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Muthiah Subramanian Department of General Medicine, TB and Pulmonary Medicine, Endocrinology, Sri Ramachandra University, 1 Ramachandra Nagar, Porur, Chennai 600116, India

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Manu Kurian Baby Department of General Medicine, TB and Pulmonary Medicine, Endocrinology, Sri Ramachandra University, 1 Ramachandra Nagar, Porur, Chennai 600116, India

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Krishna G Seshadri Department of General Medicine, TB and Pulmonary Medicine, Endocrinology, Sri Ramachandra University, 1 Ramachandra Nagar, Porur, Chennai 600116, India

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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.

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Marek Niedziela Department of Pediatric Endocrinology and Rheumatology, Institute of Pediatrics, Karol Jonscher’s Clinical Hospital, Poznan University of Medical Sciences, Poznan, Poland

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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.

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Yuerong Yan Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Lili You Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Xiaoyi Wang Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Zhuo Zhang Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Feng Li Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Hongshi Wu Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Muchao Wu Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Jin Zhang Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Jiayun Wu Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Caixia Chen Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Xiaohui Li Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Biwen Xia Department of Endocrinology, The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

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Mingtong Xu Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Li Yan Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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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
Melinda Kertész Department of Medicine and Nephrology-Diabetes Centre, Medical School, University of Pécs, Pécs, Baranya, Hungary

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Szilárd Kun Department of Medicine and Nephrology-Diabetes Centre, Medical School, University of Pécs, Pécs, Baranya, Hungary

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Eszter Sélley Department of Medicine and Nephrology-Diabetes Centre, Medical School, University of Pécs, Pécs, Baranya, Hungary

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Zsuzsanna Nagy Department of Medicine and Nephrology-Diabetes Centre, Medical School, University of Pécs, Pécs, Baranya, Hungary

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Tamás Kőszegi Department of Laboratory Medicine, Medical School, University of Pécs, Pécs, Baranya, Hungary

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István Wittmann Department of Medicine and Nephrology-Diabetes Centre, Medical School, University of Pécs, Pécs, Baranya, Hungary

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Background

Type 2 diabetes is characterized, beyond the insulin resistance, by polyhormonal resistance. Thyroid hormonal resistance has not yet been described in this population of patients. Metformin is used to decrease insulin resistance, and at present, it is assumed to influence the effect of triiodothyronine, as well.

Methods

In this open-label, pilot, hypothesis-generating, follow-up study, 21 patients were included; all of them were euthyroid with drug naïve, newly diagnosed type 2 diabetes. Before and after 4 weeks of metformin therapy, fructosamine, homeostasis model assessment for insulin resistance (HOMA-IR), thyroid hormones, T3/T4 ratio, and TSH, as well as blood pressure and heart rate using ambulatory blood pressure monitor were measured. We also conducted an in vitro study to investigate the possible mechanisms of T3 resistance, assessing T3-induced Akt phosphorylation among normal (5 mM) and high (25 mM) glucose levels with or without metformin treatment in a human embryonal kidney cell line.

Results

Metformin decreased the level of T3 (P < 0.001), the ratio of T3/T4 (P = 0.038), fructosamine (P = 0.008) and HOMA-IR (P = 0.022). All these changes were accompanied by an unchanged TSH, T4, triglyceride, plasma glucose, bodyweight, blood pressure, and heart rate. In our in vitro study, T3-induced Akt phosphorylation decreased in cells grown in 25 mM glucose medium compared to those in 5 mM. Metformin could not reverse this effect.

Conclusion

Metformin seems to improve T3 sensitivity in the cardiovascular system in euthyroid, type 2 diabetic patients, the mechanism of which may be supracellular.

