Search Results
University of Belgrade, Medical Faculty, Belgrade, Serbia
Search for other papers by Marko Stojanovic in
Google Scholar
PubMed
Search for other papers by Zida Wu in
Google Scholar
PubMed
Search for other papers by Craig E Stiles in
Google Scholar
PubMed
University of Belgrade, Medical Faculty, Belgrade, Serbia
Search for other papers by Dragana Miljic in
Google Scholar
PubMed
Insitute of Medical Statistics and Informatics, Belgrade, Serbia
Search for other papers by Ivan Soldatovic in
Google Scholar
PubMed
University of Belgrade, Medical Faculty, Belgrade, Serbia
Search for other papers by Sandra Pekic in
Google Scholar
PubMed
University of Belgrade, Medical Faculty, Belgrade, Serbia
Search for other papers by Mirjana Doknic in
Google Scholar
PubMed
University of Belgrade, Medical Faculty, Belgrade, Serbia
Search for other papers by Milan Petakov in
Google Scholar
PubMed
Search for other papers by Vera Popovic in
Google Scholar
PubMed
Search for other papers by Christian Strasburger in
Google Scholar
PubMed
Search for other papers by Márta Korbonits in
Google Scholar
PubMed
Background
Aryl hydrocarbon receptor-interacting protein (AIP) is evolutionarily conserved and expressed widely throughout the organism. Loss-of-function AIP mutations predispose to young-onset pituitary adenomas. AIP co-localizes with growth hormone in normal and tumorous somatotroph secretory vesicles. AIP protein is detectable in circulation. We aimed to investigate possible AIP and GH co-secretion, by studying serum AIP and GH levels at baseline and after GH stimulation or suppression, in GH deficiency (GHD) and in acromegaly patients.
Subjects and methods
Insulin tolerance test (ITT) was performed in GHD patients (n = 13) and age-BMI-matched normal GH axis control patients (n = 31). Oral glucose tolerance test (OGTT) was performed in active acromegaly patients (n = 26) and age-BMI-matched normal GH axis control patients (n = 18). In-house immunometric assay was developed for measuring circulating AIP.
Results
Serum AIP levels were in the 0.1 ng/mL range independently of gender, age or BMI. Baseline AIP did not differ between GHD and non-GHD or between acromegaly and patients with no acromegaly. There was no change in peak, trough or area under the curve during OGTT or ITT. Serum AIP did not correlate with GH during ITT or OGTT.
Conclusions
Human circulating serum AIP in vivo was assessed by a novel immunometric assay. AIP levels were independent of age, sex or BMI and unaffected by hypoglycaemia or hyperglycaemia. Despite co-localization in secretory vesicles, AIP and GH did not correlate at baseline or during GH stimulation or suppression tests. A platform of reliable serum AIP measurement is established for further research of its circulatory source, role and impact.
Search for other papers by Elizaveta Mamedova in
Google Scholar
PubMed
Search for other papers by Natalya Mokrysheva in
Google Scholar
PubMed
Search for other papers by Evgeny Vasilyev in
Google Scholar
PubMed
Search for other papers by Vasily Petrov in
Google Scholar
PubMed
Search for other papers by Ekaterina Pigarova in
Google Scholar
PubMed
Search for other papers by Sergey Kuznetsov in
Google Scholar
PubMed
Search for other papers by Nikolay Kuznetsov in
Google Scholar
PubMed
Search for other papers by Liudmila Rozhinskaya in
Google Scholar
PubMed
Institute of Clinical Endocrinology, Endocrinology Research Center, Moscow, Russian Federation
Search for other papers by Galina Melnichenko in
Google Scholar
PubMed
Search for other papers by Ivan Dedov in
Google Scholar
PubMed
Search for other papers by Anatoly Tiulpakov in
Google Scholar
PubMed
Background
Primary hyperparathyroidism (PHPT) is a relatively rare disorder among children, adolescents and young adults. Its development at an early age is suspicious for hereditary causes, though the need for routine genetic testing remains controversial.
Objective
To identify and describe hereditary forms of PHPT in patients with manifestation of the disease under 40 years of age.
