pHPT Patients Research Articles

RF18 | PSAT165 Effect of Age, Gender, & Ethnicity on the Prevalence of Vertebral fractures in Patients with Primary Hyperparathyroidism

Abstract Background Primary hyperparathyroidism (PHPT) is one of the known causes of secondary osteoporosis. PHPT is associated with increased bone turnover, low bone density and quality; but there have been conflicting results on the risk of fractures. There is limited information on the effects of age, gender, and ethnicity on fracture risk in PHPT. Objective To determine the prevalence of vertebral fractures (VFx) and associated risk factors in patients with PHPT Design: Retrospective cross-sectional study Setting: Academic medical center in a community setting Main outcome measured: 1) Bone mineral density (BMD), and T- and Z-scores of the lumbar spine (LS). 2) Vertebral morphometry was assessed using the Genant method to identify asymptomatic vertebral fractures (VFx) on CT spine images. 3) Biochemical measurements included serum PTH, Creatinine (Cr) and Calcium (Ca). Results In this retrospective study of consecutive 560 PHPT patients verified by surgery [447 women with a median age of 62y; 362 Caucasians (65%), 142 African Americans (AA, 25%) and 22 unspecified race (10%)] were included. Prevalence of VFx was 13% (n=75), other sites 15% (n=84), wrist fractures 3% (n=16) and hip fractures 1% (n=6). Fracture prevalence at all sites was higher in women, but significant only for VFx (71% vs 29%, p=0.04). In subgroup analysis by age (above or below 50y) and gender, there was no significant difference in LS BMD, T- or Z-score values, serum PTH, Ca and Cr in patients with and without VFx. In subgroup analysis by ethnicity: i) prevalence of all fractures was higher in Caucasians compared to AA and others ii) mean serum PTH (±SD) level was significantly higher in AA vs Caucasian patients with VFx (190 ± 124 vs 121 ± 57 pg/mL, p=0.03) and iii) no significant differences were noted in LS BMD, T-or Z-scores, serum Ca and Cr in patients with VFx. In multivariate analysis (age, serum Ca, PTH >100, and LS BMD) to predict risk of VFx in all patients, only age [OR 1.07, CI 1.03-1.11) and serum Ca [OR 1.7, CI 1.03–2.79] were significant factors. In women, multivariate analysis identified increasing age to be the only significant risk factor to predict risk of VFx. [OR 1.107, CI 1.03-1.12]. Conclusion Vertebral fractures (VFx) is more prevalent in comparison to wrist and hip fractures in patients with PHPT. Serum PTH is significantly higher in African American PHPT patients with VFx. Increasing age and serum calcium ≥11.1 mg/dL are significant predictors of VFx in PHPT patients. Presentation: Saturday, June 11, 2022 12:42 p.m. - 12:47 p.m., Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP102 Indicators for the effects of calcimimetics on hypercalcemia in the elderly patients with primary hyperparathyroidism.

