Normocalcemic Hyperparathyroidism Research Articles

Bone Mineral Density and First Line Imaging with [18F]fluorocholine PET/CT in Normocalcemic and Hypercalcemic Primary Hyperparathyroidism: Results from a Single Center

Objectives: Primary hyperparathyroidism (PHPT) is associated with normal or elevated calcium levels and affects bone mineral density. The proportion of cases predisposed to metabolic bone disease is unknown in patients with PHPT. The aim of this study was to assess bone mineral density and bone quality in patients with normo- or hypercalcemic primary hyperparathyroidism undergoing baseline parathyroid gland assessment with [18F]fluorocholine PET/CT imaging. Methods: A total of 140 consecutive patients were enrolled in this observational study. All patients with normo- or hypercalcemic primary hyperparathyroidism underwent dual-energy X-ray absorptiometry (DXA) for assessment of bone mineral density (BMD) and trabecular bone score (TBS). [18F]fluorocholine PET/CT was performed in all patients for the detection and localization of parathyroid adenoma. Hyper- and normocalcemic patients were compared with regard to the proportion of osteoporosis and osteopenia, T-Score, TBS, serum calcium, phosphorus and parathyroid hormone levels, the maximum standardized uptake value (SUVmax) in PET/CT imaging, and laboratory results. Results: The majority of patients was female (88.57%) and had a pathologic bone mineral density (52.86%). Overall, 33 patients had osteoporosis and 41 osteopenia. The mean lumbar T-Score was −1.48 (SD 1.37) and the T-Score of the femoral neck was −1.21 (SD 0.92). Mean TBS was also decreased (−2.13). No difference was found between normo- or hypercalcemic patients regarding bone metabolism and imaging parameters. Conclusions: More than half of patients with normo- or hypercalcemic PHPT showed abnormal BMD. First-line [18F]fluorocholine PET/CT identified parathyroid adenoma in a high proportion of patients, even in patients with normocalcemic PHPT. The early evaluation of metabolic bone disease seems desirable in clinical management of females with PHPT.

Long-term effect of postoperative radioactive iodine therapy on parathyroid function in patients with differentiated thyroid cancer.

The study aimed to assess the impact of postoperative radioactive iodine (RAI) therapy on parathyroid function in patients who underwent total or subtotal thyroidectomy for differentiated thyroid cancer (DTC). Data from 150 patients treated with RAI for DTC and 76 patients with low-risk DTC not receiving RAI were retrospectively analyzed. Clinical characteristics, preoperative and 1-month postoperative biochemical parameters, and adjusted calcium, phosphorus, parathyroid hormone (PTH), and 25-hydroxyvitamin D3 (25-OH-D) levels at 3months, 1year, 3years, and 5years post-RAI (or in the low-risk group) were recorded. A total of 226 DTC patients were included in the study (80.5% female, mean age 42.7 ± 13.2years). Total thyroidectomy was performed in 97.3% (n = 220) of patients, with central lymph node dissection (CLND) in 41.6% (n = 94). No significant preoperative differences in PTH, aCa, P, Mg, or 25-hydroxyvitamin D3 levels were observed. However, patients receiving ≥ 3.7GBq (or 100mCi) RAI (n = 70) had lower calcium and PTH levels at the end of the first year following RAI treatment (p = 0.048, p = 0.032). The non-RAI group showed significantly higher calcium levels at one month postoperatively (p = 0.031) and lower rates of CLND and neck dissection. No significant differences in biochemical parameters were found at the five-year follow-up, except for one patient who developed normocalcemic hyperparathyroidism after RAI. High-dose RAI therapy may lead to transient decreases in calcium and PTH levels in the early post-treatment period. However, long-term parathyroid function appears to remain unaffected in DTC patients, regardless of the RAI dose administered. Nonetheless, close monitoring of calcium and PTH levels is recommended, particularly in the early post-treatment period, to promptly manage any potential transient hypoparathyroidism.

Recurrent Kidney Stones and Normocalcemic Hyperparathyroidism: A Report of Two Cases

Recurrent Kidney Stones and Normocalcemic Hyperparathyroidism: A Report of Two Cases

Natural history and complications of normocalcemic hyperparathyroidism: a retrospective cohort study.