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Satoshi Higuchi Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan

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Hideki Ota Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Advanced MRI Collaboration Research, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Yuta Tezuka Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Radiology, The University of British Columbia, Vancouver, Canada

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Kazumasa Seiji Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan

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Hidenobu Takagi Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Radiology, The University of British Columbia, Vancouver, Canada

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Jongmin Lee Department of Radiology, School of Medicine, Kyungpook National University, Daegu, Korea

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Yi-Wei Lee Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

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Kei Omata Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Radiology, The University of British Columbia, Vancouver, Canada

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Yoshikiyo Ono Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Radiology, The University of British Columbia, Vancouver, Canada

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Ryo Morimoto Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan

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Masataka Kudo Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan

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Fumitoshi Satoh Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Kei Takase Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan

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Objectives

This study compared cardiac function, morphology, and tissue characteristics between two common subtypes of primary aldosteronism (PA) using a 3T MR scanner.

Design

A retrospective, single-center, observational study.

Methods

We retrospectively reviewed 143 consecutive patients with PA, who underwent both adrenal venous sampling and cardiac magnetic resonance. We acquired cine, late gadolinium enhancement, and pre- and postcontrast myocardial T1-mapping images.

Results

PA was diagnosed as unilateral aldosterone-producing adenoma (APA) in 70 patients and bilateral hyperaldosteronism (BHA) in 73. The APA group showed significantly higher plasma aldosterone concentration (PAC) and aldosterone to renin rate (ARR) than the BHA group. After controlling for age, sex, antihypertensive drugs, systolic and diastolic blood pressure, and disease duration, the parameters independently associated with APA were: left ventricular end-diastolic volume index (EDVI: adjusted odds ratio (aOR) = 1.06 (95% CI: 1.030–1.096), P < 0.01), end-systolic volume index (ESVI: 1.06 (1.017–1.113), P < 0.01), stroke index (SI: 1.07 (1.020–1.121), P < 0.01), cardiac index (CI: 1.001 (1.000–1.001), P < 0.01), and native T1 (1.01 (1.000–1.019), P = 0.038). Weak positive correlations were found between PAC and EDVI (R = 0.28, P < 0.01), ESVI (0.26, P < 0.01), and SI (0.18, P = 0.03); and between ARR and EDVI (0.25, P < 0.01), ESVI (0.24, P < 0.01), and native T1 (0.17, P = 0.047).

Conclusions

APA is associated with greater LV volumetric parameters and higher native T1 values, suggesting a higher risk of volume overload and myocardial damage.

Open access
Riying Liang Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China
Department of Ultrasound, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

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Meijun Wang Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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Chang Fu Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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Hua Liang Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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Hongrong Deng Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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Ying Tan Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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Fen Xu Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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Mengyin Cai Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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Background:

Obesity is associated with the development and progression of chronic kidney disease. Emerging evidence suggests that glucagon-like peptide-1 receptor agonist could reduce renal damage and albuminuria. Sirtuin 1 (SIRT1) was considered as a crucial regulator in metabolism-related kidney disease. Herein, the role of SIRT1 in liraglutide-ameliorated high-fat diet (HFD)-induced kidney injury was illustrated.

Methods:

Male C57BL/6 mice were fed HFD for 20 weeks to induce kidney injury that was then treated with liraglutide for 8 weeks to estimate its protective effect on the kidney. Also, the mechanism of the drug in SV40 MES 13 (SV40) mouse mesangial cells was elucidated.

Results:

Liraglutide treatment ameliorated HFD-induced metabolic disorders, including hyperglycemia, increasing body weight, and insulin resistance. In addition, kidney weight, urine albumin-to-creatinine, and kidney morphological changes such as vacuolated tubules, glomerulomegaly, thickened glomerular basement membrane, and tubulointerstitial fibrosis were also significantly ameliorated. Furthermore, apoptotic cells and apoptosis markers were downregulated in the kidney of liraglutide-treated mice. In addition, the expression of SIRT1 protein was upregulated, whereas thioredoxin-interacting protein (TXNIP), which serves as a mediator of oxidative stress and apoptosis in metabolism disease, was downregulated by liraglutide. In SV40 cells, the effect of liraglutide on reversing the upregulation of cleaved caspase-3 induced by high glucose (30 mM) was hampered when SIRT1 was knocked down; also, the downregulation of TXNIP by liraglutide was blocked.

