Asymptomatic Primary Hyperparathyroidism Patients Research Articles

Focus on Non-osteoporotic Post-menopausal Women with Asymptomatic Primary Hyperparathyroidism: A Monocentric Series.

Primary Hyperparathyroidism (PHPT) is a common disease, frequently diagnosed in post-menopausal women, among whom Osteoporosis (OP) is a common finding. To date, no study has specifically evaluated the asymptomatic PHPT (aPHPT) patients without OP, in particular post-menopausal women who are exposed to an increased risk of developing OP. This study involved a retrospective cross-sectional evaluation. From our database of 500 consecutive patients diagnosed with PHPT, 178 postmenopausal aPHPT were retrieved. The clinical, biochemical, and imaging data of the 85 patients without OP were not different from those of the 93 with OP, except for bone alkaline phosphatase (significantly higher in the latter group). Among these 85 patients without OP, the 45 patients meeting surgical criteria for parathyroidectomy had significantly higher values of serum PTH (240 vs. 99 ng/L, p =0.03) and calcium (total, 11.2 ± 0.7 vs. 10.6 ± 0.4 mg/dL, p <0.001; ionized, 1.45 ± 0.12 vs. 1.36 ± 0.8 mmol/L, p =0.044) and lower values of serum phosphate (2.57 ± 0.7 vs. 2.94 ± 0.5 mg/dL, p =0.009) and eGFR (68.5 ± 23.8 vs 80.8 ± 14.4 mL/min/1.73 m2, p =0.006) than the 40 aPHPT patients not meeting surgical criteria, without any difference in densitometric data and calculated fracture risk. In our series, post-menopausal aPHPT patients without OP accounted for almost a sixth of the whole PHPT series. About half of these patients did not meet surgical criteria, but their T scores and 10-year fracture risk calculated by FRAX were not significantly different from post-menopausal aPHPT without OP meeting surgical criteria.

Calcium/phosphate ratio: an additional tool for the clinical management of asymptomatic primary hyperparathyroidism?

Serum calcium/phosphate ratio (Ca/P) has been recently proposed as an additional tool to identify primary hyperparathyroidism (PHPT), especially in patients with subclinical presentation, with a proposed cut-off of 3.3 when both values are expressed in mg/dL. No data are available on the relationship between Ca/P and the clinical presentation of PHPT. We thus evaluated this relationship in a large, single-center, unselected series. 515 consecutive PHPT patients (mean age 65 ± 13.15years, 77.1% females) were retrospectively evaluated at diagnosis. Mean Ca/P was 4.54 ± 1.5 (range 2.36-13.9), being higher than 3.3 in 88.5% of patients. Ca/P was significantly higher in (1) males, (2) symptomatic PHPT, (3) patients with 25-hydroxy vitamin D levels lower than 20μg/L, (4) patients with osteitis fibrosa cystica, (5) patients with T score < - 2.5 at the radial site. In a multivariate regression analysis, Ca/P resulted significantly associated with PTH levels. After the exclusion of 57 patients with asymptomatic PHPT (aPHPT) patients and serum Ca higher than 1mg/dL above the upper limit of normal range, no differences were found in Ca/P between aPHPT meeting or not surgical criteria. In PHPT Ca/P ratio is associated with increased biochemical and clinical severity of disease and represents a direct indicator of clinical bone damage. However, it does not seem an additional tool to identify aPHPT patients reaching surgical indication.

The Impact of Moderate Hypophosphatemia on the Clinical Management of Primary Hyperparathyroidism.