Normocalcemic hyperparathyroidism (NHPT) is variably defined, and information regarding complications and natural history are scarce. We aimed to describe the phenotype of NHPT in relation to hypercalcemic hyperparathyroidism (PHPT) and controls, to determine risk of progression, and to develop a predictive model for progression to PHPT. This is a retrospective chart review of 232 patients at a tertiary medical center, comparing 75 controls, 73 patients with NHPT, and 84 with PHPT. NHPT was intermediate in biochemical profile between controls and PHPT with respect to cCa, iPTH, intraindividual coefficient of variant of cCa, phosphorus, and 25(OH)D. NHPT patients had an increased adjusted risk of urolithiasis (OR 5.34, 95%CI, 2.41-12.71, P < .001) and fragility fractures (OR 4.53, 95%CI, 1.63-14.84, P = .006) versus controls, after adjustment for age, sex, and BMI. Fewer NHPT compared with PHPTH patients achieved cure with parathyroidectomy (P = .001). NHPT more often had nonlocalizing imaging or polyglandular disease (P = .005). Parathyroidectomy improved biochemical but not BMD parameters in NHPT. Over a median follow-up of 4.23 (IQR 1.76-5.31) years, NHPT patients managed expectantly experienced no change in iPTH, and progression to PHPT occurred in 9%. An XGBoost model combining 6 factors for progression (mean index 2 iPTH, mean index 2 cCa, 24-h urinary calcium, age, 25(OH)D, and presence of urolithiasis) had an area under the curve 1.00 (95%CI, 1.00-1.00, P < .001) for predicting combined progression. NHPT is a mild variant of PHPT at intermediate risk of urolithiasis and fragility fractures. Cure was less often achieved with parathyroidectomy, which did not improve BMD parameters. Progression was infrequent with conservative management. Because only a minority progressed to PHPT, in addition to lower surgical success rates, we suggest conservative management for the majority of NHPT unless risk factors for progression are identified.

Role of PET-choline in the diagnosis of an hyperfunctioning cervical-mediastinal parathyroid adenoma: a case report of a multi-fracturative normocalcemic hyperparathyroidism

ormocalcemic primary hyperparathyroidism is a recently distinguished form of Primary hyperparathyroidism and it is mostly caused by an hyperfunctioning parathyroid adenoma. It has been consistently associated with skeletal and renal complications, and, therefore, a proper radiological diagnosis of the hyperfunctioning adenoma is crucial in patients affected. Here we report a case of a patient affected by normocalcemic primary hyperparathyroidism and a severe osteoporosis complicated with multiple fragility fractures, highlighting the role of PET-choline in the diagnosis of an hyperfunctioning cervical-mediastinal parathyroid adenoma not previously localized with conventional imaging. KEY WORDS: PET-choline, normocalcemic hyperparathyroidism, osteoporosis, fractures, parathyroid adenoma.

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.

Age-specific Reference Intervals of Abbott Intact PTH-Potential Impacts on Clinical Care.

PTH assays are not standardized; therefore, method-specific PTH reference intervals are required for interpretation of results. PTH increases with age in adults but age-related reference intervals for the Abbott intact PTH (iPTH) assay are not available. Deidentified serum PTH results from September 2015 to November 2022 were retrieved from the laboratory information system of a laboratory serving a cosmopolitan population in central-west England for individuals aged 18 years and older if the estimated glomerular filtration rate was ≥60 mL/min, serum 25-hydroxyvitamin D was >50 nmol/L, and serum albumin-adjusted calcium and serum phosphate were within reference intervals. Age-specific reference intervals for Abbott iPTH were derived by an indirect method using the refineR algorithm. PTH increased with age and correlated with age when controlled for 25-hydroxyvitamin D, estimated glomerular filtration rate, and adjusted calcium (r = 0.093, P < .001). The iPTH age-specific reference intervals for 4 age partitions of 18 to 45 years, 46 to 60 years, 61 to 80 years, and 81 to 95 years were 1.6 to 8.6 pmol/L, 1.8 to 9.5 pmol/L, 2.0 to 11.3 pmol/L, and 2.3 to 12.3 pmol/L, respectively. PTH was higher in women compared with men (P < .001). Sex-specific age-related reference intervals could not be derived because of the limited sample size. Age-specific Abbott iPTH reference intervals were derived. Application of age-specific reference intervals will impact the diagnosis and management of normocalcemic hyperparathyroidism, based on current definitions, and secondary hyperparathyroidism. Additional studies are required to clarify the effect of sex and ethnicity on PTH.

