Prevalence and risk factors for secondary hyperparathyroidism (SHPT) in patients undergoing bariatric surgery.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) after bariatric surgery has significant adverse implications for bone metabolism, increasing the risk for osteoporosis and fracture. Our aim was to characterize prevalence and identify risk factors for SHPT in bariatric surgery patients. METHODS: We performed a single-institution, retrospective chart review of patients who underwent bariatric surgery from June 2017 through December 2021. Demographic and clinical data were collected, including serum parathyroid hormone, calcium, and vitamin D3 at enrollment and 3, 6, and 12-months postoperatively. Chi-square or Fisher's exact tests were used to analyze categorical data and Mann-Whitney U test for continuous data. Multivariable analysis using binomial logistic regression assessed risk factors for SHPT. P-values ≤ 0.05 were considered significant. RESULTS: 350 patients were analyzed. SHPT prevalence at any time point was 72.9%. 65.8% had SHPT at enrollment; 45.9% resolved with intensive vitamin supplementation; and 19.7% had recurrent SHPT. New-onset SHPT occurred in 8.6%. Persistent SHPT was present in 42.4% at 1-year. Baseline SHPT correlated with black race and T2DM. SHPT at any time point correlated with T2DM and higher baseline BMI. 1-year SHPT correlated with RYGB, depression, and longer time in program. SHPT was not correlated with %TBWL at any time point. In patients with SHPT, vitamin D3 deficiency prevalence was significantly higher at baseline (77.0%) compared to all post-bariatric time points (16.7%, 17.3%, and 23.1%; P < 0.0001). CONCLUSIONS: SHPT is highly prevalent in patients with obesity seeking weight loss surgery. 42% had persistent SHPT at 1-year despite appropriate vitamin supplementation. Current vitamin D3 and calcium supplementation protocols may not effectively prevent SHPT in many post-bariatric patients. Low prevalence of concomitant vitamin D3 deficiency with SHPT after bariatric surgery suggests that there may be alternative mechanisms in this population. Further studies are needed to develop effective treatment strategies to mitigate the adverse effects of bariatric surgery on bone metabolism.

Determinants of Secondary Hyperparathyroidism 1 Year After One-Anastomosis Gastric Bypass or Sleeve Gastrectomy.

PURPOSE: Bariatric surgery alters the anatomic and physiological structure of the gastrointestinal tract, predisposing patients to the malabsorption of nutrients. The purpose of this study was to determine the prevalence and determinants of secondary hyperparathyroidism (SHPT) in the patients undergoing either one-anastomosis gastric bypass (OAGB) or sleeve gastrectomy (SG). MATERIALS AND METHODS: A total of 517 patients (without SHPT at the baseline) who had undergone OAGB or SG were prospectively assessed 1 year after the surgery. Anthropometric parameters, calcium, intact parathyroid hormone (iPTH), and 25(OH)D levels were compared according to the surgery type before and 1 year after surgery. Multiple logistic regression models were used to evaluate possible SHPT predictors after bariatric surgery. RESULTS: The overall prevalence of SHPT was 12.6% after surgery, significantly different between the OAGB and SG groups (17.1 vs. 9.9%, respectively). The serum levels of albumin-corrected calcium and 25(OH)D were not significantly different between the two groups. The patients undergoing OAGB had significantly higher serum levels of ALP (198.2 vs. 156.6) compared to the subjects undergoing SG. Higher iPTH levels preoperatively, lower 1-year excess weight loss%, and OAGB surgery seemed to be independent predictors for SHPT 1 year after surgery. CONCLUSION: Morbidly-obese patients undergoing OAGB had a higher risk of SHPT than their counterparts undergoing SG, whereas 25(OH)D deficiency and calcium levels did not differ between the two groups. The OAGB procedure, preoperative iPTH levels, and 1-year weight loss were predictors of postoperative SHPT development.

Black patients are more likely to undergo parathyroidectomy for secondary hyperparathyroidism.

BACKGROUND: Prior studies have demonstrated racial disparities in the severity of secondary hyperparathyroidism among dialysis patients. Our primary objective was to study the racial and socioeconomic differences in the timing and likelihood of parathyroidectomy in patients with secondary hyperparathyroidism. METHODS: We used the United States Renal Data System to identify 634,428 adult (age ≥18) patients who were on maintenance dialysis between 2006 and 2016 with Medicare as their primary payor. Adjusted multivariable Cox regression was performed to quantify the differences in parathyroidectomy by race. RESULTS: Of this cohort, 27.3% (173,267) were of Black race. Compared to 15.4% of White patients, 23.1% of Black patients lived in a neighborhood that was below a predefined poverty level (P < .001). The cumulative incidence of parathyroidectomy at 10 years after dialysis initiation was 8.8% among Black patients compared to 4.3% among White patients (P < .001). On univariable analysis, Black patients were more likely to undergo parathyroidectomy (adjusted hazard ratio = 1.83; 95% confidence interval, 1.74-1.93). This association persisted after adjusting for age, sex, cause of end-stage renal disease, body mass index, comorbidities, dialysis modality, and poverty level (adjusted hazard ratio = 1.35; 95% confidence interval, 1.27-1.43). Therefore, patient characteristics and socioeconomic status explained 26% of the association between race and likelihood of parathyroidectomy. CONCLUSION: Black patients with secondary hyperparathyroidism due to end-stage renal disease are more likely to undergo parathyroidectomy with shorter intervals between dialysis initiation and parathyroidectomy. This association is only partially explained by patient characteristics and socioeconomic factors.

