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Purpose: Cardiometabolic disorders are non-classical complications of hypercalcemic primary hyperparathyroidism (HC-PHPT), but whether this risk connotes normocalcemic PHPT (NC-PHPT) remains to be elucidated. We investigated cardiometabolic alterations in both forms of PHPT, looking for their association with indices of disease activity. Methods: Patients with HC-PHPT (n = 17), NC-PHPT (n = 17), and controls (n = 34) matched for age, sex, and BMI were assessed for glucose, lipid, blood pressure alterations, and history of cardiovascular events to perform a case–control study at an ambulatory referral center for Bone Metabolism Diseases. Results: NC-PHPT, in comparison to controls, showed similar glucose (mean ± SD, 88 ± 11 vs 95 ± 22 mg/dl), total cholesterol (199 ± 25 vs 207 ± 36 mg/dl), and systolic blood pressure levels (SBP, 132 ± 23 vs 132 ± 19 mmHg), together with a comparable frequency of glucose alterations (6% vs 9%), lipid disorders (41% vs 50%) and hypertension (53% vs 59%, p = NS for all comparisons). Conversely, all these abnormalities were more prevalent in HC-PHPT vs controls (p < 0.05). When compared to NC-PHPT, HC-PHPT showed higher glucose (113 ± 31 mg/dl), total cholesterol (238 ± 43 mg/dl), and SBP levels (147 ± 15 mmHg) as well as an increased frequency of glucose (41%) and lipid alterations (77%) and a higher number of cardiovascular events (18% vs 0%, p < 0.05 for all comparisons). Among indices of PHPT activity, calcium levels displayed a significant correlation with glucose (R = 0.46) and SBP values (R = 0.60, p < 0.05). Conclusion: NC-PHPT is not associated with cardiovascular alterations. The predominant pathogenetic role of hypercalcemia in the development of cardiometabolic disorders could account for the absence of such alterations in NC-PHPT. [ABSTRACT FROM AUTHOR]

Context Primary hyperparathyroidism (PHPT) is commonly diagnosed in the setting of hypercalcemia, whereas normocalcemic primary hyperparathyroidism (NHPT) may be misdiagnosed. Objective Our objective was to compare patients with hypercalcemic hyperparathyroidism (HPHPT) vs patients with NHPT hypercalciuric renal stones. Methods We took advantage of a routine calcium load test performed in patients with hypercalciuric renal stones to assess retrospectively among patients with PHPT the prevalence and characteristics of NHPT and HPHPT under a calcium-restricted diet Results Among 1671 patients with hypercalciuria, 91 patients had a final diagnosis of PHPT (postload ionized calcium [iCa] > 1.31 mmol/L and parathyroid hormone [PTH] > 30 pg/mL). Prevalence of NHPT is 40% of all PHPT; however, according to total serum calcium, 4/35 NHPT and 7/56 HPHPT cases would have been misclassified in the other group. Eighteen of 35 NHPT and 40/56 HPHPT cases underwent parathyroidectomy. No significant characteristics relating to parathyroid weight, stone composition, or bone remodeling biomarkers were detected between groups. Although iCa is higher in HPHPT in the fasting state and after calcium load, we found no difference for calcium diet, 24-hour calciuria, or calcitriol. Renal calcium excretion postload increased by 303% in NHPT but only 176% in HPHPT (P =.01) likely explained by a lesser PTH decrease (P =.02). However, a strong negative association (P <.0001) detected between pooled preload and postload iCa and PTH only in the NHPT group suggests a persistent efficient PTH-CaSR control within the parathyroid glands in this group. Conclusion Our data show the relevance of dynamic tests to unmask NHPT in patients with hypercalciuric renal stones. [ABSTRACT FROM AUTHOR]

IntroductionNormocalcemic primary hyperparathyroidism (NHPT) is considered to be an early stage in the evolution of primary hyperparathyroidism (PHPT). To formulate a correct diagnosis, secondary hyperparathyroidism due to low calcium intake must be excluded. Whether dietary calcium intake might affect the clinical presentation of PHPT or NHPT has never been addressed consistently.ObjectiveTo describe patients with a diagnosis of NHPT or PHPT in relation to their calcium intake, through three standard validated questionnaires; to describe clinical, biochemical and radiological features of NHPT and PHPT patients compared to each other and to a control group.DesignCross-sectional study.SettingOutpatient, single academic medical center.Patients109 consecutive women recruited from February 2021 through April 2023. 54 patients with mild primary hyperparathyroidism (PHPT or NHPT) were age-matched with 55 unselected women undergoing bone density test screening due to recently diagnosed hormone-positive breast cancer. NHPT diagnosis was based on multiple determinations of both total and albumin-corrected serum calcium.InterventionsAdministration of all the following during routine endocrine consultation: a country-specific food-frequency questionnaire (LOC), the International Osteoporosis Foundation Calcium Calculator (IOF) and the National Osteoporosis Foundation calcium questionnaire (NOF).Main outcome measuresAny association between dietary calcium intake and clinical, radiological, or biochemical features.ResultsAll three questionnaires confirmed that NHPT patients had similar calcium intake as those with PHPT or controls. Biochemistries and bone turnover markers were similar between the two variants of hyperparathyroidism, except for serum calcium (sCa). NHPT patients had a significantly lower BMD and T-score at one-third distal radius compared to PHPT, while the prevalence of nephrolithiasis and clinical fractures were similar. Multivariate analysis investigating predictors of serum calcium showed that age, eGFR, calcium intake and 25(OH)D did not significantly affect serum calcium, while multivariate analysis investigating predictors of PTH (age, variant NHPT vs. PHPT, eGFR, calcium intake, 25(OH)D, cholecalciferol supplements) showed that calcium intake, variant and renal function, significantly influenced PTH levels.ConclusionsAll patients with primary hyperparathyroidism, particularly those with low dietary calcium intake, should be advised not to restrict dietary calcium to prevent further increase in PTH levels. Whether maintaining adequate calcium intake might positively impact bone density or biochemistries in patients refraining from surgery, should be addressed in longitudinal studies.

