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Open access

Xichang Wang, Xiaochun Teng, Chenyan Li, Yushu Li, Jing Li, Weiping Teng, Zhongyan Shan, and Yaxin Lai

Objective

To conduct a questionnaire survey of the current clinical practice for overt hyperthyroidism in China.

Methods

An online questionnaire survey was conducted in July 2020. The two questionnaires covered 35 and 8 questions about non-pregnancy and pregnancy clinical practice for overt hyperthyroidism, respectively.

Results

One thousand, two hundred fifty-six physicians participated. Chief physicians and associate chief physicians accounted for 58.6% of the participants. Approximately 95.2% of the respondents chose the thyrotropin receptor antibody (TRAb) test to clarify the etiology of thyrotoxicosis, while only 27.0% of them chose radioactive iodine uptake (RAIU). In terms of treatment for non-pregnant patients, anti-thyroid drugs (ATDs) were the first choice, and most of the clinicians chose methimazole. Compared with clinicians in recent studies, Chinese physicians used serum TRAb to diagnose Graves’ disease more commonly, and there were obviously more physicians preferring ATDs. For maternal hyperthyroidism, most physicians preferred propylthiouracil administration before or during the first trimester, which is consistent with the 2016 American Thyroid Association (ATA) guidelines. In terms of the initial ATD dose, monitoring the treatment process, indications for ATD withdrawal and treatment of special cases, the preferences of Chinese physicians were generally consistent with the guidelines.

Conclusion

Chinese physicians can generally follow the ATA guidelines for the diagnosis and treatment of hyperthyroidism. Moreover, there are small differences from foreign studies or the guidelines with respect to particular problems. These findings provide evidence for future clinical research in China.

Open access

Lu Liu, Chunyan Li, Peng Yang, Jian Zhu, Dongmei Gan, Le Bu, Manna Zhang, Chunjun Sheng, Hong Li, and Shen Qu

Alendronate (ALN) is a commonly used drug for the treatment of osteoporosis. Atypical femur fractures (AFFs) have been associated with long-term use of ALN and have recently become the subject of considerable attention as ALN use increases. This meta-analysis aimed to determine the relationship between ALN and AFF. The Embase, PubMed, and Cochrane library databases were searched for relevant studies published before November 6, 2014. Studies clearly reporting the relationship between ALN and AFF were selected for our analysis. From these results, the relationship between ALN and AFF was analyzed. Weighted mean differences were calculated using a random-effects model. Five studies were included in this meta-analysis. The results revealed that the use of ALN will not increase the risk of AFF in short term (P>0.05), but there will be a risk of AFF (P<0.05) with long-term (>5 years) use of ALN. These findings indicate that long-term use of ALN is a risk factor for AFF and that more attention should be paid to the clinical applications of ALN.

Open access

Maria Stelmachowska-Banaś and Izabella Czajka-Oraniec

Immune checkpoint inhibitors (ICIs) belong to a new group of anticancer drugs targeting T-cell proteins involved in the activation of immune response toward malignancies. Their introduction into clinical practice was a milestone in modern cancer treatment. However, the significant advantage of ICIs over conventional chemotherapy in terms of therapeutic efficacy is accompanied by new challenges related to specific side effects. ICI-induced immune system activation could lead to the loss of self-tolerance, presenting as autoimmune inflammation and dysfunction of various tissues and organs. Thus, the typical side effects of ICIs include immune-related adverse events (irAEs), among which endocrine irAEs, affecting numerous endocrine glands, have been commonly recognized. This review aimed to outline the current knowledge regarding ICI-induced endocrine disorders from a clinical perspective. We present updated information on the incidence and clinical development of ICI-induced endocrinopathies, including the most frequent thyroiditis and hypophysitis, the rarely observed insulin-dependent diabetes mellitus and primary adrenal insufficiency, and the recently described cases of hypoparathyroidism and lipodystrophy. Practical guidelines for monitoring, diagnosis, and treatment of ICI-related endocrine toxicities are also offered. Rising awareness of endocrine irAEs among oncologists, endocrinologists, and other health professionals caring for patients receiving ICIs could contribute to better safety and efficacy. As immunotherapy becomes widespread and approved for new types of malignancies, increased incidences of endocrine irAEs are expected in the future.

