Thyroid Research最新文献

Background: Graves' disease (GD) is the main cause of hyperthyroidism in women of the fertile age. In pregnant women, the disease should be carefully managed and controlled to prevent maternal and fetal complications. Observational studies provide evidence of the adverse effects of untreated hyperthyroidism in pregnancy and have in more recent years substantiated a risk of teratogenic side effects with the use of antithyroid drugs (ATDs). These findings have challenged the clinical recommendations regarding the choice of treatment when patients become pregnant. To extend observational findings and support future clinical practice, a systematic collection of detailed clinical data in and around pregnancy is needed.

Methods: With the aim of collecting clinical and biochemical data, a Danish multicenter study entitled 'Pregnancy Investigations on Thyroid Disease' (PRETHYR) was initiated in 2021. We here describe the design and methodology of the first study part of PRETHYR. This part focuses on maternal hyperthyroidism and recruits female patients in Denmark with a past or present diagnosis of GD, who become pregnant, as well as women who are treated with ATDs in the pregnancy, irrespective of the underlying etiology. The women are included during clinical management from endocrine hospital departments in Denmark, and study participation includes patient questionnaires in pregnancy and postpartum as well as review of medical records from the mother and the child.

Results: Data collection was initiated on November 1, 2021 and covered all five Danish Regions from March 1, 2022. Consecutive study inclusion will continue, and we here report the first status of inclusion. As of November 1, 2022, a total of 62 women have been included in median pregnancy week 19 (interquartile range (IQR): 10-27) with a median maternal age of 31.4 years (IQR: 28.5-35.1). At inclusion, 26 women (41.9%) reported current use of thyroid medication; ATDs (n = 14), Levothyroxine (n = 12).

Conclusion: This report describes a newly established systematic and nationwide collection of detailed clinical data on pregnant women with hyperthyroidism and their offspring. Considering the course and relatively low prevalence of GD in pregnant women, such nationwide design is essential to establish a sufficiently large cohort.

Background: Leiomyosarcoma (LMS) is a soft tissue malignant tumor that has a predilection to the abdominopelvic and limb smooth muscles. LMS of the thyroid is exceptionally rare. Papillary thyroid cancer (PTC) is the most common thyroid malignancy and originates from the thyroid epithelial layer. To our knowledge, the presence of both tumors in the same patient has not been reported previously.

Case presentation & literature review: A 42-year-old woman presented with a progressively enlarging neck mass for a few months. She underwent left thyroid lobectomy, and the histology showed high-grade primary LMS of the thyroid. She subsequently underwent a complete thyroidectomy, which identified a classical PTC on her right lobe. Our comprehensive literature review identified 39 published cases of primary LMS of the thyroid. The average tumor size was 5.88 cm and occurred more in women. The most common presentation was neck mass, followed by compressive symptoms. Recurrence and metastasis were uncommon at 15% and 10-25%, respectively.

Conclusion: Thyroid LMS is a rare malignancy with a worse prognosis than PTC. A thorough workup must be done to rule out metastasis before labeling it as primary thyroid cancer.

Background: One of the common causes of suboptimal control of thyroid stimulating hormone (TSH) in levothyroxine-treated hypothyroidism is coadministration of proton pump inhibitors (PPIs). Morning administration of pantoprazole has been shown to suppress intragastric pH to a greater extent. We therefore aimed to determine the effect of pantoprazole at different time points of the day on thyroid function test (TFT) in levothyroxine-treated overt primary hypothyroidism.

Methods: In this single centre, hospital based, prospective, two arm cross-over study (AB, BA), participants were randomized into 2 groups based on morning (6:00 am - 7:00 am simultaneously with the scheduled levothyroxine tablet) (group M) and evening (30 min before dinner) intake of 40 mg pantoprazole tablet (group N). After the initial 6 weeks (period 1), a washout period of 1 week for pantoprazole was given, and then both the groups crossed over for another 6 weeks (period 2). Patients were instructed to continue the same brand of levothyroxine tablet at empty stomach 1-hour before breakfast. Serum TSH was measured at baseline, week 6, and week 13.

Results: Data from 30 patients, who completed the study with 100% compliance, were analysed. Mean TSH values of the study participants were significantly higher both at week 6 and week 13 compared to the baseline. Mean baseline serum TSH concentrations for groups M and N were 2.70 (± 1.36), and 2.20 (± 1.06) µlU/mL, respectively. Mean serum TSH concentrations at the end periods 1 and 2 for group M were 3.78 (± 4.29), and 3.76 (± 2.77) while the levels in group N were 3.30 (± 1.90), and 4.53 (± 4.590) µlU/mL, respectively. There was a significant rise in serum TSH concentration across periods 1 and 2 in both the groups (F_{2, 58} = 3.87, p = 0.03). Within group changes in TSH across periods 1 and 2 were not statistically significant. Similarly difference in TSH between the groups, either at 6 weeks or at 13 weeks, were also not statistically significant.

