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1.
Serum biotin interference: A troublemaker in hormone immunoassays.
Öncül, Ü, Eminoğlu, FT, Köse, E, Doğan, Ö, Özsu, E, Aycan, Z
Clinical biochemistry. 2022;:97-102
Abstract
OBJECTIVES Biotin therapy can affect the results of many immunoassay procedures. The present study investigates biotin's interference on 25-hydroxy vitamin D (25-OHD), parathyroidhormone (PTH) and thyroid-stimulating hormone (TSH) tests using four different assay systems and biotin neutralization. DESIGN AND METHODS Enrolled in the study were 50 children diagnosed with biotinidase deficiency (BTD) undergoing treatment with biotin (5-20 mg/day) who were subjected to a series of analyses involving 25-OHD (Roche Diagnostics assays, Beckman Coulter assays, HPLC, LC/MS-MS), TSH, PTH (Roche Diagnostics assays, Beckman Coulter assays) and biotin (LC/MS-MS), before and after biotin neutralization with Streptavidin-coated magnetic particles (SMP). RESULTS The median biotin concentration was found to be 175.2 [94.0-307.1] μg/L. There was no significant difference in the 25-OHD results before and after neutralization with the Beckman Coulter, HPLC and LC-MS/MS assays. In contrast, the median 25-OHD level was seen to decrease from 90.2 [35.9-105.3] ng/mL to 29.1 [22.6-37.6] ng/mL after neutralization with the Roche assay (p < 0.0001). While there was no statistically significant difference in the values recorded before and after neutralization in PTH analysis using Beckman assay, the median PTH levels increased from 7.8 [1.6-21.6] pg/mL to 28.2 [22.5-41.9] pg/mL after neutralization with the Roche assay (p < 0.0001). The cut-off values at which serum biotin interfered in the Roche assay PTH test, with 25-OHD levels determined as 51.4 μg/L and 62.9 μg/L, respectively. A significant increase was detected in the TSH levels analyzed with a Roche assay after neutralization (from 2.36 [1.85-3.00] mIU/L to 2.74 [1.93-3.70] mIU/L, p < 0.0001). CONCLUSIONS The PTH, 25-OHD and TSH results were found to be affected by high biotin concentrations in Roche assays, leading to a risk of misdiagnosis, although SMP neutralization can suppress any such interference efficiently.
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The predictive role of parathyroid hormone for non-alcoholic fatty liver disease based on invasive and non-invasive findings in candidates of bariatric surgery.
Jamialahmadi, T, Nematy, M, Jangjoo, A, Goshayeshi, L, Abdalla, MA, Akhlaghi, S, Sathyapalan, T, Sahebkar, A
Eating and weight disorders : EWD. 2022;(2):693-700
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and hepatic fibrosis are the most detrimental hepatic abnormalities associated with increased body weight with devastating clinical outcomes. Therefore, there is a substantial necessity for efficient management strategies, including significant weight reduction. Bariatric surgery has been used as a therapeutic approach in a selected obese patient with NAFLD/NASH and other cardiometabolic comorbidities. PURPOSE The study is focused on the predictive role of PTH with the indices of hepatic steatosis/NAFLD and NASH based on liver biopsy, elastography, and sonography in morbidly obese patients. METHODS Ninety patients with BMI between 35 and 40 kg/m2 with more than two comorbidities who referred to Imam Reza outpatient clinic from December 2016 to September 2017 were recruited and underwent initial assessments, including demographic profiles, psychological assessment, anthropometric measurements, hepatic biopsy, and basic laboratory tests. Liver stiffness was evaluated using two-dimensional shear wave elastography (2D-SWE) at least two weeks before liver biopsy. The histological analysis of the liver was performed using biopsy samples which obtained from left hepatic lobe during bariatric surgery under direct surgeon observation using a 16-gauge Tru-cut needle. The study was approved by the ethical committee (IR.MUMS.fm.REC.1396.312). RESULTS The level of PTH was significantly high in patients with positive histology for hepatic fibrosis, steatosis, and NASH/NAFLD compared to patients with negative histology (p = 0.005, p = 0.009, and p = 0.013, respectively). Also, patients with liver fibrosis confirmed by elastography had significantly higher serum PTH concentration than patients without fibrosis (p = 0.011). PTH was also positively correlated with hepatic fibrosis, NASH, and steatosis (p = 0.007, p = 0.012, p = 0.023, respectively). CONCLUSION High levels of PTH was significantly associated with histological indices of (hepatic fibrosis, steatosis, NAFLD and NASH) and elasticity indices. Therefore, it is imperative to assess for high levels of PTH in the morbidly obese population pre-and post-bariatric surgery. However, for a more robust and comprehensive assessment, a randomized controlled trial is needed. The study was conducted in accordance with the practice guidance in the diagnosis and management of NAFLD from the American association for the study of liver disease (AASLD) 2018. LEVEL III Evidence obtained from well-designed cohort or case-control analytic studies.