ЭПИДЕМИОЛОГИЯ ПЕРВИЧНОГО ГИПЕРПАРАТИРЕОЗА

This paper reviews epidemiological data on primary hyperparathyroidism (PHPT). PHPT is an endocrine disease caused by a tumor or hyperplastic changes in the parathyroid glands (PTG); it leads to disturbances in calcium-phosphorus homeostasis and can cause organ dysfunction. The results of epidemiological studies in various countries indicate an "epidemic" of PHPT at the end of the 20th century. Currently, PHPT ranks as the third endocrine problem in the world. Its prevalence is about 0.86-1% in people under 50 and 2% in people over 50. It was found that PHPT occurs more often in people aged 40-60 years, with an increase in the frequency of its detection after 25 years of age, especially in women after menopause. The review emphasizes the importance of PHPT, which represents a severe medical and social problem. Regular screening and the introduction of modern diagnostic methods play a vital role in the timely detection and management of PHPT, which is of great importance for improving patients' quality of life and preventing severe complications. When compiling the literature review, we used the following databases: PubMed, Embase, Medline, ScienceDirect, Cochrane Library, eLibrary, and CyberLeninka. The literature search was carried out using the following keywords: "epidemiology of primary hyperparathyroidism", "prevalence", "incidence", "normocalcemic hyperparathyroidism", "parathyroid gland", and "parathyroid hormone". The search identified more than 1070 scientific papers, from which 48 studies were selected. These studies cover the epidemiological aspects (incidence and prevalence) of PHPT conducted in various countries. The selection was done without considering each study's specific period and volume of observations. The selection process focused on studies using automated blood calcium analyzers to evaluate the impact of regular screening on the effectiveness of detecting PHPT. Works presenting both global and regional data were also included in the analysis. Studies that did not meet the established selection criteria were excluded. Keywords: Primary hyperparathyroidism, parathyroid hormone, hypercalcemia, menopause, epidemiology.

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.

Thiazide diuretics and primary hyperparathyroidism.

Thiazide diuretics exert a natriuretic and diuretic effect by inhibiting sodium reabsorption in the distal convoluted tubule. Furthermore, thiazide diuretics affect renal calcium handling by increasing calcium reabsorption, leading to hypocalciuria. The effect that thiazide diuretics exert on parathyroid hormone secretion is controversial. Some studies found parathyroid hormone levels were suppressed with the use of thiazide diuretics, while others found that thiazides were associated with initial parathyroid hormone suppression followed by raised parathyroid hormone levels. This makes the relationship between thiazide diuretics and primary hyperparathyroidism interesting. If a patient is taking thiazide diuretics, this may make it harder to establish the aetiology of hypercalcaemia and may unmask normocalcaemic or mild primary hyperparathyroidism. Thiazide diuretics may have a beneficial role in the diagnosis of patients with concomitant hyperparathyroidism and hypercalciuria by distinguishing secondary hyperparathyroidism caused by hypercalciuria from normocalcaemic primary hyperparathyroidism. In addition, thiazide diuretics may have a role in managing patients with primary hyperparathyroidism who have an indication for parathyroidectomy in view of significant hypercalciuria, but are unfit for surgery.

Normocalcemic hyperparathyroidism after successful parathyroidectomy for single parathyroid adenoma: Prevalence, etiological factors, predictive markers, treatment and evolution

Background and objectivePostparathyroidectomy normocalcemic hyperparathyroidism (PPNCHPPT) is a frequent situation for which we have no information in our country. The objective is to know our prevalence of PPNCHPPT, the associated etiological factors, the predictive markers, the treatment administered and the evolution. Patients and methodRetrospective observational cross-sectional study on 42 patients. Twelve patients with PPNCHPPT and 30 without PPNCHPPT are compared. ResultsHPPTNCPP prevalence: 28.6%. Etiological factors: vitamin D deficiency: 75%; bone remineralization: 16.7%; renal failure: 16.7%; hypercalciruria: 8.3%. No change in the set point of calcium-mediated parathormone (PTH) secretion was observed, but an increase in the preoperative PTH/albumin-corrected calcium (ACC) ratio was observed. Predictive markers: PTH/ACC ratio (AUC 0.947; sensitivity 100%, specificity 78.9%) and PTH (AUC 0.914; sensitivity 100%, specificity 73.7%) one week postparathyroidectomy. Evolution: follow-up 30 ± 16.3 months: 50% normalized PTH and 8.3% had recurrence of hyperparathyroidism. Patients with PPNCHPPT less frequently received preoperative treatment with bisphosphonates and postoperative treatment with calcium salts. ConclusionsThis is the first study in our country that demonstrates a mean prevalence of PPNCHPPT, mainly related to a vitamin D deficiency and a probable resistance to the action of PTH, which can be predicted by the PTH/ACC ratio and PTH a week post-intervention and often evolves normalizing the PTH. We disagree with the etiological effect of hypercalciuria and the change in the PTH/calcemia regulation set point, and we acknowledge the scant treatment administered with calcium salts in the postoperative period.

