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Thyroid hormones play essential roles in spermatogenesis, but their effects on infertile males remain poorly understood. This study aimed to evaluate the impact of combining carbimazole (CBZ) with vitamin E (VE) on testicular injury induced by experimental hyperthyroidism in adult albino rats, focusing on oxidative, inflammatory, and apoptotic pathways. In this experimental study, 64 adult male albino Wistar rats were divided into eight groups: Group I (control-untreated), Group II (CBZ-control), Group III (VE-control), Group IV (CBZ + VE-control), Group V (levothyroxine-induced testicular injury), Group VI (levothyroxine + CBZ-treated), Group VII (levothyroxine + VE-treated), and Group VIII (levothyroxine + CBZ + VE-treated). The study was conducted in the Faculty of Medicine, Suez Canal University (Ismailia, Egypt). After cervical decapitation, both testes and epididymis were examined histopathologically and immunohistochemically. Significant differences were observed among groups concerning malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT; all P < 0.001). Polymerase chain reaction analysis showed significant differences in tumor necrosis factor-α (TNF- α ), interleukin-10 (IL-10), Bcl-2-associated X protein (BAX), B-cell lymphoma 2 protein (Bcl2), p53, Caspase-3, Caspase-8, Caspase-9, and nuclear factor-kappa B (NF- κ B) mRNA levels (all P < 0.001). Hyperthyroid group treated with CBZ alone (Group VI) exhibited testicular side effects, affecting seminiferous tubules and spermatogenesis. However, the Group VIII showed improved spermatogenesis and a decrease in testicular side effects. The addition of VE to the treatment of hyperthyroid rats with CBZ reduced testicular side effects and seminiferous tubular affection when potentially improving spermatogenesis. Further research is needed to elucidate the underlying mechanisms fully., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Preconception evaluation of couples wishing to conceive is an important step toward a healthy pregnancy and it is especially important in people with a chronic condition or at genetic risk. The most common endocrine disorders in women at reproductive age are those involving the thyroid gland and it is well recognized that hyperthyroidism (HT), over-function of the thyroid gland, is associated with risks of maternal, fetal, and neonatal complications. The aim of this paper is to review the latest evidence regarding the components of preconception counseling in women with HT that contemplate a pregnancy. We also want to raise awareness among healthcare professionals about the importance of periconceptional counseling in improving pregnancy outcomes and avoid maternal and fetal complications related to thyroid dysfunction. In women with Graves' disease seeking pregnancy, it is essential to discuss all the treatment options along with the associated risks and benefits. Extensive prospective studies are still needed to understand the implications of current recommended strategies for the management of HT in preconception and during pregnancy.

Objective: The variability of thyroid function tests (TFTs) during antithyroid drug (ATD) therapy and its association with adverse health outcomes have not been previously studied. The aim of this study was to evaluate the association of TFT variability and cardiovascular morbidity during ATD therapy., Design: Retrospective cohort study., Patients and Measurements: Hyperthyroid patients (n = 394) treated with ATD therapy at Tampere University Hospital between March 2016 and December 2018 were followed up for a median time of 1.5 years (interquartile range 0.8-2.0). The coefficients of variation (CVs) of the follow-up thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) measurements were determined. The associations of TFT variability and baseline clinical factors with cardiovascular disease (CVD) -associated hospital visits were assessed with logistic regression analyses., Results: In the multivariable analyses, age (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.03-1.09), male gender (OR: 2.33, 95% CI: 1.03-5.28) and fT4-CV (OR: 1.02, 95% CI: 1.01-1.04) were independent risk factors for cardiovascular morbidity, whereas baseline positive thyrotropin receptor antibodies (TRAbs) were associated with lower cardiovascular morbidity (OR: 0.29, 95% CI: 0.14-0.61). When the patients with baseline TRAb positivity were studied separately, fT4-CV was associated with cardiovascular morbidity (OR: 1.03, 95% CI: 1.00-1.05)., Conclusions: During ATD therapy, fT4 variability is associated with an increased cardiovascular morbidity. Although positive TRAbs are associated with a lower cardiovascular morbidity compared with hyperthyroidism with negative autoantibodies, the variability of fT4 is associated with cardiovascular morbidity also in patients with positive TRAbs., (© 2023 The Authors. Clinical Endocrinology published by Clinical Endocrinology.)