Conclusions: Concomitant use of pantoprazole, even for 6 weeks, leads to significant elevation in serum TSH in levothyroxine-treated patients who are biochemically euthyroid, irrespective of timing of pantoprazole intake. Early morning and night-time administration of pantoprazole have similar effect on TFT in these patients.

Thyroid cancer is considered as one of the most prevalent cancers in the world. Some pesticides can play a role as a potentially important risk factor in thyroid cancer by affecting thyroid morphology and thyroid hormone homeostasis. The aim of present study was to systematically review the available epidemiological evidence for human exposure to pesticides and thyroid cancer. Articles were searched in PubMed, Scopus and Web of Science by suitable keywords from January 2000 to May 2021. Standard techniques for systematic reviews were followed in the current study and results reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Based on the inclusion and exclusion criteria, finally seven studies including four cohort studies and three case-control studies were reviewed. Organochlorines (OCPs) in more cases, Organophosphates (OPs) and Carbamates insecticides, herbicides and fungicides were the studied pesticides. Inconsistent results were reported in the surveyed articles on the OCPs. Two articles on the Carbamates (Carbaryl and Mancozeb) showed consistently an inverse association between exposure and thyroid cancer. Increased risk of thyroid cancer due to the exposure to the Malathion was reported in one article on the OPs. Due to the limited current knowledge about the effect of pesticides on thyroid cancer in humans, human health policies must be implemented to control individual's exposure to chemicals through using of botanical pesticides in agricultural. Also, more studies must be done to fill this gap of knowledge.

Background: Ultrasound-based classification systems allow stratification of thyroid nodules to recommend fine-needle aspiration (FNA) based on their malignancy risk. However, these have discrepancies that may have an impact in thyroid cancer detection. We aimed to compare European Thyroid Association (EU-TIRADS) and American College of Radiology (ACR TI-RADS), in terms of FNA indication and diagnostic performance.

Methods: Retrospective study of 665 thyroid nodules from 598 patients who underwent ultrasound and fine-needle aspiration at a tertiary-care institution between January 1^st of 2016 and July 31^st of 2019. Based on their sonographic features they were classified according to the EU-TIRADS and ACR TI-RADS classification and then their cytological results were obtained. Differences in FNA indications according to these two classifications were analysed. In patients who underwent surgical removal of the nodules, the final pathological diagnosis was obtained.

Results: A statistically significant association was found between EU-TIRADS and ACR TI-RADS classification systems (p < 0.001). ACR TI-RADS allowed greatest reduction in FNA performed (32% vs 24.5%). A different risk category was obtained in 174 (26.1%) nodules, mostly higher with EU-TIRADS. The indication to FNA changed in 54 (8.1%) nodules (49 only indicated following EU-TIRADS recommendations), of which 4 had Bethesda IV and 5 had Bethesda III cytology. The FNA indication in a higher number of nodules using EU-TIRADS was due to difference in the dimensional threshold for FNA on low-risk nodules; to the fact that hypoechogenicity in a mixed nodule ascribes it moderate risk, while using ACR TI-RADS it would only be considered of low risk, and to the use of isolated sonographic features, namely marked hypoechogenicity, microcalcifications and irregular margins, to automatically categorize a nodules as high risk in EU-TIRADS, while ACR TI-RADS requires a group of potentially suspicious features to consider a nodule of high risk. The analysis of pathology proven nodules revealed equally good sensitivity of both systems in the detection of malignancy, but weak specificity, slightly greater with ACR TI-RADS (27.1% vs 18.6%).

Conclusions: The EU-TIRADS and ACR TI-RADS are both suitable to assess thyroid nodules and through risk stratification avoid unnecessary FNA. FNA was less performed using ACR TI-RADS, which was slightly more efficiency in excluding malignancy.

Background: Thyrotoxic periodic paralysis (TPP) is a rare condition characterized by muscle paralysis, thyrotoxicosis, and hypokalemia. It presents with paralysis of both proximal and distal musculature in upper and lower limbs and may affect respiratory musculature and the cardiac conduction system. Early diagnosis is essential, as the condition is potentially reversible by oral or intravenous potassium treatment, leading to rapid resolution without lasting weakness. Overlooking the diagnosis may result in respiratory failure and cardiac arrhythmias including QT prolongation, Torsades de points, and ventricular arrhythmias.

