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Shruti Khare Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai 400012, India

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Anurag R Lila Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai 400012, India

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Hiren Patt Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai 400012, India

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Chaitanya Yerawar Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai 400012, India

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Manjunath Goroshi Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai 400012, India

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Tushar Bandgar Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai 400012, India

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Nalini S Shah Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai 400012, India

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Macroprolactinomas are the most common functional pituitary tumours. Hypotheses proposed to explain predominance of large tumours in males are: i) diagnostic delay, as hyperprolactinaemia remains under recognised in males and ii) gender-specific difference in tumour proliferation indices. Our study objectives are to compare gender differences in clinical, biochemical, radiological features, management outcomes and cabergoline responsiveness in macroprolactinomas. Drug resistance was defined as failure to achieve prolactin normalisation and >50% reduction in tumour volume with cabergoline (3.5 mg/week dose for minimum 6 months duration). The baseline characteristics of 100 patients (56 females and 44 males) with macroprolactinoma were analysed. Drug responsiveness was analysed in 88 treatment naive patients, excluding 12 post-primary trans-sphenoidal surgery cases. We found that females (30.29±10.39 years) presented at younger mean age than males (35.23±9.91 years) (P<0.01). The most common presenting symptom was hypogonadism (oligo-amenorrhoea/infertility) in females (96.15%) and symptoms of mass effect (headache and visual field defects) in males (93.18%). Baseline mean prolactin levels were significantly lower in females (3094.36±6863.01 ng/ml) than males (7927.07±16 748.1 ng/ml) (P<0.001). Maximal tumour dimension in females (2.49±1.48 cm) was smaller than males (3.93±1.53 cm) (P<0.001). In 88 treatment naïve patients, 27.77% females and 35.29% males had resistant tumours (P=0.48). On subgrouping as per maximum tumour dimension (1.1–2 cm, 2.1–4 cm and >4 cm), gender difference in response rate was insignificant. In conclusion, macroprolactinomas are equally prevalent in both sexes. Macroprolactinomas in males predominantly present with symptoms of mass effects, as against females who present with symptoms of hypogonadism. Males harbor larger tumours but are equally cabergoline responsive as those in females.

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Eva Olga Melin Department of Clinical Sciences, Endocrinology and Diabetes, Lund University, Faculty of Medicine, Lund, Sweden
Department of Research and Development, Region Kronoberg, Växjö, Sweden
Region Kronoberg, Primary Care, Växjö, Sweden

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Jonatan Dereke Department of Clinical Sciences Lund, Lund University, Faculty of Medicine, Diabetes Research Laboratory, Lund, Sweden

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Maria Thunander Department of Clinical Sciences, Endocrinology and Diabetes, Lund University, Faculty of Medicine, Lund, Sweden
Department of Research and Development, Region Kronoberg, Växjö, Sweden
Department of Internal Medicine, Endocrinology and Diabetes, Central Hospital, Växjö, Sweden

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Magnus Hillman Department of Clinical Sciences Lund, Lund University, Faculty of Medicine, Diabetes Research Laboratory, Lund, Sweden

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Objective

Neuroinflammatory responses are implicated in depression. The aim was to explore whether depression in patients with type 1 diabetes (T1D) was associated with high circulating galectin-3, controlling for metabolic variables, s-creatinine, life style factors, medication and cardiovascular complications.

Design

Cross-sectional.

Methods

Participants were T1D patients (n = 283, 56% men, age 18–59 years, diabetes duration ≥1 year). Depression was assessed by Hospital Anxiety and Depression Scale-depression subscale. Blood samples, anthropometrics and blood pressure were collected, and supplemented with data from medical records and the Swedish National Diabetes Registry. Galectin-3 ≥2.562 µg/l, corresponding to the 85th percentile, was defined as high galectin-3.