Background: Normocalcemic primary hyperparathyroidism (nPHPT) is a condition characterized by persistently high levels of parathyroid hormone (PTH) and normal serum calcium levels in the absence of other causes for secondary hyperparathyroidism. The aim of the present study was to assess the clinical presentation and the biochemical characteristics in patients with nPHPT and to compare them with those in patients with hypercalcemic PHPT (hPHPT). Materials and methods: The study included 316 patients (277 women and 39 men, average age 58.7 ± 12.1) diagnosed with PHPT. Total serum calcium, inorganic phosphates (PO4), PTH, urinary Ca (uCa), albumin, creatinine, 25(OH)D and bone markers (b-CTX and ALP) were examined in all of them. BMD of the lumbar spine (LS), distal third of the radius (DR), femoral neck (FN) and total proximal femur (TF) were measured by a dual-energy X-ray absorptiometry (DXA). The patients were divided into two groups according to albumin-corrected calcium (Ca) level – with hPHPT (Ca>2.62 mmol/L) and with nPHPT (Ca 2.12–2.62 mmol/l), without other causes for secondary hyperparathyroidism. Results: The frequency of nPHPT was 15.2%. Normocalcemic patients had lower levels of PTH, higher PO4 and 25(OH)D, and smaller parathyroid adenomas. No significant difference in the frequency of osteoporosis, low-energy fractures, nephrolithiasis and gastrointestinal disorders was found between nPHPT and hPHPT. There was no difference in BMD between the two groups. Conclusion: The patients with nPHPT show a more favorable biochemical profile compared to those with hPHPT. Nevertheless, clinical manifestations and complications are similar, without a significant difference in the frequency of osteoporosis, nephrolithiasis, gastrointestinal disorders and low-energy fractures. [ABSTRACT FROM AUTHOR]

Purpose: Hypercalcemic primary hyperparathyroidism (PHPT) is a common endocrine disorder that has been very well characterized. In contrast, many aspects of normocalcemic primary hyperparathyroidism (NPHPT) such as natural history, organ damage, and management are still matter of debate. In addition, both the pathophysiology and molecular basis of NPHPT are unclear. We investigated whether PHPT and NPHPT patient cohorts share the same pattern of genetic variation in genes known to be involved in calcium and/or bone metabolism. Research design and methods: Genotyping for 9 single nucleotide polymorphisms (SNPs) was performed by Real-Time PCR (TaqMan assays) on 27 NPHPT and 31 PHPT patients evaluated in a tertiary referral Center. The data of both groups were compared with 54 in house-controls and 503 subjects from the 1000 Genomes Project. All groups were compared for allele/haplotype frequencies, on a single locus, two loci and multi-locus basis. Results: The NPHPT group differed significantly at SNPs in OPG and ESR1. Also, the NPHPT cohort was peculiar for pairwise associations of genotypes and for the overrepresentation of unusual multilocus genotypes. Conclusions: Our NPHPT patient set harbored a definitely larger quota of genetic diversity than the other samples. Specific genotypes may help in defining subgroups of NPHPT patients which deserve ad hoc clinical and follow-up studies. [ABSTRACT FROM AUTHOR]

Background Normocalcemic primary hyperparathyroidism (NCPHPT), as a new phenotype of primary hyperparathyroidism (PHPT), has gained increasing attention. NCPHPT is easily misdiagnosed in clinical practice, and its risk factors need to be evaluated further. Objective To investigate the clinical features of NCPHPT and to explore its risk factors. Methods Patients diagnosed with PHPT (n=153) were retrospectively selected from Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2016 to December 2021, and divided into an experimental group (NCPHPT group) and a hypercalcemia PHPT group according to the corrected total serum calcium level. Meanwhile, individuals undergoing physical examination with normal parathyroid function were selected as the control group. The differences in clinical characteristics, glucose and bone metabolism, imaging and pathology results among the groups were compared. Multivariate Logistic regression analysis was used to analyze the risk factors of NCPHPT. Results The number of cases in NCPHPT, hypercalcemia PHPT and control groups was 36, 117 and 50, respectively. For biochemical indices, compared with healthy control group, the levels of alkaline phosphatase (AKP), uric acid (UA), and parathyroid hormone (PTH) were much higher in NCPHPT group, while serum phosphorus was much lower (P0.05). Multivariate Logistic regression analysis showed that urolithiasis〔OR=2.462, 95%CI (1.178, 3.552), P=0.011〕, decreased serum phosphorus〔OR=0.027, 95%CI (0.001, 0.711), P=0.031〕and increased AKP〔OR=2.809, 95%CI (1.422, 8.020), P=0.037〕were relevant factors for NCPHPT. Conclusion Patients with NCPHPT have many clinical symptoms such as elevated blood pressure, abnormal glucose metabolism, abnormal bone mineral density and urolithiasis. The presence of urolithiasis, hypophosphatemia and increased AKP indicates the possible existence of NCPHPT, which can be used for early Screening of NCPHPT to reduce the misdiagnosis rate.

Context: The contribution of [18F]F-fluorocholine (FCH)-positron emission tomography (PET)/computed tomography (CT) in normocalcemic primary hyperparathyroidism (nPHPT) remains unknown. Objective: To evaluate the sensitivity and specificity of FCH-PET/CT in a cohort of osteoporotic patients with nPHPT and discordant or negative [ 99mTc]Tc-sestamibi scintigraphy and ultrasonography who all underwent parathyroidectomy (PTX). Design: Longitudinal retrospective cohort study in patients referred for osteoporosis with mild biological primary hyperparathyroidism. Setting: Tertiary referral center with expertise in bone metabolism and surgical management of hyperparathyroidism. Patients: Among 109 patients with PHPT analyzed, 3 groups were individualized according to total serum calcium (tCa) and ionized calcium (iCa): 32 patients with hypercalcemia (HtCa group), 39 patients with normal tCa and elevated iCa (NtCa group), and 38 patients with both normal tCa and iCa (NiCa). All patients had biochemical follow-up confirming or not the success of PTX. Main outcome measures: To evaluate the performance of FCH-PET/CT in terms of sensitivity and specificity, and to compare with first-line imaging procedures in the setting of nPHPT. Results: The sensitivity of FCH-PET/CT was 67% in the hypercalcemic group, 48% in the NtCa group (P = .05 vs HtCa), and 33% in the NiCa group (P = .004 vs HtCa). Specificity ranged from 97% to 99%. FCH-PET/CT was positive in 64.3% of patients with negative conventional imaging, with biochemical resolution after PTX in 77.8% of patients. Triple negative imaging was observed in 20 patients, with PHPT resolution in 85% of these patients. Conclusion: This study highlights the contribution of FCH-PET/CT in a well-phenotyped cohort of normocalcemic patients with discordant or negative findings in [99mTc]Tc-sestamibi scintigraphy and ultrasonography. However, negative imaging in nPHPT does not rule out the possibility of surgical cure by an experienced surgeon. [ABSTRACT FROM AUTHOR]

