Hypercalcemic Primary Hyperparathyroidism Research Articles

Osteoporosis and Normocalcemic Primary Hyperparathyroidism (Conservatively or Surgically Managed)

Asymptomatic primary hyperparathyroidism (PHPT) involves 80–90% of the parathyroid tumor-associated cases of PHPT in the modern medical era, while normocalcemic PHPT (NPHPT) has a prevalence of 0.1–11%. We aimed to analyze the bone status and mineral metabolism in NPHPT amid conservative or surgical management. In this narrative review, we searched PubMed (between January 2020 and July 2024) via different keywords. Fourteen studies from the final analysis (388 patients with NPHPT; 1188 with PHPT; and 803 controls) showed that mean serum calcium levels varied between 2.57 and 2.26 mmol/L in NPHPT. Ten studies identified a similar 24 h urinary calcium in NPHPT versus hypercalcemic PHPT (HPHPT). Except for one study, a mandatory vitamin D analysis was performed, but the 25-hydroxyvitamin D cut-offs varied. Osteoporosis (n = 6 studies; N = 172 with NPHPT) was confirmed in 41.7–100% of NPHPT subjects. In surgery candidates, this rate might be overestimated. A DXA analysis was performed in eight studies (235 subjects with NPHPT, and 455 patients with HPHPT); two studies identified a lower BMD in HPHPT < NPHPT, but the results were not homogenous. A single study analyzed the TBS and found similar results in NPHPT. The prevalence of fractures (n = 9) varied between 7.4% and 42.8% in NPHPT. Bone turnover markers (N = 262 patients, n = 8 studies) showed lower bone formation markers in NPHPT versus PHPT (n = 3). Two studies analyzed the BMD and bone turnover markers following parathyroidectomy (161 patients, including 30 patients with NPHPT; mean ages over 60 years). To conclude, given the wide spectrum of complications associated with PHPT, an early diagnosis and proper management is essential. A more extensive screening in patients with osteoporosis and kidney stones might lead to the discovery of NPHPT, a more recently described form of PHPT. While it is still unclear whether NPHPT is an early stage of HPHPT or a separate entity, recent findings show similar osteoporosis and fracture occurrence, and an improvement in bone metabolism, following parathyroidectomy. More extensive prospective studies are crucial to understand the natural course of the disease, to reach a consensus regarding parathyroidectomy indications and surgery candidates’ selection, and to ensure proper personalized management for these patients. With the evolving diagnosis methods, PHPT has become a condition with a changing clinical presentation, which now requires modern evaluation and treatment approaches.

Normocalcemic primary hyperparathyroidism is not associated with cardiometabolic alterations.

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. 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. 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). 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.

Assessment of Vitamin D Status in Primary Hyperparathyroidism Patients: A Retrospective Study.

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. 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%and8/60, 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. 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.

Comparison of Normocalcemic vs Hypercalcemic Primary Hyperparathyroidism in a Hypercalciuric Renal Stone Population.

Primary hyperparathyroidism (PHPT) is commonly diagnosed in the setting of hypercalcemia, whereas normocalcemic primary hyperparathyroidism (NHPT) may be misdiagnosed. Our objective was to compare patients with hypercalcemic hyperparathyroidism (HPHPT) vs patients with NHPT hypercalciuric renal stones. 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. 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. Our data show the relevance of dynamic tests to unmask NHPT in patients with hypercalciuric renal stones.

Twenty-four hour Holter ECG in normocalcemic and hypercalcemic patients with hyperparathyroidism.