Backgruound: This study aimed to investigate the changes of incidence and treatment of choice for hyperthyroidism from 2003 to 2018 and explore the treatment-related complications and concomitant comorbidities in South Korea using data from the National Health Insurance Service., Methods: This is a retrospective observational study. Hyperthyroidism was defined as a case having two or more diagnostic codes of thyrotoxicosis, with antithyroid drug intake for more than 6 months., Results: The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively. In 2003 to 2004, hyperthyroidism was most often diagnosed in patients in their 50s, but in 2017 to 2018, people were most often diagnosed in their 60s. During the entire period, about 93.7% of hyperthyroidism patients were prescribed with antithyroid drugs, and meanwhile, the annual rates of ablation therapy decrease from 7.68% in 2008 to 4.56% in 2018. Antithyroid drug-related adverse events, mainly agranulocytosis and acute hepatitis, as well as complications of hyperthyroidism such as atrial fibrillation or flutter, osteoporosis, and fractures, occurred more often in younger patients., Conclusion: In Korea, hyperthyroidism occurred about 2.5 times more in women than in men, and antithyroid drugs were most preferred as the first-line treatment. Compared to the general population, hyperthyroid patients may have a higher risk of atrial fibrillation or flutter, osteoporosis, and fractures at a younger age.

Objective: A common problem with antithyroid drugs (ATD) treatment in patients with Graves' disease (GD) is the high recurrence rate after drug withdrawal. Identifying risk factors for recurrence is crucial in clinical practice. We hereby prospectively analyze risk factors for the recurrence of GD in patients treated with ATD in southern China., Subjects and Methods: Patients who were newly diagnosed with GD and aged > 18 years were treated with ATD for 18 months and followed up for 1 year after ATD withdrawal. Recurrence of GD during follow-up was assessed. All data were analyzed by Cox regression with P values < 0.05 considered statistically significant., Results: A total of 127 Graves' hyperthyroidism patients were included. During an average follow-up of 25.7 (standard deviation = 8.7) months, 55 (43%) had a recurrence within 1 year after withdraw of anti-thyroid drugs. After adjustment for potential confounding factors, the significant association remained for the presence of insomnia (hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.47-5.88), greater goiter size (HR 3.34, 95% CI 1.11-10.07), higher thyrotrophin receptor antibody (TRAb) titer (HR 2.66, 95% CI 1.12-6.31) and a higher maintenance dose of methimazole (MMI) (HR 2.14, 95% CI 1.14-4.00)., Conclusion: Besides conventional risk factors (i.e., goiter size, TRAb and maintenance MMI dose) for recurrent GD after ATD withdraw, insomnia was associated with a 3-fold risk of recurrence. Further clinical trials investigating the beneficial effect of improving sleep quality on prognosis of GD are warranted.

The effectiveness of potassium iodide (KI) (100 mg/day) was evaluated in 504 untreated patients with Graves' hyperthyroidism (GD). Initial response to KI within 180 days, the effect of additional methylmercaptoimidazole (MMI) or radioactive iodine (RI) in resistant or escaped patients, and long-term prognosis were evaluated. Serum fT 4 levels became low or normal in 422 patients (83.7%, KI-sensitive group) without serious side effects. Among these patients, serum TSH levels became high (n = 92, hypothyroid) or normal (n = 78) in 170 patients (33.7%) (KI-sensitive with a recovered TSH response, Group A), but remained suppressed in 252 patients (50.0%) (KI-sensitive with TSH suppression, Group B). Serum fT 4 levels decreased but remained high in 82 patients (16.3%) (KI-resistant, Group C). Older patients, or those with small goiter and mild GD were more KI-sensitive with a recovered TSH response than others. Escape from KI effect occurred in 0%, 36% and 82% in Group A, B and C, respectively. Patients in Group B and C were successfully treated with additional low-dosage MMI or RI. After 2-23 years' treatment (n = 429), remission (including possible remission) and spontaneous hypothyroidism were significantly more frequent in Group A (74.3% and 11.1%, respectively,) than in Groups B (46.3% and 2.8%, respectively) or C (53.6% and 1.5%, respectively) (p < 0.0001). In conclusion, a high KI sensitivity with a recovered TSH response was observed in about a third of the patients in GD associated with a better prognosis. Additional MMI or RI therapy was effective in escaped or KI-resistant patients with suppressed TSH level.

Complicated vomiting and hypercalcemia are clinically rare in patients with hyperthyroidism. We describe a case of a woman whose main symptoms were palpitations, sweating, and vomiting. She was diagnosed with Graves' disease by an analysis of thyroid function, thyroid-related antibodies, and color Doppler ultrasound. Biochemical tests showed that her serum calcium levels were greatly elevated. Her symptoms were relieved following the administration of antithyroid drugs, propranolol for heart rate control, fluid replacement, diuresis and calcium reduction, antiemesis, and liver protection. This case suggests that the thyroid function should be screened when hypercalcemia is seen in the clinic.