Vitamin D hydroxylation-deficient rickets type 1A is an autosomal recessive disorder caused by pathogenic variants in CYP27B1 gene, which encodes for 1α-hydroxylase, the enzyme responsible for the conversion of 25-OH vitamin D into its active form 1,25(OH)2 vitamin D. We report the case of a 3-year-old female Mexican patient with growth retardation and progressive bone deformity, whose laboratory studies showed 25-OH vitamin D deficiency, a normal serum calcium and an elevated intact parathyroid hormone level that remained high despite calcitriol, cholecalciferol, and calcium supplementation. 99mTc sestamibi gammagram showed findings suggestive of parathyroid hyperplasia. Bone histomorphometry showed an image consistent with hyperparathyroidism without findings of osteomalacia, so normocalcemic primary hyperparathyroidism was suspected and a subtotal parathyroidectomy was performed, with the patient developing postoperative hypoparathyroidism. When she arrived at our clinic at age 18 years, she showed calcium- and calcitriol-dependent hypocalcemia, with secondary hyperparathyroidism and low levels of 1,25(OH)2 vitamin D in the absence of a 25-OH vitamin D deficiency, reflecting a defect in 1α-hydroxylation. Molecular testing revealed compound heterozygous variants in CYP27B1 gene. This is the first reported case of an inherited disorder of vitamin D metabolism that was diagnosed and surgically treated as primary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

Summary: The trabecular and cortical bone assessed by bone strain index seems not to be significantly affected in NHPT. Introduction: The natural history and bone involvement of normocalcemic hyperparathyroidism (NHPT) are not fully clarified yet. The bone strain index (BSI) is a deformation index based on the finite element method and can be applied to DXA scans. In this study, we aim to assess BSI in subjects with NHPT. Method: A case–control study included 170 subjects: 40 subjects with NHPT, 50 subjects with primary hypercalcemic hyperparathyroidism (PHPT), and 80 controls (age- and sex-matched with the NPTH group). Results: Lumbar spine (LS) bone mineral density (BMD), femoral neck (FN) BMD, total hip (TH) BMD, and TBS were similar between NHPT and both PHPT and controls. FN-BSI was lower in NHPT compared to PHPT (1.52 ± 0.31 vs 1.72 ± 0.42 p = 0.031) while there were no differences between NHPT and controls. TH-BSI was lower in NHPT compared to PHPT (1.36 ± 0.23 vs 1.52 ± 0.34, p = 0.030), while there were no differences between NHPT and controls. LS-BSI was not different between NHPT and both PHPT and controls. Conclusion: The trabecular and cortical bones assessed by BSI seem not to be significantly impaired in NHPT. Further prospective studies are needed to confirm these findings and to give an insight into the natural history of NHPT to improve knowledge and management of this condition. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism (PHPT) is classically characterized by hypercalcemia with elevated or inappropriately normal parathyroid hormone (PTH) levels. Elevated PTH levels in the presence of normal calcium levels are not infrequently found during the evaluation of metabolic bone disorders or kidney stone disease. This can be caused by secondary hyperparathyroidism (SHPT) or normocalcemic primary hyperparathyroidism (NPHPT). NPHPT is due to autonomous parathyroid function whereas SHPT is caused by a physiologic stimulation to PTH secretion. Many medical conditions and medications can contribute to SHPT, and differentiation between SHPT and NPHPT may be difficult. Cases are presented to illustrate examples. In this paper, we review the distinction between SHPT and NPHPT as well as end organ effects of NPHPT and outcomes of surgery in NPHPT. We suggest that the diagnosis of NPHPT be made only after careful exclusion of causes of SHPT and consideration of medications that can increase PTH secretion. Further, we advise a conservative approach to surgery in NPHPT. [ABSTRACT FROM AUTHOR]

Introduction: Normocalcemic primary hyperparathyroidism is a variant of primary hyperparathyroidism with consistently normal albumin-adjusted or free-ionized calcium levels. It may be an early stage of classic primary hyperparathyroidism or could represent primary kidney or bone disorder characterized by permanent elevation of PTH level. Aim of the study: The study aims to compare the FGF-23 levels in patients with PHPT, NPHPT, and normal calcium and PTH levels. Methods: Our study included patients who were referred to the endocrinology clinic with a presumptive diagnosis of primary hyperparathyroidism, an isolated increased level of PTH, or reduced bone densitometry. For each patient, we performed blood analysis of FGF-23, calcium, phosphate, vitamin D [25(OH)D3], estimated glomerular filtration rate (eGFR), bone turnover markers, and urine analysis for calcium/creatinine ratio. Results: Our study included 105 patients. Thirty patients with hypercalcemic hyperparathyroidism (HPHPT group), thirty patients with elevated PTH and normal calcium levels (NPHPT group), and 45 patients with normal calcium and PTH levels in the control group. FGF 23 level was 59.5± 23 pg/ml in the NPHPT group, 77 ± 33 pg/ml in the HPHPT group, and 49.7 ± 21.7 pg/ml in the control group (p=0.012). The phosphate level was lowest in the HPHPT group: 2.9 ± 0.6 vs 3.5 ± 0.44 in the NPHPT and 3.8 ± 0.5 in the control groups (p=0.001). No differences were found in eGFR, 25(OH)D3, C-terminal telopeptide type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels, and bone densitometry scores between the three study groups. Conclusion: Our findings suggest that NPHPT is an early stage of PHPT. Further studies are needed to determine the role of FGF-23 and its usefulness in NPHPT. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia. A group of patients who were admitted with PHPT and had normal calcium levels with high parathyroid hormone (PTH) levels was defined as normocalcemic PHPT (NPHPT). The data of PHPT operated patients were retrospectively analyzed, and biochemical and clinical characteristics of hypercalcemic and normocalcemic patients were compared. METHODS: The data of patients diagnosed with PHPT between January 2012 and January 2019 were retrospectively evaluated. A total of 318 patients were divided into two subgroups, hypercalcemic and normocalcemic, according to their calcium level. The two groups were compared regarding clinical and biochemical properties. RESULTS: Female gender was dominant in both groups (P = 0.072). The mean age was similar in both groups (P = 0.362). As expected, serum corrected calcium (Ca), PTH levels, and urinary Ca excretion were higher in the hypercalcemia group (P < 0.001). There was no difference between the two groups in alkaline phosphatase, creatinine, and vitamin D levels. The percentage of localization with preoperative was similar. Also, there was no difference in adenoma features (echogenicity, cystic appearance) and localization on ultrasonography (US). The positive result obtained on neck MRI and MIBI scanning was similar. There was no difference between the two groups in terms of kidney stone and osteoporosis prevalence DISCUSSION AND CONCLUSION: In our cohort, the NHPT phenotype was found to be like the hypercalcemic group. These findings suggest that the frequency of surgical indications is similar.