Normocalcemic hyperparathyroidism: Intervention to differentiate primary from secondary hyperparathyroidism

BackgroundNormocalcemic hyperparathyroidism can occur, but surgery should not be considered until common etiologies for secondary hyperparathyroidism are comprehensively excluded. Calcium deficiency is an underrecognized cause of normocalcemic parathyroid hormone elevation, and we aim to determine if the implementation of a preoperative calcium challenge can be used to reduce unnecessary parathyroidectomy. MethodsConsecutive patients referred for parathyroidectomy (1/21–6/22) with normocalcemia (serum calcium <10 mg/dL) and concurrently elevated parathyroid hormone levels were routinely treated with supplemental calcium and vitamin D3, and follow-up laboratory studies were assessed. ResultsA total of 29/314 (9%) patients had normocalcemic parathyroid hormone elevation with mean calcium, parathyroid hormone, and vitamin D 25OH levels of 9.5 ± 0.3 mg/dL, 109.9 ± 34.9 pg/mL, and 42.7 ± 23.8 ng/mL respectively. Confounding factors included estimated glomerular filtration rate <60 in 2, loop diuretic use in 4, and prior gastric bypass or gastric sleeve surgery in 4. Follow-up biochemical evaluation was available in 27 (92%); results were unchanged in 7 patients (26%); normalization of parathyroid hormone levels with persistently normal calcium levels occurred in 15 (55%), thus confirming secondary hyperparathyroidism and hypercalcemia with elevated parathyroid hormone levels (classic primary hyperparathyroidism) was diagnosed in 5 (19%). Parathyroid exploration has been completed for 3 of 5 patients with classic primary hyperparathyroidism to date. ConclusionA preoperative calcium challenge was prospectively initiated in normocalcemic patients with parathyroid hormone elevation, and there was high compliance (92%). Short-interval calcium supplementation revealed ∼50% to have resolved secondary hyperparathyroidism due to insufficient calcium intake, which avoided unnecessary surgery. In contrast, classic patients were unveiled in 20%, allowing for prompt and correct surgical intervention.

Hiperparatiroidismo normocalcémico tras paratiroidectomía exitosa por adenoma único paratiroideo: prevalencia, factores etiológicos, marcadores predictivos, tratamiento y evolución

Background and objectivePostparathyroidectomy normocalcemic hyperparathyroidism (PPNCHPPT) is a frequent situation for which we have no information in our country. The objective is to know our prevalence of PPNCHPPT, the associated etiological factors, the predictive markers, the treatment administered and the evolution. Patients and methodRetrospective observational cross-sectional study on 42 patients. Twelve patients with PPNCHPPT and 30 without PPNCHPPT are compared. ResultsHPPTNCPP prevalence: 28.6%. Etiological factors: vitamin D deficiency: 75%; bone remineralization: 16.7%; renal failure: 16.7%; hypercalciruria: 8.3%. No change in the set point of calcium-mediated parathormone (PTH) secretion was observed, but an increase in the preoperative PTH/albumin-corrected calcium (ACC) ratio was observed. Predictive markers: PTH/ACC ratio (AUC 0.947; sensitivity 100%, specificity 78.9%) and PTH (AUC 0.914; sensitivity 100%, specificity 73.7%) one week postparathyroidectomy. Evolution: follow-up 30±16.3 months: 50% normalized PTH and 8.3% had recurrence of hyperparathyroidism. Patients with PPNCHPPT less frequently received preoperative treatment with bisphosphonates and postoperative treatment with calcium salts. ConclusionsThis is the first study in our country that demonstrates a mean prevalence of PPNCHPPT, mainly related to a vitamin D deficiency and a probable resistance to the action of PTH, which can be predicted by the PTH/ACC ratio and PTH a week post-intervention and often evolves normalizing the PTH. We disagree with the etiological effect of hypercalciuria and the change in the PTH/calcemia regulation set point, and we acknowledge the scant treatment administered with calcium salts in the postoperative period.

