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Hypoparathyroidism is genetically heterogeneous and characterized by low plasma calcium and parathyroid hormone (PTH) concentrations. X-linked hypoparathyroidism (XLHPT) in two American families is associated with interstitial deletion-insertions involving deletions of chromosome Xq27.1 downstream of SOX3 and insertions of predominantly non-coding DNA from chromosome 2p25.3. These could result in loss, gain, or movement of regulatory elements, which include ultraconserved element uc482, which could alter SOX3 expression. To investigate this, we analysed SOX3 expression in EBV-transformed lymphoblastoid cells from three affected males, three unaffected males, and four carrier females from one XLHPT family. SOX3 expression was similar in all individuals, indicating that the spatiotemporal effect of the interstitial deletion-insertion on SOX3 expression postulated to occur in developing parathyroids did not manifest in lymphoblastoids. Expression of SNTG2, which is duplicated and inserted into the X chromosome, and ATP11C, which is moved telomerically, were also similarly expressed in all individuals. Investigation of male hemizygous (Sox3 −/Y and uc482 −/Y) and female heterozygous (Sox3 +/ − and uc482 +/ −) knockout mice, together with wild-type littermates (male Sox3 +/Y and uc482 +/Y, and female Sox3 +/+ and uc482 +/+), revealed Sox3 −/Y, Sox3 +/ −, uc482 −/Y, and uc482 +/ − mice to have normal plasma biochemistry, compared to their respective wild-type littermates. When challenged with a low calcium diet, all mice had hypocalcaemia, and elevated plasma PTH concentrations and alkaline phosphatase activities, and Sox3 −/Y, Sox3 +/ −, uc482 −/Y, and uc482 +/ − mice had similar plasma biochemistry, compared to wild-type littermates. Thus, these results indicate that absence of Sox3 or uc482 does not cause hypoparathyroidism and that XLHPT likely reflects a more complex mechanism.
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Laboratório de Fisiologia Endócrina Doris Rosenthal, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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Estradiol has been used to prevent metabolic diseases, bone loss and menopausal symptoms, even though it might raise the risk of cancer. Metformin is usually prescribed for type 2 diabetes mellitus and lowers food intake and body mass while improving insulin resistance and the lipid profile. Ovariectomized rats show increased body mass, insulin resistance and changes in the lipid profile. Thus, the aim of this work was to evaluate whether metformin could prevent the early metabolic dysfunction that occurs early after ovariectomy. Female Wistar rats were divided into the following groups: SHAM-operated (SHAM), ovariectomized (OVX), ovariectomized + estradiol (OVX + E2) and ovariectomized + metformin (OVX + M). Treatment with metformin diminished approximately 50% of the mass gain observed in ovariectomized animals and reduced both the serum and hepatic triglyceride levels. The hepatic levels of phosphorylated AMP-activated protein kinase (pAMPK) decreased after OVX, and the expression of the inactive form of hepatic acetyl-CoA carboxylase (ACC) was also reduced. Metformin was able to increase the levels of pAMPK in the liver of OVX animals, sustaining the balance between the inactive and total forms of ACC. Estradiol effects were similar to those of metformin but with different proportions. Our results suggest that metformin ameliorates the early alterations of metabolic parameters and rescues hepatic AMPK phosphorylation and ACC inactivation observed in ovariectomized rats.
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Jan van Goyen Medical Center, Department of Internal Medicine, Amsterdam, the Netherlands
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Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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In this review we discuss skeletal adaptations to the demanding situation of pregnancy and lactation. Calcium demands are increased during pregnancy and lactation, and this is effectuated by a complex series of hormonal changes. The changes in bone structure at the tissue and whole bone level observed during pregnancy and lactation appear to largely recover over time. The magnitude of the changes observed during lactation may relate to the volume and duration of breastfeeding and return to regular menses. Studies examining long-term consequences of pregnancy and lactation suggest that there are small, site-specific benefits to bone density and that bone geometry may also be affected. Pregnancy- and lactation-induced osteoporosis (PLO) is a rare disease for which the pathophysiological mechanism is as yet incompletely known; here, we discuss and speculate on the possible roles of genetics, oxytocin, sympathetic tone and bone marrow fat. Finally, we discuss fracture healing during pregnancy and lactation and the effects of estrogen on this process.