IntroductionNormocalcemic primary hyperparathyroidism is a variant of primary hyperparathyroidism with consistently normal albumin-adjusted or free-ionized calcium levels. It may be an early stage of classic primary hyperparathyroidism or could represent primary kidney or bone disorder characterized by permanent elevation of PTH level. Aim of the studyThe study aims to compare the FGF-23 levels in patients with PHPT, NPHPT, and normal calcium and PTH levels.MethodsOur study included patients who were referred to the endocrinology clinic with a presumptive diagnosis of primary hyperparathyroidism, an isolated increased level of PTH, or reduced bone densitometry. For each patient, we performed blood analysis of FGF-23, calcium, phosphate, vitamin D [25(OH)D3], estimated glomerular filtration rate (eGFR), bone turnover markers, and urine analysis for calcium/creatinine ratio.ResultsOur study included 105 patients. Thirty patients with hypercalcemic hyperparathyroidism (HPHPT group), thirty patients with elevated PTH and normal calcium levels (NPHPT group), and 45 patients with normal calcium and PTH levels in the control group. FGF 23 level was 59.5± 23 pg/ml in the NPHPT group, 77 ± 33 pg/ml in the HPHPT group, and 49.7 ± 21.7 pg/ml in the control group (p=0.012). The phosphate level was lowest in the HPHPT group: 2.9 ± 0.6 vs 3.5 ± 0.44 in the NPHPT and 3.8 ± 0.5 in the control groups (p=0.001). No differences were found in eGFR, 25(OH)D3, C-terminal telopeptide type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels, and bone densitometry scores between the three study groups.ConclusionOur findings suggest that NPHPT is an early stage of PHPT. Further studies are needed to determine the role of FGF-23 and its usefulness in NPHPT.

Background: We report a case of normocalcemic primary hyperparathyroidism, a diagnosis prompted by radiographic “salt and pepper” calvarial lesions, typically described in hypercalcemic primary hyperparathyroidism or secondary hyperparathyroidism. Case Report: A 60-year-old woman noticed indentations of her scalp and presented to her primary care provider. Radiography of the calvarium demonstrated granular “salt and pepper” lesions, prompting investigation. The patient was found to have an elevated parathyroid hormone (PTH) level of 79 pg/mL (reference range, 14-54 pg/mL) and a normal albumin-corrected calcium level of 9.8 mg/dL (reference range, 8.6-10.4 mg/dL). She was referred to our endocrine clinic and described having bone aches, fevers, leg cramps, and a remote history of nephrolithiasis. Her physical examination revealed hypertension. Repeat laboratory evaluation confirmed elevated PTH and normal albumin-corrected calcium. Secondary causes of hyperparathyroidism were ruled out. Her 25-hydroxyvitamin D level was 35 ng/mL (reference range, 30-100 ng/mL), with a normal creatinine level (0.73 mg/dL; reference range, 0.5-0.99 mg/dL). The patient underwent ultrasound and sestamibi scintigraphy, with uptake in the right inferior thyroid pole. She was found to have a 6-mm parathyroid adenoma and underwent a targeted parathyroidectomy, with normalization of serum PTH. Discussion: Many cases of normocalcemic primary hyperparathyroidism are diagnosed in asymptomatic patients presenting with low bone mass; however, imaging prompted this patient's evaluation. Ultimately, the calvarial lesions were thought secondary to bone resorption from increased osteoclast activity. Conclusion: This case highlights an atypical presentation of normocalcemic primary hyperparathyroidism in that the evaluation was precipitated by unexpected radiographic evidence of metabolic bone disease, rather than by symptoms or biochemical studies.

Background: Raised parathormone (PTH) and normal calcium concentrations can be observed both in normocalcemic primary hyperparathyroidism (nPHPT) and in secondary hyperparathyroidism, e.g. due to vitamin D deficiency. We assessed the impact of season on the validity of diagnosis of nPHPT in terms of screening investigations to be performed in the primary care settings. Material and methods: On two occasions (March/April & September/October) we measured vitamin D (25OHD), PTH and total calcium in 125 healthy subjects, age range 6-50, not taking any vitamin D supplements. Results: In autumn there was an increase in 25OHD concentrations (from 18.1 ± 7.37ng/ml to 24.58 ± 7.72ng/ml, p<0.0001), a decline in PTH from 44.40 ± 17.76pg/ml to 36.63 ± 14.84pg/ml, p<0.001), without change in calcium levels. Only 45 subjects (36%) were vitamin D sufficient (25OHD>20/ml) in spring versus 83 (66.4%) in autumn, p<0.001. Elevated PTH concentrations were noted in 10 subjects in spring (8%) and in six subjects (4.8%) (p<0.05) in autumn. In spring, however, eight out of ten of these subjects (80%) had 25OHD<20 ng/ml, versus one in six (16.7%) in autumn (p<0.01). Normalization of PTH was observed in seven out ten subjects (70%), and all of them had 25-OHD<20 ng/ml in spring. Conclusions: In spring elevated PTH concentrations in the setting of normocalcemia are more likely to be caused by 25OHD deficiency rather by nPHPT. In contrast, in autumn, increased PTH concentrations are more likely to reflect nPHPT. We postulate that screening for nPHPT should be done in 25OHD replete subjects, i.e. in autumn rather than in spring. [ABSTRACT FROM AUTHOR]

BackgroundRaised parathormone (PTH) and normal calcium concentrations can be observed both in normocalcemic primary hyperparathyroidism (nPHPT) and in secondary hyperparathyroidism, e.g. due to vitamin D deficiency. We assessed the impact of season on the validity of diagnosis of nPHPT in terms of screening investigations to be performed in the primary care settings.Material and methodsOn two occasions (March/April & September/October) we measured vitamin D (25OHD), PTH and total calcium in 125 healthy subjects, age range 6-50, not taking any vitamin D supplements.ResultsIn autumn there was an increase in 25OHD concentrations (from 18.1 ± 7.37ng/ml to 24.58 ± 7.72ng/ml, p20/ml) in spring versus 83 (66.4%) in autumn, p

Objectives: Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia. A group of patients who were admitted with PHPT and had normal calcium levels with high parathyroid hormone (PTH) levels was defined as normocalcemic PHPT (NPHPT). The data of PHPT operated patients were retrospectively analyzed, and biochemical and clinical characteristics of hypercalcemic and normocalcemic patients were compared. Materials and Methods: The data of patients diagnosed with PHPT between January 2012 and January 2019 were retrospectively evaluated. A total of 318 patients were divided into two subgroups, hypercalcemic and normocalcemic, according to their calcium level. The two groups were compared regarding clinical and biochemical properties. Results: Female gender was dominant in both groups (P = 0.072). The mean age was similar in both groups (P = 0.362). As expected, serum corrected calcium (Ca), PTH levels, and urinary Ca excretion were higher in the hypercalcemia group (P < 0.001). There was no difference between the two groups in alkaline phosphatase, creatinine, and vitamin D levels. The percentage of localization with preoperative was similar. Also, there was no difference in adenoma features (echogenicity, cystic appearance) and localization on ultrasonography (US). The positive result obtained on neck MRI and MIBI scanning was similar. There was no difference between the two groups in terms of kidney stone and osteoporosis prevalence. Conclusion: In our cohort, the NHPT phenotype was found to be like the hypercalcemic group. These findings suggest that the frequency of surgical indications is similar. [ABSTRACT FROM AUTHOR]