Design
We enrolled 65 patients with PHPT diagnosed before 40 years of age. Ten of them had MEN1 mutation, and PHPT in them was the first manifestation of multiple endocrine neoplasia type 1 syndrome.
Methods
The other fifty-five patients underwent next-generation sequencing (NGS) of a custom-designed panel of genes, associated with PHPT (MEN1, CASR, CDC73, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2C, CDKN2D). In cases suspicious for gross CDC73 deletions multiplex ligation-dependent probe amplification was performed.
Results
NGS revealed six pathogenic or likely pathogenic germline sequence variants: four in CDC73 c.271C>T (p.Arg91*), c.496C>T (p.Gln166*), c.685A>T (p.Arg229*) and c.787C>T (p.Arg263Cys); one in CASR c.3145G>T (p.Glu1049*) and one in MEN1 c.784-9G>A. In two patients, MLPA confirmed gross CDC73 deletions. In total, 44 sporadic and 21 hereditary PHPT cases were identified. Parathyroid carcinomas and atypical parathyroid adenomas were present in 8/65 of young patients, in whom CDC73 mutations were found in 5/8.
Conclusions
Hereditary forms of PHPT can be identified in up to 1/3 of young patients with manifestation of the disease at <40 years of age. Parathyroid carcinomas or atypical parathyroid adenomas in young patients are frequently associated with CDC73 mutations.
Search for other papers by Nella Augusta Greggio in
Google Scholar
PubMed
Search for other papers by Elisa Rossi in
Google Scholar
PubMed
Search for other papers by Silvia Calabria in
Google Scholar
PubMed
Search for other papers by Alice Meneghin in
Google Scholar
PubMed
Search for other papers by Joaquin Gutierrez de Rubalcava in
Google Scholar
PubMed
Search for other papers by Carlo Piccinni in
Google Scholar
PubMed
Search for other papers by Antonella Pedrini in
Google Scholar
PubMed
Objective
To estimate the prevalence of subclinical hypothyroidism (SH) among children, by using levothyroxine low dosage as disease proxy, and to describe prescription pattern.
Design
An historical cohort study was performed through administrative databases of 12 Italian Local Health Units covering 3,079,141 inhabitants. A cohort of children (aged 0–13 years) was selected in the period 2001–2014. A subgroup of new users (aged 0–9 years) was identified and followed up for 5 years.
Methods
The prevalence was provided as mean value of the whole period, as annual trend, by patient gender and age. Demographic details, information on levothyroxine dosage, comorbidities and co-medications were provided. Therapy duration and medication persistence were evaluated among new users.
Results
644 children treated with levothyroxine low dosage was selected, with a mean annual prevalence of 0.20 per 1000 children. The temporal trend of prevalence was stable, with a slight reduction in the 2005–2008. Prevalence by age showed an increase after 10 years. Patients were treated with an average annual dose of 4290 µg/year and 66.9% of children were affected by comorbidities. Among 197 new users, 62.9% received therapy only for one year, whereas out of those treated two or more years, 89.0% resulted persistent to the therapy.
Conclusions
This study provides real-world epidemiology of SH among children, and it depicts the clinical and therapeutic characteristics of these subjects. Its findings showed that the SH treatment of this disorder was widely variable, also due to lack of evidence concerning paediatric population.