Open access

Adriano N Cury, Verônica T Meira, Osmar Monte, Marília Marone, Nilza M Scalissi, Cristiane Kochi, Luís E P Calliari, and Carlos A Longui

Background/aims

Treatments for Graves' disease (GD) in children and adolescents include oral antithyroid drugs (ATDs), near total thyroidectomy, and radioactive iodine (RAI). ATDs remain the preferred choice in this age group, but because persistent remission occurs in 30% of cases, RAI is becoming a common option for definitive therapy.

Methods

We performed a review of 65 medical records of GD patients under age 19 years who were followed between 1985 and 2005.

Results

The prevalence of GD was higher in females (3:1) and during puberty (for both genders). If no remission was detected during ATD treatment, RAI was indicated when the following criteria were present: non-compliance, relapse, or side effects that were related to ATDs, large goiter, and long-term use of ATDs. The majority of patients developed hypothyroidism within 6 months after RAI. A progressive higher dose regimen was implemented in the last 10 years of the study period. A second RAI dose was necessary in eight cases. During the follow-up period, three pregnancies occurred. One patient with a thyroid nodule and benign cytology was detected.

Conclusions

RAI therapy is effective and safe in the treatment of GD in children and adolescents.

Open access

Barbara J Boucher

Our knowledge of vitamin D has come a long way since the 100 years it took for doctors to accept, between 1860 and 1890, that both sunlight and cod liver oil (a well-known folk remedy) cured and prevented rickets. Vitamins D2/D3 were discovered exactly a hundred years ago, and over the last 50 years vitamin D has been found to have many effects on virtually all human tissues and not just on bone health, while mechanisms affecting the actions of vitamin D at the cellular level are increasingly understood, but deficiency persists globally. Observational studies in humans have shown that better provision of vitamin D is strongly associated, dose-wise, with reductions in current and future health risks in line with the known actions of vitamin D. Randomised controlled trials, commonly accepted as providing a ‘gold standard’ for assessing the efficacy of new forms of treatment, have frequently failed to provide supportive evidence for the expected health benefits of supplementation. Such RCTs, however, have used designs evolved for testing drugs while vitamin D is a nutrient; the appreciation of this difference is critical to identifying health benefits from existing RCT data and for improving future RCT design. This report aims, therefore, to provide a brief overview of the evidence for a range of non-bony health benefits of vitamin D repletion; to discuss specific aspects of vitamin D biology that can confound RCT design and how to allow for them.

Open access

Kennett Sprogøe, Eva Mortensen, David B Karpf, and Jonathan A Leff

The fundamental challenge of developing a long-acting growth hormone (LAGH) is to create a more convenient growth hormone (GH) dosing profile while retaining the excellent safety, efficacy and tolerability of daily GH. With GH receptors on virtually all cells, replacement therapy should achieve the same tissue distribution and effects of daily (and endogenous) GH while maintaining levels of GH and resulting IGF-1 within the physiologic range. To date, only two LAGHs have gained the approval of either the Food and Drug Administration (FDA) or the European Medicines Agency (EMA); both released unmodified GH, thus presumably replicating distribution and pharmacological actions of daily GH. Other technologies have been applied to create LAGHs, including modifying GH (for example, protein enlargement or albumin binding) such that the resulting analogues possess a longer half-life. Based on these approaches, nearly 20 LAGHs have reached various stages of clinical development. Although most have failed, lessons learned have guided the development of a novel LAGH. TransCon GH is a LAGH prodrug in which GH is transiently bound to an inert methoxy polyethylene glycol (mPEG) carrier. It was designed to achieve the same safety, efficacy and tolerability as daily GH but with more convenient weekly dosing. In phase 2 trials of children and adults with growth hormone deficiency (GHD), similar safety, efficacy and tolerability to daily GH was shown as well as GH and IGF-1 levels within the physiologic range. These promising results support further development of TransCon GH.