Normocalcemic primary hyperparathyroidism (NPHPT), a phenotype of primary hyperparathyroidism, is characterized by elevated parathyroid hormone levels in the setting of persistently normal serum calcium. Diagnosis of NPHPT can be challenging and requires that secondary causes of hyperparathyroidism be excluded. The natural history of NPHPT remains inconclusive. Although biochemically less severe, the skeletal and renal complications of NPHPT vary across studies, primarily due to underlying selection bias. Due to limited data, there is currently no consensus regarding medical and surgical treatment. Recent studies on parathyroidectomy have indicated that normocalcemic patients present more often with negative preoperative localization studies and multiglandular disease, which complicates successful surgical management. In addition, postoperative improvements in bone mineral density and nephrolithiasis vary, raising questions about the optimal treatment approach. Further studies are needed to provide better evidence-based guidance for normocalcemic patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Normocalcemic primary hyperparathyroidism (NPHT) is a subtype of primary hyperparathyroidism (PHPT) characterized by elevated levels of parathyroid hormone (PTH) within the normal range of serum calcium. In traditional PHPT, high serum calcium levels are typically seen, whereas in normocalcemic PHPT, calcium levels are within the normal range. NPHT is often diagnosed incidentally when routine blood tests reveal elevated PTH levels while calcium levels remain normal. The exact prevalence of NPHT is not well established due to variations in diagnostic criteria and inconsistent screening practices. The clinical significance and management of NPHT are still a subject of debate. Some studies suggest that NPHT may have similar long-term complications as traditional PHPT, such as kidney stones, osteoporosis, and cardiovascular disease. However, other research indicates that NPHT may have a more benign course with a lower risk of developing these complications. [ABSTRACT FROM AUTHOR]

Cure after surgery for normocalcemic primary hyperparathyroidism (NHPT) is defined as parathyroid hormone (PTH) normalization. However, an increase of PTH is frequently observed in cured patients with hypercalcemic primary hyperparathyroidism (HHPT). Therefore, this criterion must be redefined. A single-center retrospective study was performed including all patients who underwent surgery for Primary Hyperparathyroidism from 2013 to 2019. Cure rates of different types of hyperparathyroidism were analyzed. PTH reduction was studied as a possible criterion to define cure in patients with NHPT. One-hundred and eighty-six patients were included: 173 with HHPT and 13 with NHPT. After a mean follow-up of 33.4 months, 174 (93.6%) patients were considered cured. Cure was more frequent in the group of patients with HHPT (97.1% vs. 46.2%, p < 0.001). In the multivariate analysis, surgical failure was associated with NHPT and multiglandular disease. Forty-nine (30.1%) cured patients with HHPT had an increased PTH during the follow-up. When decline of PTH levels was studied in patients with HHPT to define cure, the area under curve was 0.92. A cut-off value of 40% in PTH reduction achieved a sensitivity and specificity of 83.4% and 80.0%. If cure was defined as a 40% reduction of PTH, cure rate in the group of patients with NHPT would increase to 69.2%. Patients with NHPT had a lower cure rate than patients with HHPT. A significant number of cured patients with HHPT had an increased PTH during follow-up. A 40% reduction in PTH levels is proposed as an alternative definition for cure in patients with NHPT. [ABSTRACT FROM AUTHOR]

Abstract Background Parathyroidectomy has ameliorated cardiovascular risk factors in patients with hypercalcemic primary hyperparathyroidism (PHPT), but the effect of parathyroidectomy on normocalcemic PHPT is not exactly known. This case-controlled study aimed to investigate the effect of parathyroidectomy on cardiovascular risk factors in patients with normocalcemic and hypercalcemic PHPT. Methods Subjects with normocalcemic PHPT (n = 35), age- and sex-matched hypercalcemic PHPT (n = 60) and age- and sex-matched control (n = 60) were included. Cardiometabolic disorders were investigated with traditional cardiometabolic risk factors and the Framingham cardiovascular risk score (CRS) before and 6 months after parathyroidectomy. Results Diabetes, dyslipidemia, hypertension, obesity, insulin resistance, osteoporosis, having fractures were similarly increased in the hypercalcemic and normocalcemic PHPT groups (p > 0.05) compared with the controls (p 0.05) compared with the controls (p

Background: Primary hyperparathyroidism (PHPT), a condition that manifests in various clinical forms, is a significant health concern. Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by normal calcemia despite elevated parathyroid hormone (PTH) levels. Vitamin D deficiency can contribute to the clinical spectrum and complexity of NPHPT. Low vitamin D levels can elevate PTH, making it difficult to distinguish between NPHPT and secondary hyperparathyroidism. Additionally, it might mask hypercalcemia, leading to an underestimation of the disease severity. Our study aims to shed light on these complexities by investigating normocalcemic and hypercalcemic PHPT patient's clinical, hormonal, and biochemical patterns, including their vitamin D status.    Materials: In this retrospective study, we enrolled 60 PHPT patients with autonomous parathyroid function confirmed using a combination of ultrasonography, radionuclide scan, and parathyroid function index calculation. We evaluated the albumin-corrected calcemia, calciuria, PTH, 25(OH)D level, serum phosphate, bone mineral density, and major clinical symptoms (fracture, nephrolithiasis). A comparative analysis and a correlation study were performed between normo- and hypercalcemic and vitamin D-deficient and vitamin D-non-deficient groups., Results:  The median age was 62 years, 51.66% (31/60) being normocalcemic and 46.66% (29/60) presenting a deficient 25(OH)D level. In the group with 25(OH)D below 20 ng/mL, we observed a reduced level of albumin-corrected calcemia, without a significant increase of PTH compared to the adequate 25(OH)D level group. The frequency of the NPHPT and the risk of fracture were significantly higher in the deficient 25(OH)D group (20/60, 33.33% and 8/60, 13.33%) than in the adequate one (11/60, 18.33% and 1/60, 1.66%) with OR=4.7 (p<0.004) and OR=9.7 (p<0.027), respectively. We also found a positive correlation between PTH and adenoma size, the parathyroid function index and adenoma size, as well as PTH and phosphate levels. However, the correlation between 25(OH)D and phosphate levels was negative and moderate (rho=-0.504, p<0.001), adding a new layer of complexity to our understanding of these relationships., Conclusion: Our study provided significant insight into the link between vitamin D status and normocalcemic PHPT. We found that vitamin D-deficient patients with normocalcemic PHPT have an increased fracture risk, which requires meticulous monitoring and possible supplementation with vitamin D. This should be done carefully to avoid exacerbating hypercalcemia or hypercalciuria. Further research is needed to refine these management strategies and deepen our understanding of the complex relationships between the analyzed parameters., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of the George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mures issued approval 747/18.02.2020. This study complies with the Declaration of Helsinki and was performed according to ethics committee approval. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kolcsar et al.)