Parathyroid Unit – LIM-28, Laboratório de Cirurgia de Cabeça e Pescoço, Division of Head and Neck Surgery, Department of Surgery, Hospital das Clinicas (HCFMUSP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil
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Endocrine Oncology Division, Institute of Cancer of the State of São Paulo (ICESP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, São Paulo, Brazil
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Endocrine Oncology Division, Institute of Cancer of the State of São Paulo (ICESP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, São Paulo, Brazil
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Background
Potential influences of parathyroidectomy (PTx) on the quality of life (QoL) in multiple endocrine neoplasia type 1-related primary hyperparathyroidism (HPT/MEN1) are unknown.
Method
Short Form 36 Health Survey Questionnaire was prospectively applied to 30 HPT/MEN1 patients submitted to PTx (20, subtotal; 10, total with autograft) before, 6 and 12 months after surgery. Parameters that were analyzed included QoL, age, HPT-related symptoms, general pain, comorbidities, biochemical/hormonal response, PTx type and parathyroid volume.
Results
Asymptomatic patients were younger (30 vs 38 years; P = 0.04) and presented higher QoL scores than symptomatic ones: Physical Component Summary score (PCS) 92.5 vs 61.2, P = 0.0051; Mental Component Summary score (MCS) 82.0 vs 56.0, P = 0.04. In both groups, QoL remained stable 1 year after PTx, independently of the number of comorbidities. Preoperative general pain was negatively correlated with PCS (r = −0.60, P = 0.0004) and MCS (r = −0.57, P = 0.0009). Also, moderate/intense pain was progressively (6/12 months) more frequent in cases developing hypoparathyroidism. The PTx type and hypoparathyroidism did not affect the QoL at 12 months although remnant parathyroid tissue volume did have a positive correlation (P = 0.0490; r = 0.3625) to PCS 12 months after surgery. Patients with one to two comorbidities had as pre-PTx PCS (P = 0.0015) as 12 months and post-PTx PCS (P = 0.0031) and MCS (P = 0.0365) better than patients with three to four comorbidities.
Conclusion
A variable QoL profile was underscored in HPT/MEN1 reflecting multiple factors associated with this complex disorder as comorbidities, advanced age at PTx and presence of preoperative symptoms or of general pain perception. Our data encourage the early indication of PTx in HPT/MEN1 by providing known metabolic benefits to target organs and avoiding potential negative impact on QoL.
Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, USA
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA
Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, Oregon, USA
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Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, USA
Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon, USA
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Like women, old female rhesus macaques undergo menopause and show many of the same age-associated changes, including perturbed activity/rest cycles and altered circulating levels of many hormones. Previous studies showed that administration of an estrogen agonist increased activity in female monkeys, that hormone therapy (HT) increased activity in postmenopausal women and that obesity decreased activity in women. The present study sought to determine if postmenopausal activity and circulating hormone levels also respond to HT when monkeys are fed a high-fat, high-sugar Western style diet (WSD). Old female rhesus macaques were ovo-hysterectomized (OvH) to induce surgical menopause and fed a WSD for 2 years. Half of the animals received estradiol-17β (E), beginning immediately after OvH, while the other half received placebo. Animals in both groups showed an increase in body weight and a decrease in overall activity levels. These changes were associated with a rise in both daytime and nocturnal serum leptin concentrations, but there was no change in serum concentrations of either cortisol or dehydroepiandrosterone sulfate (DHEAS). These data suggest that 2 years of HT has little or no effect on locomotor activity or circadian hormone patterns in menopausal macaques fed an obesogenic diet.
Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain
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Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain
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Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain
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Objective:
Permanent hypoparathyroidism is an uncommon disease resulting most frequently from neck surgery. It has been associated with visceral calcifications but few studies have specifically this in patients with post-surgical hypoparathyroidism. The aim of the present study was to assess the prevalence of basal ganglia and carotid artery calcifications in patients with long-term post-thyroidectomy hypoparathyroidism compared with a control population.
