Normocalcemic primary hyperparathyroidism — «new era» in diagnosis of an old disease

2017 ◽  
Vol 63 (4) ◽  
pp. 236-244
Author(s):  
Irina A. Baranova ◽  
Tatyana A. Zykova

During the last century, primary hyperparathyroidism (PHPT) passed from the category of rare severe diseases to a common endocrine disorder with a prevalence of mild forms. Over the last 10—20 years, widespread screening for osteoporosis has led to the «new era» in diagnosis of PHPT when patients are diagnosed at the stage of an isolated elevated parathyroid hormone with stable normal serum calcium levels and the absence of secondary causes of hyperparathyroidism. This phenomenon was called normocalcemic primary hyperparathyroidism (nPHPT); according to the literature data, its prevalence varies from 0.4 to 16.7% due to the lack of unified diagnostic criteria. The clinical picture and natural history of the disease are poorly explored, and it is still unclear if nPHPT is a separate disease entity or if it is an early stage of hypercalcemic PHPT. A number of studies have shown that complications of nPHPT (osteoporosis and urolithiasis) are similar to those of the symptomatic form of PHPT despite stable normocalcemia. However, these patients were often referred to specialized metabolic centers due to a decrease in the bone mass or nephrolithiasis, therefore the rate of complications in them may be overestimated. There are also controversial data on an increased risk of cardiovascular diseases due to metabolic disorders in this pathology. As a new clinical nosology, normocalcemic PHPT was first officially recognized at the Third International Workshop on Management of Asymptomatic PHPT in 2008, but there have been yet no common recommendations for its treatment. Some studies have shown a response to medical therapy and improved indicators of bone mineral density after parathyroidectomy in these patients. According to the experts of the Fourth International Workshop in 2014, nPHPT remains one of the key topics for further research.

2009 ◽  
Vol 94 (2) ◽  
pp. 351-365 ◽  
Author(s):  
Shonni J. Silverberg ◽  
E. Michael Lewiecki ◽  
Leif Mosekilde ◽  
Munro Peacock ◽  
Mishaela R. Rubin

Abstract Background: At the Third International Workshop on Asymptomatic Primary Hyperparathyroidism (PHPT) in May 2008, recent data on the disease were reviewed. We present the results of a literature review on issues arising from the clinical presentation and natural history of PHPT. Methods: Questions were developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies was reviewed, and the questions of the International Task Force were addressed by the Consensus Panel. Conclusions: 1) Data on the extent and nature of cardiovascular involvement in those with mild disease are too limited to provide a complete picture. 2) Patients with mild PHPT have neuropsychological complaints. Although some symptoms may improve with surgery, available data remain inconsistent on their precise nature and reversibility. 3) Surgery leads to long-term gains in spine, hip, and radius bone mineral density (BMD). Because some patients have early disease progression and others lose BMD after 8–10 yr, regular monitoring (serum calcium and three-site BMD) is essential in those followed without surgery. Patients may present with normocalcemic PHPT (normal serum calcium with elevated PTH concentrations; no secondary cause for hyperparathyroidism). Data on the incidence and natural history of this phenotype are limited. 4) In the absence of kidney stones, data do not support the use of marked hypercalciuria (>10 mmol/d or 400 mg/d) as an indication for surgery for patients. 5) Patients with bone density T-score −2.5 or less at the lumbar spine, hip, or distal one third radius should have surgery.


2021 ◽  
Vol 12 ◽  
pp. 204201882199537
Author(s):  
Nivaran Aojula ◽  
Shahab Khan ◽  
Neil Gittoes ◽  
Zaki Hassan-Smith

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.