• Indirect methods are often used in the selection of reference individuals. • Use of data mining approaches as alternative to inappropriate reference ranges. • The reference intervals for parathyroid hormone are sex-independent. • The age is a crucial variable in the establishment of reference intervals for PTH. Appropriately defined reference values are of vital importance for the correct interpretation of laboratory results. However, the implementation of in-house reference intervals by traditional methods is rare due to difficulties in the selection of reference individuals, so indirect methods are often alternatively used. Parathyroid hormone (PTH) is a crucial hormone for the metabolism of calcium and phosphorus whose result can lead to erroneous diagnoses and medical actions if adequate reference intervals are not readily available. Our goal was to obtain reference values ​​for adult population for PTH by using data mining. Based on possible new reference intervals, we also aimed to perform a retrospective evaluation of the individuals mistakenly classified. Retrospective observational study between 2014 and 2019. All requests from individuals aged ≥ 18 years were considered if PTH was requested together with serum creatinine, 25-hydroxyvitamin D, calcium, albumin and phosphate (within their respective reference intervals). PTH was measured on the Cobas e411 platform (Roche). Requests were grouped by age and sex. Differences among partitions were assessed by the Harris-Boyd's test and reference intervals were determined by the non-parametrical calculation of percentiles 2.5 and 97.5. A total of 2279 laboratory requests were included. Reference intervals for PTH were seen to be sex-independent, but age-dependent reference intervals were needed: 18–39, 40–59 and >60 years. Based on the reference intervals obtained, up to 20.1% of individuals were misclassified. Appropriateness of PTH reference intervals would lead to a reduction in the number of additional tests and avoid wrong medical actions, thus improving not only patient safety, but also the healthcare system as a whole. [ABSTRACT FROM AUTHOR]

The existence of normocalcemic primary hyperparathyroidism (NPHP) was acknowledged at the Third and Fourth International Proceedings on primary hyperparathyroidism PHPT but data relating to its clinical presentation, natural history, and skeletal status were limited and there was no information nor guidelines as to definitive therapy. Herein are reported biochemical, hormonal, and densitometry data in a postmenopausal woman seen initially for osteoporosis who was found to have increased serum PTH levels and normal serum total and ionized calcium levels without evidence of secondary hyperparathyroidism. Over a seven year period, the patient exhibited continuing preferential cortical bone loss at the one-third site of the radius in the face of relatively stable readings at the lumbar spine and hip that led to a subtotal parathyroidectomy for parathyroid hyperplasia with resultant normalization of serum PTH.

Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women with hypercalcemia and parathyroid hormone (PTH) levels that are either frankly elevated or inappropriately normal. The clinical presentation of PHPT includes three phenotypes: target organ involvement of the renal and skeletal systems; mild asymptomatic hypercalcemia; and more recently, high PTH levels in the context of persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these three clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is employed, the prevalence of vitamin D deficiency, and whether a medical center or practitioner tends to routinely measure PTH levels in the evaluation of low bone density or frank osteoporosis. When biochemical screening is common, asymptomatic primary hyperparathyroidism is the most likely form of the disease. In countries where vitamin D deficiency is prevalent and biochemical screening is not a feature of the health care system, symptomatic disease with skeletal abnormalities is likely to predominate. Finally, when PTH levels are part of the evaluation for low bone mass, the normocalcemic variant is seen. Guidelines for surgical removal of hyperfunctioning parathyroid tissue apply to all three clinical forms of the disease. If guidelines for surgery are not met, parathyroidectomy can also be an appropriate option if there are no medical contraindications to surgery. In settings where either the serum calcium or bone mineral density is of concern, and surgery is not an option, pharmacological approaches are available and effective. Referencing in this article the most current published articles, we review the different presentations of PHPT, with particular emphasis on recent advances in our understanding of target organ involvement and management. [ABSTRACT FROM AUTHOR]

An overview of Russian and foreign literature data with an analysis of the epidemiology of primary hyperparathyroidism (PGPT) was made. It wasnoted, that previously PHPTwas considered a severe disabling disease with the development of complications such as nephrolithiasis and osteoporosis. However,recently, the data of population-screening studies of blood calcium in several countries in Europe and North America opened the «invisible part of the iceberg» - a large number of mild (olygosymptomatic and asymptomatic) forms of the disease.According to different authors, the prevalence of PHPT is 0.5 to 34 cases per 1000 population, i.e.about 1%, and among people over 55 years – about 2%. NormocalciemicPHPT – a newly detected form nowadays is of particular interest. To date, analysis of blood calcium in Russia is not a routine biochemical test, and patients with PHPToften receive specialized care at the stage of irreversible complications. Therefore, it is necessary to increasethe awareness of physicians about the epidemiology and clinical presentation of the disease, to identify risk groups of PHPTand implement the diagnostic algorithms in the daily doctor’s practice.

Objectives: To evaluate, by means of a prospective randomized study, the efficacy of cinacalcet in the forms of nephrolithiasis associated with primary hyperparathyroidism in both the hypercalcemic and normocalcemic variant. Materials and Methods: Ten patients suffering from active nephrolithiasis associated with primary hyperparathyroidism (4 hypercalcemics and 6 normocalcemics), equally divided between males and females, were randomly but not blindly addressed to treatment with potassium citrate and allopurinol, or to the same therapeutic regimen in combination with cinacalcet. The dosage of cinacalcet was optimized for each patient in order to obtain a reduction of parathyroid hormone (PTH) within normal limits while enabling the maintenance of adequate calcemic values. All study participants were given the same diet based on a reduction in sodium intake, oxalate-rich foods and animal protein with standardized intake of calcium and an increase in hydration. After a follow up period of 10 months , cinacalcet was associated to standard therapy and diet in patients who were not taken it, conversely cinacalcet was withdrawn in the remaining patients who remained on standard therapeutic regimen and diet. Follow up was continued for a second period of observation of the same duration of the first. Results: At the end of the period of treatment with cinacalcet, for both variants of hyperparathyroidism, a statistically significant reduction in the overall number and in the diameter of renal stones was found. Conclusions: This prospective randomized study shows the effectiveness of cinacalcet used in combination with a diet with normalized calcium intake, in reducing the number and size of urinary stones in hypercalemic and normocalcemic forms of primary hyperparathyroidism.