Open access

Eric Seidel, Gudrun Walenda, Clemens Messerschmidt, Benedikt Obermayer, Mirko Peitzsch, Paal Wallace, Rohini Bahethi, Taekyeong Yoo, Murim Choi, Petra Schrade, Sebastian Bachmann, Gerhard Liebisch, Graeme Eisenhofer, Dieter Beule, and Ute I Scholl

Mitotane is the only drug approved for the therapy of adrenocortical carcinoma (ACC). Its clinical use is limited by the occurrence of relapse during therapy. To investigate the underlying mechanisms in vitro, we here generated mitotane-resistant cell lines. After long-term pulsed treatment of HAC-15 human adrenocortical carcinoma cells with 70 µM mitotane, we isolated monoclonal cell populations of treated cells and controls and assessed their respective mitotane sensitivities by MTT assay. We performed exome sequencing and electron microscopy, conducted gene expression microarray analysis and determined intracellular lipid concentrations in the presence and absence of mitotane. Clonal cell lines established after pulsed treatment were resistant to mitotane (IC50 of 102.2 ± 7.3 µM (n = 12) vs 39.4 ± 6.2 µM (n = 6) in controls (biological replicates, mean ± s.d., P = 0.0001)). Unlike nonresistant clones, resistant clones maintained normal mitochondrial and nucleolar morphology during mitotane treatment. Resistant clones largely shared structural and single nucleotide variants, suggesting a common cell of origin. Resistance depended, in part, on extracellular lipoproteins and was associated with alterations in intracellular lipid homeostasis, including levels of free cholesterol, as well as decreased steroid production. By gene expression analysis, resistant cells showed profound alterations in pathways including steroid metabolism and transport, apoptosis, cell growth and Wnt signaling. These studies establish an in vitro model of mitotane resistance in ACC and point to underlying molecular mechanisms. They may enable future studies to overcome resistance in vitro and improve ACC treatment in vivo.

Open access

Marek Niedziela

The term 'hyperthyroidism' refers to a form of thyrotoxicosis due to inappropriate high synthesis and secretion of thyroid hormone(s) by the thyroid. The leading cause of hyperthyroidism in adolescents is Graves’ disease (GD); however, one should also consider other potential causes, such as toxic nodular goitre (single or multinodular), and other rare disorders leading to excessive production and release of thyroid hormones. The term 'thyrotoxicosis' refers to a clinical state resulting from inappropriate high thyroid hormone action in tissues, generally due to inappropriate high tissue thyroid hormone levels. Thyrotoxicosis is a condition with multiple aetiologies, manifestations, and potential modes of therapy. By definition, the extrathyroidal sources of excessive amounts of thyroid hormones, such as iatrogenic thyrotoxicosis, factitious ingestion of thyroid hormone, or struma ovarii, do not include hyperthyroidism. The aetiology of hyperthyroidism/and thyrotoxicosis should be determined. Although the diagnosis is apparent based on the clinical presentation and initial biochemical evaluation, additional diagnostic testing is indicated. This testing should include: (1) measurement of thyroid-stimulating hormone receptor (TSHR) antibodies (TRAb); (2) analysis of thyroidal echogenicity and blood flow on ultrasonography; or (3) determination of radioactive iodine uptake (RAIU). A 123I or 99mTc pertechnetate scan is recommended when the clinical presentation suggests toxic nodular goitre. A question arises regarding whether diagnostic workup and treatment (antithyroid drugs, radioiodine, surgery, and others) should be the same in children and adolescents as in adults, as well as whether there are the same goals of treatment in adolescents as in adults, in female patients vs in male patients, and in reproductive or in postreproductive age. In this aspect, different treatment modalities might be preferred to achieve euthyroidism and to avoid potential risks from the treatment. The vast majority of patients with thyroid disorders require life-long treatment; therefore, the collaboration of different specialists is warranted to achieve these goals and improve patients’ quality of life.