To investigate the occurrence of arrhythmias in patients with normocalcemic (NC) primary hyperparathyroidism (PHPT) compared to both hypercalcemic PHPT patients and control subjects by means of 24-h Holter ECG. Thirteen NCPHPT postmenopausal patients were enrolled and age-matched with 13 hypercalcemic PHPT patients and 13 controls. Every subject underwent basal ECG, 24-h Holter ECG and mineral metabolism biochemical evaluation. PHPT patients had higher mean serum calcium levels compared to both NCPHPT and controls; there was no difference in mean serum calcium levels between NCPHPT and controls. Both NCPHPT and PHPT patients had significantly higher mean PTH levels compared with controls. There were no differences in ECG parameters between the three groups, except for QTc interval. PHPT patients had normal QTc interval values, but significantly shorter mean values compared with those of controls and NCPHPT patients. During 24-h Holter ECG recording, 100% of PHPT patients had supraventricular premature beats (SVPBs), compared to 46% of NCPHPT (p = 0.005) and to 53% of controls (p = 0.01). PHPT patients experienced ventricular premature beats (VPBs) (69.2%) vs 15% of NCPHPT patients (p = 0.01) and 23% of controls (p = 0.04). There was no difference between NCPHPT and controls subjects concerning occurrence of both VPBs and SVPBs. NCPHPT patients did not experience an increased occurrence of arrhythmias compared to controls, while PHPT patients showed an increased occurrence compared to both controls and NCPHPT. Our findings are most probably related to the short QTc interval caused by hypercalcemia observed in PHPT patients, but not in NCPHPT.

The Ca∗Cl/P Ratio: A Novel and More Appropriate Screening Tool for Normocalcaemic or Overt Primary Hyperparathyroidism

ObjectiveThe main purpose of this study was to explore the diagnostic performance of the Ca∗Cl/P ratio for primary hyperparathyroidism (PHPT), especially normocalcaemic PHPT (NPHPT), to assist health care providers in making reliable and rapid clinical identifications. MethodsFrom January 1, 2013, to March 31, 2023, 230 PHPT patients, including 65 with NPHPT and 230 sex- and age-matched controls, were enrolled in this retrospective study. Differences between hypercalcaemic PHPT (HPHPT) and NPHPT and between them and their respective controls were analyzed. The diagnostic accuracy of the Ca∗Cl/P ratio, Ca/P ratio, Cl/P ratio and albumin-corrected calcium was assessed by the area under the receiver operating characteristic curve. ResultsCompared with corresponding controls, NPHPT and HPHPT patients both had significantly higher Ca ∗ Cl/P ratios (271.64 ± 51.74 vs 192.71 ± 26; 419.91 ± 139.11 vs 199.14 ± 36.75, P < .001). In the overall cohort, the ROC-AUC of the Ca∗Cl/P ratio (0.964, 95% CI = 0.943-0.979) for diagnosis of PHPT patients was superior to albumin-corrected calcium (0.959, 95% CI = 0.934-0.973), the Ca/P ratio (0.956, 95% CI = 0.934-0.973), and the Cl/P ratio (0.923, 95% CI = 0.895-0.946). A Ca ∗ Cl/P ratio above 239.17 mmol/L, with sensitivity (0.952), specificity (0.922), PPV (0.924), NPV (0.951) and accuracy (0.937), can distinguish PHPT patients from healthy individuals. Furthermore, the Ca ∗ Cl/P ratio yielded a sensitivity of 0.831, specificity of 0.938, PPV of 0.931, NPV of 0.847 and accuracy of 0.885 for NPHPT. ConclusionThe Ca∗Cl/P ratio provides excellent diagnostic power for diagnosis of PHPT, especially NPHPT.

Genetic aspects underlying the normocalcemic and hypercalcemic phenotypes of primary hyperparathyroidism.

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. 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. 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. 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.

Improvement of hypertension control and left-ventricular function after cure of primary hyperparathyroidism.

