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Risk factors and evolution of calcium and parathyroid hormone levels in hungry bone syndrome after parthyroidectomy for primary hyperparathyroidism.
Guillén Martínez, AJ, Smilg Nicolás, C, Moraleda Deleito, J, Guillén Martínez, S, García-Purriños García, F
Endocrinologia, diabetes y nutricion. 2020;(5):310-316
Abstract
INTRODUCTION Hungry bone syndrome (HBS) is a complication occurring after parathyroid surgery that can cause severe and prolonged hypocalcemia. The study objective was to know the risk factors for HBS after surgery for primary hyperparathyroidism and its relationship with serum calcium and parathyroid hormone levels. MATERIAL AND METHODS A case-control, observational, analytical study was conducted in patients who had undergone surgery for primary hyperparathyroidism in the past 10 years (2007-2016). Changes over time in serum calcium and PTH levels and the general characteristics of patients were analyzed. RESULTS The incidence rate of HBS in our series was 12.2%. HBS was found to be significantly associated to thyroid surgery during the surgical procedure itself (adjusted odds ratio [aOR]=17.241), to age older than 68 years (aOR=6.666), and to lesions greater than 1.7cm (aOR=7.165). A statistically significant relationship was seen between presence of HBS and corrected serum calcium levels higher than the mean the day after surgery and one week and 3 months later, and also with PTH levels higher than the mean before, during, and one day after surgery. CONCLUSION In our series, independent risk factors for development of HBS included patient age, lesion size, and whether or not the procedure was accompanied by thyroid surgery, which requires closer monitoring of mineral metabolism during the perioperative period.
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Metabolic Syndrome in Parathyroid Diseases.
Corbetta, S, Mantovani, G, Spada, A
Frontiers of hormone research. 2018;:67-84
Abstract
Parathyroid glands are the main regulator of body mineral metabolism through parathormone (PTH) actions on bone and kidney. Experimental evidence suggests that PTH may have non-classical target organs such as adipose tissue, arterial vascular wall, cardiac muscle cells, and adrenal cortex cells, where it may play a role in controlling body energy, blood pressure, and metabolism. Cardiometabolic features have been investigated in the wide spectrum of clinical parathyroid disorders, from hyperparathyroidism to pseudohypoparathyroidism and hypoparathyroidism. Indeed, in parathyroid disorders, besides altered PTH secretion, impaired serum calcium levels and vitamin D status occur. Both calcium and vitamin D have been shown to regulate metabolism and to be associated with cardiovascular diseases. However, despite the complexity of parathyroid disorders, features of metabolic syndrome, such as obesity, insulin resistance, and glucose intolerance, arterial blood hypertension, and dyslipidemia, are frequently diagnosed in primary and secondary hyperparathyroidism as well as in pseudohyperparathyroidism. Here, we reviewed the most consistent data highlighting challenges and providing clinical remarks.
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Parathyroid hormone resistance syndromes - Inactivating PTH/PTHrP signaling disorders (iPPSDs).
Elli, FM, Pereda, A, Linglart, A, Perez de Nanclares, G, Mantovani, G
Best practice & research. Clinical endocrinology & metabolism. 2018;(6):941-954
Abstract
Metabolic disorders caused by impairments of the Gsα/cAMP/PKA pathway affecting the signaling of PTH/PTHrP lead to features caused by non-responsiveness of target organs, in turn leading to manifestations similar to the deficiency of the hormone itself. Pseudohypoparathyroidism (PHP) and related disorders derive from a defect of the α subunit of the stimulatory G protein (Gsα) or of downstream effectors of the same pathway, such as the PKA regulatory subunit 1A and the phosphodiesterase type 4D. The increasing knowledge on these diseases made the actual classification of PHP outdated as it does not include related conditions such as acrodysostosis (ACRDYS) or progressive osseous heteroplasia (POH), so that a new nomenclature and classification has been recently proposed grouping these disorders under the term "inactivating PTH/PTHrP signaling disorder" (iPPSD). This review will focus on the pathophysiology, clinical and molecular aspects of these rare, heterogeneous but closely related diseases.
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Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement.
Mantovani, G, Bastepe, M, Monk, D, de Sanctis, L, Thiele, S, Usardi, A, Ahmed, SF, Bufo, R, Choplin, T, De Filippo, G, et al
Nature reviews. Endocrinology. 2018;(8):476-500
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Abstract
This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders.