Results

Median (quartile1, quartile3) galectin-3 (µg/l) was 1.3 (0.8, 2.9) for the 30 depressed patients, and 0.9 (0.5, 1.6) for the 253 non-depressed, P = 0.009. Depression was associated with high galectin-3 in all the 283 patients (adjusted odds ratio (AOR) 3.5), in the 161 men (AOR 3.4), and in the 122 women (AOR 3.9). HbA1c, s-lipids, s-creatinine, blood pressure, obesity, smoking, physical inactivity, cardiovascular complications and drugs (antihypertensive, lipid lowering, oral antidiabetic drugs and antidepressants) were not associated with high galectin-3.

Conclusions

This is the first study to show an association between depression and galectin-3. Depression was the only explored parameter associated with high circulating galectin-3 levels in 283 T1D patients. High galectin-3 levels might contribute to the increased risk for Alzheimer’s disease, cardiovascular and all-cause mortality observed in persons with depression. Potentially, in the future, treatment targeting galactin-3 might improve the prognosis for patients with high galectin-3 levels.

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Metin Guclu Health Sciences University, Bursa Yuksek Ihtisas Education and Training Hospital, Department of Endocrinology and Metabolism, Bursa, Turkey

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Sinem Kiyici Health Sciences University, Bursa Yuksek Ihtisas Education and Training Hospital, Department of Endocrinology and Metabolism, Bursa, Turkey

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Zulfiye Gul Department of Pharmacology, Uludag University Medical Faculty, Bursa, Turkey

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Sinan Cavun Department of Pharmacology, Uludag University Medical Faculty, Bursa, Turkey

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Aim

In the present study, we investigated the long-term effects of exenatide treatment on serum fasting ghrelin levels in patients with type 2 diabetes mellitus.

Methods

Type 2 diabetic patients, who were using metformin with and without the other antihyperglycemic drugs on a stable dose for at least 3 months, were enrolled in the study. BMI>35 kg/m2 and HbA1c>7.0% were the additional inclusion criteria. Oral antihyperglycemic drugs, other than metformin, were stopped, and metformin treatment was continued at 2000 mg per day. Exenatide treatment was initiated at 5 µg per dose subcutaneously (sc) twice daily, and after one month, the dose of exenatide was increased to 10 µg twice daily. Changes in anthropometric variables, glycemic control, lipid parameters and total ghrelin levels were evaluated at baseline and following 12 weeks of treatment.

Results

Thirty-eight patients (male/female = 7/31) entered the study. The mean age of patients was 50.5 ± 8.8 years with a mean diabetes duration of 8.5 ± 4.9 years. The mean BMI was 41.6 ± 6.3 kg/m2 and the mean HbA1c of patients was 8.9 ± 1.4%. The mean change in the weight of patients was −5.6 kg and the percentage change in weight was −5.2 ± 3.7% following 12 weeks of treatment. BMI, fasting plasma glucose and HbA1c levels of patients were decreased significantly (P < 0.001 and P < 0.001; respectively), while there was no change in lipid parameters. Serum fasting ghrelin levels were significantly suppressed following 12 weeks of exenatide treatment compared with baseline values (328.4 ± 166.8 vs 245.3 ± 164.8 pg/mL) (P = 0.024).

Conclusion

These results suggest that the effects of exenatide on weight loss may be related with the suppression of serum fasting ghrelin levels, which is an orexigenic peptide.

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Stine Linding Andersen Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

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Stig Andersen Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Geriatrics, Aalborg University Hospital, Aalborg, Denmark

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The management of hyperthyroidism in pregnant patients has been a topic of raised clinical awareness for decades. It is a strong recommendation that overt hyperthyroidism of Graves’ disease in pregnant women should be treated to prevent complications. The consequences of hyperthyroidism in pregnancy are less studied than hypothyroidism, and a literature review illustrates that the main burden of evidence to support current clinical guidance emerges from early observations of severe complications in Graves’ disease patients suffering from untreated hyperthyroidism in the pregnancy. On the other hand, the more long-term consequences in children born to mothers with hyperthyroidism are less clear. A hypothesis of fetal programming by maternal hyperthyroidism implies that excessive levels of maternal thyroid hormones impair fetal growth and development. Evidence from experimental studies provides clues on such mechanisms and report adverse developmental abnormalities in the fetal brain and other organs. Only few human studies addressed developmental outcomes in children born to mothers with hyperthyroidism and did not consistently support an association. In contrast, large observational human studies performed within the last decade substantiate a risk of teratogenic side effects to the use of antithyroid drugs in early pregnancy. Thus, scientific and clinical practice are challenged by the distinct role of the various exposures associated with Graves’ disease including the hyperthyroidism per se, the treatment, and thyroid autoimmunity. More basic and clinical studies are needed to extend knowledge on the effects of each exposure, on the potential interaction between exposures and with other determinants, and on the underlying mechanisms.