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The Relationship Between Intact Parathyroid Hormone and 25-Hydroxyvitamin D in United Kingdom Resident South Asians and Whites: A Comparative, Cross-Sectional Observational Study.
Coley-Grant, D, Jawad, M, Ashby, HL, Cornes, MP, Kumar, B, Hallin, M, Nightingale, PG, Ford, C, Gama, R
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2021;(10):672-675
Abstract
Ethnic differences in intact parathyroid hormone (iPTH) at similar total 25 hydroxyvitamin D [25(OH)D] concentrations have been reported between US resident Whites, Blacks, and Hispanics, but this has not been studied between South Asians and Whites. We, therefore, compared the iPTH relationship to 25(OH)D in UK resident South Asians and Whites. A comparative, cross-sectional observational study in which demographic and laboratory data on South Asian and White residents of Wolverhampton, UK were analyzed. Log-log models measured the association between 25(OH)D and the interaction term of ethnicity and iPTH. Seven hundred and seventy-two patients consisting of 315 white subjects (208 women) and 457 South Asian subjects (331 women) were studied. Compared to South Asians, White subjects were older, had higher serum concentrations of 25(OH)D, creatinine (lower eGFR), adjusted calcium and magnesium, but similar concentrations of iPTH and phosphate. In an adjusted model, variables significantly associated with 25(OH)D included age, creatinine, adjusted calcium and ethnicity; but not iPTH and the interaction term of ethnicity and iPTH (beta coefficient -0.071, 95% CI -0.209, 0.067, p=0.32). In our study cohort, iPTH was not, per se, influenced by 25 (OH)D. We found no ethnic differences in the association between iPTH and 25(OH)D between South Asians and White UK residents.
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Parathyroid Hormone-Related Changes of Bone Structure.
Kužma, M, Jackuliak, P, Killinger, Z, Payer, J
Physiological research. 2021;(Suppl 1):S3-S11
Abstract
Parathyroid hormone (PTH) increases the release of serum calcium through osteoclasts, which leads to bone resorption. Primary, PTH stimulates osteoblasts leading to increase RANKL (receptor activator for nuclear factor kappa-B ligand) expression and thus differentiation of osteoclasts. In kidneys, PTH increases calcium and decrease phosphate reabsorption. In kidneys, PTH stimulates 1alpha-hydroxylase to synthesize active vitamin D. Primary hyperparathyroidism (PHPT) is characterized by skeletal or renal complications. Nowadays, the classical form of PHPT is less seen and asymptomatic or subclinical (oligo symptomatic) forms are more frequent. Previously, it was thought that cortical bone is preferably affected by PHPT and that predispose bones to fracture at sites with a higher amount of cortical bone. However, an increased risk of vertebral fractures has been found by most of the studies showing that also trabecular bone is affected. Bone Mass measurement (BMD) at all skeletal sites is advised, but another specific tool for fracture assessment is needed. Trabecular bone score (TBS), an indirect measure of trabecular bone, maybe a useful method to estimate fracture risk. TBS is associated with vertebral fractures in PHPT regardless of BMD, age, BMI and gender. Furthermore, there is an association between TBS and high resolution peripheral quantitative computed tomography (HR-pQCT) parameters in the trabecular and cortical compartment. However, studies considering the effect of PHPT treatment on TBS are more conflicting. Secondary hyperparathyroidism caused by vitamin D deficiency was associated with impaired bone microarchitecture in all age categories, as measured by TBS and Hr-pQCT with further improvement after treatment with vitamin D.