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Vitamin D, parathyroid hormone and metabolic syndrome - the PORMETS study.
Raposo, L, Martins, S, Ferreira, D, Guimarães, JT, Santos, AC
BMC endocrine disorders. 2017;(1):71
Abstract
BACKGROUND Vitamin D (VitD) and parathyroid hormone (PTH) play important roles in calcium metabolism and skeletal homeostasis. Estimates of the VitD status in several European countries show large variations between them. In addition, no national population-based estimate has been published. VitD and PTH may also play important roles in cardiovascular risk, which has been suggested to be associated with metabolic syndrome (MetS) and is very prevalent in Portugal. The goal of our study was to evaluate the prevalence of hypovitaminosis D and its determinants as well as PTH serum level determinants and associations of the 25-hydroxyvitamin D and PTH serum levels with MetS and its individual components in a sample of the Portuguese mainland population. METHODS PORMETS is a national cross-sectional study that includes a total sample of 4095 adults. A subsample, including 500 participants, was randomly selected for the present study. A structured questionnaire was administered to collect information on personal medical histories and socio-demographic and behavioral characteristics. Blood pressure and anthropometrics measurements were performed. Fasting venous samples were collected and PTH and 25-hydroxyvitamin D were measured. VitD adequacy was classified according to the Institute of Medicine, and MetS was classified according to the Joint Interim Statement recommendations. Multiple linear regression and unconditional logistic regression models were used to estimate the associations between the levels of PTH and 25-hydroxyvitamin D and with MetS and its individual components. RESULTS The prevalence of VitD deficiency was 37.7%, and MetS was present in 191 participants (38.4%). The serum PTH levels showed a positive association (OR: 1.014; 95%CI: 1.002, 1.026) with the waist circumference component of MetS. The serum 25-hydroxyvitamin D levels were negatively associated with MetS (OR: 0.957; 95%CI: 0.922, 0.993) as well as with its blood pressure (OR: 0.949; 95%CI: 0.912, 0.987) and triglycerides (OR: 0.930; 95%CI: 0.892, 0.969) components. CONCLUSION This study showed a high national prevalence of hypovitaminosis D. The PTH levels showed a significant positive association with the WC component of MetS, and the VitD levels were negatively associated with the BP and triglycerides components as well as with the MetS.
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Evaluation of fracture risk in chronic kidney disease.
Torres, PAU, Cohen-Solal, M
Journal of nephrology. 2017;(5):653-661
Abstract
Chronic kidney disease (CKD) is associated with mineral and bone disorders (MBD) that are now considered as a syndrome. Bone fragility and a four to tenfold increased rate of skeletal fractures are often reported in CKD patients. The evaluation of the risk of these fractures in CKD patients should explore the same risk factors identified for the general population including low body weight, menopause, personal and familial history of osteoporosis, chronic inflammatory diseases, and corticosteroid therapy. The aim of this article is to provide a critical review of the tools used for the evaluation of bone loss and the risk of fracture in CKD patients, ranging from the measurement of bone mineral density (BMD), fracture risk assessment (Frax™), quantitative computed tomography (QCT), high-resolution peripheral quantitative computed tomography (HRpQTC), to circulating biomarkers of bone metabolism including vitamin D, parathyroid hormone (PTH), bone-specific alkaline phosphatase, osteocalcin, and some collagen type 1-related molecules indicators of bone remodeling.
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Skeletal manifestations of renal disease in childhood.
Denburg, MR
Current opinion in nephrology and hypertension. 2016;(4):292-300
Abstract
PURPOSE OF REVIEW This review summarizes recent findings on musculoskeletal health in three chronic renal conditions of childhood: chronic kidney disease stages 2-5D, nephrotic syndrome, and urolithiasis. Findings with important clinical implications warranting further investigation are highlighted. RECENT FINDINGS Recent cohort studies have demonstrated a high burden of fracture and progressive deficits of cortical bone in children with chronic kidney disease. Lower cortical density is associated with incident fracture and may be an important therapeutic target. Parathyroid hormone and calcium are independent correlates of cortical density, and modifiable factors for fracture include parathyroid hormone and phosphate binder use. Children with nephrotic syndrome, even with normal renal function, have evidence of abnormal bone metabolism and structure, and vitamin D deficiency may be an important modifiable risk factor in this population. Urolithiasis has been associated with reduced bone mineral density and is increasingly common in children and adolescents. Population-based data found a significantly increased risk of fracture in adolescent males and young women. SUMMARY Recent findings substantiate concern regarding the particular vulnerability of the growing skeleton to chronic renal disease. Studies are needed to determine how to optimize assessment and management of bone health in children with these conditions, particularly in terms of calcium and vitamin D requirements, with the goal of improving childhood bone accrual for lifelong fracture prevention.
