Mild Asymptomatic Primary Hyperparathyroidism Research Articles

Efficacy of parathyroidectomy compared with active surveillance in patients with mild asymptomatic primary hyperparathyroidism: a systematic review and meta-analysis of randomized-controlled studies.

Parathyroidectomy (PTx) has an established benefit in patients with symptomatic primary hyperparathyroidism (PHPT). However, its efficacy in mild asymptomatic PHPT has not been proven. This study aimed to systematically review and meta-analyze the best available evidence from randomized-controlled trials comparing the efficacy of PTx over conservative management (non-PTx) on skeletal outcomes [fractures and bone mineral density (BMD)], nephrolithiasis risk and quality of life (QoL) in patients with mild asymptomatic PHPT. A comprehensive literature search was conducted in PubMed, Scopus and Cochrane databases, from conception to February 23, 2020. Data were extracted from the studies that fulfilled the eligibility criteria and were synthesized quantitatively (fixed or random effects model) as relative risks and percentage mean differences (MD) with 95% confidence intervals (CI). I2 index was employed for heterogeneity. Four studies were included in the meta-analysis. There was no difference in fracture risk between PTx and active surveillance. The PTx group demonstrated higher BMD [MD 3.55% (95% CI 1.81, 5.29) in lumbar spine and 3.44% (95% CI 1.39, 5.49) in total hip, without difference in femoral neck and forearm] and lower calcium concentrations (MD - 13.26%, 95% CI - 7.10, - 19.43) compared with the non-PTx group. No difference was observed between groups regarding nephrolithiasis or QoL indices, except for general health (higher in PTx group). In patients with mild asymptomatic PHPT, PTx increases BMD and reduces serum calcium concentrations. However, its superiority over active surveillance in terms of fracture risk, nephrolithiasis and QoL cannot be supported by current data.

Osteoporosis induced after sleeve gastrectomy in a patient affected of mild asymptomatic primary hyperparathyroidism

Osteoporosis induced after sleeve gastrectomy in a patient affected of mild asymptomatic primary hyperparathyroidism

Parathyroidectomy for asymptomatic primary hyperparathyroidism: A revised cost-effectiveness analysis incorporating fracture risk reduction

Recent data demonstrate decreased fracture risk after operation for asymptomatic primary hyperparathyroidism. We performed a revised cost-effectiveness analysis comparing parathyroidectomy versus observation while incorporating fracture risk reduction. A Markov transition-state model was created comparing parathyroidectomy and guideline-based medical observation for a 60-year-old female patient with mild asymptomatic primary hyperparathyroidism. Costs were estimated using published Medicare reimbursement data. Treatment strategy outcomes, including risk of fracture, were identified by literature review. Quality adjustment factors were used to weight treatment outcomes. A threshold of $100,000/quality-adjusted life year was used to determine cost-effectiveness. Sensitivity analyses and Monte Carlo simulation were performed to examine the effect of uncertainty on the model. Parathyroidectomy was the dominant strategy (less costly and more effective) with an incremental cost savings of $1,721 and an incremental effectiveness of 0.185 quality-adjusted life years. Parathyroidectomy remained dominant when the relative risk reduction of fracture after operation was ≥14%, the cost of fracture was ≥$7,600, or the probability of recurrent laryngeal nerve injury was <12.5%. Monte Carlo simulation showed parathyroidectomy was cost-effective in 995/1,000 hypothetical patients. When fracture risk reduction is considered, parathyroidectomy for mild asymptomatic primary hyperparathyroidism is the dominant strategy when compared to observation.

Impact of vitamin D replacement in patients with normocalcaemic and hypercalcaemic primary hyperparathyroidism and coexisting vitamin D deficiency.