Background: Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed., Methods: This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves' disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles., Results: Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD., Conclusion: This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.

This article reported the clinical diagnosis and treatment experience of two cases of fetal goiter in Graves' disease (GD) complicated with pregnancy. Two GD patients took antithyroid drugs regularly during pregnancy and their thyroid functions were well controlled, but the levels of thyrotropin receptor antibody (TRAb) of the two cases were still above the upper limit in the second and third trimester. Two fetuses had fetal goiter in the middle and late stages of pregnancy. After continuously controlling maternal thyroid function and closely monitoring fetal ultrasound, there was no aggravation of the fetal goiter, and the delivery went smoothly. One case had neonatal hyperthyroidism. It is suggested that although the thyroid function was well controlled during pregnancy in patients with GD, the high level of serum TRAb still needs to be alert to the occurrence of fetal goiter, and fetal ultrasound is the most direct non-invasive monitoring method.

Objective: Radioiodine has been increasingly used to treat hyperthyroidism for many years. Although widely regarded as an effective therapy, radioiodine treatment for hyperthyroidism has been suspected to be associated with the risk of mortality. This study aimed to quantify the mortality outcomes in patients who were treated for hyperthyroidism with radioiodine., Methods: Systematic search and meta-analysis were performed to determine the risk of mortality in patients treated with radioiodine for hyperthyroidism. Relevant studies were searched through August 2020 and selected in accordance with the inclusion criteria., Results: A total of 13 studies were identified. The summary odds ratios (ORs) showed an increased risk of all-cause mortality in patients who were treated with radioiodine for hyperthyroidism (OR = 1.20; 95% CI = 1.07-1.35). The risk of death attributed to all forms of circulatory, respiratory, and endocrine and metabolic diseases was significantly increased, with summary ORs of 1.23 (95% CI, 1.12-1.35), 1.43 (95% CI, 1.17-1.75), and 2.38 (95% CI, 1.85-3.06), respectively. The summary ORs revealed no significant association between radioiodine treatment for hyperthyroidism and the risk of cancer mortality (OR = 1.03; 95% CI, 0.98-1.09). Radioiodine treatment for hyperthyroidism was not associated with the risk of mortality from breast, respiratory system, gastrointestinal, and genitourinary cancers., Conclusion: Radioiodine treatment for hyperthyroidism is associated with the risk of all-cause mortality but not cancer mortality. Future research needs to address the causes of hyperthyroidism, effects of radioiodine therapy, and potential effects of confounding to identify causality., (Copyright © 2021. Published by Elsevier Inc.)

Hyperthyroidism is a serious and rare disorder in childhood characterized by the overproduction of thyroid hormones by the thyroid gland. Graves disease is the most common cause. The objective of this paper is to review and update hyperthyroidism in children and adolescents aiming to guide its early detection and referral to the pediatric endocrinologist. The disease should be suspected if typical symptoms and goiter are present and has to be confirmed with the characteristic biochemical profile. Initially, treatment to block the effect of the thyroid excess is needed. Antithyroid drugs are the recommended first-line treatment to diminish hormone production. Alternative treatments, such us radioactive iodine or thyroidectomy, are considered in cases of adverse effects to drugs, relapse or non-remission of the disease, in order to achieve hypothyroidism or euthyroidism., Competing Interests: None, (Sociedad Argentina de Pediatría.)

