Normocalcemic Hyperparathyroidism Research Articles

ODP097 Hyperparathyroidism as a major risk factor of fracture and its prevalence in patients with hip fracture

Abstract Introduction Hyperparathyroidism is a risk factor of osteoporosis. Excess parathyroid hormone (PTH) accelerates bone loss via bone reabsorption and increases the risk of fragility fracture. Fragility fractures are associated with serious consequences in older patients. [1] This study aimed to look at the prevalence of hyperparathyroidism and vitamin D deficiency in geriatric patients (age >60) who presented with hip fractures in an Irish tertiary hospital. Methods Data was collected from Irish hip fracture Database (IHFD) and the Ortho-geriatric Electronic Patient Medical System (EPMS) between July 2019 and April 2020 (n=207). Demographic data and bone health profile (PTH, Vitamin D, and Calcium) were analysed using SPSS for statistical analysis. Results The median age of patients was 81 years (SD 8.7), and 68.3% of patients were female. Median 10-year probability of major osteoporotic and hip fracture risk is 22.5% and 12.2%, respectively. 29.9% was diagnosed with hyperparathyroidism with prevalence of primary and secondary hyperparathyroidism of 6.7% and 23.1%, respectively. The majority of these (87.3%) were normocalcaemic hyperparathyroidism. 50.7% were vitamin D deficient, with 11.5% being severely deficient (Vitamin D <20nmol/L). Conclusion The prevalence of hyperparathyroidism is higher in the hip fracture group than in the general population. [2] Vitamin D deficiency is also prevalent in this group. FRAX score indicated significant proportion of patients with high major osteoporosis and hip fracture risks. Routine bone health profile checks in this high-risk group allow early identification and management of hyperparathyroidism and vitamin D depletion, which can potentially reduce the risk of future fracture. Reference: 1. Bukata SV, DiGiovanni BF, Friedman SM, Hoyen H, Kates A, Kates SL, Mears SC, Mendelson DA, Serna Jr FH, Sieber FE, Tyler WK. A guide to improving the care of patients with fragility fractures. Geriatric Orthopaedic Surgery & Rehabilitation. 2011 Jan;2(1): 5-37.2. Press DM, Siperstein AE, Berber E, Shin JJ, Metzger R, Jin J, Monteiro R, Mino J, Swagel W, Mitchell JC. The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: a population-based analysis from the electronic medical record. Surgery. 2013 Dec 1;154(6): 1232-8 Presentation: No date and time listed

How to manage normocalcaemic hyperparathyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Normocalcemic non-renal hyperparathyroidism

Parathyroid hormone (PTH) is produced by the parathyroid glands, which are the main regulators of calcium and phosphorus metabolism. Hyperparathyroidism is a clinical condition associated with an increase in serum PTH content. The state of parathyroid glands depends very much on the amount of vitaminD, magnesium and boron in the blood because, according to official data, substantiated by a number of scientific studies, the majority of the world population (80%) has a lack/deficiency of vitamin D. This fact explains the high prevalence of thyroid diseases (hyperplasia, adenoma, hyperparathyroidism) and associated pathology. Previous studies have shown that a deficiency/lack of vitaminD was found in 85–94% of Ukraine population. A deficiency/lack of vitamin D compensatorily stimulates an increase in PTH synthesis. Doctors very rarely determine the level of PTH, which prolongs the progression of hyperparathyroidism, and they detect it only with severe associated changes in other systems. Hyperparathyroidism occurs when one or more of the parathyroid glands become hyperactive, gradually leading to elevated serum parathyroid hormone levels and hypercalcemia. The diagnostic criteria for hyperparathyroid conditions are very vague, which is confusing and leads to unnecessary surgeries instead of simple vitamin D and boron therapy. Normocalcemic primary hyperparathyroidism is a diagnosis of exclusion, and it can be considered only after careful assessment of the causes of secondary hyperparathyroidism, including that associated with a lack of vitamin D. The most common form of hyperparathyroidism is normocalcemic non-renal hyperparathyroidism. Prophylactic use of vitamin D in the correct individualized doses (25(OH)D range of 100–150 nmol/l or 40–60 ng/ml) should reduce the risk of parathyroid pathology but only 10% of the population receives such therapy, others do not know that it is useful. The only way to eliminate the gradual progression of parathyroid disorders is to administer individual prophylactic or therapeutic doses of vitaminD.