Resolution of Secondary Hyperparathyroidism After Kidney Transplantation and the Effect on Graft Survival.

Hyperparathyroidism (HPT) is nearly universal in patients with end-stage kidney disease. Kidney transplantation (KT) reverses HPT in many patients, but most studies have only focused on following calcium and not parathyroid hormone (PTH) levels. We sought to study the prevalence of persistent HPT post-KT at our center and its effect on graft survival. Patients who underwent KT from January 2015 to August 2021 were included and characterized by post-KT HPT status at the most recent follow-up: resolved (achieving normal PTH post-KT) versus persistent HPT. Those with persistent HPT were further stratified by the occurrence of hypercalcemia (normocalcemic versus hypercalcemic HPT). Patient demographics, donor kidney quality, PTH and calcium levels, and allograft function were compared between groups. Multivariable logistic regression and Cox regression with propensity score matching were conducted. Of 1554 patients, only 390 (25.1%) patients had resolution of renal HPT post-KT with a mean (±SD) follow-up length of 40±23 months. The median (IQR) length of HPT resolution was 5 (0-16) months. Of the remaining 1164 patients with persistent HPT post-KT, 806 (69.2%) patients had high PTH and normal calcium levels, while 358 (30.8%) patients had high calcium and high PTH levels. Patients with persistent HPT had higher parathyroid hormone (PTH) at the time of KT [403 (243-659) versus 277 (163-454) pg/mL, P <0.001] and were more likely to have received cinacalcet treatment before KT (34.9% vs. 12.3%, P <0.001). Only 6.3% of patients with persistent HPT received parathyroidectomy. Multivariable logistic regression showed race, cinacalcet use pre-KT, dialysis before KT, receiving an organ from a deceased donor, high PTH, and calcium levels at KT were associated with persistent HPT post-KT. After adjusting for patient demographics and donor kidney quality by propensity score matching, persistent HPT (HR 2.5, 95% CI 1.1-5.7, P =0.033) was associated with a higher risk of allograft failure. Sub-analysis showed that both hypercalcemic HPT (HR 2.6, 95% CI 1.1-6.5, P =0.045) and normocalcemic HPT (HR 2.5, 95% CI 1.3-5.5, P =0.021) were associated with increased risk of allograft failure when compared with patients with resolved HPT. Persistent HPT is common (75%) after KT and is associated with a higher risk of allograft failure. PTH levels should be closely monitored after kidney transplantation so that patients with persistent HPT can be treated appropriately.

Primary normocalcemic hyperparathyroidism

Primary normocalcemic hyperparathyroidism

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.

B-mode ultrasound assessment of carotid artery structural features in patients with normocalcaemic hyperparathyroidism.

Normocalcaemic hyperparathyroidism is a condition first defined in 2008, characterized by normal serum calcium and high parathormone levels. Although normocalcaemic hyperparathyroidism is considered to have a milder clinical picture compared to asymptomatic primary hyperparathyroidism, recent studies have shown that it may be associated with osteoporosis, insulin resistance, metabolic syndrome, and cardiovascular risk factors. Considering that normocalcaemic hyperparathyroidism may pose a cardiovascular risk in the setting of carotid atherosclerosis, we sought to examine the structural features of the carotid artery in patients with normocalcaemic hyperparathyroidism compared to a control group. After excluding patients with hypertension, diabetes, and dyslipidaemia (other factors contributing to atherosclerosis), 37 (32 females, 5 males) patients with normocalcaemic hyperparathyroidism with a mean age of 51.2 ± 8 (min: 32, max: 66) years and 40 controls (31 females, 9 males) with a mean age of 49.3 ± 7.5 (min: 34, max: 64) years with normal serum albumin-corrected calcium and parathyroid hormone levels were included in the study. Structural features of the carotid artery including intima-media thickness (mean and maximum), lumen diameter, and the presence of plaque were assessed using B-mode ultrasound. On ANCOVA analysis corrected for atherosclerotic factors (body mass index, waist circumference, fasting plasma glucose, serum cholesterol, lipid, and blood pressure), greater mean intima-media thickness was found in patients with normocalcaemic hyperparathyroidism than in controls (0.65 mm vs. 0.59 mm, respectively) (p = 0.023). Maximum carotid intima-media thickness was also greater in patients with normocalcaemic hyperparathyroidism compared to controls (0.80 mm vs. 0.75 mm, respectively) (p = 0.044). The study groups did not show a significant difference in lumen diameter and the presence of carotid plaque. In addition, a negative correlation was found between parathormone (PTH) level and lumen diameter. The findings of this study show that as with asymptomatic primary hyperparathyroidism, normocalcaemic hyperparathyroidism may be associated with increased cardiovascular risk by predisposing to atherosclerosis.

