly-iodinated thyroglobulin (Tg) is more immunogenic. The recent introduction of universal salt iodisation can have a similar, although transient, effect. Iron: iron deficiency impairs thyroid metabolism. TPO is a haem enzyme that becomes active only after binding haem. AITD patients are frequently iron-deficient since autoimmune gastritis, which reduces iron absorption and coeliac disease which causes iron loss, are frequent co-morbidities. In two-thirds of women with persistent symptoms of hypothyroidism despite appropriate levothyroxine therapy, restoration of serum ferritin above 100 µg/l ameliorated symptoms. Selenium: selenoproteins are essential to thyroid action. In particular, the glutathione peroxidases remove excessive hydrogen peroxide produced there for the iodination of Tg to form thyroid hormones. There is evidence from observational studies and randomised controlled trials that selenium, probably as selenoproteins, can reduce TPO-antibody concentration, hypothyroidism and postpartum thyroiditis. Appropriate status of iodine, iron and selenium is crucial to thyroid health.

Effects of the environmental endocrine disrupting compound benzo[a]pyrene on thyroidal status of abu mullet (Liza abu) during short-term exposure.

Benzo[a]Pyrene (BaP) is a ubiquitous polycyclic aromatic hydrocarbon (PAH) that has been shown to disrupt the metabolism of thyroid hormone. Then, the present investigation aimed to study the effects of BaP on thyroid function in Liza abu. Fish were injected with 2, 10 and 25 mg/kg-bw of BaP. Samples were taken from blood, thyroid and muscle tissues at days 1, 2, 4, 7, and 14. Blood was evaluated for changes in the plasma levels of TSH, T3 and T4. Also, BaP bioaccumulation in the fish muscle was measured. Thyroid tissues were processed for routine histology. BaP concentration in the muscle of treated fish reached a maximum level after 4 days. Exposure of fish to BaP resulted in a significant decrease in T3 and T4 plasma level and increase in TSH concentration up to day 4. Also some pathological alterations were observed in BaP-exposed fish such as hemorrhage and increased number of large follicles with squamous epithelium. In conclusion, according to the results of the present investigation, short term exposure to sublethal concentrations of BaP significantly affected thyroid function in fish. The results revealed BaP ability to alter thyroid function.

Circulating thyrotropin is upregulated by estradiol.

After encountering two women with serum thyrotropin (TSH) levels greater in periovulatory phase than in other days of the menstrual cycle, we hypothesized that TSH levels could be sensitive to changes in circulating estrogens in women. The objective of this study was to evaluate whether serum TSH increases after an induced acute increase of serum estradiol, and compare serum TSH increase with that of prolactin (PRL) which is a classic estradiol-upregulated pituitary hormone. In this retrospective study, we resorted to stored frozen sera from 55 women who had undergone the GnRH agonist (buserelin)-acute stimulation test of ovarian steroidogenesis. This test, that is preceded by dexamethasone administration to suppress adrenal steroidogenesis, had been performed to show an increased buserelin-stimulated response of 17-hydroxyprogesterone, a response that is frequent in polycystic ovary syndrome. Fifty-five women had enough serum volume at pertinent times (first observation early in the follicular phase and all times of the test) to permit assay of serum estradiol, TSH and PRL. Before dexamethasone administration, estradiol averaged 26.4 ±â€¯15.5 pg/ml (reference range 23-139, follicular phase), TSH 1.78 ±â€¯0.86 mU/L (reference range 0.3-4.2) and PRL 409.4 ±â€¯356 mU/L (reference range 70.8-556) (mean ±â€¯SD). Serum estradiol, TSH and PRL averaged 47.2 ±â€¯27 pg/ml, 0.77 ±â€¯0.48 mU/L and 246.4 ±â€¯206.8 mU/L just prior to the buserelin injection, but they peaked at 253.4 ±â€¯113.5 pg/ml (nv 83-495, midcycle), 3.30 ±â€¯1.65 mU/L and 540.3 ±â€¯695.2 mU/L after injection. The responses to buserelin of estradiol, TSH and PRL were of wide magnitude. There was a significant correlation between TSH peak and serum estradiol peak, betweeen AUC0-24 h-TSH and AUC0-24 h-estradiol, or between PRL peak and estradiol peak and AUC0-24 h -PRL and AUC0-24 h-estradiol in only a subgroup of women. Therefore, women with estradiol-dependent increase in serum TSH do exist. Reference bands of serum TSH dependent on the phases of the menstrual cycle should be available.