Introduction: The incidence of fetal goiters is reported to be around 1 per 40,000 births. The risk of complications is first of all obstetric, directly related to goiter size, but it may also affect longer term fetal and child development, depending on whether the goiter is due to hypo- or hyperthyroidism. Management is multidisciplinary, but not yet consensual and not always optimal by either endocrinologists or obstetricians. Objectives: The principal objective of this retrospective study was to analyze the data that enabled the physicians to assess whether the goiter was hypo- or hyperthyroid and then to analyze the obstetric practices used in the Pays de Loire network to describe in detail the tools used to diagnose and characterize the goiters and the management chosen in these cases. The secondary objectives are to assess, in our small cohort, the effectiveness of the in utero treatments provided, based on the examination of the children at birth and their outcome at 6 months of life, and to suggest a strategy for monitoring these women at risk that takes current guidelines into consideration. Materials and methods: This multicenter retrospective study covers a 6-year period and focused on the prenatal diagnosis centers (CPDPN) of the Pays de Loire perinatal network: in Nantes, Angers, and Le Mans. The network is responsible for around 42,000 births a year, and the study included 17 women, for a prevalence of 1 per 15,000 births. Results: Ten of the 17 fetuses had a hypothyroid goiter, 4 a hyperthyroid goiter, and 3 normal thyroid findings on fetal blood sample (FBS). For four women, these goiters were secondary to fetal dyshormonogenesis, for 9 more to Graves disease with TSH receptor antibodies (TRAb), and for four women to thyrotoxicosis at the start of pregnancy, managed by synthetic antithyroid drugs. Two newborns had severe complications associated with maternal transmission of Graves disease (TRAb positive at birth): one with exophthalmos and one with neonatal tachycardia. The other 14 had normal psychomotor development at 6 months, based on a clinical examination by a pediatric endocrinologist; only one child was lost to follow-up. Conclusion: Together, ultrasound and multidisciplinary expertise (of an endocrinologist and an obstetrician experienced with this disease) remain the best means for avoiding, or otherwise for accurately characterizing fetal goiter. An ultrasound diagnostic score, of the type proposed by Luton et al. in 2009, may make it possible to homogenize practices and thus to defer or delay the - currently too common - performance of invasive FBS procedures, which must remain rare in this management to limit comorbidities. A threshold TRAb value (>5 IU/l) makes it possible to define this group of women as at risk of fetal and neonatal hyperthyroidism and thus requiring close monitoring. The value of prenatal intra-amniotic thyroxine treatment for hypothyroid goiters (including dyshormonogenesis) remains to be demonstrated.

Objective: To analyze the effects of methimazole (MMI)-containing combination regimens on the thyroid status and relapse rates in patients with Graves hyperthyroidism (GH) using a network meta-analysis to provide guidance for clinical application. Methods: We conducted a literature review, which identified 21 trials for inclusion. The major outcomes were serum free triiodothyronine (FT3) and free thyroxine (FT4) concentrations. The secondary outcome was relapse rate. A network meta-analysis was used to compare multiple regimens to identify the most advantageous regimen. Results: The types of combined drugs included anti-oxidant complexes, selenium, vitamin D3, cholestyramine, risedronate, iodine, potassium bromide, immunosuppressants, and β-adrenergic antagonists. Regarding the FT3 results, the rank probability of the best result showed that potassium bromide (0.897) and vitamin D3 (0.833) had relative advantages in reducing FT3 at the 1-month time point. According to the time trend analysis, compared with the control treatment, cholestyramine and iodine showed advantages in reducing FT3 during the early stage (0 to 3 months). The immunosuppressants showed advantages in reducing FT3 during the late stage (>9 months) but not the early stage. Regarding the FT4 results, potassium bromide had the highest P -score (.965) at the 1-month time point. Iodine and cholestyramine had advantages in reducing FT4 during the early stage. The immunosuppressants had advantages during both the early and late stages. Conclusion: MMI combined with cholestyramine or iodine was shown to regulate serum FT3 and FT4 during the early stage of GH. MMI combined with immunosuppressants had a long-term advantage in FT3/FT4 regulation and reduced the relapse rate. Abbreviations: ATD = antithyroid drug; CI = confidence interval; FT3 = free triiodothyronine; FT4 = free thyroxine; GH = Graves hyperthyroidism; MMI = methimazole; OR = odds ratio; RCT = randomized controlled trial; SMD = standard mean difference; TCM = traditional Chinese medicine.

Objective: The present study aimed to investigate the adverse effects of the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating hyperthyroidism. Methods: Qualitative analysis was performed for studies identified in a literature search up to April 20, 2019, and 30 studies were selected for meta-analysis. The study designs included case-control, randomized controlled, and retrospective cohort. Patients were in four age groups: childhood, gestating mothers, older adults, and other ages, and all were receiving PTU or MMI/CMZ. Adverse reactions to MMI/CMZ and PTU were evaluated and compared. Results: Odds of liver function injury were higher in the PTU group than in the MMI/CMZ group (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.16 to 4.96; P = .02). Odds of elevated transaminase were much higher in the PTU group than in the MMI/CMZ group (OR, 3.96; 95% CI, 2.49 to 6.28; P <.00001). No significant between-group differences were found in odds of elevated bilirubin, agranulocytosis, rash, or urticaria; incidence of other adverse events; or in children. Odds of birth defects during the first trimester of pregnancy were higher in the MMI/CMZ group than in the PTU group (OR, 1.29; 95% CI, 1.09 to 1.53; P = .003). Conclusion: The impact of PTU on liver injury and transaminase levels is greater than that of MMI/CMZ, but no significant between-group differences are found in the drugs' effects on bilirubin, agranulocytosis and rash, urticaria, or in children. In treating pregnancy-related hyperthyroidism, PTU should be used in the first trimester and MMI reserved for use in late pregnancy. Abbreviations: ALT = alanine aminotransferase; ATD = antithyroid drug; CI = confidence interval; CMZ = carbimazole; GD = Graves disease; MMI = methimazole; MTU = methylthiouracil; NOS = Newcastle-Ottawa Scale; OR = odds ratio; PTU = propylthiouracil; RAI = radioactive iodine.