Cardiovascular mortality is significantly higher in patients with primary hyperparathyroidism (PHPT) compared to the general population. The role of the renin-angiotensin-aldosterone system (RAAS) as a mediator of cardiovascular pathology in PHPT is unclear, as is the question whether successful parathyroidectomy (PTX) mitigates hypertension (HT), and left-ventricular (LV) dysfunction. In 45 consecutive, hypercalcemic PHPT patients (91% female, 20 normotensive, mean age 54.6 ± 14.6), laboratory examinations, and 24h ambulatory blood pressure monitoring (ABPM) were performed before, one and six months after successful PTX, while transthoracic echocardiography (TTE) pre- and six months post-PTX. Both in patients with normotension (NT) and HT, lower calcemia and parathyroid hormone (PTH) as well as higher phosphatemia were observed on follow-up, while B-type natriuretic peptide, aldosterone, plasma renin activity, and aldosterone-to-renin ratios were comparable. Six months post-PTX, only in patients with HT, median 24-hour SBP/DBP decreased by 12/6 mmHg, daytime SBP by 10, and nighttime DBP by 5 mmHg. Improvement in BP was observed in approximately 78% of patients with HT. Six months post-PTX, TTE revealed: 1) decrease in median LV mass index (by 2 g/m2) and end-diastolic dimension (by 3mm) among patients with HT; 2) normalization of global longitudinal strain in 22% of patients (comparable between those with NT and HT); 3) a mean 12.7% reduction in left-atrium volume index among patients with HT, which underlay normalization of indeterminate diastolic function in 3 out of 6 patients with HT, who exhibited it at baseline (dysfunction persisted in 2). PTX was shown to significantly reduce BP, LV hypertrophy and diastolic dysfunction parameters in PHPT patients with HT, and improve systolic function in all PHPT patients.

The prevalence of primary and secondary hyperparathyroidism and its cardiometabolic implications in primary aldosteronism.

The aim of this study was to analyze the prevalence of primary and secondary hyperparathyroidism in patients with primary aldosteronism (PA), and its implication on cardiovascular and metabolic outcomes. A retrospective study of patients with PA (exposed cohort, N.=44) and all hypertensive (EH) patients with adrenal lesions without PA nor other adrenal hypersecretion (non-exposed cohort, N.=41) on follow-up at our center between 2016 and 2020. The mean age of patients with PA and EH was 55.1±14.13 and 66.3±10.93 (P<0.001), and 50% of PA and 39.0% of EH were women (P=0.309). At diagnosis, the prevalence of primary hyperparathyroidism in PA was of 18.2%, and all were normocalcemic hyperparathyroidism cases. Globally, no differences were found in the prevalence of primary hyperparathyroidism compared to EH (18.2% vs. 29.3%, P=0.229), but hypercalcemic primary hyperparathyroidism was significantly more prevalent in EH patients than in PA (22.0% vs. 0%, P=0.001). There were 47.7% (N.=21) cases of secondary hyperparathyroidism in patients with PA (4 due to chronic kidney disease (CKD) and vitamin D deficiency, and 17 due to vitamin D deficiency alone). The cardiometabolic profile of patients with PA and hyperparathyroidism (N.=29) was similar to of those patients without hyperparathyroidism (N.=15) at diagnosis and after a median follow-up of 3.6 years (interquartile range 1.1-5.9). Although primary and secondary hyperparathyroidism are common in patients with PA, their prevalence was similar than the observed in EH patients. Primary hyperparathyroidism is usually mild in PA, appearing as normocalcemic forms. No negative implications of the hyperparathyroidism in the cardiometabolic profile of PA were observed.

Approach to the Patient: Management of Parathyroid Diseases Across Pregnancy.

Taking care of patients with parathyroid disorders during pregnancy requires consideration of the physiological fundamental changes in bone and mineral metabolism occurring in these women. Diagnostic and therapeutic procedures regarding primary hyperparathyroidism (PHPT) and hypoparathyroidism significantly differ from the nonpregnant population. PHPT should preferably be cured by parathyroidectomy before pregnancy since in women with hypercalcemic PHPT, maternal and fetal pregnancy complications seem to increase according to the degree of hypercalcemia. Parathyroidectomy, if needed during pregnancy, is preferentially performed in the second trimester. Conservative treatment is recommended for milder cases and is mainly restricted to hydration, with only limited evidence regarding drug treatment. Women with hypoparathyroidism can be informed that there are no major concerns regarding disease-associated infertility and that the risk of pregnancy complications is low if the disease is properly managed. Regular active surveillance is recommended, as requirements for calcium and active vitamin D may change during the course of pregnancy in either direction, with an overall trend for rather reduced doses. Any woman suffering from parathyroid disorders during pregnancy requires further surveillance in the postpartum period and during lactation, as there is an increased risk of hypercalcemia after delivery. Newborns of mothers with parathyroid diseases should, depending on disease severity, be carefully monitored for calcium levels in the first days (to weeks) after delivery since intrauterine exposure to hyper- or hypocalcemia may impact their postnatal regulation of calcium metabolism.