Traditional hypercalcemic primary hyperparathyroidism is a common endocrine disease. Patients with a history of nephrolithiasis or a suspected metabolic bone disease are increasingly being identified with elevated PTH concentrations in the setting of consistently normal serum and ionized calcium concentrations. In the absence of secondary causes of hyperparathyroidism, a diagnosis of normocalcemic primary hyperparathyroidism is reasonable. As most cohorts described in the literature are from referral populations, involvement of the skeleton and the kidneys is common, two traditional target organs of primary hyperparathyroidism. Data from small cohorts show patients with normocalcemic disease respond similarly to hypercalcemic primary hyperparathyroidism with regard to medical and surgical approaches. In normocalcemic patients, multiglandular disease may be more common. In this article, we review the available literature on the epidemiology, diagnosis, clinical features, medical and surgical management of this newer phenotype of primary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women with hypercalcemia and parathyroid hormone (PTH) levels that are either frankly elevated or inappropriately normal. The clinical presentation of PHPT includes three phenotypes: target organ involvement of the renal and skeletal systems; mild asymptomatic hypercalcemia; and more recently, high PTH levels in the context of persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these three clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is employed, the prevalence of vitamin D deficiency, and whether a medical center or practitioner tends to routinely measure PTH levels in the evaluation of low bone density or frank osteoporosis. When biochemical screening is common, asymptomatic primary hyperparathyroidism is the most likely form of the disease. In countries where vitamin D deficiency is prevalent and biochemical screening is not a feature of the health care system, symptomatic disease with skeletal abnormalities is likely to predominate. Finally, when PTH levels are part of the evaluation for low bone mass, the normocalcemic variant is seen. Guidelines for surgical removal of hyperfunctioning parathyroid tissue apply to all three clinical forms of the disease. If guidelines for surgery are not met, parathyroidectomy can also be an appropriate option if there are no medical contraindications to surgery. In settings where either the serum calcium or bone mineral density is of concern, and surgery is not an option, pharmacological approaches are available and effective. Referencing in this article the most current published articles, we review the different presentations of PHPT, with particular emphasis on recent advances in our understanding of target organ involvement and management. [ABSTRACT FROM AUTHOR]

Summary: No data on the pharmacological treatment of normocalcemic hyperparathyroidism (NPHPT) are available. We treated 30 NPHPT postmenopausal women with alendronate/cholecalciferol (treated group) or vitamin D alone (control group). Over 1 year, bone mineral density (BMD) increased significantly in treated group, but not in control group. Both treatments did not affect serum or urinary calcium. Introduction: Normocalcemic primary hyperparathyroidism (NPHPT) is defined by normal serum calcium and consistently elevated PTH levels after ruling out the causes of secondary hyperparathyroidism. It is likely that subjects with NPHPT may develop kidney and bone disease. As no data on the pharmacological treatment of NPHPT are available, we aimed to investigate the effects of alendronate and cholecalciferol on both BMD and bone biochemical markers in postmenopausal women with NPHPT. Safety of vitamin D was evaluated as secondary endpoint. Methods: The study was a prospective open label randomized trial comparing 15 postmenopausal women with NPHPT (PMW-NPHPT), treated with oral alendronate plus cholecalciferol (treated group) and 15 PMW-NPHPT treated only with cholecalciferol (control group). Blood samples were obtained at baseline and after 3, 6, and 12 months. Bone turnover markers (BTM) were measured at baseline, 3, and 6 months, respectively. BMD was assessed at baseline and after 12 months. Results: After 1 year of treatment, BMD increased significantly at the lumbar, femoral neck, and hip level in the treated group, but not in the control group ( p = 0.001). No differences were found between or within groups in serum calcium, PTH, and urinary calcium levels. BTM significantly decreased in the treated group but not in the control group, at 3 and 6 months ( p < 0.001), respectively. No cases of hypercalcemia or hypercalciuria were detected during the study. Conclusion: The results of this study indicate that alendronate/cholecalciferol increases BMD in postmenopausal women with NPHPT. Alendronate/cholecalciferol or vitamin D alone does not affect serum or urinary calcium. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate, by means of a prospective randomized study, the efficacy of cinacalcet in the forms of nephrolithiasis associated with primary hyperparathyroidism in both the hypercalcemic and normocalcemic variant. Materials and Methods: Ten patients suffering from active nephrolithiasis associated with primary hyperparathyroidism (4 hypercalcemics and 6 normocalcemics), equally divided between males and females, were randomly but not blindly addressed to treatment with potassium citrate and allopurinol, or to the same therapeutic regimen in combination with cinacalcet. The dosage of cinacalcet was optimized for each patient in order to obtain a reduction of parathyroid hormone (PTH) within normal limits while enabling the maintenance of adequate calcemic values. All study participants were given the same diet based on a reduction in sodium intake, oxalate-rich foods and animal protein with standardized intake of calcium and an increase in hydration. After a follow up period of 10 months, cinacalcet was associated to standard therapy and diet in patients who were not taken it, conversely cinacalcet was withdrawn in the remaining patients who remained on standard therapeutic regimen and diet. Follow up was continued for a second period of observation of the same duration of the first. Results: At the end of the period of treatment with cinacalcet, for both variants of hyperparathyroidism, a statistically significant reduction in the overall number and in the diameter of renal stones was found. Conclusions: This prospective randomized study shows the effectiveness of cinacalcet used in combination with a diet with normalized calcium intake, in reducing the number and size of urinary stones in hypercalemic and normocalcemic forms of primary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

This review discusses recent findings on the clinical presentation, evaluation, medical and surgical management of primary hyperparathyroidism. Medical management includes the use of cinacalcet and bisphosphonates for bone loss and correction of vitamin D deficiency. Surgical updates reviewed recent studies on the preoperative localization of the disease, specifically, sestamibi scans, 4DCT and MRI. Focused parathyroidectomy continues to be the preferred surgical approach for a select group of patients, guided by intraoperative use of PTH and new technology, such as endoscopic and robotic platforms; however, there appears to be no difference in long-term success compared to the traditional approach. [ABSTRACT FROM AUTHOR]

Abstract: Primary hyperparathyroidism, a common endocrine disorder, is traditionally defined by hypercalcemia and elevated levels of parathyroid hormone (PTH). A newer presentation of primary hyperparathyroidism has been described over the past decade, in which PTH is elevated but serum calcium is consistently normal, in the absence of secondary causes of hyperparathyroidism, such as renal disease or vitamin D deficiency. Recognition of this phenotype of primary hyperparathyroidism, normocalcemic primary hyperparathyroidism, supports a biphasic chronological time course in some individuals in which PTH levels are first elevated but serum calcium is normal, followed by the development of frank hypercalcemia. This review focuses on the available literature regarding this newly described phenotype of primary hyperparathyroidism. [Copyright &y& Elsevier]