Whether or not Graves' hyperthyroidism can be really cured, depends on the definition of "cure." If eradication of thyroid hormone excess suffices for the label "cure," then all patients can be cured because total thyroidectomy or high doses of ¹³¹I will abolish hyperthyroidism albeit at the expense of creating another disease (hypothyroidism) requiring lifelong medication with levothyroxine. I would not call this a "cure," which I would like to define as a state with stable thyroid stimulating hormone (TSH), free thyroxine, and triiodothyronine serum concentrations in the normal range in the absence of any thyroid medication. Surgery and radioiodine are unlikely to result in so-defined cures, as their preferable aim as stated in guidelines is to cause permanent hypothyroidism. Discontinuation of antithyroid drugs is followed by 50% recurrences within 4 years; before starting therapy the risk of recurrences can be estimated with the Graves' Recurrent Events After Therapy (GREAT) score. At 20-year follow-up about 62% had developed recurrent hyperthyroidism, 8% had subclinical hypothyroidism, and 3% overt hypothyroidism related to TSH receptor blocking antibodies and thyroid peroxidase antibodies. Only 27% was in remission, and might be considered cured. If the definition of "cure" would also include the disappearance of thyroid antibodies in serum, the proportion of cured patients would become even lower., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Endocrine Society.)

Background: Although hyperthyroidism is associated with high turnover osteopenia and its recovery after treatment, the extent of recovery with different forms of therapy remains controversial. This prospective study evaluated the bone mineral density in thyrotoxic subjects undergoing total thyroidectomy and 131 I radioactive iodine therapy., Methods: Newly diagnosed subjects with hyperthyroidism undergoing total thyroidectomy (group 1; n = 127) and 131 I radioactive iodine therapy (group 2; n = 30) were evaluated for bone mineral density by dual energy x-ray absorptiometry at the time of diagnosis (point A), on achieving euthyroidism with antithyroid drugs (point B), and 6 months after definitive treatment (point C)., Results: In group 1, bone mineral density (expressed as g/sq cm; mean ± standard deviation) in the hip (0.842 ± 0.157) and spine (0.97 ± 0.155) at point A, improved at point B (hip, 0.853 ± 0.157 and spine, 0.982 ± 0.155), and further improved at point C (hip, 0.91 ± 0.158 and spine, 1.053 ± 0.161, each P < .001). In group 2, at point C, bone mineral density in the hip (0.761 ± 0.168 versus point A, 0.741 ± 0.146) and spine (0.831 ± 0.159 versus point A, 0.823 ± 0.158) were less than group 1 (each P < .01)., Conclusion: Bone mineral density improved significantly after all forms of treatment of hyperthyroidism and was greatest in lumbar vertebrae (8.6%) as early as 6 months after total thyroidectomy. The delayed recovery of bone mineral density after 131 I radioactive iodine therapy needs long-term evaluation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g) and triiodothyronine (0.5-50 µg/100 g) for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P) days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold). Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60%) ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold), and decreased heart rate (5%), fast muscle myoglobin mRNA (30%) and body weight (20%) in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30%) and body weight (14%). These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood.

The plasticity and vulnerability of the rat spinal cord (SC) during postnatal development has been less investigated compared to other CNS structures. In this study, we determined the effects of thyroid hormonal (TH) deficiency and excess on postnatal growth and neurochemical development of the rat SC. The growth as well as the specific and total activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes of the SC were determined in hypo- and hyperthyroid rat pups at postnatal (P) days P1, P5, P10 and P21 (weaning), and were compared to age-matched untreated normal controls. AChE is a cholinergic synaptic enzyme while BuChE is a metabolic enzyme mainly found in glial cells and neurovascular cells. The SC is rich in somatic motor, autonomic cholinergic neurons and associated interneurons. Daily subcutaneous injection of pups with thyroxine (T4) and administration of antithyroid goitrogen propylthiouracil (PTU) in the litter's drinking water were used to induce hyper- and hypothyroidism, respectively. Enzyme assays were carried out spectrophotometrically at the above-mentioned ages, using SC homogenates with acetylthiocholine-chloride as the substrate, together with specific cholinesterase inhibitors, which specifically target AChE and BuChE. SC weights were significantly lower at P10 and P21 in hypothyroid pups but unchanged in the hyperthyroid ones. Hypothyroidism significantly reduced both specific and total AChE activity in SC of P10 and P21 rat pups, while having no effects on the BuChE activity, although total BuChE activity was decreased due to reduced total tissue weight. In contrast both specific and total AChE activities were markedly and significantly increased (>100%) in the P10 and P21 hyperthyroid pups. However, BuChE specific activity was unaffected by this treatment. The results indicate that hypothyroid condition significantly reduces, while hyperthyroidism increases, the postnatal development of cholinergic synapses, thereby influencing the functional development of this major sensory and motor structure. However, the neurochemical development of glia and other non-neuronal cells, where BuChE is mainly localized, is comparatively unaffected in these abnormal developmental conditions., (Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.)