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Stefan Pilz Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Armin Zittermann Clinic for Thoracic and Cardiovascular Surgery, Herz- und Diabeteszentrum NRW, Ruhr University Bochum, Bad Oeynhausen, Germany

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Christian Trummer Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Verena Theiler-Schwetz Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Elisabeth Lerchbaum Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Martin H Keppel University Institute for Medical and Chemical Laboratory Diagnostics, Paracelsus Medical University, Salzburg, Austria

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Martin R Grübler Department of Cardiology, Swiss Cardiovascular Center Bern, Bern University Hospital, University of Bern, Bern, Switzerland

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Winfried März Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, Ruperto-Carola University of Heidelberg, Heidelberg, Germany
Synlab Medical Center of Human Genetics Mannheim, Mannheim, Germany

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Marlene Pandis Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Vitamin D testing and treatment is a subject of controversial scientific discussions, and it is challenging to navigate through the expanding vitamin D literature with heterogeneous and partially opposed opinions and recommendations. In this narrative review, we aim to provide an update on vitamin D guidelines and the current evidence on the role of vitamin D for human health with its subsequent implications for patient care and public health issues. Vitamin D is critical for bone and mineral metabolism, and it is established that vitamin D deficiency can cause rickets and osteomalacia. While many guidelines recommend target serum 25-hydroxyvitamin D (25[OH]D) concentrations of ≥50 nmol/L (20 ng/mL), the minimum consensus in the scientific community is that serum 25(OH)D concentrations below 25–30 nmol/L (10–12 ng/mL) must be prevented and treated. Using this latter threshold of serum 25(OH)D concentrations, it has been documented that there is a high worldwide prevalence of vitamin D deficiency that may require public health actions such as vitamin D food fortification. On the other hand, there is also reason for concern that an exploding rate of vitamin D testing and supplementation increases costs and might potentially be harmful. In the scientific debate on vitamin D, we should consider that nutrient trials differ from drug trials and that apart from the opposed positions regarding indications for vitamin D treatment we still have to better characterize the precise role of vitamin D for human health.

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Kennett Sprogøe Ascendis Pharma A/S, Hellerup, Denmark

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Eva Mortensen Ascendis Pharma, Inc., Palo Alto, California, USA

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David B Karpf Ascendis Pharma, Inc., Palo Alto, California, USA

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Jonathan A Leff Ascendis Pharma, Inc., Palo Alto, California, USA

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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.

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Anastasia K Armeni Division of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, University of Patras Medical School, Patras, Greece

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Konstantinos Assimakopoulos Department of Psychiatry, University of Patras Medical School, Patras, Greece

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Dimitra Marioli Division of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, University of Patras Medical School, Patras, Greece

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Vassiliki Koika Division of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, University of Patras Medical School, Patras, Greece

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Euthychia Michaelidou Department of Biology, University of Patras, Patras, Greece

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Niki Mourtzi Department of Biology, University of Patras, Patras, Greece

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Gregoris Iconomou Department of Psychiatry, University of Patras Medical School, Patras, Greece

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Neoklis A Georgopoulos Division of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, University of Patras Medical School, Patras, Greece