Background and objective The impact of moderate hypophosphatemia (hypoP) on primary hyperparathyroidism (PHPT) and its use as an independent surgical criterion has not been adequately evaluated in the literature. In light of this, we conducted this study to address the scarcity of data on this topic. Methods We conducted a retrospective evaluation of data related to 164 (133 females and 31 males) patients with PHPT who met the criteria for inclusion in the study. HypoP, which is indicated by phosphorus (P) levels lower than 2.5 mg/dL, was found in 78 (47.5%) patients, and moderate hypoP (1-1.99 mg/dL) was found in 25 patients (15.2%). Results PHPT severity was worse in hypoP patients than non-hypoP patients, as evidenced by higher levels ofmean serum calcium (12.9 ±1.0 mg/dL vs. 11.1 ±0.3 mg/dL respectively,p<0.001), parathormone (PTH) [median (interquartile range, IQR): 455.3 (455.3)ng/L vs.124.0 (84.0)ng/L respectively, p<0.001] and mean 24-hour urinary calcium (414.6 ±168.5 mg/day vs. 291.5 ±161.4 mg/day respectively, p=0.026) as well as lower levels of mean BMI (25.6 ±3.9 kg/m2vs. 29.0 ±4.0 kg/m2 respectively, p=0.18) and mean 25-hydroxy vitamin D3 (13.8 ±7.3 µg/L vs. 18.2 ±7.8 µg/L respectively, p=0.001). Among the whole study populationas well as among patients with Ca levels <1.0 mg/dLaccording to the upper limit of normal, P level was determined to be an independent factor affecting the indication for surgical treatment [β: -1.96,p=0.038, odds ratio (OR): 0.14, 95% confidence interval (CI): 0.02-0.89 and β: -2.3, p=0.034, OR: 0.10, 95% CI: 0.12-0.84 respectively]. Conclusion We found a strong correlation between moderate hypoP and the severity of the biochemical manifestations of PHPT. In asymptomatic PHPT patients, moderate hypoP was predictive of surgical indication, independent of age and level of hypercalcemia.

Revisiting Age Criterion for Surgery in Asymptomatic Primary Hyperparathyroidism.

To revisit the current age criterion (50 years) for surgical candidacy in patients diagnosed with asymptomatic primary hyperparathyroidism (PHPT). A predictive model relying on past publications using the electronic databases "PubMed," "Embase," "Medline,"and "Google Scholar." Hypothetical large cohort. A Markov model was constructed, based on relevant literature, to compare 2 potential treatment algorithms for asymptomatic PHPT patients, parathyroidectomy (PTX), and observation. The various potential health states were characterized for the 2 treatment options and included potential surgical complications, end-organ deterioration, and death. A 1-way sensitivity analysis was performed to calculate the quality-adjusted life year (QALY) gains of both strategies. A Monte-Carlo simulation for 30,000 subjects was performed and cycled per annum. On the basis of the model's assumptions, the QALY value for the PTX strategy was 19.17 versus17.82 for the observation strategy. The incremental QALY gains for various ages according to the sensitivity analyses for PTX in comparison to observation were: 2.84 QALY for 40-year-old patients, 2.2 QALY for 50-year-old patients, 1.81 QALY for 55-year-old patients, 1.35 QALY for 60-year-old patients, and 0.86 QALY for 65-year-old patients. The incremental QALY is below 0.5 after the age of 75 years. This study found PTX to be advantageous for asymptomatic PHPT patients older than the current age criterion of 50 years. The calculated QALY gains support a surgical approach for medically fit patients in their 50s. The current guidelines for the surgical treatment of young asymptomatic PHPT patients should be revisited by the next steering committee.

Serum Phosphate: A Neglected Test in the Clinical Management of Primary Hyperparathyroidism.

Although the inverse correlation between serum PTH and phosphate (P) levels in patients with primary hyperparathyroidism (PHPT) is well known, the relationship between P levels and the clinical picture of the disease has not been well investigated. This was thus the aim of this paper. A total of 472 consecutive patients with PHPT attending our center were retrospectively evaluated at diagnosis. P levels lower than 2.5 mg/dL (HypoP) were found in 198/472 patients (41.9%). HypoP was mild (2-2.5 mg/dL), moderate (1-1.9 mg/dL), and severe (<1 mg/dL) in 168 (84.9%), 30 (15.1%), and 0 cases, respectively. P levels were lower in males than females. Patients with more severe bone density impairment at the radial (but not the vertebral or femoral) site had P levels significantly lower than other patients. PHPT severity was worse in HypoP patients, both clinically (higher prevalence of renal stones, but not of osteoporosis) and biochemically (higher serum calcium and PTH levels). All patients in the moderate HypoP group were either symptomatic or asymptomatic reaching surgical indication according to the latest guidelines. We observed a relationship between P levels and biochemical and clinical features of PHPT severity. In asymptomatic PHPT patients, even moderate HypoP is predictive of surgical indication, regardless of age and hypercalcemia severity.