Vitamin D deficiency is increasingly recognized in patients with primary hyperparathyroidism but some clinicians are reluctant to replace vitamin D due to concerns with aggravating hypercalcaemia. We investigated the impact of vitamin D repletion in asymptomatic patients with normocalcaemic and hypercalcaemic primary hyperparathyroidism. This is a retrospective analysis of 111 patients with elevated parathyroid hormone concentrations (>6.4 pmol/L) referred to our endocrine clinic between January and December 2012; we identified 39 patients with primary hyperparathyroidism and vitamin D deficiency, i.e. 25 hydroxy vitamin D <20 µg/L. Patients were categorized into normocalcaemic (n = 23) and hypercalcaemic (n = 16) groups and the impact on biochemical parameters was recorded after at least six months treatment with either 1600 or 3200 units daily of cholecalciferol. Both normocalcaemic and hypercalcaemic groups showed a rise in 25 hydroxy vitamin D concentrations after replacement (p <0.0001). Parathyroid hormone concentrations fell in the normocalcaemic group (p = 0.08) but individually, five patients showed a rise (8-38% of baseline). In the hypercalcaemic group, parathyroid hormone remained static but the adjusted calcium concentration fell significantly (p = 0.006) except in two patients who showed mild rises (3 and 6%, respectively). There was no deterioration in renal function or calcium-related adverse events in any of the groups. Our study supports the safety of vitamin D replacement in patients with mild asymptomatic primary hyperparathyroidism and coexistent vitamin D deficiency. Repletion does not aggravate hypercalcaemia and may limit disease progression. Patients with normocalcaemic primary hyperparathyroidism need further characterization from longitudinal studies.

Нефролитиаз при первичном гиперпаратиреозе, современный взгляд

Primary hyperparathyroidism (PHPT) has attracted a growing attention of medical doctors of different specialties in the last few years. The ability to predict the risk of the development of visceral manifestations (nephrolithiasis, nephrocalcinosis, cardiovascular disease, peptic ulcer disease) in the mild asymptomatic PHPT can define indications for conservative treatment of such patients because of the high prevalence of the mild form of the disease. Nephrolithiasis is one of the most common manifestations of the PHPT and is one of the indications for surgery. Mechanisms of nephrolithiasis and nephrocalcinosis in PHPT remain unclear and many investigations are devoted to studying the possible predictors of its development. In this paper we review the current knowledge of nephrolithiasis, clinical features and risk factors of its development in patients with PHPT.

Nephrolithiasis in primary hyperparathyroidism: a contemporary look

Primary hyperparathyroidism (PHPT) has attracted a growing attention of medical doctors of different specialties in the last few years. The ability to predict the risk of the development of visceral manifestations (nephrolithiasis, nephrocalcinosis, cardiovascular disease, peptic ulcer disease) in the mild asymptomatic PHPT can define indications for conservative treatment of such patients because of the high prevalence of the mild form of the disease. Nephrolithiasis is one of the most common manifestations of the PHPT and is one of the indications for surgery. Mechanisms of nephrolithiasis and nephrocalcinosis in PHPT remain unclear and many investigations are devoted to studying the possible predictors of its development. In this paper we review the current knowledge of nephrolithiasis, clinical features and risk factors of its development in patients with PHPT.

Renal impairment as a surgical indication in primary hyperparathyroidism: do the data support this recommendation?

Management of primary hyperparathyroidism has evolved over the past two decades, yet impaired renal function has consistently been a surgical indication. This recommendation has been based upon the historical association between primary hyperparathyroidism and renal impairment, and a review of the literature is needed to determine whether such a recommendation is warranted. PubMed was utilized to identify English-language articles published between January 1990 and February 2014 using keywords related to hyperparathyroidism and renal function. The keywords were "primary hyperparathyroidism," "surgery," "parathyroidectomy," "kidney," "renal," "glomerular filtration rate," and "creatinine." Of the 1926 articles obtained with this search, all articles germane to the topic that quantified the relationship between primary hyperparathyroidism and renal function were included. All references within these articles were investigated for inclusion. When helpful, data tables were constructed to summarize the results succinctly. A secondary elevation of PTH levels has not been consistently shown to occur at the threshold currently indicated for surgical intervention. While renal impairment is seen with more significant disease, mild asymptomatic primary hyperparathyroidism has not been conclusively associated with renal impairment. Furthermore, there is no evidence to suggest that surgically curing primary hyperparathyroidism via a parathyroidectomy has any impact upon renal function.