[Evolution of the incidence and results at 12 months of parathyroidectomy: 40 years of experience in a dialysis center with two successive surgical departments]. / Évolution de l'incidence et des résultats à 12 mois de la parathyroïdectomie : 40 ans d'expérience dans un centre de dialyse avec deux services de chirurgie successifs.

INTRODUCTION: Secondary hyperparathyroidism remains the main complication of mineral and bone metabolism in patients with chronic kidney disease. In case of resistance to medical treatment (native and active vitamin D, calcium and calcimimetics), surgical parathyroidectomy is indicated. The aim of this retrospective study is to show the evolution of the incidence and results of surgical parathyroidectomy in our center between 1980 and 2020 as patient characteristics, diagnostic and therapeutic strategies have changed. PATIENTS AND METHODS: We collected data from dialysis patients who had a first surgical parathyroidectomy between 2000 and 2020 (period 2) in the same surgical department and compared them with historical data between 1980 and 1999 (period 1) operated in one other center. RESULTS: In period 1, 53 surgical parathyroidectomy were performed (2.78/year, 0 to 5, 8.5/1000 patients-year) vs.56 surgical parathyroidectomy in period 2 (2.8/year, 0 to 9, 8/1000 patients-year). The patients of the 2 periods were comparable except for the higher dialysis vintage in period 1 (149±170 vs.89±94 months; P=0.02). In comparison with dialysis patients not requiring surgical parathyroidectomy during the same period, patients who had surgical parathyroidectomy were younger, had higher dialysis vintage and lower diabetes prevalence, but more frequently carriers of glomerulopathy or polycystosis. Systematically performed in period 2, cervical ultrasound identified at least one visible gland in 78.6% of cases while the scintigraphy, performed only in 66% of cases, found at least one gland in 81% of cases. Twelve months after surgery, PTH > 300 pg/mL (marker of secondary hyperparathyroidism recurrence or surgery failure) was present in 30% of patients in period 1 vs. 5.3% in period 2. Hypoparathyroidism was also more frequently observed in period 2 (35.7 vs. 18.8%). Surgical complications were also higher in period 1. CONCLUSION: Despite therapeutic and strategic advances, severe secondary hyperparathyroidism is still as common as ever. It is favored by excessively high PTH targets, by suboptimal prevention before dialysis and poor tolerance of calcimimetics. The surgical parathyroidectomy is effective and safe in the hands of a specialized team with an ultrasound and scintigraphic preoperative assessment.

Prevalence and associated factors of secondary hyperparathyroidism after Roux-en-Y gastric bypass: A meta-analysis.

This study aimed to investigate the prevalence and factors associated with secondary hyperparathyroidism (SHPT) after Roux-en-Y gastric bypass (RYGB). We searched PubMed, EMBASE, and CENTRAL for relevant studies using search terms gastric bypass, RYGB and hyperparathyroidism. Thirty-four cohort studies with 4331 patients were incorporated into the final meta-analysis. Overall estimates of the prevalence of SHPT following RYGB were 39%. Subgroup analyses indicated the pooled prevalences of SHPT were 25%, 42%, 48%, and 54% for ≤1 year, >1 and ≤5 years, >5 and ≤10 years, and >10 years, respectively, after RYGB. Meta-regression showed that SHPT occurred was positively related to follow-up durations (p = 0.001). Additionally, SHPT prevalence was higher in studies in which calcium and vitamin D supplementation were considered inadequate than in those which were adequate (p = 0.002). SHPT is highly prevalent in individuals with obesity after RYGB. It seems to progress with time after surgery. Routine calcium and vitamin D supplementation post-RYGB together with targeted treatment of vitamin D deficiency, reasonable adjustment of the doses of supplementation with regular follow-up, and improved patient compliance, as well as long-term screening, are necessary to prevent the development of SHPT.

Hyperuricemia is associated with secondary hyperparathyroidism in patients with chronic kidney disease.