Differences in Clinicopathological Characteristics of Papillary Thyroid Carcinoma between Symptomatic and Asymptomatic Patients with Primary Hyperparathyroidism.

Background Popularization of cervical ultrasound led to higher detection of papillary thyroid carcinoma (PTC) and primary hyperparathyroidism (PHPT), as well as increasing percentage of asymptomatic PHPT in China. Although the coexistence of PTC and PHPT has been reported, it is unknown whether the clinicopathological features of PTC differ between asymptomatic and symptomatic PHPT patients. Methods We retrospectively reviewed the medical records of 304 PHPT patients treated in our hospital between January 2009 and July 2020, including 217 females and 87 males with the average age of 53.27 ± 13.54 years. Of the 304 patients, 181 were symptomatic PHPT patients and 123 were asymptomatic PHPT patients. We analyzed the laboratory results, postoperative pathology, and the TNM stage of PTC between asymptomatic and symptomatic PHPT patients. Results Concurrent thyroid nodules were found in 61.51% of PHPT patients, and the prevalence of PTC in thyroidectomized PHPT patients was 29.89% in our cohort. Lower serum parathyroid hormone (PTH) (p < 0.05) and calcium (p < 0.05) were found in PHPT patients with PTC compared to patients with benign thyroid lesion. Compared with the symptomatic PHPT patients, the asymptomatic PHPT patients showed lower serum calcium (p < 0.05), serum chlorine (p < 0.05), alkaline phosphatase (p < 0.05), PTH (p < 0.05), and bone turnover markers (p < 0.05) but higher prevalence of thyroid nodules (70.73% versus 55.24%, p < 0.05) and PTC (15.44% versus 3.87%, p < 0.05). All the PTC in symptomatic PHPT patients were papillary microcarcinoma limited to the thyroid, while 68.42% and 15.78% of the PTC in asymptomatic PHPT patients showed microscopic extrathyroidal extension and lymph node metastases, respectively. Moreover, 36.84% (7/19) of the PTC patients in asymptomatic group showed multifocality, which was much higher than 14.29% (1/7) in the symptomatic group; however, no statistical significance was found (p=0.24). Conclusions The concomitant PTC in asymptomatic PHPT patients showed a higher rate of microscopic extrathyroidal invasion when compared to symptomatic PHPT patients. So the FNA is essential to the asymptomatic PHPT patients with suspicious thyroid nodules and once the PTC is confirmed, concurrent parathyroidectomy should be performed with thyroidectomy in asymptomatic PHPT patients.

Clinical characteristics of the patients with asymptomatic primary hyperparathyroidism.

The prevalence of asymptomatic primary hyperparathyroidism (PHPT) in China is lower than that in European and American countries and the study about the characteristics of asymptomatic PHPT was rare in China. This study aims to explore the characteristics of asymptomatic PHPT. Clinical data of 150 patients with PHPT confirmed by operation and pathological examination were retrospectively analyzed. The patients were assigned into a symptomatic PHPT group (n=124) and an asymptomatic PHPT group (n=26). The proportion of adenomas was higher than that of adenocarcinoma in the asymptomatic PHPT group. The proportion of the first diagnosis due to hypercalcemia found via biochemical examination in the asymptomatic PHPT group was higher than that in the symptomatic PHPT group (76.92% vs 25.81%, P<0.001). The duration was shorter in the asymptomatic PHPT patients than that in the symptomatic PHPT patients (median 12 months vs 24 months, P=0.004). The serum calcium, the albumin-corrected serum calcium, and parathyroid hormone (PTH) were lower in the asymptomatic PHPT patients than those in the symptomatic PHPT (P=0.003, P=0.006, and P=0.042, respectively). The serum 1,25-dihydroxyvitamin D3 was higher (P<0.001), the diameter was shorter (P=0.028), and the bone mineral densities (BMD) of L2~4 and femoral neck were higher in the asymptomatic PHPT patients than those in the symptomatic PHPT patients (both P<0.001). Only a minority of PHPT patients are asymptomatic. Compared with the symptomatic PHPT patients, the primary cause of diagnosis is hypercalcemia, the duration of diagnosis and the diameter of parathyroid gland are shorter, the levels of serum calcium, and PTH are lower, the proportion of adenomas, vitamin D, and the BMD of L2-4 and femoral neck are higher, and the pathological type is benign in the asymptomatic PHPT patients.