Cinacalcet hydrochloride more efficiently controls serum calcium levels in mild-asymptomatic primary hyperparathyroidism without surgery criteria, as compared with surgical cases

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

Cinacalcet hydrochloride more efficiently controls serum calcium levels in mild-asymptomatic primary hyperparathyroidism without surgery criteria, as compared with surgical cases

Cinacalcet hydrochloride more efficiently controls serum calcium levels in mild-asymptomatic primary hyperparathyroidism without surgery criteria, as compared with surgical cases

Cinacalcet HCl Reduces Hypercalcemia in Primary Hyperparathyroidism across a Wide Spectrum of Disease Severity

Primary hyperparathyroidism (PHPT) is characterized by elevated serum calcium (Ca) and increased PTH concentrations. 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. The study was a pooled analysis of data from three multicenter clinical trials of cinacalcet in PHPT. 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). The intervention in this study was treatment with cinacalcet for up to 4.5 yr. 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. 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. Cinacalcet is equally effective in the medical management of PHPT patients across a broad spectrum of disease severity, and overall cinacalcet is well tolerated.

Evaluation of subclinical coronary atherosclerosis in mild asymptomatic primary hyperparathyroidism patients

Although there is sufficient data supporting the increased cardiovascular risk in patients with advanced stage of primary hyperparathyroidism (pHPT), it is not clear whether same is valid for patients with subclinical forms of this disease. In this study we aimed to evaluate coronary atherosclerosis burden of asymptomatic pHPT patients by using tomographic coronary calcification scoring. Thirty-one mild asymptomatic pHPT patients (28 female, 3 male; mean age: 54.4 +/- 12.1 years) and 19 gender- and age-matched normotensive healthy controls (17 female, 2 male; mean age: 50.6 +/- 5.8) constituted our study population. Asymptomatic pHPT patients were subdivided according to presence of hypertension (19 hypertensive and 12 non-hypertensive patients). All subjects in study population underwent tomographic coronary calcification scoring by using 16-multidetector computed tomography (16-MDCT). Median tomographic coronary calcification score was comparable between the whole group of pHPT patients [0.0 (Interquartile Range, IQR:18.70] and the controls [0.0 (IQR: 0.90). Median tomographic coronary calcification scores of pHPT patients with hypertension was 0.90 (IQR: 75.0) HU, whereas no calcification was noted in coronary arteries of normotensive pHPT patients. Calcification scores of hypertensive pHPT patients were significantly higher than both normotensive pHPT patients (P = 0.014) and controls (P = 0.046). There was no significant difference regarding calcification scores of normotensive pHPT patients versus controls. In the binary logistic regression model, only the presence of hyperlipidemia was found to be independently associated with presence of calcification on coronary arteries (relative risk 6.56, 95% CI 1.18-36.56, P = 0.032). These results suggest that mild asymptomatic pHPT with serum calcium levels in the high-normal range does not constitute an independent risk factor for coronary atherosclerosis. The combined presence of classic cardiovascular risk factors determines the severity of coronary atherosclerosis in these patients.

Surgery or Surveillance for Mild Asymptomatic Primary Hyperparathyroidism: A Prospective, Randomized Clinical Trial

Surgery or Surveillance for Mild Asymptomatic Primary Hyperparathyroidism: A Prospective, Randomized Clinical Trial

Surgery or Surveillance for Mild Asymptomatic Primary Hyperparathyroidism: A Prospective, Randomized Clinical Trial

Surgery or Surveillance for Mild Asymptomatic Primary Hyperparathyroidism: A Prospective, Randomized Clinical Trial

Surgery or Surveillance for Mild Asymptomatic Primary Hyperparathyroidism: A Prospective, Randomized Clinical Trial

Surgery or Surveillance for Mild Asymptomatic Primary Hyperparathyroidism: A Prospective, Randomized Clinical Trial

Another Comparison of Surgery and Observation for Mild Hyperparathyroidism

Several previously published randomized trials have examined the effects of surgery in patients with mild asymptomatic primary hyperparathyroidism. In

Surgery or Surveillance for Mild Asymptomatic Primary Hyperparathyroidism: A Prospective, Randomized Clinical Trial