PURPOSE: Hyperuricemia is common among patients with chronic kidney disease (CKD). In the general population, hyperuricemia is associated with secondary hyperparathyroidism (SHPT), in a mechanism that involves vitamin D metabolism. Data for patients with CKD, however, are scarce. We aimed to evaluate the relationship between hyperuricemia and mineral and bone metabolism, particularly hyperparathyroidism. METHODS: This is a retrospective study that included 922 adult patients with stages 3, 4, or 5 CKD, not on dialysis. Clinical, demographic, and biochemical data were collected from charts and included uric acid, parathyroid hormone (PTH), 25(OH)-vitamin D, calcium, phosphate, renal function (estimated glomerular filtration rate-eGFR), and medications such as allopurinol, furosemide, and cholecalciferol. SHPT was defined as PTH > 65 pg/ml. RESULTS: Our patients were mostly Caucasian women, with a mean age of 64 ± 16 years. SHPT and hyperuricemia were observed in 70% and 62.4% of patients, respectively. Patients with SHPT presented higher levels of uric acid (7.2 ± 1.8 vs. 6.6 ± 1.7 mg/dL, p = 0.0001) and a higher frequency of hyperuricemia (66% vs. 33%, p = 0.0001). Patients with hyperuricemia were mostly female, with lower eGFR, higher phosphate, and higher PTH. The risk of hypovitaminosis D was higher among patients with SHPT (69.7% vs. 53.1%, p = 0.0001). Hyperuricemia remained independently associated with hyperparathyroidism, (p = 0.033) even after adjustments for eGFR, calcium, phosphate, hypovitaminosis D, and use of allopurinol, calcitriol, furosemide, and cholecalciferol. CONCLUSION: Hyperuricemia seems to be a contributing factor for SHPT in patients with CKD. The mechanisms behind this finding have yet to be elucidated.

Secondary Hyperparathyroidism, Bone Density, and Bone Turnover After Bariatric Surgery: Differences Between Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

PURPOSE: Bariatric surgery may lead to metabolic bone disease. MATERIALS AND METHODS: In this cross-sectional study, we compared the prevalence of secondary hyperparathyroidism (SHPT), impact on bone mass and turnover markers, and serum leptin after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) in 117 patients (91% female, 51% RYGB, age 41.8 ± 6.7 years, time of surgery 4.3 ± 3.4 years) at different times (1-2 years, > 2 and < 5 years and ≥ 5 years). Body composition, bone mineral density (BMD), by dual-energy X-ray absorptiometry, and bone parameters (PTH, serum calcium, 25OHD, alkaline phosphatase (AP), C-telopeptide (CTX)) were analyzed. RESULTS: Prevalence of SHPT (PTH ≥ 65 pg/ml) was 26%, RYGB > SG (18.4% vs. 7.8%, p = 0.039), despite similar 25OHD and calcium levels. Mean PTH, CTX, and AP were higher in RYGB vs. SG (61.3 ± 29.5 vs 49.5 ± 32.3 pg/ml, p = 0.001; 0.596 ± 0.24 vs. 0.463 ± 0.23 ng/ml; 123.9 ± 60.8 vs. 100.7 ± 62.0 U/l). There were 13.5% decreases in femoral neck BMD in all patients, over the study period. In the last group, the RYGB group showed greater bone loss in total body BMD (1.016 vs. 1.151 g/cm2, - 8.1%, p = 0.003) and total femur BMD (1.164 vs. 1.267 g/cm2, - 11.7%, p = 0.007). Mean leptin was lower in the RYGB vs. SG group, with no correlation with BMD in any site. CONCLUSION: Our data suggest a more deleterious role of RYGB on bone remodeling up to 5 years postoperatively in comparison with SG.

Ultrasound-guided bilateral superficial cervical plexus block enhances the quality of recovery of uremia patients with secondary hyperparathyroidism following parathyroidectomy: a randomized controlled trial.

