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Journal of Bone and Mineral Research :... Dec 2022The efficacy and safety of parathyroid hormone (PTH) therapy for managing long-term hypoparathyroidism is being evaluated in ongoing clinical trials. We undertook a... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of parathyroid hormone (PTH) therapy for managing long-term hypoparathyroidism is being evaluated in ongoing clinical trials. We undertook a systematic review and meta-analysis of currently available randomized controlled trials to investigate the benefits and harms of PTH therapy and conventional therapy in the management of patients with chronic hypoparathyroidism. To identify eligible studies, published in English, we searched Embase, PubMed, and Cochrane CENTRAL from inception to May 2022. Two reviewers independently extracted data and assessed the risk of bias. We defined patients' important outcomes and used grading of recommendations, assessment, development, and evaluation (GRADE) to provide the structure for quantifying absolute effects and rating the quality of evidence. Seven randomized trials of 12 publications that enrolled a total of 386 patients proved eligible. The follow-up duration ranged from 1 to 36 months. Compared with conventional therapy, PTH therapy probably achieves a small improvement in physical health-related quality of life (mean difference [MD] 3.4, 95% confidence interval [CI] 1.5-5.3, minimally important difference 3.0, moderate certainty). PTH therapy results in more patients reaching 50% or greater reduction in the dose of active vitamin D and calcium (relative risk [RR] = 6.5, 95% CI 2.5-16.4, 385 more per 1000 patients, high certainty). PTH therapy may increase hypercalcemia (RR =2.4, 95% CI 1.2-5.04, low certainty). The findings may support the use of PTH therapy in patients with chronic hypoparathyroidism. Because of limitations of short duration and small sample size, evidence from randomized trials is limited regarding important benefits of PTH therapy compared with conventional therapy. Establishing such benefits will require further studies. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Hypercalcemia; Hypoparathyroidism; Parathyroid Hormone; Quality of Life; Vitamin D
PubMed: 36385517
DOI: 10.1002/jbmr.4676 -
Journal of Bone and Mineral Research :... Dec 2022The approach utilized a systematic review of the medical literature executed with specifically designed criteria that focused on the etiologies and pathogenesis of...
The approach utilized a systematic review of the medical literature executed with specifically designed criteria that focused on the etiologies and pathogenesis of hypoparathyroidism. Enhanced attention by endocrine surgeons to new knowledge about parathyroid gland viability are reviewed along with the role of intraoperative parathyroid hormone (ioPTH) monitoring during and after neck surgery. Nonsurgical etiologies account for a significant proportion of cases of hypoparathyroidism (~25%), and among them, genetic etiologies are key. Given the pervasive nature of PTH deficiency across multiple organ systems, a detailed review of the skeletal, renal, neuromuscular, and ocular complications is provided. The burden of illness on affected patients and their caregivers contributes to reduced quality of life and social costs for this chronic endocrinopathy. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Hypoparathyroidism; Parathyroid Hormone; Quality of Life; Parathyroid Glands
PubMed: 36153665
DOI: 10.1002/jbmr.4714 -
The Journal of Clinical Endocrinology... May 2020Atypical femur fractures (AFFs) are serious adverse events associated with bisphosphonates and often show poor healing.
CONTEXT
Atypical femur fractures (AFFs) are serious adverse events associated with bisphosphonates and often show poor healing.
EVIDENCE ACQUISITION
We performed a systematic review to evaluate effects of teriparatide, raloxifene, and denosumab on healing and occurrence of AFF.
EVIDENCE SYNTHESIS
We retrieved 910 references and reviewed 67 papers, including 31 case reports, 9 retrospective and 3 prospective studies on teriparatide. There were no RCTs. We pooled data on fracture union (n = 98 AFFs on teriparatide) and found that radiological healing occurred within 6 months of teriparatide in 13 of 30 (43%) conservatively managed incomplete AFFs, 9 of 10 (90%) incomplete AFFs with surgical intervention, and 44 of 58 (75%) complete AFFs. In 9 of 30 (30%) nonoperated incomplete AFFs, no union was achieved after 12 months and 4 (13%) fractures became complete on teriparatide. Eight patients had new AFFs during or after teriparatide. AFF on denosumab was reported in 22 patients, including 11 patients treated for bone metastases and 8 without bisphosphonate exposure. Denosumab after AFF was associated with recurrent incomplete AFFs in 1 patient and 2 patients of contralateral complete AFF. Eight patients had used raloxifene before AFF occurred, including 1 bisphosphonate-naïve patient.