Comparative utility of preoperative imaging in normocalcemic versus hypercalcemic primary hyperparathyroidism

BackgroundNormocalcemic primary hyperparathyroidism (PHPT) has been shown to benefit from parathyroidectomy. PHPT may be localized preoperatively with various imaging modalities, but the utility of preoperative imaging in normocalcemic PHPT compared to hypercalcemic PHPT is not well defined. MethodsRetrospective review was performed on all PHPT patients who underwent parathyroidectomy from 2001 to 2019. Patients were stratified into normocalcemic and hypercalcemic groups. Patient and outcomes data were analyzed. ResultsAll 2218 patients in this database were included. 433 patients had normocalcemic PHPT (19.5%) and 1785 had hypercalcemic PHPT (80.5%). Among normocalcemic patients, equivalent cure rates were seen between patients with preoperative imaging versus those without (100% vs 99%). No differences in postoperative complications were demonstrated except for a slightly increase in transient hypocalcemia in patients without imaging. ConclusionsNormocalcemic PHPT patients had equivalent cure and similar complication rates with or without preoperative imaging compared to hypercalcemic patients. Routine localization studies in normocalcemic PHPT may be safely omitted in favor of exploration with intraoperative adjuncts by experienced surgeons.

Normocalcaemic primary hyperparathyroidism: is nephrolithiasis more common than osteoporosis?

Normocalcaemic primary hyperparathyroidism (NPHPT) is often under-recognised in clinical practice. To determine the prevalence and clinical significance of NPHPT in an unselected sample in an acute hospital setting. Patients aged >18 years who had measurement of an elevated serum parathyroid hormone (PTH ≥ 7 pmol/L) during 12 months from 1 January 2017 to 31 December 2017 were retrospectively studied. NPHPT was defined by the presence of elevated serum PTH with normal albumin-corrected serum calcium on two or more occasions after excluding secondary causes. Patients were followed up for 2 years. Relevant data were collected by review of electronic medical records. Of the 2593 patients who had PTH measured during the study period, 1278 had serum PTH ≥ 7 pmol/L. Hypercalcaemic primary hyperparathyroidism (PHPT) was diagnosed in 174 patients. Secondary causes for elevated serum PTH were identified in 993 patients: 815 (chronic kidney disease - estimated glomerular filtration rate < 60 mL/min/1.73 m2 or renal transplant), 98 (vitamin D deficiency - 25(OH)D < 50 nmol/L), 28 (gastric bypass surgery), 38 (medications), 13 (malabsorption or post-thyroidectomy) and 1 (hypercalciuria). Data were incomplete for 80 patients. The prevalence of NPHPT with and without the exclusion of hypercalciuria was 0.19% (5) and 0.39% (10) respectively. The prevalence of nephrolithiasis in NPHPT was higher than PHPT (100% vs 15% among five patients (P < 0.001) and 50% vs 15% among 10 patients (P = 0.014)). The prevalence of osteoporosis was not significantly different between NPHPT and PHPT (20% vs 45% among five patients (P = 0.389) and 30% vs 45% among 10 patients (P = 0.518)). These findings give further credence to the diagnosis of NPHPT as a clinical entity. Nephrolithiasis may be a greater problem than osteoporosis in NPHPT compared with PHPT. This needs prospective evaluation.