BACKGROUND: Parathyroidectomy has been proposed as a method for reducing parathyroid hormone levels. We evaluated the effects of ultrasound-guided bilateral superficial cervical plexus block (BSCPB) on the quality of recovery of uremia patients with secondary hyperparathyroidism (SHPT) following parathyroidectomy. METHODS: Eighty-two uremia patients who underwent parathyroidectomy and exhibited SHPT were randomly allocated to the BSCPB group or the control group (CON group). The patients received ultrasound-guided BSCPB with 7.5 ml of ropivacaine 0.5% on each side (BSCPB group) or equal amount of 0.9% normal saline (CON group). The primary outcome of the Quality of Recovery-40(QoR-40) score was recorded on the day before surgery and postoperative day 1(POD1). Secondary outcomes including total consumption of remifentanil, time to first required rescue analgesia, number of patients requiring rescue analgesia, and total consumption of tramadol during the first 24 h after surgery were recorded. The occurrence of postoperative nausea or vomiting (PONV) and the visual analogue scale (VAS) scores were assessed and recorded. RESULTS: The scores on the pain and emotional state dimensions of the QoR-40 and the total QoR-40 score were higher in the BSCPB group than in the CON group on POD1 (P = 0.000). Compared with the CON group, the total consumption of remifentanil was significantly decreased in the BSCPB group (P = 0.000). The BSCPB group exhibited longer time to first required rescue analgesia (P = 0.018), fewer patients requiring rescue analgesia (P = 0.000), and lower postoperative total consumption of tramadol during the first 24 h after surgery (P = 0.000) than the CON group. The incidence of PONV was significantly lower in the BSCPB group than in the CON group (P = 0.013). The VAS scores in the BSCPB group were lower than those in the CON group at all time-points after surgery (P = 0.000). CONCLUSION: Ultrasound-guided BSCPB with ropivacaine 0.5% can enhance the quality of recovery, postoperative analgesia, and reduce the incidence of PONV in uremia patients with SHPT following parathyroidectomy. TRIAL REGISTRATION: ChiCTR1900027185 . (Prospective registered). Initial registration date was 04/11/2019.

Analyzing Genetic Differences Between Sporadic Primary and Secondary/Tertiary Hyperparathyroidism by Targeted Next-Generation Panel Sequencing.

Secondary hyperparathyroidism (SHPT) is characterized by excessive serum parathyroid hormone levels in response to decreasing kidney function, and tertiary hyperparathyroidism (THPT) is often the result of a long-standing SHPT. To date, several genes have been associated with the pathogenesis of primary hyperparathyroidism (PHPT). However, the molecular genetic mechanisms of uremic hyperparathyroidism (HPT) remain uncharacterized. To elucidate the differences in genetic alterations between PHPT and SHPT/THPT, the targeted next-generation sequencing of genes associated with HPT was performed using DNA extracted from parathyroid tissues. As a result, 26 variants in 19 PHPT or SHPT/THPT appeared as candidate pathogenic mutations, which corresponded to 9 (35%) nonsense, 8 (31%) frameshift, 6 (23%) missense, and 3 (11%) splice site mutations. The MEN1 (23%, 6/26), ASXL3 (15%, 4/26), EZH2 (12%, 3/26), and MTOR (8%, 2/26) genes were frequently mutated. Sixteen of 25 patients with PHPT (64%) had one or more mutations, whereas 3 (21%) of 21 patients with SHPT/THPT had only 1 mutation (p = 0.001). Sixteen of 28 patients (57%) with parathyroid adenoma (PA) had one or more mutations, whereas 3 of 18 patients (17%) with parathyroid hyperplasia (PH) had just one mutation (p = 0.003). Known driver mutations associated with parathyroid tumorigenesis such as CCND1/PRAD1, CDC73/HRPT2, and MEN1 were identified only in PA (44%, 7/16 with mutations). Our results suggest that molecular genetic abnormalities in SHPT/THPT are distinct from those in PHPT. These findings may help in analyzing the molecular pathogenesis underlying uremic HPT development.

Secondary Hyperparathyroidism Among Bariatric Patients: Unraveling the Prevalence of an Overlooked Foe.

INTRODUCTION: Bariatric surgery (BS) is the most effective therapeutic approach to obesity. It is associated with great gastrointestinal anatomic changes, predisposing the patients to altered nutrient absorption that impacts phosphocalcium metabolism. This study aimed to clarify the prevalence of secondary hyperparathyroidism (SHPT) and its predictors in patients submitted to BS. METHODS: Retrospective study of 1431 patients who underwent metabolic surgery between January 2010 and June 2017 and who were followed for at least 1 year. We compared the clinical and biochemical characteristics of patients with and without secondary hyperparathyroidism (considering SHPT a PTH ˃ 69 pg/mL). Two different analyses were performed: (1) paired analysis of participants before and 1 year after surgery (N = 441); (2) Cross sectional analysis of participants submitted to bariatric surgery before (N = 441), 1 year after (N = 1431) and 4 years after surgery (N = 333). Multiple logistic regression models were used to evaluate possible predictors of SHPT after BS. RESULTS: The overall prevalence of SHPT was 24.9% before surgery, 11.2% 1 year after surgery and 21.3% 4 years after surgery. Patients submitted to LAGB had the highest prevalence of SHPT 1 year after surgery (19.4%; vs RYGB, 12.8%, vs SG, 5.3%). Four years after surgery, RYGB had the highest prevalence of SHPT (27.0%), followed by LAGB (13.2%) and SG (6.9%). Higher body mass index and age, decreased levels of vitamin D and RYGB seem to be independent predictors of SHPT 1 year after surgery. The only independent predictor of SHPT 4 years after surgery was RYGB. CONCLUSION: The prevalence of SHPT is higher before and 4 years after BS than 1 year after surgery. This fact raises some questions about the efficacy of the implemented follow-up plans of vitamin D supplementation on the long term, mainly among patients submitted to RYGB.