Introduction: Radioiodine (I-131) is a useful therapeutic modality of hyperthyroidism when medical therapy fails. Traditionally, the nuclear physicians undertake the prescription of I-131 therapy. However, endocrinologists are increasingly being recognized for their competence in prescribing individualized doses of I-131 for the treatment of various thyroid disorders., Methods: In this pilot prospective study, we collaborated with our nuclear medicine colleagues to determine the outcomes of 80 patients with hyperthyroidism who underwent I-131 ablation as prescribed by the endocrinologist. Doses administered were based primarily on thyroid volume with adjustments contingent on adverse factors, and fixed assumptions on target absorbed dose (R) and uptake (U) were used. Seventy-three had Graves' disease (GD) and seven had toxic nodular goitre (TNG) or toxic adenomas (AFTN). Therapeutic success was defined as achievement of hypothyroidism or euthyroidism., Results: 95.9 percent (70 of 73) of GD patients and 85.7 percent (6 of 7) of those with TNG/AFTN achieved successful outcomes after a single dose of endocrinologist-directed I-131 therapy. More than 50 percent of patients became hypothyroid by three months and about two-thirds became hypothyroid by six months post I-131 therapy., Conclusion: Our results indicate that the success rate of endocrinologist-directed I-131 therapy exceeds 95 percent with a single dose and compares favourably with nuclear physician-directed therapy outcomes., (Copyright J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart . New York.)

Expression of all of the isoforms of the subunits of AMP-activated protein kinase (AMPK) and AMPK activity is increased in skeletal muscle of hyperthyroid rats. Activity of AMPK in skeletal muscle is regulated principally by the upstream kinase, LKB1. This experiment was designed to determine whether the increase in AMPK activity is accompanied by increased expression of the LKB1, along with binding partner proteins. LKB1, MO25, and downstream targets were determined in muscle extracts in control rats, in rats given 3 mg of thyroxine and 1 mg of triiodothyronine per kilogram chow for 4 wk, and in rats given 0.01% propylthiouracil (PTU; an inhibitor of thyroid hormone synthesis) in drinking water for 4 wk (hypothyroid group). LKB1 and MO25 increased in the soleus of thyroid hormone-treated rats vs. the controls. In other muscle types, LKB1 responses were variable, but MO25 increased in all. In soleus, MO25 mRNA increased with thyroid hormone treatment, and STRAD mRNA increased with PTU treatment. Phospho-AMPK and phospho-ACC were elevated in soleus and gastrocnemius of hyperthyroid rats. Thyroid hormone treatment also increased the amount of phospho-cAMP response element binding protein (CREB) in the soleus, heart, and red quadriceps. Four proteins having CREB response elements (CRE) in promoter regions of their genes (peroxisome proliferator-activated receptor-gamma coactivator-1alpha, uncoupling protein 3, cytochrome c, and hexokinase II) were all increased in soleus in response to thyroid hormones. These data provide evidence that thyroid hormones increase soleus muscle LKB1 and MO25 content with subsequent activation of AMPK, phosphorylation of CREB, and expression of mitochondrial protein genes having CRE in their promoters.

The thyroid hormones (THs) are crucial determinants of normal development and metabolism, especially in the central nervous system. The metabolic rate is known to increase in hyperthyroidism and decrease in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect the activities of acetylcholinesterase (AChE), (Na+,K+)- and Mg2+-adenosinetriphosphatase (ATPase) in the frontal cortex and the hippocampus of adult rats. Hyperthyroidism was induced by subcutaneous administration of thyroxine (25 microg/100 g body weight) once daily for 14 days, and hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal pools. A region-specific behavior was observed concerning the examined enzyme activities in hyper- and hypothyroidism. In hyperthyroidism, AChE activity was significantly increased only in the hippocampus (+22%), whereas Na+,K+-ATPase activity was significantly decreased in the hyperthyroid rat hippocampus (-47%) and remained unchanged in the frontal cortex. In hypothyroidism, AChE activity was significantly decreased in the frontal cortex (-23%) and increased in the hippocampus (+21%). Na+,K+-ATPase activity was significantly decreased in both the frontal cortex (-35%) and the hippocampus (-43%) of hypothyroid rats. Mg2+-ATPase remained unchanged in the regions of both hyper- and hypothyroid rat brains. Our data revealed that THs affect the examined adult rat brain parameters in a region- and state-specific way. The TH-reduced Na+,K+-ATPase activity may increase the synaptic acetylcholine release and, thus, modulate AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems in the examined brain regions.