Conclusions:

Liraglutide might have a beneficial effect on metabolism-related kidney damage by inhibiting apoptosis via activation of SIRT1 and suppression of TXNIP pathway.

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Guido Zavatta Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

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Bart L Clarke Mayo Clinic, Rochester, Minnesota, USA

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The first adjunctive hormone therapy for chronic hypoparathyroidism, recombinant human parathyroid hormone (1–84) (rhPTH(1–84)) was approved by the FDA in January 2015. Since the approval of rhPTH(1–84), growing interest has developed in other agents to treat this disorder in both the scientific community and among pharmaceutical companies. For several reasons, conventional therapy with calcium and activated vitamin D supplementation, magnesium supplementation as needed, and occasionally thiazide-type diuretic therapy remains the mainstay of treatment, while endocrinologists and patients are constantly challenged by limitations of conventional treatment. Serum calcium fluctuations, increased urinary calcium, hyperphosphatemia, and a constellation of symptoms that limit mental and physical functioning are frequently associated with conventional therapy. Understanding how conventional treatment and hormone therapy work in terms of pharmacokinetics and pharmacodynamics is key to effectively managing chronic hypoparathyroidism. Multiple questions remain regarding the effectiveness of PTH adjunctive therapy in preventing or slowing the onset and progression of the classical complications of hypoparathyroidism, such as chronic kidney disease, calcium-containing kidney stones, cataracts, or basal ganglia calcification. Several studies point toward an improvement in the quality of life during replacement therapy. This review will discuss current clinical and research challenges posed by treatment of chronic hypoparathyroidism.

Key points:

  • Conventional therapy with calcium and activated forms of vitamin D are currently the mainstays of treatment for most patients with chronic hypoparathyroidism.

  • Hormone therapy can be administered through FDA-approved once-daily rhPTH(1–84), or off-label multiple-daily injections of teriparatide. The former is the only FDA-approved drug, with safety and efficacy supported by a randomized placebo-controlled trial and open-label long-term extension trial data.

  • Twice-daily teriparatide has been used in children safely for up to 10 years.

  • New pharmacological options that replace the deficient hormone wi ll likely be available within the next few years.

Open access
Lili Liu Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China

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Zhuo Shao Department of General Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, Shanghai, China

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Ying Xia Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China

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Jiabi Qin Department of Epidemiology & Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China

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Yang Xiao Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China

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Zhiguang Zhou Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China

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Zubing Mei Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Objective

Combined treatment with an incretin-based drug, such as a glucagon-like peptide 1 receptor agonist (GLP-1 RA) or a dipeptidyl peptidase-4 (DPP-4) inhibitor, and basal insulin is a new strategy for improving glucose control in type 1 diabetes mellitus (T1DM). We performed a meta-analysis to assess the effect of this combined treatment on glycaemic control, insulin dose, severe hypoglycaemia, weight gain and gastrointestinal side effects in T1DM patients.

Methods

We searched PubMed, EMBASE and the Cochrane Library for relevant studies published before July 16, 2018. The primary outcome was glycosylated haemoglobin (HbA1c). Secondary outcomes included total daily insulin dose, body weight, severe hypoglycaemia and gastrointestinal side effects.

Results

Nine randomized controlled trials (RCTs) involving 2389 patients were ultimately included in the meta-analysis. The pooled data suggested that incretin-based therapy was associated with a reduction in HbA1c levels (weighted mean difference (WMD) −0.17%, 95% confidence interval (CI) −0.24 to −0.11, P < 0.001), total daily insulin dose (WMD −5.53 IU/day, 95% CI −8.89 to −2.17, P = 0.001) and body weight (WMD −3.24 kg, 95% CI −4.43 to −2.04, P < 0.001). Incretins did not increase the risk of severe hypoglycaemia (odds ratio (OR) 0.83, 95% CI 0.60–1.16, P = 0.287) but increased the occurrence of gastrointestinal side effects (OR 3.46, 95% CI 2.20–5.45, P < 0.001).