A rare case of adult hypophosphatasia masked with primary hyperparathyroidism

Abstract Introduction Hypophosphatasia (HPP) is a rare inherited disorder of bone and mineral metabolism due to mutations in the Alkaline Phosphatase-Liver (ALPL) gene encoding the tissue nonspecific alkaline phosphatase (TNSALP). Clinical features of HPP in adults include early loss of teeth, muscle weakness, musculoskeletal pain, osteoporosis and fragility fractures with delayed healing. The most typical biochemical manifestation of the disease is persistently low level of alkaline phosphatase (ALP). Primary hyperparathyroidism (PHPT) is a relatively common endocrine disorder leading to increase in bone turnover markers including ALP. Coexistence of HPP and PHPT is a very rare condition. Herein we present an adult HPP patient who presented with primary hyperparathyroidism and normal serum ALP levels, which decreased significantly after parathyroidectomy. Clinical Case A 33-year-old female with a past medical history of Hashimoto's thyroiditis and acne rosacea admitted to our outpatient clinic because of gradually increasing bone pain, fatigue and weakness. She had early teeth loss and dental problems, but she denied history of fractures and kidney stones. Her family history was remarkable for nephrolithiasis in both parents. On physical examination the patient had facial rash and telangiectasia. She also had teeth loss and many dental cavities. Her vital signs were within normal limits. In biochemical investigations creatinine was 0.45 mg/dL (0.7–1.4), ALP 81 U/L (35–105), PTH 531 pg/mL (15–65), calcium 10.84 mg/dL (8.5–10.5), albumin 4.9 g/dL (3.2–5.5), phosphorus 2.25 mg/dL (2.7–4.5), Vitamin D 5 ng/mL and urine calcium excretion 613 mg/day. Laboratory results were compatible with normocalcemic hyperparathyroidism and severe vitamin D deficiency. Bone mineral density of the lumbar spine and the femoral neck revealed osteopenia and 1/3 distal radius revealed osteoporosis. There was no evidence of nephrolithiasis and nephrocalcinosis on abdominal ultrasound. Neck ultrasound and CT scan and Tc-99m MIBI scanning of the patient revealed a parathyroid adenoma in the posteroinferior of thyroid gland's left lobe. A successful parathyroidectomy was performed. During follow-up the patient's serum ALP levels decreased significantly to 29 U/L with a repeat being 26 U/L. Bone-specific ALP was 4.2 μg/L (3–14 μg/L). Urine phosphoethanolamine was elevated to 68.6 μmol/g.Cr (0–48), which supported the diagnosis of HPP. Genetic analysis was performed and heterozygous p.N190del (c.568_570delAAC/c.566_568delACA) mutation was detected. This mutation was previously reported as pathogenic and has been associated with adult hypophosphatasia. Conclusion Although persistently low level of ALP is characteristic of HPP, disorders that increase bone turnover may result in an increase in serum ALP levels, which may mask underlying HPP. Acknowledgements We are thankful to Alexion Pharmaceuticals, Inc for providing fund for ALP substrates and genetic analysis of the patient.

Assessment of Metabolic Syndrome Components in Patients with Normocalcemic Hyperparathyroidism: A Retrospective Study

Assessment of Metabolic Syndrome Components in Patients with Normocalcemic Hyperparathyroidism: A Retrospective Study

DXA-based bone strain index in normocalcemic primary hyperparathyroidism.

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. 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). 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. 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.