Phenotypes of primary hyperparathyroidism: Does parathyroidectomy improve clinical outcomes for all?

BackgroundPrimary hyperparathyroidism consists of 3 biochemical phenotypes: classic, normocalcemic, and normohormonal primary hyperparathyroidism. The clinical outcomes of patients with normocalcemic primary hyperparathyroidism and normohormonal primary hyperparathyroidism are not well described. MethodA retrospective review of patients who underwent parathyroidectomy at a single institution was performed. A logistical regression analysis of postoperative nephrolithiasis and highest percentage change in dual-energy x-ray absorptiometry scan comparison using Kruskal-Wallis test and Cox proportional hazard analysis of recurrence-free survival were performed. ResultsA total of 421 patients were included (340 classic, 39 normocalcemic primary hyperparathyroidism, 42 normohormonal primary hyperparathyroidism). Median follow-up was 8.8 months (range 0–126). Higher rates of multigland disease were seen in normocalcemic primary hyperparathyroidism (64.1%) and normohormonal primary hyperparathyroidism (56.1%) compared to the classic (25.8%), P < .001. There were no differences in postoperative complications. The largest percentage increases in bone mineral density at the first postoperative dual-energy x-ray absorptiometry scan were higher for classic (mean ± SD, 6.4 ± 9.1) and normocalcemic primary hyperparathyroidism (4.8 ± 11.9) compared to normohormonal primary hyperparathyroidism, which remained stable (0.2 ± 14.2). Normocalcemic primary hyperparathyroidism were more likely to experience nephrolithiasis postoperatively, 6/13 (46.2%) compared to 11/68 (16.2%) classic, and 2/13 (15.4%) normohormonal primary hyperparathyroidism, P = .0429. Normocalcemic primary hyperparathyroidism was the only univariate predictor of postoperative nephrolithiasis recurrence (odds ratio [95% confidence interval] 4.44 [1.25–15.77], P = .029). Normocalcemic primary hyperparathyroidism was significantly associated with persistent disease with 6/32 (18.8%) compared to 1/36 (2.8%) and 3/252 (1.2%) in normohormonal primary hyperparathyroidism and classic (P < .001). ConclusionThree phenotypes of primary hyperparathyroidism are distinct clinical entities. Normocalcemic primary hyperparathyroidism had higher incidence of persistent disease and postoperative nephrolithiasis but demonstrated improvements in postoperative bone density. These data should inform preoperative discussions with patients with normocalcemic primary hyperparathyroidism and normohormonal primary hyperparathyroidism regarding postoperative expectations.

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.

The short test with hydrochlorothiazide in differential diagnosis between primary normocalcemic and secondary hyperparathyroidism for inpatient treatment