Design:
Case–control study.
Methods:
A cross-sectional review comparing 29 consecutive patients with permanent postoperative hypoparathyroidism followed-up in a tertiary reference unit for Endocrine Surgery with a contemporary control group of 501 patients who had an emergency brain CT scan. Clinical variables and prevalence of basal ganglia and carotid artery calcifications were recorded.
Results:
From a cohort of 46 patients diagnosed with permanent hypoparathyroidism, 29 were included in the study. The mean duration of disease was 9.2 ± 7 years. Age, diabetes, hypertension, smoking and dyslipidemia were similarly distributed in case and control groups. The prevalence of carotid artery and basal ganglia calcifications was 4 and 20 times more frequent in patients with permanent hypoparathyroidism, respectively. After propensity score matching of the 28 the female patients, 68 controls were matched for age and presence of cardiovascular factors. Cases showed a four-fold prevalence of basal ganglia calcifications, whereas that of carotid calcifications was similar between cases and controls.
Conclusion:
A high prevalence of basal ganglia calcifications was observed in patients with post-surgical permanent hypoparathyroidism. It remains unclear whether carotid artery calcification may also be increased.
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Background
The effect of parathyroid autotransplantation on hypoparathyroidism is not fully understood. The purpose of the study was to determine the effect of autotransplantation of a parathyroid gland on the incidence of hypoparathyroidism and recovery of parathyroid function at 6 months after total thyroidectomy with central neck dissection for papillary thyroid carcinoma.
Methods
All patients with autotransplantation of a parathyroid gland (no inadvertent parathyroidectomy) (group A), in situ preservation of all parathyroid glands (no autotransplantation and inadvertent parathyroidectomy) (group B) or inadvertent removal of a parathyroid gland (no autotransplantation) (group C) who underwent first-time total thyroidectomy with central neck dissection for papillary thyroid carcinoma between January 2013 and June 2016 were included retrospectively.
Results
Of the 702 patients, 383, 297 and 22 were respectively included in the groups A, B and C. The overall rates of transient and permanent hypoparathyroidism were 37.6% and 1.0%. The incidence of transient hypoparathyroidism was 43.9, 29.0 and 45.5% (A vs B, P = 0.000; A vs C, P = 1.000), and the incidence of permanent hypoparathyroidism was 1.0, 0.7 and 4.5% (P > 0.05). The recovery rates of serum parathyroid hormone levels were 71.4, 72.2 and 66.0% at 6-month follow-up (P > 0.05).
Conclusion
Autotransplantation of a parathyroid gland does not affect the incidence of permanent hypoparathyroidism, but increases the risk of transient hypoparathyroidism when the rest of parathyroid glands are preserved in situ. At least 2 parathyroid glands should be preserved during total thyroidectomy with central neck dissection to prevent permanent hypoparathyroidism.
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Aim
Ensuring adequate calcium (Ca) intake during childhood and adolescence is critical to acquire good peak bone mass to prevent osteoporosis during older age. As one of the primary strategies to build and maintain healthy bones, we aimed to determine whether dietary Ca intake has an influence on bone mineral density (BMD) in children and adolescents.
Methods
We conducted a cross-sectional study composed of 10,092 individuals from the National Health and Nutrition Examination Survey (NHANES). Dietary Ca intake and total BMD were taken as independent and dependent variables, respectively. To evaluate the association between them, we conducted weighted multivariate linear regression models and smooth curve fittings.
Results
There was a significantly positive association between dietary Ca intake and total BMD. The strongest association was observed in 12–15 year old whites, 8–11 year old and 16–19 year old Mexican Americans, and 16–19 year old individuals from other race/ethnicity, in whom each quintile of Ca intake was increased. We also found that there were significant inflection points in females, blacks, and 12–15 year old adolescents group, which means that their total BMD would decrease when the dietary Ca intake was more than 2.6–2.8 g/d.