Blood ◽  
1984 ◽  
Vol 63 (4) ◽  
pp. 949-957 ◽  
Author(s):  
BD Cheson ◽  
HS Walker ◽  
ME Heath ◽  
RJ Gobel ◽  
J Janatova

Abstract Patients with multiple myeloma (MM) are at an increased risk for infections with bacteria that require opsonization with complement. Because Streptococcus pneumoniae is the most frequently encountered pathogen in these patients, we investigated the ability of serum from patients with MM to mediate the binding of C3b, the major opsonin of the complement system, to S. pneumoniae. S. pneumoniae types 3, 14, and 25 were chosen for study, since S. pneumoniae type 3 activates primarily the classical complement pathway (CCP), type 25 primarily the alternative complement pathway (ACP), and type 14 both pathways. S. pneumoniae were treated with normal serum or serum from 17 patients with MM, and the bound C3b was quantified with fluorescein-conjugated anti-C3 in a spectrophotofluorometric assay. Despite normal or elevated serum concentrations of C3, total hemolytic complement, and C-reactive protein in all of the MM sera, factor B in 16/17 such sera, and C4 in 14/17 MM sera studied, all 17 sera demonstrated a defect in C3b binding to type 3 (32.7% +/- 6% of normal). In addition, serum from 15/17 patients bound decreased amounts of C3b to types 14 (39.6% +/- 8%) and 25 (52.2% +/- 8%). Mixing normal serum with MM serum restored MM C3b binding activity to all three S. pneumoniae types, suggesting that the defect was related to a deficiency rather than an inhibitor of C3 activation. Although MM patients are unable to produce specific antibodies to bacterial antigens, the addition of anti-S. pneumoniae antibodies to MM serum did not enhance C3b binding to any of the S. pneumoniae types. However, when S. pneumoniae were opsonized in a mixture of MM serum and C3-depleted normal serum, C3b binding was restored to all three S. pneumoniae types, demonstrating that MM C3 functions normally in the presence of other normal serum factors. In the present studies, the MM C3b binding defect appeared to correlate with the incidence of S. pneumoniae infections. Serum from patients with a history of an S. pneumoniae infection bound significantly less C3 (20.5% +/- 4%) than those study patients without a history of an S. pneumoniae infection (55.8% +/- 8%) (p less than 0.0025). Thus, MM serum has a defect in the activation of C3, and this may contribute to the increased susceptibility of MM patients to S. pneumoniae infections.


2008 ◽  
Vol 93 (9) ◽  
pp. 3462-3470 ◽  
Author(s):  
Mishaela R. Rubin ◽  
John P. Bilezikian ◽  
Donald J. McMahon ◽  
Thomas Jacobs ◽  
Elizabeth Shane ◽  
...  

Context: Primary hyperparathyroidism (PHPT) often presents without classical symptoms such as overt skeletal disease or nephrolithiasis. We previously reported that calciotropic indices and bone mineral density (BMD) are stable in untreated patients for up to a decade, whereas after parathyroidectomy, normalization of biochemistries and increases in BMD ensue. Objective: The objective of the study was to provide additional insights in patients with and without surgery for up to 15 yr. Design: The study had an observational design. Setting: The setting was a referral center. Patients: Patients included 116 patients (25 men, 91 women); 99 (85%) were asymptomatic. Intervention: Fifty-nine patients (51%) underwent parathyroidectomy and 57 patients were followed up without surgery. Main Outcome Measure: BMD was measured. Results: Lumbar spine BMD remained stable for 15 yr. However, BMD started to fall at cortical sites even before 10 yr, ultimately decreasing by 10 ± 3% (mean ± sem; P < 0.05) at the femoral neck, and 35 ± 5%; P < 0.05 at the distal radius, in the few patients observed for 15 yr. Thirty-seven percent of asymptomatic patients showed disease progression (one or more new guidelines for surgery) at any time point over the 15 yr. Meeting surgical criteria at baseline did not predict who would have progressive disease. BMD increases in patients who underwent surgery were sustained for the entire 15 yr. Conclusions: Parathyroidectomy led to normalization of biochemical indices and sustained increases in BMD. Without surgery, PHPT progressed in one third of individuals over 15 yr; meeting surgical criteria at the outset did not predict this progression. Cortical bone density decreased in the majority of subjects with additional observation time points and long-term follow-up. These results raise questions regarding how long patients with PHPT should be followed up without intervention.