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Over the past decades, research attention has increasingly been paid to the neurobiological component of sexual behavior. The aim of the present study was to investigate the correlation of estrogen receptor α (ERA) gene polymorphism (rs2234693-PvuII) (T→C substitution) and oxytocin receptor gene polymorphism (rs53576) (G→A substitution) with sexuality parameters of young, healthy women. One hundred thirty-three Greek heterosexual women, students in higher education institutions, 20–25 years of age, sexually active, with normal menstrual cycles (28–35 days), were recruited in the study. Exclusion criteria were chronic and/or major psychiatric diseases, use of oral contraceptive pills (OCs), polycystic ovary syndrome (PCOS), thyroid diseases as well as drugs that are implicated in hypothalamus–pituitary–gonadal axis. T allele (wildtype) of rs2234693 (PvuII) polymorphism of ERA gene was correlated with increased levels of arousal and lubrication, whereas A allele (polymorphic) of rs53576 (OXTR) polymorphism was correlated with increased arousal levels. The simultaneous presence of both T allele of rs2234693 (PvuII) and A allele of rs53576 (OXTR) polymorphisms (T + A group) was correlated with increased arousal, orgasm levels as well as female sexual function index full score. To our knowledge, this is the first study to investigate the interaction between ERA and OXTR with regard to sexual function in women. Female sexuality is a complex behavioral trait that encompasses both biological and psychological components. It seems that variability in female sexual response stems from genetic variability that characterizes endocrine, neurotransmitter and central nervous system influences.

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Adriano N Cury Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Verônica T Meira Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Osmar Monte Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil
Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Marília Marone Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Nilza M Scalissi Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Cristiane Kochi Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Luís E P Calliari Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Carlos A Longui Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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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
Aldo Bonaventura Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

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Fabrizio Montecucco Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

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Franco Dallegri Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

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The prevalence of type 2 diabetes mellitus (T2DM) is increasing all over the world. Targeting good glycemic control is fundamental to avoid the complications of diabetes linked to hyperglycemia. This narrative review is based on material searched for and obtained via PubMed up to April 2015. The search terms we used were: ‘hypoglycemia, diabetes, complications’ in combination with ‘iatrogenic, treatment, symptoms.’ Serious complications might occur from an inappropriate treatment of hyperglycemia. The most frequent complication is iatrogenic hypoglycemia that is often associated with autonomic and neuroglycopenic symptoms. Furthermore, hypoglycemia causes acute cardiovascular effects, which may explain some of the typical symptoms: ischemia, QT prolongation, and arrhythmia. With regards to the latter, the night represents a dangerous period because of the major increase in arrhythmias and the prolonged period of hypoglycemia; indeed, sleep has been shown to blunt the sympatho-adrenal response to hypoglycemia. Two main strategies have been implemented to reduce these effects: monitoring blood glucose values and individualized HbA1c goals. Several drugs for the treatment of T2DM are currently available and different combinations have been recommended to achieve individualized glycemic targets, considering age, comorbidities, disease duration, and life expectancy. In conclusion, according to international guidelines, hypoglycemia-avoiding therapy must reach an individualized glycemic goal, which is the lowest HbA1c not causing severe hypoglycemia and preserving awareness of hypoglycemia.

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Ashley N Reeb Department of Otolaryngology, Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

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Andrea Ziegler Department of Otolaryngology, Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

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Reigh-Yi Lin Department of Otolaryngology, Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

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Follicular thyroid cancer (FTC) is the second most common type of thyroid cancers. In order to develop more effective personalized therapies, it is necessary to thoroughly evaluate patient-derived cell lines in in vivo preclinical models before using them to test new, targeted therapies. This study evaluates the tumorigenic and metastatic potential of a panel of three human FTC cell lines (WRO, FTC-238, and TT1609-CO2) with defined genetic mutations in two in vivo murine models: an orthotopic thyroid cancer model to study tumor progression and a tail vein injection model to study metastasis. All cell lines developed tumors in the orthotopic model, with take rates of 100%. Notably, WRO-derived tumors grew two to four times faster than tumors arising from the FTC-238 and TT2609-CO2 cell lines. These results mirrored those of a tail vein injection model for lung metastasis: one hundred percent of mice injected with WRO cells in the tail vein exhibited aggressive growth of bilateral lung metastases within 35 days. In contrast, tail vein injection of FTC-238 or TT2609-CO2 cells did not result in lung metastasis. Together, our work demonstrates that these human FTC cell lines display highly varied tumorigenic and metastatic potential in vivo with WRO being the most aggressive cell line in both orthotopic and lung metastasis models. This information will be valuable when selecting cell lines for preclinical drug testing.

Open access