Except from well-known the most frequent reasons of the hyperthyroidism such as the Graves-Basedow disease, multinodular goitre and the autonomous adenoma we should also remember the other rarer illnesses leading to the excess of thyroid hormones in the serum. Authors presented the problem of atypical forms of thyrotoxicosis which run without the overproduction of thyroid hormones and are characterized by low 24 h 131 J uptake by the thyroid gland. So called masks of hyperthyroidism such as apathetic, neuromuscular, gastrointestinal and cardiovascular forms were also discussed in the article.

Introduction: It is claimed in a limited number of studies carried out on human beings that plasma homocysteine levels increased in hypothyroid patients and decreased in hyperthyroid patients., Objective: The aim of this study is to determine total plasma homocysteine, thyroid function tests, vitamin B12, folic acid and lipid levels and to explore the relations among them in rat models with induced hypothyroidism and hyperthyroidism with a view to investigating whether hypothyroid and hyperthyroid rat models could represent human hypothyroidism and hyperthyroidism models., Material and Method: The study included 30 male Wistar Albino species rats with a mean weight of 200 - 250 g. Rats were randomly divided into 3 groups as 1) hypothyroid group, 2) hyperthyroid group and 3) control group. Hypothyroidism was induced by adding 10 mg/kg/day propylthiouracil to rats' drinking water for 30 days. In order to induce hyperthyroidism, rats were administered 10 microg/100 g L-thyroxin ampule via intraperitoneal route for 10 days., Results: We found that total plasma homocysteine level of the hypothyroid group was significantly lower than those of the control group (p<0.05) and the hyperthyroid group (p<0.001). Total plasma homocysteine level of the hypothyroid group was found insignificantly higher than that of the control group (p>0.05) and significantly higher than that of the hyperthyroid group (p<0.001). We established a significant and positive correlation between total plasma homocysteine level and thyroid hormone levels. We did not identify a significant relation between total plasma homocysteine level and serum folic acid and serum vitamin B12 levels., Conclusion: Our findings are different from the findings reported in human hypothyroidism and hyperthyroidism studies. We believe that hypothyroid and hyperthyroid rat models cannot represent human hypothyroidism and hyperthyroidism models.

Four patients with Graves' disease in whom antithyroid drugs could not be used were treated by plasmapheresis preoperatively. On admission all patients had severe hyperthyroidism. All patients were treated by beta blockers, cholestyramine and inorganic iodine before plasmapheresis. Plasmapheresis course consisted of three sessions. Removed plasma was replaced by a synthetic colloid solution and human albumin other than fresh-frozen plasma. Plasmapheresis led to decreases in serum T3 concentrations >78-40% and free T4 concentrations >69%. Near-total thyroidectomy could be performed in all patients. Although screening coagulation tests were within normal limits, patients 1 and 4 experienced more blood loss than usual during the operative procedure. Plasmapheresis could be used as an alternative therapeutic option in the preoperative management of severe hyperthyroid patients with contraindications to antithyroid drugs. However, this is an invasive procedure and patients should be followed carefully for prolonged clinic/subclinic coagulopathy due to plasma exchange.

The ethanolic extract from the fruits of Emblica officinalis Gaertn (Euphorbiaceae) was investigated to evaluate its possible ameliorating effects, on the L-thyroxine (L-T4) induced hyperthyroidism and on hepatic lipid peroxidation in mice. While an increase in serum T3 (triiodothyronine) and T4 (thyroxine) concentrations, and in a thyroid dependent parameter, hepatic glucose 6-phospatase (glu-6-pase) activity was observed in L-T4 (0.5 mg/kg/d) treated animals, simultaneous oral administration of the plant extract at a dose of 250 mg/kg/d (p.o.) for 30 days in hyperthyroid mice reduced T3 and T4 concentrations by 64 and 70% respectively as compared to a standard antithyroid drug, propyl thiouracil (PTU) that decreased the levels of the thyroid hormones by 59 and 40% respectively. The plant extract also maintained nearly normal value of glu-6-pase activity in hyperthyroid mice. The plant extract also decreased hepatic lipid peroxidation (LPO) and increased the superoxide dismutase (SOD) and catalase (CAT) activities in hyperthyroid mice, exhibiting its hepatoprotective nature. Our findings suggest that the test material may potentially ameliorate the hyperthyroidism with an additional hepatoprotective benefit.

