European Thyroid Journal最新文献

Objective: To investigate the prevalence of endogenous normal thyroid function 3 years after hemithyroidectomy for low-risk differentiated thyroid cancer if a postoperative thyroid-stimulating hormone increase up to 4 mIU/L is accepted.

Method: A retrospective review of a total of 162 Eastern Danish patients was conducted. Patients were initially followed up without levothyroxine treatment after hemithyroidectomy for differentiated thyroid cancer if thyroid-stimulating hormone was below 4 mIU/L, in accordance with the Danish treatment guideline. Patients' hospital charts were reviewed, and data on the initiation of levothyroxine treatment, pre- and postoperative thyroid-stimulating hormone, recurrence, and remnant lobe nodularity were collected.

Results: A total of 143/162 (88%) did not take levothyroxine before hemithyroidectomy, with a median (interquartile range) age of 53 (43-65) years; 80% were women. During follow-up, the prevalence of endogenous normal thyroid function gradually decreased to 80, 69, and 66% after 1, 2, and 3 years. Concomitantly, hypothyroidism developed with thyroid-stimulating hormone >4.0 mIU/L in 20, 31, and 34% of patients, who were replaced with levothyroxine. In patients not on levothyroxine, TSH was significantly increased within the normal range 1, 2, and 3 years after hemithyroidectomy for DTC (P < 0.0001). 4/143 (3%) had completion thyroidectomies due to growth of preexisting nodules; no patient had a recurrence.

Conclusion: One-third of differentiated thyroid cancer patients require levothyroxine treatment 3 years after hemithyroidectomy if postoperative thyroid-stimulating hormone levels up to 4 mIU/L are accepted. Avoidance of levothyroxine treatment happens at the expense of a significant increase in thyroid-stimulating hormone levels.

Background: Accurate assessment of thyroid status is essential for maternal and fetal management during pregnancy. This study measured human chorionic gonadotropin (HCG), albumin, and thyroxine-binding globulin (TBG) levels during pregnancy to clarify how their fluctuations affect thyroid hormone measurements by two immunoassays - chemiluminescent immunoassay (CLIA) and electrochemiluminescence immunoassay (ECLIA).

Method: Free thyroxine (FT4), free triiodothyronine (FT3), and thyrotropin (TSH) levels were measured in 897 serum samples obtained from 604 pregnant women by two immunoassays. In 176 cases selected from each trimester, thyroid hormone concentrations were also measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following ultrafiltration. Associations between thyroid function and relevant determinants were evaluated using multivariable regression analysis.

Results: Throughout pregnancy, 64 samples (7.13%) measured by CLIA and 241 samples (26.87%) measured by ECLIA had TSH concentrations less than 0.01 mIU/L. The upper limits of thyroid hormone concentrations were observed between 8 and 15 weeks of gestation. In late pregnancy, the lower limits of thyroid hormone concentrations determined by the immunoassays fell below the lower limits of the nonpregnant reference intervals. Thyroid hormone concentrations measured by immunoassay correlated significantly with LC-MS/MS concentrations. In multivariable regression analysis, only HCG was significantly associated with immunoassay measurements of thyroid hormones. Under conditions of TBG ≥31 μg/mL, women with albumin <3.8 g/dL had lower thyroid hormone concentrations than those with ≥3.8 g/dL.

Conclusion: Gestational thyroid hormone concentrations appear to be influenced by HCG levels. As with LC-MS/MS use, immunoassay measurements may vary with albumin and TBG concentrations. These findings underscore the need to consider such fluctuations when interpreting thyroid function tests in pregnant women.

Objective: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine thyroid tumor, with only 30 new patients annually in the Netherlands. PET imaging provides information on distant metastases, after which tyrosine kinase inhibitors (TKIs) may be initiated. The rarity of the disease impedes large controlled trials, and therefore the challenge of selecting the best TKI and PET tracer for individual patients persists. To explore whether an in vitro model could be developed to guide the selection of appropriate PET tracers or TKI therapies in the future, we aimed to establish an MTC organoid model for the first time.

Methods: Dispersed cells from MTC biopsies were suspended in Matrigel, allowing organoid formation. The self-renewal potential was tested by dissociation and re-plating cells and determining organoid-forming efficiency. MTC-specific gene and protein expression were characterized by qPCR and immunofluorescent staining. Moreover, MTC-organoids (MTOs) were exposed to TKIs and PET tracers in proof-of-principle experiments.

Results: Ten MTC biopsies were processed and successfully cultured as MTOs. MTC-derived cells showed self-renewal potency for several passages, indicating the presence of putative stem cells. Gene and protein expression of MTC-specific markers in tissue and MTOs, and function measurements showed the production of calcitonin and CEA. Interpretation of the preliminary experiments with TKIs and PET tracers was limited by sample size but demonstrates their future potential.