Conclusions

In T1DM patients, GLP-1 RAs, but not DPP-4 inhibitors, combined with insulin appear to be an effective therapy but may increase the occurrence of gastrointestinal side effects.

Open access
Matilde Calanchini Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
Endocrinology & Metabolism Unit, CTO A. Alesini Hospital ASL Roma 2, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy

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Michael Tadman Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, Oxford, UK

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Jesper Krogh Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, Oxford, UK

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Andrea Fabbri Endocrinology & Metabolism Unit, CTO A. Alesini Hospital ASL Roma 2, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy

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Ashley Grossman Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, Oxford, UK

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Brian Shine Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, Oxford, UK

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Background

The 24-h urinary output of 5-hydroxyindoleacetic acid (5-HIAA) is used to monitor disease progression and treatment responses of neuroendocrine neoplasms (NENs). Several conditions are required for 5-HIAA assay, involving urine collection/preservation and food/drug restrictions.

Aim

To evaluate the correlation between 5-HIAA concentration in a spot urine sample and the output in a 24-h urine collection, and whether spot urine specimens can replace 24-h collection.

Methods

Patients with NENs or symptoms suggestive of NENs were asked to provide a separate spot urine at the end of the 24-h urine collection for 5-HIAA assessment. The upper reference limit for 24-h urinary 5-HIAA was 40 µmol/24 h. 5-HIAA measurements in spot urine samples were corrected for variation in urine flow rate by expressing results as a ratio to creatinine concentration.

Results

We included 136 paired urinary samples for 5-HIAA assessment from 111 patients (100 NENs). The correlation between 5-HIAA values measured in 24-h and spot urines was r = +0.863 (P < 0.001) and r = +0.840 (P < 0.001) including only NEN patients. Using the 24-h urinary 5-HIAA as reference method, the AUC on ROC analysis for spot urinary 5-HIAA was 0.948 (95% CI, 0.914–0.983; P < 0.001), attaining a sensitivity of 83% and specificity of 95% using 5.3 mol/mmol as cut-off for the spot urine. The AUC among NEN patients alone was 0.945 (95% CI, 0.904–0.987; P < 0.001).

Conclusions

The ratio of 5-HIAA to creatinine in a spot urine could replace the measurement of 5-HIAA output in a 24-h urine collection, especially for follow-up of patients with known elevated 5-HIAA levels.

Open access
Nelma Veronica Marques Neuroendocrinology Research Center, Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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Luiz Eduardo Armondi Wildemberg Neuroendocrinology Research Center, Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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Monica R Gadelha Neuroendocrinology Research Center, Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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Pasireotide long-acting release is effective in achieving biochemical control and reducing tumour volume in patients with acromegaly inadequately controlled by first-line therapy. As part of a long-term, real-world study at our centre, 20 of 50 patients receiving pasireotide benefited from a reduction in pasireotide dose. Pasireotide reduced insulin-like growth factor 1 (IGF1) levels to below the upper limit of the normal range, with some patients responding within 1−3 months of treatment (n = 11) and others after ≥4 months (n = 9). Following pasireotide dose reduction, IGF1 levels showed a mild increase but remained within the normal range after a median of 39 months in the early responders and 17 months in the late responders. Glucose and glycated haemoglobin levels decreased following dose reduction. Identifying patients who may benefit from a reduction in pasireotide dose warrants further research as it may improve the management of pasireotide-associated hyperglycaemia in susceptible patients.

Significance statement

Patients with acromegaly often need medical therapy for extended periods of time, and pasireotide is an effective, long-term treatment option. However, pasireotide may increase blood glucose levels in some patients, such as those with pre-existing diabetes. In this single-centre study, we show that following dose reduction of pasireotide over time, patients with acromegaly maintained their biochemical response (IGF1 < ULN) and had improved glycaemic control. As such, dose reductions may be an effective, personalised treatment approach for managing some patients receiving long-term pasireotide therapy and could allow patients to achieve early and long-term biochemical control while minimising adverse drug effects.

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