Abstract: The clinical profile of primary hyperparathyroidism (PHPT) as it is seen in the United States and most Western countries has evolved significantly over the past half century. The introduction of the multichannel serum autoanalyzer in the 1970s led to the recognition of a cohort of individuals with asymptomatic hypercalcemia, in whom evaluation led to the diagnosis of PHPT. The term “asymptomatic primary hyperparathyroidism” was introduced to describe patients who lack obvious signs and symptoms referable to either excess calcium or parathyroid hormone. Although it was expected that asymptomatic patients would eventually develop classical symptoms of PHPT, observational data suggest that most patients do not evolve over time to become overtly symptomatic. In most parts of the world, the asymptomatic phenotype of PHPT has replaced classical PHPT. This report is a selective review of data on asymptomatic PHPT: its demographic features, presentation and natural history, as well as biochemical, skeletal, neuromuscular, psychological, and cardiovascular manifestations. In addition, we will summarize available information on treatment indications and options for those with asymptomatic disease. [Copyright &y& Elsevier]

Primary hyperparathyroidism is a common endocrine disorder. It used to present as a highly symptomatic disease before the advent of the multichannel autoanalyzer, now usually presenting as mild asymptomatic hypercalcemia. A newer presentation has been increasingly identified in the past two decades, normocalcemic primary hyperparathyroidism, presenting with elevated parathyroid hormone concentrations and consistently normal serum calcium. These patients are usually symptomatic, with parathyroid hormone levels measured in the evaluation for kidney stones or osteoporosis. It is important to exclude causes of secondary hyperparathyroidism. This review will focus on the evaluation and management of elevated parathyroid hormone levels in normocalcemic patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Primary hyperparathyroidism (PHPT) can be characterized as either symptomatic or asymptomatic, or, most recently, as normocalcemic. In the current issue of the journal, Cakir et al. report that insulin resistance and glucose intolerance is not an aspect of normocalcemic PHPT. However, both the current study as well as the literature are compromised by the lack of appropriate classification of normocalcemic PHPT subjects. Rigorously characterized cohorts are necessary to determine whether glucose intolerance is in fact present in normocalcemic PHPT. [ABSTRACT FROM AUTHOR]

We have previously described increased fasting plasma glucose levels in patients with normocalcemic primary hyperparathyroidism (NPHPT) and co-existing prediabetes, compared to prediabetes per se. This study evaluated the effect of parathyroidectomy (PTx) (Group A), versus conservative follow-up (Group B), in a small cohort of patients with co-existing NPHPT and prediabetes. Sixteen patients were categorized in each group. Glycemic parameters (levels of fasting glucose (fGlu), glycosylated hemoglobin (HbA1c), and fasting insulin (fIns)), the homeostasis model assessment for estimating insulin secretion (HOMA-B) and resistance (HOMA-IR), and a 75-g oral glucose tolerance test were evaluated at baseline and after 32 weeks for both groups. Measurements at baseline were not significantly different between Groups A and B, respectively: fGlu (119.4 ± 2.8 vs. 118.2 ± 1.8 mg/dL, p = 0.451), HbA1c (5.84 ± 0.3 %vs. 5.86 ± 0.4%, p = 0.411), HOMA-IR (3.1 ± 1.2 vs. 2.9 ± 0.2, p = 0.213), HOMA-B (112.9 ± 31.8 vs. 116.9 ± 21.0%, p = 0.312), fIns (11.0 ± 2.3 vs. 12.8 ± 1.4 μIU/mL, p = 0.731), and 2-h post-load glucose concentrations (163.2 ± 3.2 vs. 167.2 ± 3.2 mg/dL, p = 0.371). fGlu levels demonstrated a positive correlation with PTH concentrations for both groups (Group A, rho = 0.374, p = 0.005, and Group B, rho = 0.359, p = 0.008). At the end of follow-up, Group A demonstrated significant improvements after PTx compared to the baseline: fGlu ((119.4 ± 2.8 vs. 111.2 ± 1.9 mg/dL, p = 0.021) (−8.2 ± 0.6 mg/dL)), and 2-h post-load glucose concentrations ((163.2 ± 3.2 vs. 144.4 ± 3.2 mg/dL, p = 0.041), (−18.8 ± 0.3 mg/dL)). For Group B, results demonstrated non-significant differences: fGlu ((118.2 ± 1.8 vs. 117.6 ± 2.3 mg/dL, p = 0.031), (−0.6 ± 0.2 mg/dL)), and 2-h post-load glucose concentrations ((167.2 ± 2.7 vs. 176.2 ± 3.2 mg/dL, p = 0.781), (+9.0 ± 0.8 mg/dL)). We conclude that PTx for individuals with NPHPT and prediabetes may improve their glucose homeostasis when compared with conservative follow-up, after 8 months of follow-up. [ABSTRACT FROM AUTHOR]

Objective: There are no data regarding echocardiographic parameters in patients with normocalcemic primary hyperparathyroidism (NCPHPT). We compared the echocardiographic findings in postmenopausal women with NCPHPT with those in patients with hypercalcemic primary hyperparathyroidism (PHPT) and controls., Methods: Seventeen consecutive Caucasian postmenopausal women with NCPHPT were compared with 20 women with hypercalcemic PHPT and 20 controls. Obesity, diabetes, kidney failure, and previous cardiovascular diseases were considered exclusion criteria. Each patient underwent biochemical evaluation, bone mineral density scan, and echocardiographic measurements. Patients with parathyroid disorders underwent kidney ultrasound evaluation., Results: Patients with PHPT had significantly higher mean total serum calcium, ionized calcium, 24-hour urinary calcium, and parathyroid hormone and lower mean phosphorus levels compared with those in the controls (all P < .05). The only differences between patients with NCPHPT and PHPT were significantly lower mean total serum calcium, ionized calcium, and 24-hour urinary calcium and higher phosphorus levels in patients with NCPHPT (all P < .05). The only biochemical difference between patients with NCPHPT and the controls was a higher level of mean parathyroid hormone in patients with NCPHPT. There were no differences in cardiovascular risk factors between patients with NCPHPT and PHPT and the controls. Hypertension was the most frequent cardiovascular risk factor, diagnosed in 65% of patients with PHPT. This high prevalence was not statistically significant compared with that observed in patients with NCPHPT (59%) and in the controls (30%). Echocardiography parameters were not different between patients with NCPHPT and PHPT and the controls when subdivided according to the presence of hypertension (ANOVA followed by Bonferroni correction)., Conclusion: In a population with a low cardiovascular risk, we found no differences in cardiovascular risk factors and echocardiographic parameters between patients with NCPHPT and PHPT and the controls., (Copyright © 2020 AACE. Published by Elsevier Inc. All rights reserved.)