Case presentation: A 19-year-old Caucasian man was admitted acutely with paralysis in upper and lower limbs and tachycardia. Over several months, he had experienced anxiousness, sweating more than usual, had daily palpitations, shortness of breath on exertion, and loose stools, and had lost 21 kg over the last year. Initial blood gas showed very low potassium of 1.4 mM, and blood tests showed decreased Thyroid-stimulating hormone (TSH) < 0.01 × 10^- 3 IU/L, elevated free thyroxine (fT4) of 63.5 pM (reference interval (RI): 12.0-22.0 pM), and elevated total triiodothyronine (T3) of 8.2 nM (RI: 1.0-2.6 nM). He was diagnosed with TPP and treated with liquid oral potassium chloride (30 mmol every 30 minutes) and propylthiouracil (initial dose of 400 mg followed by 200 mg three times daily). TSH-receptor antibodies (TRAB) and thyroid-peroxidase antibodies (TPO-ab) were highly elevated. Thyroid ultrasound showed a normal-sized gland and color Doppler sonography showed increased vascularity throughout the gland, compatible with Graves' disease. He was discharged on day 4 with a normal potassium level and followed in the outpatient clinic where he received standard care for Graves' disease. Genetic testing using whole-genome sequencing found no genetic variants in genes previously associated with TPP.

Conclusion: TPP is very rare in Caucasians but more often affects young men in East Asian populations. The case presents a Caucasian man with TPP where genetic testing of CACNA1S, KCNJ18, SCN4A, KCNJ2, KCNE3, and ABCC8 shows no pathogenic variants in genes previously associated with TPP.

Background: The thyroid gland is an uncommon site for metastatic deposits from non-thyroid malignancies, occurring in only 1.4 - 3% of surgical specimens where malignancy is suspected. It is even rarer for the source of thyroid metastases to be of colorectal origin. In most cases reported, colorectal metastases in the thyroid occurs many years later after the primary colorectal cancer has been diagnosed and treated. In this unique case, a primary sigmoid carcinoma metastasised to the thyroid gland and presented synchronously as a thyroid nodule.

Case presentation: We describe a case of a 64-year-old Caucasian woman who presented with clinical features of metastatic cancer of unknown origin. Her medical history included underlying hyperthyroidism. She had a large pelvic mass adjacent to the sigmoid colon, a left lower lobe lung mass and a suspicious nodule in the left thyroid lobe. A fine-needle aspiration biopsy of the thyroid nodule was performed, which remarkably showed malignant cells originating from primary colorectal cancer on immunohistochemical staining. The patient was managed with palliative chemotherapy given the poor prognosis due to disseminated colorectal malignancy.

Conclusions: Colorectal adenocarcinoma metastases can rarely present as a metastatic thyroid nodule. Fine-needle aspiration should be performed in suspicious thyroid nodules and may be the least invasive way of identifying a metastatic colorectal or other non-thyroidal malignancy in patients presenting with an unknown primary. The pathologist should be vigilant to this possibility and specific immunohistochemical markers should be used to ensure accurate diagnosis. In thyroid metastases, the prognosis is ultimately determined by the primary tumour but thyroidectomy still has a role in alleviating compressive symptoms and can potentially improve survival in selected cases.

Background: Thyroid hormones are key determinants of health and well-being. Normal thyroid function is defined according to the standard 95% confidence interval of the disease-free population. Such standard laboratory reference intervals are widely applied in research and clinical practice, irrespective of age. However, thyroid hormones vary with age and current reference intervals may not be appropriate across all age groups. In this review, we summarize the recent literature on age-related variation in thyroid function and discuss important implications of such variation for research and clinical practice.

Main text: There is now substantial evidence that normal thyroid status changes with age throughout the course of life. Thyroid stimulating hormone (TSH) concentrations are higher at the extremes of life and show a U-shaped longitudinal trend in iodine sufficient Caucasian populations. Free triiodothyronine (FT3) levels fall with age and appear to play a role in pubertal development, during which it shows a strong relationship with fat mass. Furthermore, the aging process exerts differential effects on the health consequences of thyroid hormone variations. Older individuals with declining thyroid function appear to have survival advantages compared to individuals with normal or high-normal thyroid function. In contrast younger or middle-aged individuals with low-normal thyroid function suffer an increased risk of adverse cardiovascular and metabolic outcomes while those with high-normal function have adverse bone outcomes including osteoporosis and fractures.

Conclusion: Thyroid hormone reference intervals have differential effects across age groups. Current reference ranges could potentially lead to inappropriate treatment in older individuals but on the other hand could result in missed opportunities for risk factor modification in the younger and middle-aged groups. Further studies are now needed to determine the validity of age-appropriate reference intervals and to understand the impact of thyroid hormone variations in younger individuals.