The differences between normocalcemic and hypercalcemic primary hyperparathyroidism: a tertiary center′s experience

The differences between normocalcemic and hypercalcemic primary hyperparathyroidism: a tertiary center′s experience

Insulin resistance is more severe in patients with primary hyperparathyroidism

BackgroundPrimary hyperparathyroidism is associated with an increased cardiovascular mortality, and its underlying mechanisms remain unclear. Insulin resistance has been suggested with low level of evidence. The goal of this study was to evaluate glucose metabolism and insulin resistance in primary hyperparathyroidism patients, to compare with control subjects, and to identify risk factors for insulin resistance in patients with primary hyperparathyroidism. MethodsCross-sectional study of consecutive primary hyperparathyroidism patients without history of diabetes or severe chronic kidney disease (glomerular filtration rate ≤30 mL/min/1.73 m2). Fasting glucose and insulin were evaluated before parathyroidectomy. Glucose metabolism was compared with population-based control subjects (n = 171). ResultsOne hundred and seventy-four patients with primary hyperparathyroidism (140 females) were included. Mean fasting glucose was 0.983 ± 0.129 g/L, and 63 patients (36%) had prediabetes (>1.0 g/L). Mean Homeostatic model assessment of insulin resistance (HOMA-IR) was 3.386 ± 3.111 mUI/L, and 78 patients (45%) had insulin resistance (HOMA-IR >2.6). Blood calcium levels (0.171; P = .023) and body mass index (0.450; P < .001) were correlated positively with HOMA-IR. Insulin secretion (HOMA-B%) was correlated positively with preoperative systolic blood pressure in mm Hg (0.187; P = .013). In multivariate analysis, classic hypercalcemic primary hyperparathyroidism (18.47, 6.84–49.87; <.001), mild hypercalcemic primary hyperparathyroidism (5.35, 2.40–11.95; <.001), and body mass index (1.27, 1.17–1.38; <.001) remained independent predictors for insulin resistance (HOMA-IR >2.6). When compared with control subjects, mean HOMA-IR was significantly higher in primary hyperparathyroidism patients (3.386 ± 3.111 vs 1.919 ± 1.158; P < .001). ConclusionInsulin resistance was significantly higher in primary hyperparathyroidism patients than in control subjects. The impact of parathyroidectomy on insulin resistance should be evaluated in patients with higher calcium levels.

What happens to the bone structure after normocalcemic primary hyperparathyroidism surgery?

BackgroundBone disease in primary hyperparathyroidism is a clear indication for surgical treatment. However, it is not known whether surgery benefits hypercalcemic primary hyperparathyroidism and normocalcemic primary hyperparathyroidism equally. The aim of our study was to evaluate the bone changes in patients undergoing parathyroidectomy based on the biochemical profile 1 and 2 years after surgery. MethodsThis prospective study included 87 consecutive patients diagnosed with primary hyperparathyroidism who underwent surgery between 2016 and 2018. Bone densitometry (1/3 distal radius, lumbar, and femur) and bone remodeling markers (osteocalcin, type 1 procollagen [P1NP], β-cross-linked telopeptide of type I collagen [BCTX]) were performed preoperatively and postoperatively. Postoperative changes in bone mineral density and bone markers were compared and evaluated according to the clinical characteristics and the individual biochemical profile. ResultsOne year after surgery, all patients showed an increase in bone mineral density at the lumbar site (mean, 0.029 g/cm2; range, 0.017–0.04; P < .001) and femur neck (mean, 0.025 g/cm2; range, 0.002–0.05; P < .001); however, there were no changes in the distal third of the radius (mean, -0.003 g/cm2; range, -0.008 to 0.002; P = NS). There were no significant differences when comparing normocalcemic primary hyperparathyroidism and hypercalcemic primary hyperparathyroidism. Serum osteocalcin (37 ± 17.41), P1NP (67.53 ± 31.81) and BCTX (0.64 ± 0.37) levels were elevated before surgery. One year after the surgery, we observed a significant decrease in P1NP (33.05 ± 13.16, P = .001), osteocalcin (15.80 ± 6.19, P = .001), and BCTX (0.26 ± 0.32, P < .001) levels. ConclusionOur findings indicate that parathyroidectomy has similar benefits for normocalcemic primary hyperparathyroidism and hypercalcemic primary hyperparathyroidism in terms of bone improvement. Although the most substantial improvement occurred during the first postoperative year in both groups, we consider that studies with longer follow-up are warranted.