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Safety and diagnostic performance of parathyroid hormone assay in fine-needle aspirate in suspicious parathyroid adenomas.
Carral, F, Jiménez, AI, Tomé, M, Alvarez, J, Díez, A, García, C, Vega, V, Ayala, C
Endocrinologia, diabetes y nutricion. 2021;(7):481-488
Abstract
OBJECTIVE To evaluate the safety and diagnostic performance of parathyroid hormone assay in fine-needle aspirate (PTH-FNA) in patients with primary hyperparathyroidism and suspicious parathyroid adenomas. METHODOLOGY A retrospective observational study was performed in 47 patients (57.7 ± 11.2 years of average age, 74% women) attending an endocrinology clinic for primary hyperparathyroidism (average calcemia: 11.6 ± 1.6 mg/dl and PTH: 276 ± 477 pg/mL) in which PTH-FNA was made. Sensibility, specificity, positive predictive value and negative predictive value were calculated in all surgical patients. RESULTS Forty-seven lesions were punctured (mean adenoma maximum diameter: 1.8 ± 2.6 cm): negative image in the sestamibi scan (26 patients); the discordance between ultrasonography and the sestamibi scan (6 patients); possible intrathyroidal adenomas (4 patients); a positive sestamibi scan in 2 or more localizations (4 patients); ectopic adenoma (3 patients); persistent primary hyperparathyroidism (2 patients) and atypical adenomas (2 patients). Mean PTH-FNA was 2853 ± 3957 pg/mL and 68% were considered positive (PTH-FNA ≥ 100 pg/mL). No complications were detected during or after the puncture. Thirty-seven patients were operated on, 95% were cured and no parathyromatosis cases were detected. PTH-FNA ≥ 100 pg/mL as a diagnostic test had a sensitivity of 93.7%, a specificity of 100%, a positive predictive value of 100% and an negative predictive value of 71.4%. CONCLUSION PTH-FNA is an easy and safe diagnostic test and has a high sensitivity and specificity for differentiating between parathyroid adenomas and other cervical masses in patients with primary hyperparathyroidism.
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Vitamin D status in pubertal children.
Önal, ZE, Tekin, A, Gürbüz, T, Sağ, Ç, Nuhoğlu, Ç
Minerva pediatrics. 2021;(2):173-179
Abstract
BACKGROUND Optimal vitamin D status has a great importance in puberty, which is a period of peak bone mineral acquisition. In this study, we aimed to assess the effect of pubertal period on vitamin D status. METHODS The study included totally 200 healthy children, aged between 4 and 14 years. Group 1 included 100 prepubertal, children, aged between 4 and 8 years. Group 2 included 100 pubertal children, aged between 9 and 14 years. They had no chronic illnesses. Ages, heights, weights, genders, Body Mass Indexes (BMIs), socioeconomic and educational status of families were established. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured by high performance liquid chromatography (HPLC). Serum parathyroid hormone (PTH) was evaluated using an immunoradiometric assay kit. Serum calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) levels were measured. RESULTS We determined that 25(OH)D levels were lower with higher PTH levels in the group aged 9 to 14 years (pubertal children), compared to the group aged 4 to 8 (prepubertal children). Gender, weight, height or BMI, family socioeconomic and education status did not affect serum 25(OH)D levels of children in each group. CONCLUSIONS We demonstrated that vitamin D deficiency was more commonly seen in the pubertal children, compared to pre pubertal period. Children should be supported with vitamin D supplements during the puberty, which has a great importance for rapid increase in bone mass.
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Normocalcemic and Normohormonal Primary Hyperparathyroidism: Laboratory Values and End-Organ Effects.