Differential diagnosis between the normocalcemic primary hyperparathyroidism (nPHPT) and secondary hyperparathyroidism (SHPT) due to hypercalciuria remains a challenge. The aim of this study was to investigate the capability of short test with hydrochlorothiazide for the differential diagnosis of nPHPT and SHPT. A retrospective study was conducted with the participation of 28 patients who underwent a functional test with thiazide diuretics during hospitalization in the Department of parathyroid glands pathology and mineral disorders of the Endocrinology Research Centre, Russia. Parameters of mineral metabolism were evaluated before and 3-5 days after taking hydrochlorothiazide 50 mg/day. According to baseline and dynamic biochemical evaluation patients were divided into 3 groups. Group 1 (n=21) included patients with confirmed PHPT, who reached hypercalcemia accompanying with an elevated level of iPTH (n=19) or an increased level of iPTH accompanying with normocalcemia (n=2). In group 1, baseline Caadj. was 2.48 mmol/l [2.47; 2.52], iPTH 107.5 pg/ml [86.8; 133.0], after short test - 2.63 mmol/l [2.59; 2.66] and 102.1 pg/ml [95,7; 124,1]. Group 2 included only one who was diagnosed with SHPT, a normal value of iPTH with concomitant normocalcemia was achieved after 4 days of hydrochlorothiazide therapy (baseline Caadj. 2.35 mmol/l, iPTH 74.5 pg/ml vs at 2.27 mmol/l and 50.7 pg/ml respectively). Patients with doubtful results of the test entered in group 3 (n=6), they did not achieve significant changes in the calcium and iPTH levels, so it was recommended to continue the test on an outpatient basis (baseline Caadj. 2.39 mmol/l [2.33;2.45], iPTH 97.0 pg/ml [83.1;117.0]); after short test - 2.47 mmol/l [2.42; 2.48] and 91.3 pg/ml [86.9; 124.0] respectively). Groups with PHPT and SHPT and doubtful results significantly differed from each other in Caadj (р=0.003, U-test, Bonferroni correction Р0=0.006), but not in iPTH, daily calciuria, eGFR, and phosphorus. There were no significant differences in the incidence of classical complications of PHPT. The diagnosis of PHPT was confirmed in 21/28 patients 3-5 days after taking hydrochlorothiazide 50 mg/day. The obtained results are significant for the differential diagnosis in hospitalized patients with an unspecified genesis of hyperparathyroidism.

The Diagnosis of Normocalcaemic Hyperparathyroidism is Strikingly Dissimilar Using Different Commercial Laboratory Assays.

We assessed the impact of intact parathyroid hormone (iPTH) and adjusted calcium analyses on Abbott, Roche and Siemens analytical platforms in the diagnosis of normocalcaemic primary hyperparathyroidism (NCPHPT). These assays are used by over 85% of clinical laboratories in the UK. Over five months, consecutive serum samples from outpatients with NCPHPT in the laboratory with Abbott assays were identified, aliquoted and stored at -80°C. Frozen aliquots were transported monthly to the other two laboratories. After thawing, samples were mixed and analysed immediately for calcium, albumin and iPTH in the laboratories with Abbott, Roche and Siemens analytical platforms. Adjusted calcium was calculated using the equation used in the respective laboratory. Diagnostic concordance of iPTH and adjusted calcium were assessed using manufacturer-provided assay-specific reference intervals and the pathology harmony reference interval respectively. Fifty-five patients with NCPHPT were identified using Abbott assays. Of these, 16 (29.1%) and 11 (20.0%) had NCPHPT, 9 (16.4%) and 13 (23.6%) had hypercalcaemic primary hyperparathyroidism, and 30 (54.6%) and 31 (56.4%) patients had normal results when analysed in laboratories with Roche and Siemens assays, respectively. The diagnosis of NCPHPT was strikingly different depending on the commercial assay used. There is a pressing need for iPTH assay harmonisation and robust reference intervals. Reference intervals may become invalid if an assay drifts, as exemplified by adjusted calcium in this study.