Conclusions
This cross-sectional study indicated that a considerable proportion of children and adolescents aged 8–19 years would attain greater total BMD if they increased their dietary Ca intake. However, higher dietary Ca intake (more than 2.6–2.8 g/d) is associated with lower total BMD in females, blacks, and 12–15 year old adolescents group.
College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
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Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
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Department of Nephrology, China Medical University Hospital, Taichung, Taiwan
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Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
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Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
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Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
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Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
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Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
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Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
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Secondary hyperparathyroidism (SHPT) is a common complication of end-stage kidney disease (ESKD). Hungry bone syndrome (HBS) occurs frequently in patients on maintenance dialysis receiving parathyroidectomy for refractory SHPT. However, there is scanty study investigating the clinical risk factors that predict postoperative HBS, and its outcome in peritoneal dialysis (PD) patients. We conducted a single-center retrospective study to analyze 66 PD patients who had undergone parathyroidectomy for secondary hyperparathyroidism at Chang Gung Memorial Hospital between 2009 and 2019. The patients were stratified into two groups based on the presence (n=47) or absence (n=19) of HBS after parathyroidectomy. Subtotal parathyroidectomy was the most common surgery performed (74.2%), followed by total parathyroidectomy with autoimplantation (25.8%). Pathological examination of all surgical specimens revealed parathyroid hyperplasia (100%). Patients with HBS had lower levels of postoperative nadir corrected calcium, higher alkaline phosphate (ALP), and higher potassium levels compared with patients without HBS (all P<0.05). A multivariate logistic regression model confirmed that lower preoperative serum calcium level (OR 0.354, 95% CI 0.133–0.940, P=0.037), higher ALP (OR 1.026, 95% CI 1.008–1.044, P=0.004), and higher potassium level (OR 6.894, 95% CI 1.806–26.317, P=0.005) were associated with HBS after parathyroidectomy. Patients were followed for 58.2±30.8 months after the surgery. There was no significant difference between HBS and non-HBS groups in persistence (P=0.496) or recurrence (P=1.000) of hyperparathyroidism. The overall mortality rate was 10.6% with no significant difference found between both groups (P=0.099). We concluded that HBS is a common complication (71.2%) of parathyroidectomy for SHPT and should be managed appropriately.
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Endocrine Unit 2, Department of Clinical and Experimental Medicine, Laboratory of Chemistry and Endocrinology, University Hospital of Pisa, Via Paradisa 2, 56124 Pisa, Italy
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We investigated the prevalence of normocalcemic primary hyperparathyroidism (NPHPT) in the adult population living in a village in Southern Italy. All residents in 2010 (n=2045) were invited by calls and 1046 individuals accepted to participate. Medical history, calcium intake, calcium, albumin, creatinine, parathyroid hormone (PTH) and 25OHD were evaluated. NPHPT was defined by normal albumin-adjusted serum calcium, elevated plasma PTH, and exclusion of common causes of secondary hyperparathyroidism (SHPT) (serum 25OHD <30 ng/ml, estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2 and thiazide diuretics use), overt gastrointestinal and metabolic bone diseases. Complete data were available for 685 of 1046 subjects. Twenty subjects did not meet the inclusion criteria and 341 could not be evaluated because of thawing of plasma samples. Classical PHPT was diagnosed in four women (0.58%). For diagnosing NPHPT the upper normal limit of PTH was established in the sample of the population (n=100) who had 25OHD ≥30 ng/ml and eGFR ≥60 ml/min per 1.73 m2 and was set at the mean+3s.d. Three males (0.44%) met the diagnostic criteria of NPHPT. These subjects were younger and with lower BMI than those with classical PHPT. Our data suggest, in line with previous studies, that NPHPT might be a distinct clinical entity, being either an early phenotype of asymptomatic PHPT or a distinct variant of it. However, we cannot exclude that NPHPT might also represent an early phase of non-classical SHPT, since other variables, in addition to those currently taken into account for the diagnosis of NPHPT, might cumulate in a normocalcemic subject to increase PTH secretion.