Is the ghost of brown tumor back again? Features of hypercalcaemic primary hyperparathyroidism we must not forget

Is the ghost of brown tumor back again? Features of hypercalcaemic primary hyperparathyroidism we must not forget

Assessment of Clinical Utility of Assaying FGF-23, Klotho Protein, Osteocalcin, NTX, and Sclerostin in Patients with Primary Hyperparathyroidism.

The purpose of this study was to assess the clinical usefulness of assaying the fibroblast growth factor (FGF-23), Klotho, osteocalcin, N-terminal telopeptide of type I collagen (NTX), and sclerostin levels in patients with primary hyperparathyroidism (PHPT) as markers of bone damage as well as for surgical treatment success. Seventeen patients with hypercalcemic PHPT and normal kidney function were studied. In all patients, PTH (parathormone), serum calcium, and creatinine were performed before and six months after parathyroidectomy (PTX). The studied group included patients whose PTH and calcium concentrations normalized post-operatively and with confirmed histopathological diagnosis. The control group consisted of nine age-matched healthy volunteers. The PHPT patients had elevated concentrations of FGF-23, osteocalcin, and NTX and reduced levels of sclerostin, as compared to the control group. After PTX, osteocalcin, NTX, and sclerostin levels normalized. The plasma values of FGF-23 decreased significantly, but remained higher than in healthy subjects. Serum Klotho protein levels did not differ significantly in the two groups. These results suggest that osteocalcin and NTX may potentially be considered as markers of PHPT progression. Additionally, serum normalization of osteocalcin, NTX, and sclerostin might be considered as indicators of PTX success. On the other hand, FGF-23 can represent a parameter reflecting the degree of calcium–phosphate imbalance in PHPT patients, but its usefulness in monitoring the effects of PTX requires further research. The clinical utility of assaying Klotho in PHPT remains to be confirmed.

How should we define cure after parathyroidectomy for normocalcemic primary hyperparathyroidism? A retrospective cohort study.

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 33.4months, 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.

Comparison of patients with normocalcemic and hypercalcemic primary hyperparathyroidism

Comparison of patients with normocalcemic and hypercalcemic primary hyperparathyroidism

Normocalcaemic primary hyperparathyroidism: what is the role of parathyroid surgery?

Primary hyperparathyroidism (PHPT) is classically associated with both an elevated or ‘inappropriately normal’ parathyroid hormone (PTH) level and raised serum calcium. However, in clinical practice, increasing numbers of patients present with raised PTH but normal serum calcium, renal function and vitamin D; this is known as normocalcaemic PHPT (nPHPT). Studies investigating the clinical presentation of this condition have shown that patients may present with hypertension, nephrolithiasis, impaired glucose tolerance, osteoporosis and fragility fractures. The prevalence of such complications in nPHPT is similar to that in classical hypercalcaemic PHPT (hPHPT). Although the National Institute for Health and Care Excellence (NICE) have developed guidelines for the management of PHPT generally, a consensus is yet to be reached on the optimal management of nPHPT specifically. A review of the literature on parathyroidectomy in the treatment of nPHPT revealed that nPHPT patients were more likely to present with multi-glandular disease and significantly less nPHPT patients had an intra-operative PTH fall of >50% compared with those with hPHPT. These findings demonstrate that patients with nPHPT are more likely to receive bilateral neck explorations and require remedial surgery compared with hPHPT patients. Following surgery, improvements in bone mineral density (BMD) and renal stones are generally observed in those with nPHPT. Where surgery is not possible, medical management with alendronate has been shown to be effective in nPHPT patients. Given the higher incidence of multi-gland disease and greater possibility of remedial surgery in nPHPT, careful consideration of risks and benefits should be made on an individualised basis and surgery should be performed by surgeons experienced in four gland exploration.