Elevated parathyroid hormone one year after kidney transplantation is an independent risk factor for graft loss even without hypercalcemia

BackgroundHypercalcemic hyperparathyroidism has been associated with poor outcomes after kidney transplantation (KTx). However, the clinical implications of normocalcemic hyperparathyroidism after KTx are unclear. This retrospective cohort study attempted to identify these implications.MethodsNormocalcemic recipients who underwent KTx between 2000 and 2016 without a history of parathyroidectomy were included in the study. Those who lost their graft within 1 year posttransplant were excluded. Normocalcemia was defined as total serum calcium levels of 8.5–10.5 mg/dL, while hyperparathyroidism was defined as when intact parathyroid hormone levels exceeded 80 pg/mL. The patients were divided into two groups based on the presence of hyperparathyroidism 1 year after KTx. The primary outcome was the risk of graft loss.ResultsAmong the 892 consecutive patients, 493 did not have hyperparathyroidism (HPT-free group), and 399 had normocalcemic hyperparathyroidism (NC-HPT group). Ninety-five patients lost their grafts. Death-censored graft survival after KTx was significantly lower in the NC-HPT group than in the HPT-free group (96.7% vs. 99.6% after 5 years, respectively, P < 0.001). Cox hazard analysis revealed that normocalcemic hyperparathyroidism was an independent risk factor for graft loss (P = 0.002; hazard ratio, 1.94; 95% confidence interval, 1.27–2.98).ConclusionsNormocalcemic hyperparathyroidism 1 year after KTx was an independent risk factor for death-censored graft loss. Early intervention of elevated parathyroid hormone levels may lead to better graft outcomes, even without overt hypercalcemia.

The short test with active metabolites of vitamin D in differential diagnosis between primary normocalcemic and secondary hyperparathyroidism for inpatient treatment

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Nutritional and clinical manifestations of normocalcemic hyperparathyroidism in women: interim results from a case-control cross-sectional study evaluating dietary calcium intake with three validated questionnaires

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1185089: Recognition of The Oral Calcium Loading Test in the Setting of Normocalcemic Hypercalcemia: A case series report

Context: Normocalcemic hyperparathyroidism is characterized by the persistence of normal serum calcium levels and elevated intact parathyroid hormone (PTH) values, after the exclusion of other secondary hyperparathyroidism causes. Patients with this condition can present with progressive complications, such as the conversion to primary hyperparathyroidism, as well as the development of osteoporosis and nephrolithiasis. The diagnosis can be challenging due to a vast number of issues including the differentiation between normocalcemic hypercalcemia and primary hyperparathyroidism, since both have similar biochemical findings.

An unusual case report: normocalcemic markers and their relationship with multiple sclerosis in primary hyperparathyroidism disease revealed by radiological markers with the diagnosis of brown tumor

BackgroundBrown tumor is a giant cell focal bone lesion associated with hyperparathyroidism and is more common in long bones such as the femur, ribs, pelvis, and clavicle, rather than in the head and neck region. Brown tumors occur less frequently in patients with primary hyperparathyroidism and are not usually a diagnostic marker of the disease. In addition, when primary hyperparathyroidism shows normocalcemic values and this disease is accompanied by multiple sclerosis, diagnosis becomes difficult.Case presentationA 57-year-old female patient presented with a painless, firm, irregularly circumscribed lesion extending from the upper palate to the nasal cavity. The lesion was first noticed by the patient about 2 months ago because it started to form asymmetry. The patient, whose anamnesis was learned to have Multiple Sclerosis (MS) and Chronic Obstructive Pulmonary Disease (COPD), was immobile. The patient was using medication only for COPD. After radiological and clinical examinations, the image in the maxilla was thought to be Brown Tumor and blood values were examined. After the incisional biopsy was also performed, it was evaluated together with the blood results and the diagnosis of brown tumor due to normocalcemic primary hyperparathyroidism was made. As in this case, brown tumor cases in which the calcium level remains within normal ranges, that is, due to Normocalcemic Hyperparathyroidism, are extremely rare, and 7 cases have been reported in the literature.ConclusionsIn the presented case, the importance of the radiological and clinical markers of the brown tumor developing due to normocalcemic hyperparathyroidism in the diagnosis is stated, the relationship of MS and the effects of the drugs used for MS at brown tumor formation is examined, and the importance of the treatment follow-up with radiological findings is stated. The features of the much rarer subgroups of relatively common diseases should be well known, and it should not be forgotten that the less frequently observed features can sometimes be the first indicator. And when large-limited lesions are identified, additional systemic features should be sought instead of direct surgical intervention.