It is unclear whether patients with asymptomatic primary hyperparathyroidism (PHPT) do better with parathyroidectomy (PTx) as compared with conservative medical management. The aim of the study was to evaluate the beneficial effect of PTx vs. conservative management in patients with mild asymptomatic PHPT. We conducted a prospective, randomized study. The study took place at a referral center. We studied 50 patients who did not meet any guidelines for parathyroid surgery as recommended by the National Institutes of Health Consensus Development Conference on Asymptomatic PHPT. Patients were randomly assigned to PTx or no PTx and were evaluated at 6 months and at 1 yr. We compared changes (percentage of basal) of lumbar spine bone mineral density (BMD) between the two groups at 1 yr. The change in BMD at lumbar spine was greater after PTx (+4.16 +/- 1.13 for PTx vs. -1.12 +/- 0.71 for no PTx; P = 0.0002). The change in BMD at the total hip was also significantly greater in the PTx group (+2.61 +/- 0.71 for PTx vs. -1.88 +/- 0.60 for no PTx; P = 0.0001). There was no difference in BMD after 1 yr between both groups at the one-third radius site. In comparison with those who did not undergo surgery, the PTx subjects, after 1 yr, showed significant differences in four quality of life measures as determined by the 36-item short form health survey scale: bodily pain (P = 0.001), general health (P = 0.008), vitality (P = 0.003), and mental health (P = 0.017). In patients with mild asymptomatic PHPT, successful PTx is followed by an improvement in BMD and quality of life. Most patients followed without surgery did not show evidence of progression.

The Role of the Extracellullar Calcium-Sensing Receptor in Health and Disease

The calcium-sensing receptor has a key role in calcium homeostasis, it is involved in the regulation of the serum calcium level within minutes via the secretion and action of parathyroid and the excretion of calcium in the kidney in a negative feedback manner. Mutations of the calcium sensing receptor gene leads to inactivating and activating mutations resulting in diseases with hypercalcaemia and hypocalcaemia. The loss of function mutations are associated with familial benign hypocalciuric hypercalcaemia (FHH), an autosomal dominant disease characterised by lifelong mild hypercalcaemia, low urinary calcium excretion, and inappropriate high parathyroid hormone levels, sometimes difficult to distinguish from mild asymptomatic primary hyperparathyroidism. Patients with FHH did not profit from parathyroidectomy, a calcium lowering therapy is not necessary. The gain of function mutations of the calcium-sensing receptor are associated with autosomal dominant hypocalcaemia (ADH), a disease characterised by a generally asymptomatic hypocalcaemia, inappropriately high urinary calcium excretion and normal PTH levels. A therapy to raise the serum calcium concentration has to be done carefully and is only indicated in symptomatic patients, because of enhancement of hypercalciuria with the risk of nephrocalcinosis and nephrolithiasis. Molecular genetic analysis of the calcium sensing receptor gene facilitates the sometimes difficult diagnosis. The development of compounds modulating the calcium sensing receptor function and thereby the section of PTH may become an important role in treatment of diseases of calcium metabolism.

Positive effect of parathyroidectomy on bone mineral density in mild asymptomatic primary hyperparathyroidism*

Patients with mild primary hyperparathyroidism (pHPT) often appear asymptomatic, and have previously been regarded as not requiring treatment. However, increased cardiovascular morbidity and dyslipidaemia have also been recognized in mild pHPT, which also seem to be normalized after parathyroidectomy. The present study explores whether postmenopausal women with mild pHPT have decreased bone mineral density (BMD) compared with age-matched healthy controls, and the effects on BMD of parathyroidectomy. A population-based health screening of 5202 postmenopausal women identified 87 overtly asymptomatic patients with mild pHPT as well as age-matched healthy controls. A 5-year follow-up included 49 cases who had undergone parathyroidectomy. BMD was measured with DXA at the femoral neck, the lumbar spine and the total body. At study entry, BMD was 5-6% lower in the lumbar spine (L2-L4) and femoral neck in cases compared with matched controls. After the 5-year follow-up, BMD increased in L2-L4 by 2.9% (P = 0.002) in the parathyroidectomized cases and remained stable in the femoral neck. However, femoral neck BMD increased 4.1% (P = 0.013) for cases <67 years old (50% of the cohort). In accordance with recent NIH guidelines for pHPT treatment, the level of BMD per se in the investigated group of patients justifies parathyroidectomy in almost half of the cases with mild pHPT. Surgery could be expected to increase BMD in L2-L4 to the level of the controls, to increase femoral neck BMD in patients <67 years of age and to preserve femoral neck BMD in the elderly population.