2020 ◽  
Vol 10 (2) ◽  
pp. 94-101
Author(s):  
L. M. Farkhutdinova

The article is devoted to one of the actual medical and social problems — primary hyperparathyroidism, the late diagnosis of which leads to the development of severe complications and an increased risk of premature death. Unlike developed countries, where 80% of cases are represented by mild forms of the disease, in the Russian Federation this indicator does not exceed 30%, while 70% are manifest forms. Widespread awareness of doctors of various specialties in the diagnosis of parathyroid adenoma is necessary for the timely detection of the disease. The article reflects the main stages of the study of the disease, the pathogenesis of the clinical manifestations of primary hyperparathyroidism, the classic symptoms of which are changes in the target organs of the parathyroid hormone — bone tissue, urinary system and gastrointestinal tract, is considered. Bone disorders are the most common manifestation of hyperparathyroidism and are characterized by increased bone metabolism with a progressive decrease in bone mineral density. Typical changes in the kidneys include nephrolithiasis and nephrocalcinosis, causing the formation of renal failure. Gastrointestinal signs of hyperparathyroidism are erosion and ulcers of the stomach and duodenum, prone to bleeding, recurrent pancreatitis. Diagnosis of the disease is based on laboratory results, characterized by elevated levels of calcium and parathyroid hormone in the blood. Visualization of the paradenomas in most cases is provided by ultrasound and scintigraphy. Removal of parathyroid adenoma is the most effective treatment. A clinical case of a severe form of the disease is presented, indicating an urgent need to take measures to solve the problem of primary hyperparathyroidism.


Author(s):  
John Newell-Price ◽  
Alia Munir ◽  
Miguel Debono

Primary hyperparathyroidism is a disorder of bone mineralization and renal physiology due to excess parathyroid hormone secretion. Parathyroid hormone (PTH) is produced and released by the parathyroid chief cells, under regulation of the G- protein-coupled calcium-sensing receptor. Primary hyperparathyroidism occurs when there is a loss of the inhibitory feedback of PTH release by extracellular calcium. The rise in PTH levels is initially associated with a normal serum calcium, and then over time with hypercalcaemia. The most common cause of primary hyperparathyroidism is a benign solitary adenoma (80%). Other causes include multiple adenomas and hyperplasia. This chapter reviews the causes, clinical features, and management of primary hyperparathyroidism.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4685-4685
Author(s):  
M. Cem Ar ◽  
Serdar Sahin ◽  
Sevil Sadri ◽  
Isil Erdogan ◽  
Ayse Salihoglu ◽  
...  