The non-classical primary hyperparathyroidism; a surgical dilemma pre and intra-operatively

DR. RICHARD A. PRINZ (Evanston, Illinois): So primary hyperparathyroidism is diagnosed by demonstrating an inappropriate level of parathyroid hormone for the level of circulating calcium. We typically think that this means that both calcium and parathyroid hormone should be elevated. But like most things in medicine and life, these are not always straight forward, and there are variations. There's normocalcemic hyperparathyroidism and normohormonal hyperparathyroidism.

Comparison of Parathyroid Autofluorescence Signals in Different Types of Hyperparathyroidism.

There are scant data in the literature regarding whether parathyroid autofluorescence (AF) signal patterns vary based on the etiology of hyperparathyroidism. The aim of this study was to compare AF signals of parathyroid glands across different etiologies of hyperparathyroidism. As a prospective institutional review board-approved study between 2016 and 2019, AF intensities and heterogeneity indexes (HIs) of parathyroid glands in patients who underwent parathyroidectomy using AF were calculated and compared using Chi-square, Kruskal Wallis, Mann Whitney U, and logistic regression tests. Of the total of 183 patients, 127 patients had sporadic classic primary hyperparathyroidism, 30 patients had sporadic normohormonal primary hyperparathyroidism, 10 patients had sporadic normocalcemic primary hyperparathyroidism, 12 patients had tertiary hyperparathyroidism, and 4 patients had familial primary hyperparathyroidism related to multiple endocrine neoplasia (MEN) 2A. There were no statistical differences in AF signals of abnormal parathyroid glands in classic, normohormonal or normocalcemic sporadic hyperparathyroidism. Parathyroid glands in patients with tertiary hyperparathyroidism were similar in intensity, but more homogenous compared to those in sporadic primary hyperparathyroidism. The pattern of AF exhibited by abnormal parathyroid glands was similar across different spectrums of primary hyperparathyroidism, in accordance with observations in the literature. However, parathyroid glands in tertiary hyperparathyroidism were more homogeneous, despite exhibiting a similar intensity of AF compared to those in sporadic primary hyperparathyroidism. These differences should be kept in mind when using the AF pattern as an adjunct to visual assessment in parathyroid exploration.

The short test with active metabolites of vitamin D in differential diagnosis between primary normocalcemic and secondary hyperparathyroidism for inpatient treatment

The short test with active metabolites of vitamin D in differential diagnosis between primary normocalcemic and secondary hyperparathyroidism for inpatient treatment

Effects of Parathyroidectomy on Normocalcemic Primary Hyperparathyroidism and the Role of Intraoperative PTH Measurement.

Normocalcemic primary hyperparathyroidism (NCpHPT) and normohormonal primary hyperparathyroidism (NHpHPT) are recently recognized variants of primary hyperparathyroidism. Current guidelines for the management hyperparathyroidism recognize NCpHPT as one of the areas that are recommended for more research due to limited available data. A retrospective review of patients who had parathyroidectomy between 2014 and 2019. We excluded patients with multiple endocrine neoplasia syndromes and secondary and tertiary hyperparathyroidism. Included patients were classified based on the biochemical profile into classic or normocalcemic hyperparathyroidism group. Collected data included demographics, preoperative localizing imaging, intraoperative parathyroid hormone levels, and postoperative cure rates. 261 patients were included: 160 patients in the classic and 101 patients in the normocalcemic group. Patients in the normocalcemic group had significantly more negative sestamibi scans (n = 58 [8.2%] vs 78 [51.3%], P = <.01), smaller parathyroid glands (mean weight 436.0 ± 593.0 vs 742.4 ± 1109.0mg, P = .02), higher parathyroid hyperplasia rates (n = 51 [50.5%] vs 69 [43.1%]), and significantly higher intraoperative parathyroid hormone at 10minutes (78.1 ± 194.6vs 43.9 ± 62.4 1, P = .04). Positive predictive value of both intraoperative parathyroid hormone and cure rate was lower in the normocalcemic group (84.2% vs 95.7%) and (80.5% vs 95%), respectively. Normocalcemic hyperparathyroidism is a challenging disease. Surgeons should be aware of the lower cure rate in this group, interpret intraoperative parathyroid hormone with caution, and have a lower threshold for bilateral neck exploration and 4 glands visualization.