Hollowoa, BR, Spencer, HJ, Stack, BC
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2021;(3):387-397
Abstract
OBJECTIVE Variants of primary hyperparathyroidism (pHPT), described as normocalcemic (NC) and normohormonal (NH), can confuse the diagnosis of classic pHPT. DATA SOURCES A MEDLINE search was performed for variants of pHPT using the PubMed database (last queried October 2019). REVIEW METHODS The search was restricted to articles published after 1960 that were specific to humans. Studies were included in our analysis if laboratory values and incidence of end-organ involvement were reported for NCpHPT and NHpHPT variants. The search returned 189 articles; 27 additional studies were identified and included for a total of 216. Non-English-language studies were excluded. Abstracts were screened, full-text articles were then assessed, and 82 articles were excluded. Data were pooled using a random-effects model in studies that compared NC or NH pHPT to classic pHPT. Comparative laboratory values are presented. CONCLUSION This analysis compares NCpHPT and NHpHPT to classic pHPT. Nephrolithiasis was 21.7% (NCpHPT), 15.9% (classic pHPT), and 25.4% (NHpHPT). Decreased bone mineral density was 49.7% (NCpHPT), 39.7% (classic pHPT), and 40.3% (NHpHPT). Fractures in the NCpHPT group were not significantly different from the classic pHPT. Hypertension in the NCpHPT group was significantly less than classic pHPT (odds ratio, 0.59; 95% CI, 0.40-0.88). IMPLICATIONS FOR CLINICAL PRACTICE This information may serve to inform clinicians of the laboratory subtleties of these variants that are being seen with greater frequency in contemporary practice.
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The role of Rapid Intraoperative Parathyroid Hormone (ioPTH) assay in determining outcome of parathyroidectomy in primary hyperparathyroidism: A systematic review and meta-analysis.
Medas, F, Cappellacci, F, Canu, GL, Noordzij, JP, Erdas, E, Calò, PG
International journal of surgery (London, England). 2021;:106042
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Abstract
BACKGROUND Primary hyperparathyroidism (PHPT) is a common endocrine disorder. In the last few decades, the introduction of Rapid Intraoperative Parathyroid Hormone (ioPTH) monitoring has allowed to ensurance of the excision of all hyperfunctioning parathyroid tissues, reducing the risks of persistent and recurrent PHPT. However, the use of ioPTH is still debated among endocrine surgeons. MATERIAL AND METHODS The objective of this systematic review and meta-analysis was to assess if ioPTH monitoring is able to reduce the incidence of persistent or recurrent PHPT. A systematic literature search was performed using PubMed, Scopus, ISI-Web of Science and Cochrane Library Database. Prospective and retrospective studies addressing the efficacy of ioPTH monitoring were included in the systematic review and meta-analysis. The random-effects model was assumed to account for different sources of variation among studies. The overall effect size was computed through the inverse variance method. Heterogeneity across studies, possible outlier studies, and publication bias were evaluated. RESULTS A total of 28 studies with 13,323 patients were included in the quantitative analysis. The incidence of operative failure was 3.2% in the case group and 5.8% in the control group. After excluding three outlier studies, the quantitative analysis revealed that ioPTH reduced significantly the incidence of postoperative persistent or recurrent PHPT. (Risk Difference = -0.02; CI = -0.03, -0.01; p < 0.001). There was no evidence of heterogeneity among the studies (Q = 19.92, p = 0.70; I2 = 0%). The analysis of several continuous moderators revealed that the effectiveness of ioPTH was larger in studies with lower preoperative serum calcium values and higher incidences of multiple gland disease. CONCLUSION ioPTH monitoring is effective in reducing the incidence of persistent and recurrent PHPT. Its routine use should be suggested in the next guidelines regarding management of PHPT.
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Citrate dose for continuous hemofiltration: effect on calcium and magnesium balance, parathormone and vitamin D status, a randomized controlled trial.