Open access

Yuerong Yan, Lili You, Xiaoyi Wang, Zhuo Zhang, Feng Li, Hongshi Wu, Muchao Wu, Jin Zhang, Jiayun Wu, Caixia Chen, Xiaohui Li, Biwen Xia, Mingtong Xu, and Li Yan

Objectives

A variety of factors differed between rural and urban areas may further influence iodine status and thyroid structure. Hence, this study compared iodine nutrition, the prevalence of thyroid goiter, and nodules between rural and urban residents in Guangzhou, a southern coastal city of China.

Methods

A total of 1211 rural residents and 1305 urban residents were enrolled in this cross-sectional study. A questionnaire regarding personal characteristics was administered. Urinary iodine concentration (UIC) was examined. Ultrasonography of the thyroid was performed to evaluate thyroid goiter and nodules. Multiple logistic analysis was used to identify the potential associated factors.

Results

The median UIC was significantly lower in rural residents than in urban residents (120.80 μg/L vs 136.00 μg/L, P < 0.001). Although the coverage rate of iodized salt was much higher in rural residents than in urban residents (99.59% vs 97.29%, P < 0.001), the percentages of seafood intake (8.60% vs 29.29%, P < 0.001), iodine-containing drug consumption (0.33% vs 1.24%, P = 0.011), and iodine contrast medium injection (0.58% vs 1.87%, P = 0.004) were lower in rural residents than in urban residents. Both the prevalence of thyroid goiters and nodules was significantly higher in rural residents than in urban residents (goiter: 8.06% vs 1.20%, P < 0.001; nodules: 61.89% vs 55.04%, P = 0.023). Living in rural areas was associated with thyroid goiter (OR 5.114, 95% CI 2.893–9.040, P < 0.001).

Conclusions

There were differences in iodine nutrition and the prevalence of thyroid goiter and nodules in rural and urban residents in Guangzhou. Differentiated and specialized monitoring is recommended in our area.

Open access

Muthiah Subramanian, Manu Kurian Baby, and Krishna G Seshadri

Antithyroid drugs (ATDs) have been shown to attenuate the effectiveness of radioiodine (radioiodine ablation, RIA) therapy in Graves' disease. We undertook a study to look at the impact of iodine uptakes on the outcome of 131I therapy. To determine the effect of prior ATD use on the duration of time to achieve cure in patients with high vs intermediate uptake Graves' disease who received a fixed dose (15 mCi) of 131I radioiodine. In a retrospective study of patients with Graves' disease, 475 patients who underwent RIA were followed-up on a two-monthly basis with thyroid function tests. Of the 123 patients with a documented preablation RAIU and consistent follow-up it was observed that 40 patients had an intermediate RAIU (10–30%) and 83 subjects had a distinctly increased uptake (>30%). Successful cure was defined as the elimination of thyrotoxicosis in the form of low free thyroxin and rising TSH levels. When a standard dose of 15 mCi 131I was administered, a cure rate of 93% was achieved. The median duration of time to cure (TC) was 129 days. Surprisingly, a direct proportional linear relationship (R 2=0.92) was established between time to cure and radioiodine uptake (TC> 3 0%=172days, TC10 3 0%=105 days, P<0.001). Patients who used ATD medications took a proportionately longer duration to achieve remission (TCNO ATD=102days, TCATD=253days, P<0.001). The effect of prior ATD therapy in delaying remission was amplified in the subset of patients with higher uptakes (TC> 3 0% + ATD=310days, TC> 3 0% + NO ATD=102days, P<0.001) compared to those with the intermediate uptakes (TC10 3 0% + ATD=126 days, TC10 3 0% + NO ATD=99 days, P<0.001). RIA, using a dose of 15 mCi achieved a high cure rate. Higher uptakes predicted longer time to achieve remission, with prior ATD use amplifying this effect.