Surgical indications of primary hyperparathyroidism

Clinical profile of primary hyperparathyroidism (PHPT) had shifted from symptomatic disorder, with hypercalcemic symptoms, kidney stones, overt bone disease, or a specific neuromuscular dysfunction toward a more asymptomatic state. Patients with symptomatic PHPT absolutely require parathyroidectomy (PTX). Surgical treatment is the well established and definitive treatment for PHPT. Consensus Conference at National Institute of Health (NIH) proposed the guidelines for PTX in asymptomatic PHPT. They included (1) serum calcium level was 1.0 mg/dL above upper limit of normal, (2) 24-h urinary calcium was over 400 mg, (3) creatinine clearance is reduced by 30%, (4) bone mineral density (T-score) reduced 2.5 SD below the peak bone mass at any site, and (5) patients under 50 years of age, and (6) patients for whom medical surveillance was either not desirable or not possible. Because in about 25% of patients asymptomatic PHPT will show progression, because it is important to monitor patients who are not undergoing PTX. Normocalcemic PHPT has been frequently found in patients whose bone mineral density is reduced. This diagnostic consideration requires that all potential causes of secondary HPT. The surgical procedure has been progressive induced by the developments of preoperative image diagnosis and intraoperative PTH assay. Minimally invasive PTX could expand surgical indications in patients with mild asymptomatic PHPT.

Randomized Controlled Clinical Trial of SurgeryVersusNo Surgery in Patients with Mild Asymptomatic Primary Hyperparathyroidism

Parathyroidectomy is the definitive therapy for patients with symptomatic primary hyperparathyroidism. However, the role of surgery in mild asymptomatic primary hyperparathyroidism remains controversial. Accordingly, we conducted a prospective, randomized, controlled clinical trial of parathyroidectomy to determine the benefits of surgery vs. adverse effects of no surgery. Fifty-three patients were randomly assigned to either parathyroidectomy (n = 25) or regular follow-up (n = 28). Bone mineral density (BMD), biochemical indices of the disease, quality of life, and psychological function were measured at 6- or 12-month intervals for at least 24 months. Twenty-three of the 25 patients randomized to parathyroidectomy had surgery within the specified time of the protocol and three of the 28 patients randomized to regular follow-up had parathyroidectomy during follow-up. After parathyroidectomy, there was an increase in BMD of the spine (1.2%/yr, P < 0.001), femoral neck (0.4%/yr, P = 0.031), total hip (0.3%/yr, P = 0.07), and forearm (0.4%/yr, P < 0.001) and an expected fall in serum total and ionized calcium, serum PTH, and urine calcium (P < 0.001 for all). In contrast, patients followed up without surgery lost BMD at the femoral neck (-0.4%/yr, P = 0.117) and total hip (-0.6%/yr, P = 0.007) but gained at the spine (0.5%/yr; P = ns) and forearm (0.2%/yr, P = 0.047), with no significant changes in biochemical indices of disease. Consequently, a significant effect of parathyroidectomy on BMD was evident only at the femoral neck (a group difference of 0.8%/yr; P = 0.01) and total hip (a group difference of 1.0%/yr; P = 0.001) but not at the spine (a group difference of 0.6%/yr) or forearm (a group difference of 0.2%/yr). Quality-of-life scores as measured by a 36-item short-form health survey showed significant declines in five of the nine domains (social functioning, physical problem, emotional problem, energy, and health perception) in patients followed up without surgery but in only one of the nine domains (physical function) in the patients who had parathyroidectomy. Consequently, a modest measurable benefit of parathyroidectomy was evident in social and emotional role function (P = 0.007 and 0.012, respectively). Psychological function as assessed by the symptom checklist revised did not change significantly in either group, except for a significant decline in anxiety (P = 0.003) and phobia (P = 0.024) in patients who had surgery in comparison with those who did not. We conclude that it is feasible to conduct a randomized, controlled clinical trial of parathyroidectomy in patients with mild asymptomatic primary hyperparathyroidism, and measurable benefits of surgery on BMD, quality of life, and psychological function can be demonstrated. However, the small but significant benefits of parathyroidectomy must be weighed against the risks of surgery in these otherwise healthy individuals.