Normocalcaemic hyperparathyroidism: Impact of assay and reference range differences on the diagnosis

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Normocalcemic Hyperparathyroidism in Calcium Kidney Stone Formers

Normocalcemic Hyperparathyroidism in Calcium Kidney Stone Formers

Post-pregnancy recurrent biliary colic with intraoperative diagnosis of limy bile syndrome.

IntroductionLimy bile syndrome (LBS) is an unusual condition in which gallbladder and/or bile ducts are filled with paste-like radiopaque material with a high calcium carbonate content. It can be rarely associated with PTH disorder and hypercalcemia.Presentation of caseA 35-year-old woman presented with epigastric and right hypochondrium pain since a few hours. Similar attacks occurred in the past months soon after a pregnancy with vaginal delivery. Laboratory findings were not significant. The abdominal ultrasound highlighted a micro-lithiasis of gallbladder without complications. Considering the recurrent biliary attacks, laparoscopic cholecystectomy was performed with intraoperative diagnosis of LBS. A subsequent endocrinological screening highlighted a normocalcemic hyperparathyroidism associated with Vitamin D deficiency, likely related to the recent pregnancy and not to LBS.DiscussionLBS is a rare condition with not clear etiology, frequently associated with cholelithiasis, of which it shares clinical presentation and potential complications. Diagnosis of LBS is based on abdominal X-ray/computed tomography scan, or it could be an intraoperative finding. The gold standard treatment is represented by laparoscopic cholecystectomy. The pregnancy with its related cholestatic phenotype could facilitate the LBS manifestation. An endocrinological screening should be performed to rule out a concomitant calcium metabolism disorder.ConclusionKnowledge of this rare condition could help general surgeons handle it properly.

Bone Quality as Measured by Trabecular Bone Score in Normocalcemic Primary Hyperparathyroidism

ObjectiveThe impact of normocalcemic hyperparathyroidism (NHPT) on bone quality remains largely unexplored. We aimed to investigate the usefulness of trabecular bone score (TBS) assessment in NHPT and the accuracy of TBS in predicting vertebral fractures (VFs) in NHPT. MethodsIn this multicentric cross-sectional study, we assessed the TBS in 47 subjects with NHPT, 41 with primary hyperparathyroidism (PHPT), and 39 age- and sex-matched control subjects. ResultsTBS values did not differ among the 3 groups. The prevalence of low TBS (TBS < 1.2) was 23.4% in NHPT, 26.8% in PHPT, and 15.4% in controls, without statistically significant differences between groups. However, we found a lower lumbar spine Z-score adjusted for TBS (LS Z-score∗TBS) in PHPT participants when compared with controls (-0.48 ± 1.06 vs 0.07 ± 0.93, P = .017). In NHPT group, LS Z-score∗TBS did not detect patients with overall VFs (threshold, -0.15; area under the curve, 0.45; 95% CI, 0.253-0.648; accuracy, 55.3%). Instead, it was useful for moderate-severe VFs (threshold, 0.55; area under the curve, 0.81; 95% CI, 0.62-0.996; accuracy, 83%). In PHPT subjects also, TBS did not predict VFs. ConclusionIn NHPT, TBS is not reduced. When adjusted for TBS, the LS Z-score might predict moderate-to-severe VFs.