CONCLUSIONS
There is no evidence-based indication in patients with AFF for teriparatide apart from reducing the risk of typical fragility fractures, although observational data suggest that teriparatide might result in faster healing of surgically treated AFFs. Awaiting further evidence, we formulate recommendations for treatment after an AFF based on expert opinion.
Topics: Bone Density Conservation Agents; Denosumab; Diphosphonates; Europe; Femoral Fractures; Humans; Osteoporotic Fractures; Practice Patterns, Physicians'; Raloxifene Hydrochloride; Risk Assessment; Risk Factors; Societies, Medical; Teriparatide
PubMed: 31867670
DOI: 10.1210/clinem/dgz295 -
Journal of Bone and Mineral Research :... Dec 2022This narrative report summarizes diagnostic criteria for hypoparathyroidism and describes the clinical presentation and underlying genetic causes of the nonsurgical...
This narrative report summarizes diagnostic criteria for hypoparathyroidism and describes the clinical presentation and underlying genetic causes of the nonsurgical forms. We conducted a comprehensive literature search from January 2000 to January 2021 and included landmark articles before 2000, presenting a comprehensive update of these topics and suggesting a research agenda to improve diagnosis and, eventually, the prognosis of the disease. Hypoparathyroidism, which is characterized by insufficient secretion of parathyroid hormone (PTH) leading to hypocalcemia, is diagnosed on biochemical grounds. Low albumin-adjusted calcium or ionized calcium with concurrent inappropriately low serum PTH concentration are the hallmarks of the disease. In this review, we discuss the characteristics and pitfalls in measuring calcium and PTH. We also undertook a systematic review addressing the utility of measuring calcium and PTH within 24 hours after total thyroidectomy to predict long-term hypoparathyroidism. A summary of the findings is presented here; results of the detailed systematic review are published separately in this issue of JBMR. Several genetic disorders can present with hypoparathyroidism, either as an isolated disease or as part of a syndrome. A positive family history and, in the case of complex diseases, characteristic comorbidities raise the clinical suspicion of a genetic disorder. In addition to these disorders' phenotypic characteristics, which include autoimmune diseases, we discuss approaches for the genetic diagnosis. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Calcium; Hypocalcemia; Hypoparathyroidism; Parathyroid Hormone
PubMed: 36375809
DOI: 10.1002/jbmr.4667 -
The Journal of Clinical Endocrinology... Aug 2023Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by...
CONTEXT
Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by pathogenic variants in TBCE and FAM111A, respectively. Clinically the phenotypes are difficult to distinguish.
OBJECTIVE
The objective was to determine and expand the phenotypic spectrum of KCS1 and KCS2 in order to anticipate complications that may arise in these disorders.
METHODS
We clinically and genetically analyzed 10 KCS2 patients from 7 families. Because we found unusual phenotypes in our cohort, we performed a systematic review of genetically confirmed KCS cases using PubMed and Scopus. Evaluation by 3 researchers led to the inclusion of 26 papers for KCS1 and 16 for KCS2, totaling 205 patients. Data were extracted following the Cochrane guidelines and assessed by 2 independent researchers.
RESULTS
Several patients in our KCS2 cohort presented with intellectual disability (3/10) and chronic kidney disease (6/10), which are not considered common findings in KCS2. Systematic review of all reported KCS cases showed that the phenotypes of KCS1 and KCS2 overlap for postnatal growth retardation (KCS1: 52/52, KCS2: 23/23), low parathyroid hormone levels (121/121, 16/20), electrolyte disturbances (139/139, 24/27), dental abnormalities (47/50, 15/16), ocular abnormalities (57/60, 22/23), and seizures/spasms (103/115, 13/16). Symptoms more prevalent in KCS1 included intellectual disability (74/80, 5/24), whereas in KCS2 bone cortical thickening (1/18, 16/20) and medullary stenosis (7/46, 27/28) were more common.
CONCLUSION
Our case series established chronic kidney disease as a new feature of KCS2. In the literature, we found substantial overlap in the phenotypic spectra of KCS1 and KCS2, but identified intellectual disability and the abnormal bone phenotype as the most distinguishing features.
Topics: Humans; Intellectual Disability; Hyperostosis, Cortical, Congenital; Phenotype; Electrolytes; Hypoparathyroidism
PubMed: 36916904
DOI: 10.1210/clinem/dgad147 -
Archives of Gerontology and Geriatrics 2020To systematically estimate the association between elevated parathyroid hormone (PTH) levels and cognitive function.