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Vitamin D status and parathyroid hormone levels in patients with obstructive sleep apnea.
Barceló, A, Esquinas, C, Piérola, J, De la Peña, M, Sánchez-de-la-Torre, M, Montserrat, JM, Marín, JM, Duran, J, Arqué, M, Bauça, JM, et al
Respiration; international review of thoracic diseases. 2013;(4):295-301
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Abstract
BACKGROUND Vitamin D insufficiency and high levels of parathyroid hormone (PTH) appear to be emerging risk factors for metabolic syndrome (MS), diabetes and cardiovascular disease, conditions that occur frequently in patients with obstructive sleep apnea syndrome (OSAS). OBJECTIVES This study examined whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH were associated with the presence of MS, diabetes and hypertension among an OSAS population. METHODS A total of 826 patients (635 men and 191 women) with newly diagnosed OSAS were studied. The occurrence of the MS was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III clinical criteria. Serum levels of 25(OH)D, PTH, glucose, triglycerides, cholesterol, HDL cholesterol, creatinine and uric acid were determined. RESULTS In 55.3% of the men and in 63.2% of the women, the serum 25(OH)D level was less than 30 ng/ml (insufficient status). After adjusting for age, sex and seasonality, there was a significant trend of decreasing odds for diabetes [odds ratio (OR) 0.55, 95% confidence interval (CI) 0.33-0.94, ptrend = 0.038] and MS (OR 0.34, 95% CI 0.21-0.56, ptrend < 0.001) with increasing vitamin D levels. Higher PTH levels were associated with a higher prevalence of obesity (OR 2.05, 95% CI 1.06-3.09, ptrend < 0.001) and hypertension (OR 1.83, 95% CI 1.01-3.05, ptrend = 0.049). CONCLUSIONS These data suggest an inverse association of 25(OH)D with diabetes and MS and a positive association of PTH with obesity and hypertension among patients with OSAS. Based on our observational study, the causative nature of the associations cannot be established. These findings require further examination in prospective studies including clinical trials.
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Association of plasma parathyroid hormone with metabolic syndrome and risk for cardiovascular disease.
Huang, C, Shapses, SA, Wang, X
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2013;(4):712-7
Abstract
OBJECTIVE To review the current literature investigating the association of plasma parathyroid hormone (PTH) with the prevalence of metabolic syndrome and the risk for cardiovascular disease (CVD). METHODS We conducted a search of PubMed and Medline database using the terms hyperparathyroidism, metabolic syndrome, hypertension, hyperlipidemia, hyperglycemia, and CVD. We reviewed relevant studies from 2004 to 2012. RESULTS The current literature assessing the association of plasma PTH levels with metabolic syndrome and CVD is inconsistent; however, positive associations among hyperparathyroidism, metabolic syndrome, and CVD were found in a majority of the studies. The differences in the study populations may partly explain the mixed results. CONCLUSION In the general population, a high serum PTH level predisposes patients to CVD mortality. Further research is needed to determine the role of PTH in the etiology of metabolic syndrome and CVD.
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Parathyroid hormone and heart failure: novel biomarker strategy.
Altay, H, Colkesen, Y
Endocrine, metabolic & immune disorders drug targets. 2013;(1):100-4
Abstract
Heart failure (HF) is a clinical syndrome featuring cardiac pump failure along with signs and symptoms arising from salt and water retention mediated by activated renin-angiotensin-aldosterone system (RAAS). In addition to this cardiorenal perspective, HF is accompanied by a systemic illness, especially in advanced stages characterized by oxidative stress in various tissues, causing damage to soft tissue and bone. Secondary hyperparathyroidism (SHPT) which is also considered to contribute this systemic illness is therefore prominent in advanced HF. SHPT in HF occurs as a result of RAAS activation, prominent hyperaldosteronism, loop diuretic usage and decreased calcitriol level, all of which results in calcium excretion. We review the evidence that high parathyroid hormone (PTH) is associated with advanced HF, as well as evidence that it's associated with HF with preserved ejection fraction (HFPEF).