Secondary hyperparathyroidism, weight loss, and longer term mortality in haemodialysis patients: results from the DOPPS.

BACKGROUND: Wasting is a common complication of kidney failure that leads to weight loss and poor outcomes. Recent experimental data identified parathyroid hormone (PTH) as a driver of adipose tissue browning and wasting, but little is known about the relations among secondary hyperparathyroidism, weight loss, and risk of mortality in dialysis patients. METHODS: We included 42,319 chronic in-centre haemodialysis patients from the Dialysis Outcomes and Practice Patterns Study phases 2-6 (2002-2018). Linear mixed models were used to estimate the association between baseline PTH and percent weight change over 12 months, adjusting for country, demographics, comorbidities, and labs. Accelerated failure time models were used to assess 12 month weight loss as a mediator between baseline high PTH and mortality after 12 months. RESULTS: Baseline PTH was inversely associated with 12 month weight change: 12 month weight loss >5% was observed in 21%, 18%, 18%, 17%, 15%, and 14% of patients for PTH ≥600 pg/mL, 450-600, 300-450, 150-300, 50-150, and <50 pg/mL, respectively. In adjusted analyses, 12 month weight change compared with PTH 150-299 pg/mL was -0.60%, -0.12%, -0.10%, +0.15%, and +0.35% for PTH ≥600, 450-600, 300-450, 50-150, and <50 pg/mL, respectively. This relationship was robust regardless of recent hospitalization and was more pronounced in persons with preserved appetite. During follow-up after the 12 month weight measure [median, 1.0 (interquartile range, 0.6-1.7) years; 6125 deaths], patients with baseline PTH ≥600 pg/mL had 11% [95% confidence interval (CI), 9-13%] shorter lifespan, and 18% (95% CI, 14-23%) of this effect was mediated through weight loss ≥2.5%. CONCLUSIONS: Secondary hyperparathyroidism may be a novel mechanism of wasting, corroborating experimental data, and, among chronic dialysis patients, this pathway may be a mediator between elevated PTH levels and mortality. Future research should determine whether PTH-lowering therapy can limit weight loss and improve longer term dialysis outcomes.

Environmental chemicals and metabolic disruption in primary and secondary human parathyroid tumors.

BACKGROUND: The incidence of primary hyperparathyroidism has increased 300% in the United States in the past 30 years, and secondary hyperparathyroidism is almost universal in patients with end-stage renal disease. We assessed the presence of environmental chemicals in human hyperplastic parathyroid tumors as possible contributing factors to this increase. METHODS: Cryopreserved hyperplastic parathyroid tumors and normal human parathyroids were analyzed by gas chromatography and liquid chromatography coupled to ultra-high-resolution mass spectrometry, bioinformatics, and biostatistics. RESULTS: Detected environmental chemicals included polychlorinated biphenyls, polybrominated diphenyl ethers, dichloro-diphenyl-trichloroethane derivatives, and other insecticides. A total of 99% had p,p'-dichlorodiphenyldichloroethylene. More than 50% contained other environmental chemicals, and many classified as endocrine disruptors. Polychlorinated biphenyl-28 and polychlorinated biphenyl-49 levels correlated positively with parathyroid tumor mass. Polybrominated diphenyl ether-47 concentrations in tumors were inversely correlated with patients' serum calcium levels. Cellular metabolites in pathways of purine and pyrimidine synthesis and mitochondrial energy production were associated with tumor growth and with p,p'-dichlorodiphenyldichloroethylene in primary hyperparathyroidism tumors. In normal parathyroids, p,p'-dichlorodiphenyldichloroethylene , polychlorinated biphenyl-28, polychlorinated biphenyl-74, and polychlorinated biphenyl-153, but not p,p'-dichlorodiphenyldichloroethylene or polychlorinated biphenyl-49, were detected. CONCLUSION: Environmental chemicals are present in human parathyroid tumors and warrant detailed epidemiologic and mechanistic studies to test for causal links to the growth of human parathyroid tumors.

New parathyroid function index for the differentiation of primary and secondary hyperparathyroidism: a case-control study.