Progressive rise in the prevalence of asymptomatic primary hyperparathyroidism in India: Data from PHPT registry.

Primary hyperparathyroidism (PHPT), a third common endocrine disorder,varies from asymptomatic disease, mostly seen in the West where routine biochemical screening is practiced, to the classical symptomatic disease mostly seen in the Eastern countries. We aimed to compare the demographic, clinical, biochemical measurements in patients with asymptomatic and symptomatic PHPT from the Indian PHPT registry. Data of PHPT patients from the last 25years (1995-2019) were analyzed for demographic, clinical presentation and biochemical measurements, and compared these characteristics between asymptomatic and symptomatic PHPT patients. Of the 554 patients, 54 (10%) patients had asymptomatic PHPT. There was a sharp rise in the proportion of asymptomatic PHPT patients of 3% in the first decade to 13% in the second decade of the century (p = 0.003). Patients with asymptomatic PHPT were significantly older (50 vs. 42years; p < 0.0001) and had higher mean body mass index (27.8 vs. 23.5kg/m2; p < 0.0001) compared to the symptomatic PHPT group. In addition, asymptomatic PHPT patients had significantly lower median plasma iPTH (180 vs. 370pg/mL; p < 0.0001), serum alkaline phosphatase (119 vs. 172IU/L; p < 0.0001), and parathyroid adenoma weight (1.0 vs. 2.62g; p = 0.006) compared to the symptomatic PHPT group. Although symptomatic PHPT is still most prevalent (> 90%) in India with higher indices of the disease and tumor weights, there is a progressive rise in the prevalence of asymptomatic PHPT patients in the last decade. Improvements in calcium and vitamin D nutrition might account for this change as in the Western series.

A detailed appraisal of renal manifestations in primary hyperparathyroidism from Indian PHPT registry: Before and after curative parathyroidectomy.

Primary hyperparathyroidism (PHPT) is a systemic disorder characterized by hypercalcaemia and inappropriately elevated parathyroid hormone (PTH). Renal manifestations are one of the main presenting features both in symptomatic and asymptomatic PHPT patients. We aimed to compare demographic, clinical and biochemical parameters of PHPT patients with and without renal manifestations and also analysed the influence of curative parathyroidectomy on renal functions. We retrospectively analysed the data of PHPT patients from the last 25years (1995- March 2019) and compared the demographic and clinical presentation and biochemical measurements between patients with and without renal manifestations and evaluated the changes in renal functions after 1year of curative parathyroidectomy. Of the total 544 PHPT patients, 299 (55%) including 91 out of 141 (65%) males had renal manifestations. Among renal manifestations, nephrolithiasis and nephrocalcinosis were found in 41.7% and 27.6% PHPT patients, respectively. PHPT patients with renal manifestations had significantly higher creatinine (109.7 vs 79.6µmol/L; P<.0001) and lower eGFR level (78.8 vs 93.9mL/min/1.73m2 ; P<.0001) compared to patients without renal manifestations. Parathyroidectomy resolved the clinical symptoms with biochemical cure in the patients from both the groups. Patients with renal manifestations showed improvement in creatinine and eGFR levels after 1year of curative parathyroidectomy; however, patients without renal manifestations showed no change in creatinine and eGFR levels. Young age and male gender are predictors of renal manifestations in PHPT. Curative parathyroidectomy improves renal functions in PHPT patients with renal manifestations compared to PHPT patients without renal manifestation.