Conclusion: We were able to culture MTC organoids that resemble the original tissue in gene expression, protein expression, and functionality. However, international, multi-center studies are required to meet the standards for future clinical applications.

Objective: At present, total thyroidectomy and central neck dissection are the surgical approaches recommended for the initial treatment of medullary thyroid cancer (MTC) independently of the size, number of tumor foci, age of patients, and other demographic and clinico-pathological parameters. The aims of the present study were to assess the prevalence of multifocality in hereditary (hMTC) and sporadic (sMTC) patients and to correlate the presence of multifocality with clinico-pathological parameters to provide a proof of concept that lobectomy can be safely performed in selected cases.

Methods: We analyzed the epidemiological, pathological, and clinical data of 389 MTC (311 sMTC and 78 hMTC) diagnosed in our center from 2005 to 2018.

Results: Multifocality was found in 89/389 cases (22.9%), (45/311 (14.5%) sMTC and 44/78 (56.4%) hMTC). Bilaterality was detected in 27/311 (8.7%) of all sMTC, particularly in 27/45 (60%) of multifocal ones, and in 44/78 of hMTC (56.4%). Multifocality was correlated with a more aggressive phenotype in both sMTC and hMTC, and the multivariate analysis showed that it was statistically and independently associated with tumoral extrathyroidal extension and N1 status in sMTC and with N1 status and persistent disease in hMTC. However, none of the presurgical factors could predict the presence of both multifocality and bilaterality.

Conclusions: Our study demonstrated that the rarity of multifocality and, in particular, of bilaterality, in sMTC represents the proof of concept for considering a more conservative surgical approach in selected sMTC cases. This approach cannot be considered in hMTC due to the high prevalence of multifocal and bilateral cases.

Background: Globally prevalent, thyroid diseases are linked to environmental factors such as air pollution. This study examines the link between particulate matter (PM)1 exposure and thyroid disease rates in China.

Methods: We analyzed data from 73,900 adults across 31 Chinese provinces, using a high-resolution spatial-temporal extremity tree model to estimate PM1 and PM2.5 levels, and thyroid function tests to assess disease prevalence. Multivariate-adjusted ORs evaluated PM1's link to thyroid disease. This cross-sectional study is adept at identifying associations but cannot establish causality due to its single-time data collection limitation.

Results: Higher PM1 level exposure was significantly linked to an increased prevalence of thyroid diseases, including overt hypothyroidism, autoimmune thyroiditis (AIT), and TgAb positivity. A linear dose-response relationship was observed between PM1 concentration and both AIT and TgAb positivity. The study also revealed a significant association between PM1 exposure and autoimmune overt hypothyroidism, suggesting that thyroid dysfunction may be primarily mediated through autoimmune mechanisms. In addition, iodine status significantly influenced PM1's effects, with lower levels enhancing susceptibility to thyroid issues. Furthermore, every 1% increase in the PM1/PM2.5 ratio was related to the prevalence of overt hypothyroidism (OR = 1.03; 95% CI: 1.03-1.04) and subclinical hypothyroidism (OR = 1.03; 95% CI: 1.03-1.04).

Conclusions: PM1 exposure is associated with thyroid diseases, particularly AIT and TgAb positivity, with iodine status playing a modifying role. PM1 may be a key factor in PM2.5-related thyroid disease risk. Further prospective cohort studies are warranted to validate these findings.

Objective: To evaluate differences in the presentation, diagnostic/therapeutic approaches, and outcome of differentiated thyroid cancer (DTC) in an Italian and a Dutch referral centre.

Methods: We retrospectively included 919 patients (586 Italian, 333 Dutch), and compared the two cohorts as a whole and according to ATA risk classes. Dynamic risk stratification (DRS) and Kaplan-Meier curves were used to compare progression-free survival (PFS) and disease-specific survival (DSS).

Results: Several differences (P < 0.001) were found in clinicopathological features and in diagnostic/therapeutic modalities. The Dutch cohort had a higher age at diagnosis, a higher number of patients presenting with metastatic disease, and patients with stage III/IV. Most Italian patients showed a low/intermediate ATA risk, while high-risk patients represented half of the Dutch cohort. The Dutch cohort received a more intensive first treatment and more additional treatments during follow-up (i.e. surgery, radiotherapy, and systemic treatments). DRS analysis showed comparable excellent and biochemical incomplete responses, while the Dutch cohort had a lower rate of indeterminate and a higher rate of structural incomplete responses (P < 0.001). The Dutch cohort had a significantly worse 5-year PFS, and TC-related mortality was 10 and 1% for the Dutch and Italian cohorts, respectively, in line with the higher rate of advanced disease at presentation, with DSS still excellent for both.

Conclusion: Data reported in the present comparison between two European countries highlight a different prevalence, presentation, and outcome of DTC, likely due to variabilities in healthcare systems, iodine nutritional status, and diagnostic and treatment approaches.