BACKGROUND: Patients with primary hyperparathyroidism (PHPT) may be asymptomatic, and some may present with normocalcemic PHPT (NPHPT). Patients with vitamin D deficiency may also be asymptomatic, with normal calcium and elevated PTH concentrations. These latter patients are usually diagnosed with vitamin D deficiency-induced secondary hyperparathyroidism (VD-SHPT). Therefore, it is very difficult to distinguish PHPT and NPHPT from VD-SHPT based on calcium or PTH concentrations in clinical settings. In this case-control study, we aimed to verify the diagnostic power of a new parathyroid function index (PFindex = Ca*PTH/P). METHODS: This study enrolled 128 patients with surgically and pathologically confirmed PHPT, including 36 with NPHPT, at a hospital in West China between January 2009 and September 2017. Thirty-seven patients with VD-SHPT and 45 healthy controls were selected from the population of a cross-sectional epidemiological study as the SHPT and healthy groups, respectively. We used the PFindex to describe the characteristics of PHPT, NPHPT, and VD-SHPT.. Differences between the four groups were compared, and a receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic power of PFindex. RESULTS: The PHPT group had the highest PFindex (454 ± 430), compared to the other three groups (NPHPT: 101 ± 111; SHPT: 21.7 ± 6.38; healthy: 12.2 ± 2.98, all p < 0.001). A PFindex cut-off value of 34 yielded sensitivity and specificity rates of 96.9 and 97.6% and of 94.4 and 94.6% for the diagnoses of PHPT and NPHPT, respectively. The use of a PFindex > 34 to differentiate NPHPT from VD-SHPT yielded the highest positive likelihood ratio and lowest negative likelihood ratio. CONCLUSION: The PFindex provided excellent diagnostic power for the differentiation of NPHPT from VD-SHPT. This simple tool may be useful for guiding timely decision-making processes regarding the initiation of vitamin D treatment or surgery for PHPT.

Risk Factors of Severe Hypocalcemia After US-Guided Percutaneous Microwave Ablation of the Parathyroid Gland in Patients with Secondary Hyperparathyroidism.

Our aim was to identify potential risk factors associated with severe hypocalcemia (SH) after microwave ablation (MWA) in patients with secondary hyperparathyroidism (SHPT). This retrospective cross-sectional study enrolled 204 consecutive patients (with 387 parathyroid glands) who underwent MWA between July 2015 and May 2018. Clinical parameters, laboratory indices, and parathyroid gland characteristics were analyzed to assess risk factors associated with SH after MWA. SH was defined as serum calcium level lower than 1.875 mmol/L (7.5 mg/dL) after MWA. Two models (I and II) for pre-MWA and post-MWA prediction were established, respectively. In accordance with the KDIGO guidelines, the target value for intact parathyroid hormone (iPTH) less than 300 pg/mL within 7 days after MWA was considered as a successful procedure. The success rate of MWA was 71.6% (146/204). The incidence of hypocalcemia and SH after MWA was 35.8% and 22.06%, respectively. The pre-MWA prediction models I and II showed that high pre-MWA iPTH, a dramatic reduction in iPTH, low pre-MWA serum calcium, multiple ablated gland, and lack of pruritus symptoms were risk factors for developing SH. The accuracy (82.23% versus 83.25% in models I and II, respectively), sensitivity (34.88% versus 44.19%), specificity (95.45% versus 94.59%), positive predictive value (PPV) (68.18% versus 70.37%), and negative predictive value (NPV) (84% versus 85.37%) of both models were promising. The logistic regression fitting of the nomograms showed high prediction efficiency (0.845 and 0.863). High pre-MWA iPTH, dramatic reductions in iPTH, low pre-MWA serum calcium, multiple gland ablation, and no pruritus symptoms were predictors of SH. © 2019 American Society for Bone and Mineral Research.

Primary and Secondary Hyperparathyroidism in Patients with Primary Aldosteronism - Findings From the German Conn's Registry.

CONTEXT: Recent studies support a bidirectional interaction between aldosterone and parathyroid hormone (PTH), possibly increasing the individual cardiovascular risk. Primary aldosteronism (PA) and primary hyperparathyroidism can occur simultaneously. OBJECTIVE: Our aim was to investigate the prevalence of hyperparathyroidism in PA. PATIENTS: We performed a case finding of primary hyperparathyroidism in a retrospective series of 503 patients with PA (cohort 1). We analysed primary and secondary hyperparathyroidism in 141 prospective PA patients who underwent PTH, serum calcium and phosphate measurements at time of diagnosis of PA (cohort 2). RESULTS: The prevalence for primary hyperparathyroidism was 1.2% in cohort 1, and 2.1% in cohort 2. Secondary hyperparathyroidism was found in 54.6% of the patients. Patients with secondary hyperparathyroidism had significantly higher aldosterone and lower potassium levels and took more antihypertensive medications compared to those with normal PTH levels. In multivariate analysis, aldosterone and 25-hydroxyvitamin D levels were significantly correlated with serum PTH levels. There was a nonsignificant trend to a higher cardiovascular morbidity in patients with secondary hyperparathyroidism. Patients with aldosterone producing adenoma had significantly higher PTH levels compared to patients with bilateral adrenal hyperplasia. After treatment, there was a significant decrease of PTH levels in both groups. CONCLUSION: Patients with PA frequently have primary or secondary hyperparathyroidism, which is alleviated by correction of PA by surgical or medical means. Patients affected by secondary hyperparathyroidism seem to have a more severe phenotype of PA and have a trend towards more cardiovascular co-morbidities.