Radiologic Manifestation of Bone Involvement in Primary Hyperparathyroidism: Prevalence and Clinical Significance in a Southern European Series

Clinically overt symptomatic bone disease in primary hyperparathyroidism (PHPT) is rarely seen today, and osteoporosis is the dominant finding. Subperiosteal bone resorption in the fingers and skull mottling are typical bone PHPT findings, the contemporary prevalence of which is unknown. We evaluated these mild lesions and investigated the impact of their occurrence on PHPT clinical management. We evaluated retrospectively a monocentric series of 363 PHPT patients classified in Group 1 (n = 100) or Group 2 (n = 263) according to the presence or absence of bone involvement, respectively. Patients belonging to Group 1, in turn, were subdivided into Group 1A, with severe and symptomatic lesions (n = 48), and Group 1B, with milder signs of osteitis fibrosa cystica (OFC) without brown tumors or fractures (n = 52). Serum total and ionized calcium, parathyroid hormone, osteocalcin, alkaline phosphatase, and its bone fraction levels were higher in Group 1 than in Group 2, while no gender or age differences were observed between the groups. Osteoporosis prevalence was similar in Group 1B and Group 2 patients but lower than in Group 1A. Mild OFC findings did not modify the surgical indication in any patient of Group 1B. Minor radiologic signs of OFC are not uncommon in the modern PHPT phenotype and occur in patients with more active disease. These signs could identify PHPT patients in an earlier stage of typical bone involvement. However, these features do not seem to upgrade either the clinical classification of asymptomatic PHPT patients or the propensity toward surgical choice.

Hypomagnesuria is Associated With Nephrolithiasis in Patients With Asymptomatic Primary Hyperparathyroidism.

The pathogenesis of nephrolithiasis in primary hyperparathyroidism (PHPT) remains to be elucidated. The latest guidelines suggest parathyroidectomy in patients with asymptomatic PHPT with hypercalciuria (> 400 mg/d) and increased stone risk profile. The objective of this work is to evaluate the association of urinary stone risk factors and nephrolithiasis in patients with asymptomatic sporadic PHPT and its clinical relevance. A total of 157 consecutive patients with sporadic asymptomatic PHPT were evaluated by measurement of serum and 24-hour urinary parameters and kidney ultrasound. Urinary parameters were tested in the univariate analysis as continuous and categorical variables. Only hypercalciuria and hypomagnesuria were significantly associated with nephrolithiasis in the univariate and multivariate analysis adjusted for age, sex, body mass index, estimated glomerular filtration rate, parathyroid hormone, 25-hydroxyvitamin D, serum calcium, and urine volume (odds ratio, OR 2.14 [1.10-4.56]; P = .04; OR 3.06 [1.26-7.43]; P = .013, respectively). Hypomagnesuria remained associated with nephrolithiasis in the multivariate analysis (OR 6.09 [1.57-23.5], P = .009) even when the analysis was limited to patients without concomitant hypercalciuria. The urinary calcium/magnesium (Ca/Mg) ratio was also associated with nephrolithiasis (univariate OR 1.62 [1.27-2.08]; P = .001 and multivariate analysis OR 1.74 [1.25-2.42], P = .001). Hypomagnesuria and urinary Ca/Mg ratio had a better, but rather low, positive predictive value compared with hypercalciuria. Hypomagnesuria and urinary Ca/Mg ratio are each associated with silent nephrolithiasis and have potential clinical utility as risk factors, besides hypercalciuria, for kidney stones in asymptomatic PHPT patients. The other urinary indices that have been commonly thought to be associated with kidney stones in PHPT are not supported by our results.

Non-surgical management of primary hyperparathyroidism in the aging population

Primary hyperparathyroidism (PHPT) is commonly observed in the aging population, and the average age at diagnosis has increased in the last 20 years. Parathyroidectomy, the only definitive cure for PHPT, is indicated in symptomatic and asymptomatic older PHPT patients with skeletal and renal disease. It is as effective in older patients as it is in younger patients. Nevertheless, older patients may present with comorbidities and greater frailty, leading to the possibility of more complications, higher morbidity and mortality after surgery. This review focuses on the non-surgical clinical management of PHPT in elderly patients. We also summarize the most recent literature regarding the pharmacological management of PHPT to reduce serum calcium levels, to improve bone mineral density or to do both in the aging population.