Boer, W, Fivez, T, Vander Laenen, M, Bruckers, L, Grön, HJ, Schetz, M, Oudemans-van Straaten, H
BMC nephrology. 2021;(1):409
Abstract
BACKGROUND Regional citrate anticoagulation may cause a negative calcium balance, systemic hypocalcemia and parathormone (PTH) activation but randomzed studies are not available. Aim was to determine the effect of citrate dose on calcium (Ca) and magnesium (Mg) balance, PTH and Vitamin D. METHODS Single center prospective randomized study. Patients, requiring continuous venovenous hemofiltration (CVVH) with citrate, randomized to low dose citrate (2.5 mmol/L) vs. high dose (4.5 mmol/L) for 24 h, targeting post-filter ionized calcium (pfiCa) of 0.325-0.4 mmol/L vs. 0.2-0.275 mmol/L, using the Prismaflex® algorithm with 100% postfilter calcium replacement. Extra physician-ordered Ca and Mg supplementation was performed aiming at systemic iCa > 1.0 mmol/L. Arterial blood, effluent and post-filter aliquots were taken for balance calculations (area under the curve), intact (i), oxidized (ox) and non-oxidized (nox) PTH, 25-hydroxy-Vitamin D (25D) and 1,25-dihydroxy-Vitamin D (1,25D). RESULTS 35 patients were analyzed, 17 to high, 18 to low citrate. Mean 24-h Ca balance was - 9.72 mmol/d (standard error 1.70) in the high vs - 1.18 mmol/d (se 1.70)) (p = 0.002) in the low citrate group and 24-h Mg-balance was - 25.99 (se 2.10) mmol/d vs. -17.63 (se 2.10) mmol/d (p = 0.008) respectively. Physician-ordered Ca supplementation, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH, oxPTH or noxPTH were not different between groups. Over 24 h, median PTH decreased from 222 (25th-75th percentile 140-384) to 162 (111-265) pg/ml (p = 0.002); oxPTH from 192 (124-353) to 154 pg/ml (87-231), p = 0.002. NoxPTH did not change significantly. Mean 25 D (standard deviation), decreased from 36.5 (11.8) to 33.3 (11.2) nmol/l (p = 0.003), 1,25D rose from 40.9 pg/ml (30.7) to 43.2 (30.7) pg/ml (p = 0.046), without differences between groups. CONCLUSIONS A higher citrate dose caused a more negative CVVH Ca balance than a lower dose, due to a higher effluent Calcium loss. Physician-ordered Ca supplementation, targeting a systemic iCa > 1.0 mmol/L, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH and oxPTH declined, suggesting decreased oxidative stress, while noxPTH did not change. 25D decreased while 1,25-D rose. Mg balance was negative in both groups, more so in the high citrate group. TRIAL REGISTRATION ClinicalTrials.gov : NCT02194569. Registered 18 July 2014.
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PTH and cardiovascular risk.
Gruson, D
Annales d'endocrinologie. 2021;(3-4):149-150
Abstract
Cardiovascular diseases remain the leading cause of non-communicable chronic diseases, are related to high morbidity and mortality and are associated to a huge impact on healthcare budgets. Biomarkers play an important role for the diagnosis and prognosis of cardiovascular diseases and are recognized tools for value-based care. Parathyroid hormone (PTH) is a major systemic calcium-regulating hormone and an important regulator of bone and mineral homeostasis. PTH 1-84, the biologically active hormone produced by the parathyroid glands and secreted into the systemic circulation, exerts its biological effects through the interaction of its first 34 amino acids with PTH receptors. PTH levels are raised in several cardio-renal disorders and hyperparathyroidism have detrimental effects on the heart and cardiac cells such as cardiac hypertrophy, remodeling and arrhythmias. High circulating PTH levels, through an increase in intracellular calcium, contribute also to the impairment of mitochondrial function and ATP production and to oxidative stress as well as inflammation states and, at the end, to cardiomyocytes necrosis. The interplay between PTH, fibroblast growth factor 23 and aldosterone is also detrimental for cardiovascular system and participate to endothelial dysfunction. Measurement of PTH levels could be therefore relevant in high risk individuals and could provide added value to established cardiac biomarkers for the sub-phenotyping of patients and treatment selection.