Search for other papers by A V Dreval in
Google Scholar
PubMed
Search for other papers by I V Trigolosova in
Google Scholar
PubMed
Search for other papers by I V Misnikova in
Google Scholar
PubMed
Search for other papers by Y A Kovalyova in
Google Scholar
PubMed
Search for other papers by R S Tishenina in
Google Scholar
PubMed
Search for other papers by I A Barsukov in
Google Scholar
PubMed
Search for other papers by A V Vinogradova in
Google Scholar
PubMed
Search for other papers by B H R Wolffenbuttel in
Google Scholar
PubMed
Early carbohydrate metabolism disorders (ECMDs) and diabetes mellitus (DM) are frequently associated with acromegaly. We aimed to assess the prevalence of ECMDs in patients with acromegaly and to compare the results with those in adults without acromegaly using two population-based epidemiologic surveys. We evaluated 97 patients with acromegaly in several phases of their disease (mean age, 56 years and estimated duration of acromegaly, 12.5 years). An oral glucose tolerance test was done in those not yet diagnosed with DM to reveal asymptomatic DM or ECMDs (impaired glucose tolerance+impaired fasting glucose). Comparisons were made between patients with acromegaly and participants from the general adult population (n=435) and an adult population with multiple type 2 diabetes risk factors (n=314), matched for gender, age and BMI. DM was diagnosed in 51 patients with acromegaly (52.5%) and 14.3% of the general population (P<0.001). The prevalence of ECMDs was also higher in patients with acromegaly than in the general population and in the high-risk group; only 22% of patients with acromegaly were normoglycaemic. The prevalence of newly diagnosed ECMDs or DM was 1.3–1.5 times higher in patients with acromegaly compared with the high-risk group. Patients with acromegaly having ECMDs or DM were older, more obese and had longer disease duration and higher IGF1 levels (Z-score). Logistic regression showed that the severity of glucose derangement was predicted by age, BMI and IGF1 levels. In patients with acromegaly, the prevalence of DM and ECMDs considerably exceeds that of the general population and of a high-risk group, and development of DM depends on age, BMI and IGF1 levels.
Search for other papers by Li Li in
Google Scholar
PubMed
Search for other papers by Qifa Song in
Google Scholar
PubMed
Search for other papers by Xi Yang in
Google Scholar
PubMed
Insufficient insulin release plays a crucial role in the development of unhealthy status in patients with obesity; the present study aimed to classify these patients by the indices for insulin resistance and insulin release. After the indices from OGTT were assessed to achieve high differentiability and low redundancy in classifying patients, HOMA-IR and IGI30min were chosen to classify the patients using K-means clustering method. A total of 249 non-diabetic patients with obesity were classified into four groups. In Group 1, 19 patients were characteristic of high insulin resistance and high insulin release, as well as well-controlled glucose levels, the highest BMI, the youngest age, and the highest early phase release of insulin. In Group 2, 38 patients were unhealthiest in terms of high insulin resistance, reduced insulin release and IGT status. Group 3 consisted of 63 patients that were healthiest with low insulin resistance and high insulin release. In Group 4, 46 IGT patients and 14 IFG patients were identified among 129 patients that showed low insulin resistance, low insulin release, moderate obesity and older age. These concurrent impotent insulin release, older age, and moderate obesity indicated decreasing obesity with increasing age and reduced insulin release. The classification of patients with obesity using K-means clustering method by HOMA-IR and IGI30min provides more information about the development of obesity and unhealthy status. The patients with distinct insulin resistance and insulin release should be followed up, especially for those with reduced or even absent insulin response to glucose stimulation.
Division of Endocrinology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
Search for other papers by Volha V Zhukouskaya in
Google Scholar
PubMed
APHP, Department of Endocrinology and Diabetology for Children, Bicêtre Paris Saclay Hospital, Le Kremlin-Bicêtre, France
Search for other papers by Anya Rothenbuhler in
Google Scholar
PubMed
Search for other papers by Annamaria Colao in
Google Scholar
PubMed
IRCCS SDN, Naples, Italy
Search for other papers by Carolina Di Somma in
Google Scholar
PubMed
APHP, Department of Endocrinology and Reproductive Diseases, Bicêtre Paris-Saclay Hospital, Le Kremlin-Bicêtre, France
Paris Sud – Paris Saclay University, Faculté de Médecine, Le Kremlin-Bicêtre, France
Search for other papers by Peter Kamenický in
Google Scholar
PubMed
APHP, Department of Molecular Genetics, Pharmacogenetics and Hormonology, Bicêtre Paris-Saclay Hospital, Le Kremlin-Bicêtre, France
Search for other papers by Séverine Trabado in
Google Scholar
PubMed
Hôpital Necker EnfantsMalades APHP, INSERM U1151, Paris, France
Search for other papers by Dominique Prié in
Google Scholar
PubMed
Search for other papers by Christelle Audrain in
Google Scholar
PubMed
Search for other papers by Anna Barosi in
Google Scholar
PubMed
Search for other papers by Christèle Kyheng in
Google Scholar
PubMed
APHP, Department of Endocrinology and Diabetology for Children, Bicêtre Paris Saclay Hospital, Le Kremlin-Bicêtre, France
APHP, Department of Adolescent Medicine, Bicêtre Paris Saclay Hospital, Le Kremlin-Bicêtre, France
Search for other papers by Anne-Sophie Lambert in
Google Scholar
PubMed
APHP, Department of Endocrinology and Diabetology for Children, Bicêtre Paris Saclay Hospital, Le Kremlin-Bicêtre, France
Paris Sud – Paris Saclay University, Faculté de Médecine, Le Kremlin-Bicêtre, France
Search for other papers by Agnès Linglart in
Google Scholar
PubMed
Background/aim
X-linked hypophosphatemia (XLH) is a rare disease characterized by low phosphate levels. Scientific evidence points to a link between hypophosphatemia and obesity in general population. The aim of our longitudinal observational study was to investigate the prevalence of obesity and associated factors in a large cohort of children with XLH.