OBJECTIVE
To systematically estimate the association between elevated parathyroid hormone (PTH) levels and cognitive function.
METHODS
This review was conducted on ten papers identified through database searches from inception to 31 October 2018. The quality of studies was assessed using the Downs and Black checklist.
RESULTS
There is a low volume of data reporting on the impact of elevated PTH levels on cognitive impairment. The quality of the identified studies ranged from poor (37 %) to good (76 %). Although the results from studies were mixed, one cross-sectional study and one prospective study suggested a link between elevated PTH levels and a decrease in the Mini-Mental State Examination (MMSE) score. Three cross-sectional studies that assessed other cognitive domain in specific domains, such as language, memory and executive function provided mixed results for an association between elevated PTH levels and cognitive function. Two studies showed mixed evidence for a link between elevated PTH levels and poor executive function. One prospective study, one cross-sectional study and three case-control studies provide mixed evidence for an association between higher PTH levels and Alzheimer´s disease (AD). Two studies showed limited evidence for an association between elevated PTH levels and vascular dementia.
CONCLUSION
This review presented that the level of evidence available to support an association between elevated PTH levels and cognitive function was generally weak and inconsistent. Future studies with more better methodological quality are needed.
Topics: Cognition; Cognitive Dysfunction; Executive Function; Humans; Memory; Parathyroid Hormone
PubMed: 31770681
DOI: 10.1016/j.archger.2019.103985 -
Endocrine Practice : Official Journal... Jan 2023To review diagnostic imaging modalities for parathyroid cystic adenomas (PCA). Since PCAs are a rare (0.5%-1%) subclass of parathyroid adenomas, and due to their cystic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To review diagnostic imaging modalities for parathyroid cystic adenomas (PCA). Since PCAs are a rare (0.5%-1%) subclass of parathyroid adenomas, and due to their cystic component, imaging modalities known to be efficient for diagnosing solid adenomas might fail in localizing them.
METHODS
We conducted a systematic review using the PubMed and Cochrane databases for English articles on PCAs published between 1995 and 2020. A meta-analysis of the retrieved data was performed.
RESULTS
Overall, 39 studies, reporting on a total of 160 patients, were included in the analysis. Two thirds (68%) of the patients were female, with a mean age of 53.9 years. A single cystic adenoma was detected in 98.1% of cases. The mean blood calcium corrected for albumin level was 12.6 ± 2.7 mg/dL, and the mean parathyroid hormone level was 565.5 ± 523.8 pg/mL. The mean PCA sizes as measured by ultrasound (US), computed tomography (CT), and ex vivo measurement were 4.8 ± 3.6, 5.2 ± 3.2, and 3.5 cm, respectively. The median weight was 8.1 g. PCA was detected in 86% of US examinations; 100% of US-guided fine needle aspiration, 4-dimensional computed tomography (4D-CT), or magnetic resonance imaging examinations; and 61% of 99m-technetium sestamibi scan with single-photon emission computed tomography ((99m)Tc-SPECT). (99m)Tc-SPECT showed a significantly lower diagnostic rate than US (odds ratio, 3.589), US-guided fine needle aspiration, CT combined with 4D-CT, and the combination of US, CT, 4D-CT, and magnetic resonance imaging (P < .001).
CONCLUSION
Although US and 4D-CT showed a significantly high rate in diagnosing PCA, (99m)Tc-SPECT showed a lower PCA diagnostic rate. These findings suggest that larger cystic lesions suspected as PCAs should be further evaluated using 4D-CT rather than (99m)Tc-SPECT.
Topics: Humans; Female; Middle Aged; Male; Parathyroid Neoplasms; Parathyroid Glands; Technetium Tc 99m Sestamibi; Four-Dimensional Computed Tomography; Adenoma; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Radiopharmaceuticals
PubMed: 36370985
DOI: 10.1016/j.eprac.2022.11.004 -
Frontiers in Endocrinology 2022Patients with primary aldosteronism (PA) tend to exhibit a high prevalence of osteoporosis (OP) that may vary by whether PA is unilateral or bilateral, and responsive to... (Meta-Analysis)
Meta-Analysis
PURPOSE
Patients with primary aldosteronism (PA) tend to exhibit a high prevalence of osteoporosis (OP) that may vary by whether PA is unilateral or bilateral, and responsive to PA treatment. To explore relationships between bone metabolism, PA subtypes, and treatment outcomes, we performed a systematic review and meta-analysis.