Primary congenital hypothyroidism (CH) is the most common endocrinopathy of developmental age. In recent years, several studies from different countries have reported a significant increase in CH incidence detected by newborn screening programs, primarily 'mild' forms of CH with gland in situ (GIS). However, more than one-third of affected children with GIS present transient CH and recover endogenous thyroid function in early childhood, permitting the cessation of levothyroxine treatment by the end of the third year of life. Therefore, in CH patients with GIS, a clinical and biochemical reassessment is needed to determine whether the hypothyroidism is transient or permanent and to search for the underlying causes of the thyroid defect. Despite the presence of consensus guidelines for the management of CH in pediatric age, the screening strategy and management of the disease, especially at re-evaluation, differ significantly between centers and present some points of discussion. The following review summarizes the main pathophysiological mechanisms of transient and permanent forms of CH, also underlining the importance of new genetic tools in order to guarantee each patient the best diagnostic and therapeutic approach.

Background: Pediatric differentiated thyroid carcinoma (pedDTC) is rare but increasingly prevalent, requiring multidisciplinary care to ensure optimal outcomes. In 2021, the pediatric national reference program of the German Malignant Endocrine Tumor (MET) registry was established to standardize the management of pedDTC, with a particular focus on radioactive iodine (RAI) use and minimizing treatment variability.

Methods: This study evaluated the program's first 3.5 years, including 43 inquiries concerning 39 patients with confirmed or suspected pedDTC. A weekly national expert tumor board provided individualized recommendations based on multidisciplinary input and risk stratification. Data were analyzed for demographic trends, therapeutic decisions, and short-term outcomes.

Results: Among 34 patients with confirmed pedDTC, RAI use was reduced or omitted in 70.6% of cases, particularly among low-risk patients, in alignment with the American Thyroid Association 2015 guidelines. Surgical strategies were modified in 61.5% of cases to balance disease control with treatment-related morbidity. No systemic medical therapy was recommended during initial management. At a mean follow-up of 0.7 years, all patients were alive; persistent disease was observed in 15.4%.

Conclusions: The national reference program has successfully introduced a structured, individualized approach to the management of pedDTC in Germany. Ongoing data collection and longer follow-up will be essential to assess the long-term impact of this centralized, risk-adapted model.

Sodium levothyroxine (LT4) as a monotherapy represents the mainstay of treatment of hypothyroidism, and its use has increased over time. Nevertheless, it faces several potential barriers in its 'real life' utilization, and hence its clinical effectiveness may be marred. This is suggested by the frequent situation of patients failing to reach the therapeutic goals of symptom relief and serum TSH control. Thus, an expert task force was approved by the Guidelines Board of the European Thyroid Association to examine the available data and to formulate recommendations based on the available evidence and the experts' deduction. The task force provides a body of suggestions to optimize the levothyroxine treatment in monotherapy, considering the key point in the individualization of treatment. Furthermore, the nutritional, pharmacological and pathological factors, potentially leading to the increased need for levothyroxine, are discussed, with a specific focus on the use of liquid and softgel formulations of the hormone.

Background: To account for pregnancy-specific changes in thyroid physiology, international guidelines recommend the use of trimester-specific reference intervals. However, the pragmatic division in trimesters does not necessarily align with the changes in thyroid physiology. While the goal of treating gestational thyroid dysfunction is to prevent thyroid hormone-mediated adverse events, it remains unclear which method of standardizing to gestational age, if any, is most effective in identifying individuals at higher risk of adverse pregnancy events.

Methods: We included 5,675 women participating in a population-based prospective cohort with data on thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroperoxidase antibodies (TPOAbs) during early pregnancy (median: 13.2 weeks, 95% range: 9.8-17.6). We studied the association of TSH and FT4 with pre-eclampsia, premature delivery, birth weight and offspring IQ with or without full gestational age standardization of TSH and FT4 using multivariable regression models.

Results: There was a positive association of gestational age at blood sampling with TSH (difference in mean TSH: +9.6%; P < 0.001) and a negative association with FT4 (difference in mean FT4: -20.2%; P < 0.001). Standardizing TSH to gestational age led to reclassification of 36 women as having normal TSH (9.9%) and 27 as having abnormal TSH (0.5%). For FT4, 62 women were reclassified as having normal FT4 (20.3%) and 57 as having abnormal FT4 (1.1%). Standardization of TSH and FT4 concentrations led to an attenuation of the associations with any outcome of up to 71% as compared to non-standardized TSH or FT4.

Conclusions: Full standardization of TSH and FT4 to gestational age either does not affect or weakens their associations with clinical outcomes, suggesting that accounting for gestational age offers no benefit with regard to identifying high-risk thyroid dysfunction during early pregnancy.