Primary Hyperparathyroidism: Comparing Cardiovascular Morbidity and Mortality in Patients Treated With Parathyroidectomy Versus Conservative Management

Background: There is emerging evidence suggestive of endothelial and cardiovascular dysfunction in patients with mild or asymptomatic primary hyperparathyroidism (PHPT) although there is a lack of clear consensus regarding potential cardiovascular benefits post elective parathyroidectomy. Methods: We carried out a retrospective observational study on patients with a biochemically confirmed diagnosis of PHPT who were under follow-up at our district general hospital between 1995 and 2016. The primary objective of the study was to compare all-cause mortality in patients who underwent elective parathyroidectomy versus the patients who were managed conservatively. The secondary objective of our study was to compare the rate of development of atherosclerotic cardiovascular disease (ASCVD) in the two groups. Results: Our results showed no statistically significant difference in all-cause mortality rate in the patients managed conservatively as compared to the surgically treated group. However, the rate of ASCVD events, including coronary artery disease and hypertension, were lower in the latter group. Conclusions: The adverse impact of PHPT on the cardiovascular system remains underrecognized with most of the evidence being derived from observational studies supporting a correlation between parathyroid hormone (PTH) levels and ASCVD events. All patients with PHPT should undergo clinical evaluation for ASCVD risks during initial workup as well as during follow-up visits. As elective parathyroidectomy is a relatively safe procedure and ASCVD risk is known to increase with age, there is a rationale to consider surgery for the majority of asymptomatic PHPT patients aged < 60 years. J Endocrinol Metab. 2019;9(4):95-107 doi: https://doi.org/10.14740/jem573

Maximal foot force and plantar pressure distribution assessed by Footscan is not affected in asymptomatic primary hyperparathyroidism patients

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

Occult urolithiasis in asymptomatic primary hyperparathyroidism

ABSTRACTObjective: Recent international guidelines suggest renal imaging to detect occult urolithiasis in all patients with asymptomatic primary hyperparathyroidism (PHPT), but data regarding their prevalence and associated risk factors are limited. We evaluated the prevalence and risk factors for occult urolithiasis. Methods: Cross-sectional analysis of 96 asymptomatic PHPT patients from a university hospital in the United States with and without occult nephrolithiasis. Results: Occult urolithiasis was identified in 21% of patients. Stone formers had 47% higher 24-hour urinary calcium excretion (p = 0.002). Although available in only a subset of patients (n = 28), activated vitamin D [1,25(OH)2D] was 29% higher (p = 0.02) in stone formers. There was no difference in demographics, BMI, calcium or vitamin D intake, other biochemistries, renal function, BMD, or fractures. Receiver operating characteristic curves indicated that urinary calcium excretion and 1,25(OH)2D had an area under the curve of 0.724 (p = 0.003) and 0.750 (p = 0.04), respectively. A urinary calcium threshold of >211mg/day provided a sensitivity of 84.2% and a specificity of 55.3% while a 1,25(OH)2D threshold of >91pg/mL provided a sensitivity and specificity of 62.5% and 90.0% respectively for the presence of stones. Conclusion: Occult urolithiasis is present in about one-fifth of patients with asymptomatic PHPT and is associated with higher urinary calcium and 1,25(OH)2D. Given that most patients will not have occult urolithiasis, targeted imaging in those most likely to have occult stones rather than screening all asymptomatic PHPT patients may be useful. The higher sensitivity of urinary calcium versus 1,25(OH)2D suggests screening those with higher urinary calcium may be an appropriate approach.