METHODS
The PubMed, Embase, and Cochrane databases were searched for clinical studies related to PA and bone metabolism markers. Articles that met the criteria were screened and included in the systematic review; the data were extracted after evaluating their quality. R software (ver. 2022-02-16, Intel Mac OS X 11.6.4) was used for the meta-analysis.
RESULTS
A total of 28 articles were subjected to systematic review, of which 18 were included in the meta-analysis. We found that PA patients evidenced a lower serum calcium level (mean difference [MD] = -0.06 mmol/L, 95% confidence interval [CI]: -0.10 ~ -0.01), a higher urine calcium level (MD = 1.29 mmol/24 h, 95% CI: 0.81 ~ 1.78), and a higher serum parathyroid hormone (PTH) level (MD = 2.16 pmol/L, 95% CI: 1.57 ~ 2.75) than did essential hypertension (EH) subjects. After medical treatment or adrenal surgery, PA patients exhibited a markedly increased serum calcium level (MD = -0.08 mmol/L, 95% CI: -0.11 ~ -0.05), a decreased urine calcium level (MD = 1.72 mmol/24 h, 95% CI: 1.00 ~ 2.44), a decreased serum PTH level (MD = 2.67 pmol/L, 95% CI: 1.73 ~ 3.62), and an increased serum 25-hydroxyvitamin D (25-OHD) level (MD = -6.32 nmol/L, 95% CI: -11.94 ~ -0.70). The meta-analysis showed that the ser um PTH level of unilateral PA patients was significantly higher than that of bilateral PA patients (MD = 0.93 pmol/L, 95% CI: 0.36 ~ 1.49) and the serum 25-OHD lower than that of bilateral PA patients (MD = -4.68 nmol/L, 95% CI: -7.58 ~ 1.77). There were, however, no significant differences between PA and EH patients of 25-OHD, or BMD of femoral neck and lumbar spine. BMDs of the femoral neck or lumbar spine did not change significantly after treatment. The meta-analytical results were confirmed sensitivity and subgroup analyses.
CONCLUSION
Excess aldosterone was associated with decreased serum calcium, elevated urinary calcium, and elevated PTH levels; these effects may be enhanced by low serum 25-OHD levels. The risks of OP and fracture might be elevated in PA patients, especially unilateral PA patients, but could be reduced after medical treatment or adrenal surgery. In view, however, of the lack of BMD changes, such hypothesis needs to be tested in further studies.
Topics: Humans; Bone Density; Calcium; Bone and Bones; Parathyroid Hormone; Osteoporosis; Essential Hypertension; Hyperaldosteronism; Minerals
PubMed: 36387892
DOI: 10.3389/fendo.2022.1027841 -
Disease-a-month : DM Feb 2022
Topics: Epithelium; Humans; Intestines; Magnesium; Magnesium Deficiency; RNA, Messenger; TRPM Cation Channels
PubMed: 34511254
DOI: 10.1016/j.disamonth.2021.101285 -
American Journal of Surgery Aug 2023We aim to evaluate the body of evidence reporting on normohormonal primary hyperparathyroidism (NHpHPT) patients to help guide their diagnosis, characterization and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We aim to evaluate the body of evidence reporting on normohormonal primary hyperparathyroidism (NHpHPT) patients to help guide their diagnosis, characterization and treatment.
BACKGROUND
Normohormonal primary hyperparathyroidism is a term used to describe patients with a normal PTH and elevated calcium levels. There is limited understanding regarding the presentation and appropriate management of these patients.
METHODS
A systematic review was conducted: abstract and full-text screening were independently conducted by 2 investigators. Odds ratios (OR), standard mean differences (SMD) and 95% confidence intervals were calculated.
RESULTS
Twenty-two studies were identified. Patients with NHpHPT were more likely to present with lower PTH (p < 0.00001) and calcium (p < 0.00001) levels. Intraoperatively, the NHpHPT group was 1.8 times more likely to undergo bilateral neck exploration (BNE) and harbor multigland disease. The rates of surgical cure were 93% in the NHpHPT and 96% in the pHPT groups (p = 0.0003).
CONCLUSION
Symptomatic patients with NHpHPT benefit from parathyroidectomy with prolonged intraoperative PTH monitoring, and a low threshold for conversion to BNE.
Topics: Humans; Calcium; Parathyroid Hormone; Hyperparathyroidism, Primary; Retrospective Studies; Parathyroidectomy
PubMed: 37100740
DOI: 10.1016/j.amjsurg.2023.04.004