Abstract Introduction: Recent studies indicate an increased risk for developing low bone mineral density (BMD) in patients with haemophilia. This has been suggested to result from less physical activity, and impaired vitamin D metabolism due to viral liver disease. Here we present the preliminary results of an ongoing study aiming to identify the risk factors for impaired bone health in adult haemophilia patients. Material and Method: Twenty-nine severe and 7 moderate haemophilia A and B patients were included in the study. Patient characteristics were given in Table-1. All patients had haemophilic arthropathy in ≥1 joints and were on prophylactic factor replacement therapy except 2 on demand patients. None of the patients had decompensated chronic liver disease. Eleven patients had a history of joint intervention (RAS or joint replacement). None of the patients had received on vitamin D supplementation. DEXA scans to screen BMD, blood chemical analysis including liver and kidney function tests, vit. D (25 hydroxy vitamin D) calcium, parathormone, alkaline phosphatase were obtained from all patients at study entry. Results: Osteoporosis and/or osteopenia according to WHO criteria were detected by DEXA scans in 2/3 of the patients. Twenty-six patients (72%) had vit. D levels below 20ng/mL, with half of them having levels less than 10ng/mL. Median lumbar and femur T scores were in the osteopenia range, being -1.2 and -2.2, respectively. Osteoporosis/penia rates and vit. D levels did not significantly differ between patients with severe and moderate haemophilia. However, patients with severe haemophilia had lower lumbar T scores (p=0.048) and seemed to acquire low BMD 2 times more likely than moderate haemophiliacs. Patients with a history of joint intervention had significantly lower vit. D levels (p=0.005) and 1.4 times more risk for low BMD. Conclusion: Preliminary results of our study are in line with the recent literature indicating an increased frequency for osteopenia and osteoporosis in patients with haemophilia. Despite their young age our cohort of patients had lower BMD and vitamin D levels than the age-matched healthy population. This is an interesting finding in a country like Turkey where the average yearly total number of hours of bright sunshine is over 3000. Data at hand suggest increased risk for reduced BMD especially in severe haemophiliacs with impaired joint mobility. The most probable underlying cause for reduced BMD seems to be haemophilic arthropathy related inactivity. Furthermore, impaired bone health seems to be partially associated with less sunlight exposure, which is probably a result of increased home confinement of patients with haemophilia due to joint disease. The study is still recruiting. We hope to clarify other questions regarding factors influencing bone health in haemophiliacs when the study is completed and additional data on radiological and physical examination as well as on quality of life are obtained. Table. Patient Characteristics (n=36) Age, years (median [range]) 35 [20 - 55] Type of haemophilia ( A/B), n 32/4 Genotype (severe/moderate), n 29/7 Factor activity level, % (median [range]) 0.4 [0.1 - 4.2] Type of treatment (prophylaxis/on demand) 34/2 Annual bleeding rate (median [range]) 4 [1 - 12] Joint replacement, number of patients (%) 7 (19) Radioactive synoviectomy, number of patients (%) 7 (19) Any joint intervention, number of patients (%) 11 (30.5) Lumbar T scores (median [range]) -1.2 [-5.2 - 1] Femur T scores (median [range]) -2.2 [-3.9 - 0.6] Vit. D, ng/mL (median [range]) 10.5 [1.3 - 45] Calcium, mg/dL (median [range]) 9.6 [8.9 - 10.2] Alkaline phosphatase, U/L (median [range]) 91.5 [53 - 177] Parathormon, pg/mL (median [range]) 39 [20 - 179] Haemoglobin, g/dL (median [range]) 14.75 [8.9 - 16] Osteopenia, number of patients (%) 12 (33) Osteoporosis, number of patients (%) 12 (33) HBV/HCV/HIV, n 1/11/0 Disclosures No relevant conflicts of interest to declare.


2011 ◽  
Vol 96 (1) ◽  
pp. E9-E18 ◽  
Author(s):  
Munro Peacock ◽  
J. P. Bilezikian ◽  
M. A. Bolognese ◽  
Michael Borofsky ◽  
Simona Scumpia ◽  
...  

Context: Primary hyperparathyroidism (PHPT) is characterized by elevated serum calcium (Ca) and increased PTH concentrations. Objective: The objective of the investigation was to establish the efficacy of cinacalcet in reducing serum Ca in patients with PHPT across a wide spectrum of disease severity. Design and Setting: The study was a pooled analysis of data from three multicenter clinical trials of cinacalcet in PHPT. Patients : Patients were grouped into three disease categories for analysis based on the following: 1) history of failed parathyroidectomy (n = 29); 2) meeting one or more criteria for parathyroidectomy but without prior surgery (n = 37); and 3) mild asymptomatic PHPT without meeting criteria for either above category (n = 15). Intervention: The intervention in this study was treatment with cinacalcet for up to 4.5 yr. Outcomes: Measurements in the study included serum Ca, PTH, phosphate, and bone-specific alkaline phosphatase, and areal bone mineral density (aBMD). Vital signs, safety biochemical and hematological indices, and adverse events were monitored throughout the study period. Results: The extent of cinacalcet-induced serum Ca reduction, proportion of patients achieving normal serum Ca (≤10.3 mg/dl), reduction in serum PTH, and increase in serum phosphate were similar across all three categories. Except for decreased aBMD at the total femur indicated for parathyroidectomy group at 1 yr, no significant changes in aBMD occurred. The efficacy of cinacalcet was maintained for up to 4.5 yr of follow-up. AEs were mild and similar across the three categories. Conclusions: Cinacalcet is equally effective in the medical management of PHPT patients across a broad spectrum of disease severity, and overall cinacalcet is well tolerated.