Parathyroid hormone independently predicts fracture, vascular events, and death in patients with stage 3 and 4 chronic kidney disease.

Doctors do not know whether treatment of high parathyroid hormone levels is linked to better outcomes in their patients with kidney disease. In this study, lower parathyroid hormone levels at baseline were linked to lower risk of fracture, vascular events, and death in people with kidney disease. PURPOSE: Chronic kidney disease (CKD) affects ~ 20% of older adults, and secondary hyperparathyroidism (HPT) is a common condition in these patients. To what degree HPT predicts fractures, vascular events, and mortality in pre-dialysis CKD patients is debated. In stage 3 and 4 CKD patients, we assessed relationships between baseline serum PTH levels and subsequent 10-year probabilities of clinical fractures, vascular events, and death. METHODS: We used Marshfield Clinic Health System electronic health records to analyze data from adult CKD patients receiving care between 1985 and 2013, and whose PTH was measured using a second-generation assay. Covariates included PTH, age, gender, tobacco use, vascular disease, diabetes, hypertension, hyperlipidemia, obesity, GFR, and use of osteoporosis medications. RESULTS: Five thousand one hundred eight subjects had a mean age of 68 ± 17 years, 48% were men, and mean follow-up was 23 ± 10 years. Fractures, vascular events, and death occurred in 18%, 71%, and 56% of the cohort, respectively. In univariate and multivariate models, PTH was an independent predictor of fracture, vascular events, and death. The hazards of fracture, vascular events and death were minimized at a baseline PTH of 0, 69, and 58 pg/mL, respectively. CONCLUSIONS: We found that among individuals with stage 3 and 4 CKD, PTH was an independent predictor of fractures, vascular events, and death. Additional epidemiologic studies are needed to confirm these findings. If a target PTH range can be confirmed, then randomized placebo-controlled trials will be needed to confirm that treating HPT reduces the risk of fracture, vascular events, and death.

Bone Metabolism in Adolescents and Adults Undergoing Roux-En-Y Gastric Bypass: a Comparative Study.

OBJECTIVE: To compare the bone metabolism of adolescents and adults with obesity before undergoing a Roux-en-Y gastric bypass (RYGB) and 6 and 12 months after the surgery. MATERIALS AND METHODS: Adolescents (G1) and adults (G2) with obesity assessed before (T0), six (T1), and 12 months after (T2) RYGB. Sun exposure, serum concentrations of 25(OH)D, calcium, phosphorous, magnesium, zinc, alkaline phosphatase, parathyroid hormone (PTH), and bone mineral density (BMD) were evaluated. RESULTS: Sixty adolescents and 60 adults were assessed. At T0, there was no significant difference between the groups' serum 25(OH)D levels (G1 21.87 + 7.52 ng/mL, G2 21.73 + 7.60 ng/mL, p = 0.94) or sun exposure (G1 17 ± 2.0 min/day, G2 13.2 ± 5.2 min/day, p = 0.85). G1 had high levels of inadequacy of calcium (66.7%), phosphorous (80.0%), and zinc (18.3%) at T0 and had a significant fall in their 25(OH)D (p < 0.01) and magnesium (p < 0.01) levels from T1 to T2. G2 saw a significant lowering of their serum zinc levels from T0 to T1 and T2 (T1 p < 0.01; T2 p < 0.01). In both groups, there was a significant rise in PTH from T1 to T2 (G1 p = 0.04, G2 p = 0.02) and from T0 to T2 (G1 and G2 p < 0.01). In G2, 40.4% of individuals with osteopenia and osteoporosis presented inadequacy of 25(OH)D. CONCLUSION: RYGB was found to worsen the inadequacy of micronutrients related to bone metabolism and was associated with secondary hyperparathyroidism and low BMD values, especially among the adolescents. The irreversible damaging effects of obesity on bone metabolism can occur in adolescence.

Total versus subtotal parathyroidectomy for secondary hyperparathyroidism.