Surgical management of primary hyperparathyroidism: A single-center experience

Primary hyperparathyroidism (PHPT) can occur at any age. This study aimed to compare the necessity, feasibility, safety, and outcomes of parathyroidectomy in the management of minor-symptomatic or asymptomatic PHPT patients according to age (young vs. old). We retrospectively reviewed the medical records of 146 consecutive patients who underwent surgery for PHPT from January 2005 to June 2016 in our institution. The patients ranged in age from 12 to 85 years. For the analysis, the included patients (n=137) were separated into young (age <50 years; n=31, 22.6%) and old (age ≥50 years; n=106, 77.4%) patients. The biochemical characteristics (parathyroid hormone, calcium, and creatinine levels), T-score of bone densitometry, surgical reports, pathology reports, perioperative intensive care unit care, and 30-day mortality were reviewed. The average medical treatment course after diagnosis tended to be longer in the old group (33.3 vs. 26.2 weeks, p=0.62). During the medical treatment course, the old group had a higher risk of developing new symptoms or severe complications (5.6% vs. 3.2%, p=0.05), and the older patients seemed to have a longer postoperative hospitalization (p=0.17). However, there were no significant differences in the 30-day mortality, immediate complications, and follow-up duration. In older patients, surgical treatment of PHPT is safe and feasible, with comparable outcomes to in younger patients, and helps prevent the development or progression of symptoms and complication. Hence, parathyroidectomy should be the recommended treatment and should be performed in PHPT patients as early as possible, regardless their age and initial symptoms.

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects.

Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. Kidney is a target of both chronic elevated PTH and calcium in PHPT. The classic PHPT complications of symptomatic kidney stones and nephrocalcinosis have become rare and the PHPT current presentation is asymptomatic with uncertain and long-lasting progression. Nonetheless, the routine use of imaging and of biochemical determinations have revealed the frequent occurrence of asymptomatic kidney stones, hypercalciuria and reduced kidney function in asymptomatic PHPT patients. Though the pathogenesis is far from being elucidated, PHPT is associated with reduced renal function, in terms of estimated glomerular filtration rate, and related increased morbidity and mortality. In the last decade, the effort of the Kidney Disease: Improving Global Outcomes (KDIGO) panel of experts highlighted that even mild reduction of kidney function is associated with increased risk of cardiovascular disease. These considerations provided the basis for the Fourth Workshop recommendations of a more extensive diagnostic workout about kidney features and of wider criteria for parathyroid surgery including asymptomatic kidney disease. Moreover, kidney involvement in PHPT is likely to be affected by variants of genes coding the key molecules regulating the calcium and ions renal handling; these features might have clinical relevance and should be considered both during diagnostic workout and follow-up. Finally, the effects of parathyroid surgery and of medical treatment on kidney involvement of PHPT are reviewed.

The natural history and hip geometric changes of primary hyperparathyroidism without parathyroid surgery

There have been few reports on changes in bone geometry in asymptomatic patients with primary hyperparathyroidism (PHPT) not treated surgically. We reviewed the records concerning biochemical parameters, bone mineral density (BMD), and hip geometry in 119 PHPT patients who did not undergo parathyroidectomy, followed up at one of three hospitals affiliated to Seoul National University from 1997 to 2013. We examined biochemical parameters over 7years and BMD and hip geometry over 5years of follow-up. We further compared hip geometry and BMD derived from dual-energy X-ray absorptiometry (DXA) between patients and age- and sex-matched controls. The median follow-up duration of 56 patients for whom surgery was not indicated was 33.9months (range 11.2-131.2months), and 19.6% of these patients had disease progression during follow-up. Serum calcium levels remained stable for 7years in all 119 patients. From a comparison of the PHPT patients for whom surgery was not indicated with controls, both male and postmenopausal female patients had significantly lower hip axis length (P<0.001), cross-sectional moment of inertia (P<0.001), cross-sectional area (P<0.001), and section modulus (P<0.001). In addition, cortical thickness was significantly decreased at 5years compared with individual baseline values (P=0.003). However, there was no significant change in BMD for the duration of the 5-year follow-up. DXA-derived geometry can detect skeletal change in asymptomatic PHPT patients for whom surgery is not indicated, supporting the concept that even mild PHPT can eventually compromise the cortical bones. Hip geometry is a potential tool for monitoring skeletal complication in asymptomatic PHPT patients.