2007 ◽  
Vol 190 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Louise Howard ◽  
Graham Kirkwood ◽  
Morven Leese

BackgroundThere is evidence of an association between decreased bone mineral density schizophrenia, and prolactin-raising antipsychotic medication. However, it is not known whether this is clinically significant.AimsTo investigate whether patients with a history of schizophrenia are at increased risk of hip fracture.MethodIn a case-control study, we compared cases of ‘hip fracture’ on the General Practice Research Database (n=16 341) with matched controls (n=29 889).ResultsHip fracture was associated with schizophrenia (OR=1.73; 95% CI 1.32-2.28), and prolactin-raising antipsychotics (OR=2.6; 95% CI 2.432.78), in the univariate analysis. In the multivariate analysis, prolactin-raising antipsychotics were independently associated with hip fracture but schizophrenia was not. A significant interaction between gender and antipsychotics was found in the association with hip fracture (P=0.042); OR=2.12 (95% C11.73-2.59)for men, OR=l.93 (95% C11.78-2.10) for women.ConclusionsThe association between prolactin-raising antipsychotic medication and hip fracture may have serious implications for public health. Mental health service patients may require preventive measures including dietary and lifestyle advice.


2017 ◽  
Vol 46 (1) ◽  
pp. 30-36 ◽  
Author(s):  
Adam S. Tenforde ◽  
Allyson L. Parziale ◽  
Kristin L. Popp ◽  
Kathryn E. Ackerman

Background: While sports participation is often associated with health benefits, a subset of athletes may develop impaired bone health. Bone stress injuries (BSIs) are a common overuse injury in athletes; site of injury has been shown to relate to underlying bone health in female athletes. Hypothesis/Purpose: This case series characterizes the association of type of sports participation and anatomic site of BSIs with low bone mineral density (BMD), defined as BMD Z-score <–1.0. Similar to female athletes, it was hypothesized that male athletes who participate in running and sustain BSIs in sites of higher trabecular bone content would be more likely to have low BMD. Study Design: Cohort study; Level of evidence, 3. Methods: Chart review identified 28 male athletes aged 14 to 36 years with history of ≥1 lower-extremity BSI who were referred for evaluation of overall bone health, including assessment of lumbar spine, hip, and/or total body less head BMD per dual-energy x-ray absorptiometry. BMD Z-scores were determined via age, sex, and ethnicity normative values. Prior BSIs were classified by anatomic site of injury into trabecular-rich locations (pelvis, femoral neck, and calcaneus) and cortical-rich locations (tibia, fibula, femur, metatarsal and tarsal navicular). Sport type and laboratory values were also assessed in relationship to BMD. The association of low BMD to anatomic site of BSI and sport were evaluated with P value <.05 as threshold of significance. Results: Of 28 athletes, 12 (43%) met criteria for low BMD. Athletes with a history of trabecular-rich BSIs had a 4.6-fold increased risk for low BMD as compared with those with only cortical-rich BSIs (9 of 11 vs 3 of 17, P = .002). Within sport type, runners had a 6.1-fold increased risk for low BMD versus nonrunners (11 of 18 vs 1 of 10, P = .016). Laboratory values, including 25-hydroxy vitamin D, were not associated with BMD or BSI location. Conclusion: Low BMD was identified in 43% of male athletes in this series. Athletes participating in sports of running and with a history of trabecular-rich BSI were at increased risk for low BMD.


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