The effect of thyroid status on arterial baroreflex function and autonomic contributions to resting blood pressure and heart rate (HR) were evaluated in conscious rats. Rats were rendered hyperthyroid (Hyper) or hypothyroid (Hypo) with triiodothyronine and propylthiouracil treatments, respectively. Euthyroid (Eut), Hyper, and Hypo rats were chronically instrumented to measure mean arterial pressure (MAP), HR, and lumbar sympathetic nerve activity (LSNA). Baroreflex function was evaluated with the use of a logistic function that relates LSNA or HR to MAP during infusion of phenylephrine and sodium nitroprusside. Contributions of the autonomic nervous system to resting MAP and HR were assessed by blocking autonomic outflow with trimethaphan. In Hypo rats, the arterial baroreflex curve for both LSNA and HR was shifted downward. Hypo animals exhibited blunted sympathoexcitatory and tachycardic responses to decreases in MAP. Furthermore, the data suggest that in Hypo rats, the sympathetic influence on HR was predominant and the autonomic contribution to resting MAP was greater than in Eut rats. In Hyper rats, arterial baroreflex function generally was similar to that in Eut rats. The autonomic contribution to resting MAP was not different between Hyper and Eut rats, but predominant parasympathetic influence on HR was exhibited in Hyper rats. The results demonstrate baroreflex control of LSNA and HR is attenuated in Hypo but not Hyper rats. Thyroid status alters the balance of sympathetic to parasympathetic tone in the heart, and the Hypo state increases the autonomic contributions to resting blood pressure.

Ninety-three hyperthyroid patients were treated with 1 dose of iodine-131 (131I) during the past 10 years. Thirty-three were pretreated with propylthiouracil (PTU), 22 with methimazole (MMI), and 38 received no antithyroid drugs (ATD). ATD were discontinued 5-55 days before 131I therapy in three fourths of the cases and more than 4 months before therapy in one fourth of the cases. The frequency of cures in the 3 groups, 6-8 months after radioiodine therapy, was retrospectively studied. The cure rate among those who discontinued PTU for 5-55 days before 131I was significantly reduced (24%), compared with those who discontinued MMI for the same duration (61%) or those who received no ATD (66%). When PTU was discontinued for more than 4 months, the cure rate was similar to those who received no ATD. It is concluded that if ATD are used as initial therapy for hyperthyroidism, then PTU (but not MMI) may reduce the therapeutic efficacy of subsequent 131I. The reduction in cure rate was observed even when PTU was discontinued for as long as 55 days before 131I therapy. To our knowledge, this is the first report to compare, in one study, the effects of pretreatment with PTU and MMI on 131I therapy.

To determine how lipid peroxides and free radical scavengers are changed in the brain of hyper- or hypothyroid rats, we examined the behavior of lipid peroxide and free radical scavengers in the cerebral cortex of aged (1.5 years old) rats that had been made hyper- or hypothyroid by the administration of thyroxine or methimazol for 4 weeks. Concentrations of catalase, Mn-superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased in hyperthyroid rats compared with euthyroid rats. Concentrations of total SOD, Cu,Zn-SOD and GSH-PX were increased but that of Mn-SOD was decreased in hypothyroid animals. There were no differences among hyperthyroid, hypothyroid and euthyroid rats in the levels of coenzymes 9 or 10. The concentration of lipid peroxides, determined indirectly by the measurement of thiobarbituric acid reactants, was decreased in hyperthyroid rats but not in hypothyroid rats when compared with euthyroid animals. These findings suggest that free radicals and lipid peroxides are scavenged to compensate for the changes induced by hyper- or hypothyroidism.

Fifteen patients with thyrotoxicosis were treated with low dose sustained release lithium carbonate 400 mg, combined with carbimazole 40 mg daily, and the therapeutic response was followed over a two week period. This response was compared with that obtained in a similar group of patient treated with carbimazole alone. Li-carbimazole treatment brought about a fall in the mean total serum T4 of 57.4% compared with a drop of 32.8% in patients treated with carbimazole alone. The mean serum T3 fell by 69.4% in the Li-carbimazole group compared with 47.3% in the group treated with carbimazole only. No lithium adverse effects were encountered.