Evaluation of acute and chronic MRI features of sacroiliitis in asymptomatic primary hyperparathyroid patients.

Asymptomatic primary hyperparathyroidism (PHPT) is characterized with autonomous overproduction of parathyroid hormone without signs or symptoms associated with hyperparathyroidism. Before symptoms become obvious, PHPT may affect structures like sacroiliac joints, which consist of bone. So, in the asymptomatic PHPT patients, structural and inflammatory changes in sacroiliac joints may lead to confusion during diagnosis workup of axial spondyloarthropathy. In this study, we evaluated active and chronic sacroiliac magnetic resonance imaging (MRI) changes relevant to sacroiliitis in the patients with asymptomatic PHPT and interpreted bone marrow edema within the scope of Assessment of SpondyloArthritis International Society-Outcome Measures in Rheumatology Clinical Trials (ASAS-OMERACT) criteria. Forty-nine patients with asymptomatic PHPT, 26 patients with newly diagnosed axial spondyloarthropathy (SpA), and 37 healthy controls were enrolled. All subjects were evaluated by sacroiliac MRI for four active (bone marrow edema, enthesitis, capsulitis, and synovitis) and four chronic (subchondral sclerosis, subchondral/periarticular erosions, periarticular fat deposition, and bony bridges/ankylosis) lesions relevant to sacroiliitis. Bone marrow edema compatible with ASAS-OMERACT active sacroiliitis criteria in sacroiliac MRI was fulfilled by 16.3% (8/49) of the asymptomatic PHPT patients which was similar with controls but statistically lower than axial SpA. Moreover, asymptomatic PHPT patients and controls were similar for other chronic or active MRI findings. Also, we detected lower frequency of all other MRI findings, except enthesis, in asymptomatic PHPT patients according to axial SpA. Acute inflammatory including bone marrow edema fulfilling ASAS-OMERACT active sacroiliitis criteria and chronic structural sacroiliac lesions relevant to sacroiliitis in MRI were detected in asymptomatic PHPT similar frequency with controls but as expected, lower than axial SpA. But, these findings could not be attributed to excessive secretion of parathyroid hormone.

Parathyroidectomy in asymptomatic primary hyperparathyroidism reduces carotid intima-media thickness and arterial stiffness.

Although an International Workshop has suggested that cardiovascular assessment in asymptomatic primary hyperparathyroidism (PHPT) patients is not necessary, improvements in risk factors of subclinical atherosclerosis have been shown following parathyroidectomy. The objectives of this study were to determine whether parathyroidectomy in asymptomatic PHPT patients causes any change in carotid intima-media thickness (CIMT), arterial stiffness [pulse wave velocity (PWV)] and soluble CD40 ligand (sCD40L) levels. Prospective study evaluating female patients diagnosed with asymptomatic PHPT in a single centre over a 6-month period. A total of 48 subjects were included: 17 hypercalcaemic (HC, mean age: 51 ± 8 years, Ca: 2·73 ± 0·17 mmol/l) and 16 normocalcaemic (NC, mean age: 58 ± 7 years, Ca: 2·30 ± 0·10 mmol/l) PHPT patients, and 15 healthy controls (mean age: 52 ± 4 years, Ca: 2·27 ± 0·07 mmol/l). Biochemical tests, CIMT, PWV and sCD40L levels were compared at baseline and 6 months after parathyroidectomy (PTx). At baseline, CIMT and PWV values in the HC and NC patients were higher than in the control group. While there was a significant reduction in CIMT (601 ± 91 μm vs 541 ± 65 μm, P = 0·006) and PWV (9·6 ± 1·8 vs 8·4 ± 1·5 m/s, P = 0·000) in the hypercalcaemic group at the end of the 6th month after PTx, no change was observed in normocalcaemic group (P = 0·686 and P = 0·196 respectively). No differences were observed in sCD40L levels between patient and control groups or between baseline and 6 months in patients undergoing parathyroidectomy. Parathyroidectomy leads to an improvement in the structural and functional impairment associated with atherosclerosis in the vascular wall in asymptomatic hypercalcaemic PHPT patients.