BACKGROUND: It remains unclear whether total or subtotal parathyroidectomy for secondary hyperparathyroidism yields the best outcomes. We investigated mortality, cardiovascular events, hip fracture, and recurrent parathyroidectomy after total versus subtotal parathyroidectomy in patients on renal replacement therapy. METHODS: Using the Swedish Renal Registry, the surgical registry for thyroid and parathyroid surgery, and the National Inpatient Registry, we identified patients who underwent parathyroidectomy between 1991 and 2013. We calculated the risk of outcome after total versus subtotal parathyroidectomy using COX's regression, adjusting for age, sex, cause of renal disease, time with a functioning graft before and after parathyroidectomy, Charlson comorbidity index, year of surgery, prevalent cardiovascular disease, time on dialysis, renal transplantation at parathyroidectomy, and treatment with calcimimetics before parathyroidectomy. RESULTS: There were 824 patients who underwent parathyroidectomy, 388 total and 436 subtotal. There was no difference in mortality or risk of incident hip fracture between groups. Comparing the subtotal with the total parathyroidectomy, the adjusted hazard ratio (95% confidence interval) for cardiovascular events was 0.43 (0.25-0.72) and for recurrent parathyroidectomy 3.33 (1.33-8.32). CONCLUSION: There was a higher risk of cardiovascular events in patients after total parathyroidectomy compared with subtotal parathyroidectomy, but a lower risk of recurrent parathyroidectomy.

Secondary Hyperparathyroidism in Patients with Biliopancreatic Diversion After 10 Years of Follow-up, and Relationship with Vitamin D and Serum Calcium.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a matter of concern after biliopancreatic diversion (BPD). The aim of this study was to investigate the relationship between SHPT, 25(OH)D, and calcium after BPD. DESIGN: A retrospective analysis in obese patients after BPD performed between 1998 and 2016. METHODS: Patients with at least 1 year of follow-up were included. SHPT was considered when PTH > 65 pg/mL in the absence of an elevated corrected calcium. 25(OH)D (ng/mL) status was defined as: deficiency < 20, insufficiency 20-29.9, and sufficiency ≥ 30. RESULTS: In total, 321 patients were included (76.6% women), with mean age 43.0 (10.5) years. Median follow-up was 6.0 (IQR 3.0-9.0) years. Mean body mass index was 49.8 (7.0) kg/m2. SHPT increased to a maximum of 81.9% in the ninth year of follow-up (95% CI: 1.5-9.1). Two years after surgery, 33.9% of patients with 25(OH)D sufficiency had SHPT (p = 0.001). Corrected calcium levels were lower in patients with PTH > 65 pg/mL when compared with PTH < 65 pg/mL; 1 year: 8.96 vs 9.1 mg/dL and 5 years: 8.75 vs 9.12 mg/dL (p < 0.01). After surgery, patients with PTH > 65 pg/mL and 25(OH)D sufficiency had lower corrected calcium levels when compared with subjects with PTH and 25(OH)D in normal range. Two years: 9.0 vs 9.2 mg/dL (p < 0.05) and 4 years: 8.9 vs 9.2 mg/dL (p < 0.01). CONCLUSIONS: Once 25(OH)D is sufficient, the increase in PTH persists associated with a decrease in serum corrected calcium. It is important to ensure a sufficient calcium intake in these patients in order to avoid SHPT and osteomalacia in the future.

Multicenter study on parathyroidectomy (PTX) in Italy: preliminary results.

BACKGROUND: When medical therapy is unable to achieve biochemical control of secondary hyperparathyroidism, parathyroidectomy (PTX) is indicated, fortunately in a minority of patients. Thus, data on PTX prevalence and biochemical control are limited and, in particular in Italy, date back to 1999. METHODS: We designed a prospective, observational and multicenter study to collect data from dialysis units distributed throughout the Italian regions. Clinical data were collected with a dedicated data sheet. RESULTS: From January to December 2010, 149 Centers serving a total of 12,515 patients provided data on 528 living PTX cases (PTX prevalence = 4.2%). Prevalence was higher in hemo- than in peritoneal dialysis (4.5 vs. 1.9%, X2 = 21.52; p < 0.001), with non-significant regional differences (range 0.8-7.4%). PTX patients were younger (57.6 ± 12.5 vs. 67.1 ± 14.5 years; p < 0.001), more frequently female (56 vs. 38%, X2 = 68.05, p < 0.001) and had been on dialysis for a longer time (14.63 ± 8.37 vs. 4.8 ± 6.0 years, p < 0.001) compared to the 11,987 who did not undergo neck surgery. Median time since surgery was 6.0 years (3.0-9.0; 50%, IQR). The most frequent type of surgery was subtotal PTX (sPTX = 55.0%), significantly higher than total PTX (tPTX = 38.7%) or total PTX plus auto-transplantation (aPTX = 6.3%) (X2 = 5.18; Bonferroni post-hoc test, sPTX vs. tPTX + aPTX = p < 0.05). As for parathyroid hormone (PTH), calcium and phosphate control, cases targeting the KDOQI ranges were 18, 50.1 and 54.4%, respectively. The most prevalent biochemical condition was low PTH (62.7%). CONCLUSION: PTX prevalence in Italy is stable compared to previous observations, is higher in hemodialysis than in peritoneal dialysis and results in a suboptimal biochemical control.