Patients/methods
We studied 172 XLH-children 5–20 years of age (113 girls/59 boys). Anthropometric parameters (weight, height, and BMI) were collected at birth and during follow-up at mean ages of 5.3, 8.2, 11.3, and 15.9 years (groups 1, 2, 3, and 4, respectively). In each group, subjects were classified based on International Obesity Taskforce (IOTF) cut off values of BMI for age and sex as overweight or obese (IOTF 25–30 or ≥30 kg/m2, respectively).
Results
In each age-group, almost 1/3 of XLH-patients were classified as overweight or obese (29.4, 28.7, 27.5, and 36.7% in groups 1, 2, 3, and 4, respectively). Children without a XLH-family history had higher BMI-IOTF at every point of follow-up, compared to those with positive XLH-family history. Similarly, higher BMI-IOTF was significantly associated with treatment duration (23.3 ± 4.4 vs 23.8 ± 3.8 vs 25.2 ± 4.5 kg/m2, for subjects with treatment duration of <5, 5–10 and >10 years, respectively, P for trend = 0.025). Multiple regression analysis confirmed an association of treatment duration and lack of XLH-family history with higher BMI-IOTF.
Conclusion
One out of three of XLH-children have phenotypically unfavourable metabolic profile expressed as increased prevalence of overweight or obesity in comparison to general population. Both the lack of XLH family history and the duration of treatment increase the risk of higher BMI-IOTF. BMI should be carefully monitored in children, and later in adults, with XLH.
Search for other papers by Ling Hu in
Google Scholar
PubMed
Search for other papers by Ting Li in
Google Scholar
PubMed
Search for other papers by Xiao-Ling Yin in
Google Scholar
PubMed
Search for other papers by Yi Zou in
Google Scholar
PubMed
Objective:
The purpose of this study was to explore the prevalence of thyroid nodules (TN) and metabolic syndrome (MS) and to analyze the correlation between TN and the components of MS.
Methods:
A total of 1526 subjects were divided into two groups: a TN group and a non-thyroid nodules (NTN) group. The height, weight, blood pressure, fasting blood glucose level, fasting plasma insulin level, serum lipid profile, uric acid level, serum thyroid-stimulating hormone (TSH) level, free triiodothyronine (FT3) level, and free thyroxine (FT4) level of each patient were measured. Insulin resistance (IR) was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). Fatty liver and TN were detected by color Doppler ultrasonography.
Results:
(i) The overall prevalence of TN was 39.5%; it was significantly higher in women than in men (P < 0.01) and progressively increased with age in both sexes. (ii) The overall prevalence of MS was 25.6%; it was significantly higher in men than in women (P < 0.01) and progressively increased with age in both sexes. (iii) FT3 was significantly lower in the TN group than in the NTN group (P < 0.01). (iv) BMI, triglycerides, and HOMA-IR were higher in the TN group than in the NTN group (P < 0.05). (v) The existence of TN was significantly associated with overweight/obesity (OR = 1.03, 95% CI = 1.024–1.089), and with insulin resistance (IR) (OR = 1.98, 95% CI = 1.645–2.368), after adjusting for age and sex.
Conclusions:
The prevalence of thyroid nodules and metabolic syndrome in the Nanchang area increases with age, and overweight/obesity and IR in patients are associated with thyroid nodules.
Search for other papers by Alberto Bongiovanni in
Google Scholar
PubMed
Search for other papers by Federica Recine in
Google Scholar
PubMed
Search for other papers by Flavia Foca in
Google Scholar
PubMed
Search for other papers by Valentina Fausti in
Google Scholar
PubMed
Search for other papers by Nada Riva in
Google Scholar
PubMed
Search for other papers by Greta Fabbri in
Google Scholar
PubMed
Search for other papers by Stefano Severi in
Google Scholar
PubMed
Search for other papers by Chiara Liverani in
Google Scholar
PubMed
Search for other papers by Alessandro De Vita in
Google Scholar
PubMed
Search for other papers by Chiara Spadazzi in
Google Scholar
PubMed
Search for other papers by Giacomo Miserocchi in
Google Scholar
PubMed
Search for other papers by Laura Mercatali in
Google Scholar
PubMed
Search for other papers by Dino Amadori in
Google Scholar
PubMed
Search for other papers by Toni Ibrahim in
Google Scholar
PubMed
The incidence of neuroendocrine neoplasia (NEN) is higher in individuals ≥70 years of age (elderly) who are underrepresented in clinical trials because of comorbidities and low performance status. We retrospectively analyzed the outcome of elderly patients with metastatic NEN (mNEN). Comorbidities were summarized by Charlson Comorbidity Index (CCI), Kaplan–Meier method was applied to estimate overall survival (OS) and Cox’s proportional hazard model was used to assess the impact of known prognostic factors. We retrieved data on 145 mNEN patients aged ≥70 years seen at our center from June 2007 to March 2016. Fifty-six (38.6%) were aged ≥75 years. ECOG PS was 0 in 45.7% of cases and CCI was 0 in 41.0% and 1 in 37.4%. A total of 75.4% of patients had grade (G)1/G2 NEN and 24.6%, G3. Octreoscan/Gallium PET/CT and FDG-PET/CT were positive in 94.2% and 70.3% of cases, respectively. Median follow-up was 72.3 (53.2–85.1) months. Seventy-nine patients received first-line somatostatin analogs (SSA), 23 peptide receptor radionuclide therapy (PRRT) and 36 chemotherapy (CHT). Seven did not undergo first-line therapy and 102 received more than one line. Median overall survival (mOS) was 5.1 years (95% CI: 3.4–6.6). No differences in mOS were seen according to CCI. First-line PRRT patients had a mOS of 6.5 years (95% CI: 3.3–not reached (NR)), SSA 5.7 years (95% CI: 4.2–7) and CHT 5.9 years (95% CI: 0.4–NR). mOS in CHT-treated G3 patients was 1.5 years (1.0–2.5). ECOG PS and FDG PET/CT were identified as independent prognostic factors. Results suggest that the above treatments positively impacted OS in elderly mNEN patients, including those aged ≥75 years.
Search for other papers by Christin Krause in
Google Scholar
PubMed
Search for other papers by Martina Grohs in
Google Scholar
PubMed
Search for other papers by Alexander T El Gammal in
Google Scholar
PubMed
Search for other papers by Stefan Wolter in
Google Scholar
PubMed
Search for other papers by Hendrik Lehnert in
Google Scholar
PubMed
Search for other papers by Oliver Mann in
Google Scholar
PubMed
Search for other papers by Jens Mittag in
Google Scholar
PubMed
Search for other papers by Henriette Kirchner in
Google Scholar
PubMed
Hepatic thyroid hormone signaling has an important role in the development and progression of nonalcoholic steatohepatitis (NASH). While the systemic levels of thyroid hormone might remain stable, there is evidence that the intracellular signaling machinery consisting of transporters, deiodinases and receptors could be altered in NASH. However, clinical material from human liver biopsies of individuals with NASH has not been studied to date. In a cross-sectional study, we analyzed 85 liver biopsies from patients with different stages of NASH that underwent bariatric surgery. Using qPCR, we analyzed gene expression of thyroid hormone transporters NTCP (SLC10A1), MCT8 (SLC16A2) and OATP1C1 (SLCO1C1), thyroid hormone receptor α and β (THRA and THRB) and deiodinase type I, II and III (DIO1, DIO2, DIO3). The expression was correlated with serum TSH, triglyceride, HbA1c and NASH score and corrected for age or gender if required. While DIO2, DIO3 and SLCO1C1 were not expressed in human liver, we observed a significant negative correlation of THRB and DIO1 with age, and SLC16A2 with gender. THRB expression was also negatively associated with serum triglyceride levels and HbA1c. More importantly, its expression was inversely correlated with NASH score and further declined with age. Our data provide unique insight into the mRNA expression of thyroid hormone transporters, deiodinases and receptors in the human liver. The findings allow important conclusions on the intrahepatic mechanisms governing thyroid hormone action, indicating a possible tissue resistance to the circulating hormone in NASH, which becomes more prominent in advanced age.
Division of General and Emergency Medicine, University Department of Medicine, Kantonsspital Aarau AG, Aarau, Switzerland
Search for other papers by Marlena Mueller in
Google Scholar
PubMed
University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital, Basel, Switzerland
Search for other papers by Fahim Ebrahimi in
Google Scholar
PubMed
Search for other papers by Emanuel Christ in
Google Scholar
PubMed
Search for other papers by Christian Andreas Nebiker in
Google Scholar
PubMed
Division of General and Emergency Medicine, University Department of Medicine, Kantonsspital Aarau AG, Aarau, Switzerland
Faculty of Medicine, University Hospital Basel, Basel, Switzerland
Search for other papers by Philipp Schuetz in
Google Scholar
PubMed
Division of General and Emergency Medicine, University Department of Medicine, Kantonsspital Aarau AG, Aarau, Switzerland
Faculty of Medicine, University Hospital Basel, Basel, Switzerland
Search for other papers by Beat Mueller in
Google Scholar
PubMed
Division of General and Emergency Medicine, University Department of Medicine, Kantonsspital Aarau AG, Aarau, Switzerland
Search for other papers by Alexander Kutz in
Google Scholar
PubMed
Background
Primary hyperparathyroidism is a prevalent endocrinopathy for which surgery is the only curative option. Parathyroidectomy is primarily recommended in younger and symptomatic patients, while there are still concerns regarding surgical complications in older patients. We therefore assessed the association of age with surgical outcomes in patients undergoing parathyroidectomy in a large population in Switzerland.
Methods
Population-based cohort study of adult patients with primary hyperparathyroidism undergoing parathyroidectomy in Switzerland between 2012 and 2018. The cohort was divided into four age groups (<50 years, 50–64 years, 65–74 years, ≥75 years). The primary outcome was a composite of in-hospital postoperative complications. Secondary outcomes were intensive care unit (ICU) admission, unplanned 30-day-readmission, and prolonged length of hospital stay.
Results
We studied 2642 patients with a median (IQR) age of 62 (53–71) years. Overall, 111 patients had complications including surgical re-intervention, hypocalcemia, and vocal cord paresis. As compared to <50 year-old patients, older patients had no increased risk for in-hospital complications after surgery (50–64 years: odds ratio (OR): 0.51 (95% CI, 0.28 to 0.92); 65–74 years: OR: 0.72 (95% CI, 0.39 to 1.33); ≥75 years: OR: 1.03 (95% CI, 0.54 to 1.95), respectively. There was also no association of age and rates of ICU-admission and unplanned 30-day-readmission, but oldest patients had longer hospital stays (OR: 2.38 (95% CI, 1.57 to 3.60)).
Conclusion
≥50 year-old patients undergoing parathyroidectomy had comparable risk of in-hospital complications as compared with younger ones. These data support parathyroidectomy in even older patients with primary hyperparathyroidism as performed in clinical routine.