Abstract Primary hyperparathyroidism (PHPT) is the most common disorder causing hypercalcemia, in which parathyroid hormone (PTH) is excessively secreted from a parathyroid tumor. PHPT occurs mainly in elderly women, and patient with PHPT present symptoms including nephrolithiasis, bone fracture, and cognitive impairment or can be asymptomatic. Excessive secretion of PTH leads to elevated serum levels of alkaline phosphatase as well as calcium and decreased serum inorganic phosphate level. Parathyroid surgery is the only established treatment, and the treatment reduces elevated serum levels of calcium and PTH, increases bone mineral density, reduces the occurrence of bone fractures, and decreases the risk of renal stones. However, some PHPT patients, especially elderly patients, refuse to undergo surgical therapy for various reasons including perceived risk. Calcimimetic treatment, including cinacalcet and evocalcet administration, has also been reported to be effective for reducing serum calcium level in patients with PHPT. However, the relationship between the efficacy of calcimimetic treatment for PHPT and patient characteristics related to the effectiveness of calcimimetics remains to be elucidated. To investigate the relevance of clinical parameters to the effectiveness of calcimimetics for PHPT, we retrospectively analyzed patients with PHPT who received calcimimetic treatment in our department. We included nine patients including 8 females (88.9%) and one male (11.1%) in the study. The median age of the patients was 81 years (interquartile range (IQR): 61-86 years). Laboratory tests before calcimimetic treatment revealed that median level of serum corrected calcium (cCa) was high (11.1 (IQR: 10.5-12.7) mg/dL), serum inorganic phosphate was low (2.3 (2.3-2.4) mg/dL), and plasma intact PTH was high (251. 0 (198.3-498.5) pg/mL). The fractional excretion of calcium was higher than 1% (1.3% (1.12-1.48%)), %tubular reabsorption of phosphate was low (79.9% (77.1-83.9%)), nephrogenous cyclic adenosine monophosphate (cAMP) was high (3.4 (2.4-4. 0) nmoL/dL GF), and urinary cAMP was normal (4.3 (4. 0-5.3) μmoL/day). Median reduction rate of serum cCa level due to calcimimetic treatment was 5.8% (0-13.4%) at the first follow-up (median treatment duration: 22 (20-29) days). Notably, reduction rate of serum cCa level had significant correlations with age (R=0.95), dual energy X-ray absorptiometry % young adult mean (DEXA %YAM) in the femoral neck (R=-0.92), and urinary cAMP level (R=-0.85). Thus, the present study suggested that elevated serum cCa levels may be reduced by treatment with calcimimetics more effectively in PHPT patients of relatively advanced age, patients with low DEXA %YAM, and patients with low urinary cAMP. Presentation: No date and time listed

Parathyroidectomy for Normocalcemic Primary Hyperparathyroidism is Associated with Improved Bone Mineral Density Regardless of Postoperative Parathyroid Hormone Levels.

Biochemical cure in normocalcemic primary hyperparathyroidism (nPHPT) is defined as parathyroid hormone (PTH) level normalization 6 months after parathyroidectomy. However, recent studies show that a significant number of nPHPT patients have persistent PTH elevation postoperatively. We sought to correlate changes in PTH levels with skeletal outcomes after parathyroidectomy in nPHPT patients. Adult patients who underwent parathyroidectomy at a tertiary referral center for sporadic PHPT between 2010 and 2020 were reviewed. Pre- and postoperative (6 months, 18 months, and last follow-up) laboratory and bone mineral densities (BMD) were recorded. Primary outcome was 18-month postoperative BMD change in the lumbar spine (LS), total hip (TH) and femoral neck (FN) in normocalcemic and hypercalcemic PHPT (hPHPT) patients. Of 661 patients included, 68 had nPHPT. nPHPT patients frequently had multigland disease (31% vs. 18%, p = 0.014), more bilateral cervical explorations (22% vs. 13%, p = 0.042), and fewer achieved biochemical cure (76% vs. 95%, p < 0.001) than hPHPT patients. Twenty-eight nPHPT patients had BMD data for comparison. Overall, nPHPT patients had improvement in the LS (1.84%, p = 0.002) and TH (1.64%, p = 0.014). When stratified by postoperative PTH levels, nPHPT patients with persistent PTH elevation had more BMD improvement at the TH than those who normalized PTH (3.73% vs. - 0.83%, p = 0.017). There was no difference in improvement at the LS or FN (p = NS). Parathyroidectomy is associated with improved BMD in nPHPT patients with bone disease. Although one in four nPHPT patients had elevated postoperative PTH levels persisting throughout the study, BMD improvement was still seen regardless of postoperative PTH level normalization.

461 A Retrospective Audit of the Success Rate and Complications of Parathyroidectomy in Primary Hyperparathyroidism

Abstract Aim Primary hyperparathyroidism (pHPT) is a clinical disorder which presents with hypercalcaemia. The definitive management for such cases is a Parathyroidectomy. Few centres have reported their success rate for this procedure. We conducted a retrospective review to compare the success rate and complications in Parathyroidectomy at our centre. Method After approval from the ethical committee, data was collected from the case files of the patients. Inclusion criteria was a Parathyroidectomy performed for pHPT between 2013 and 2020 at our institute. The Data included the demographics with pre- and post-operative Calcium / Parathyroid hormone levels to calculate the success rate. The procedure was defined as successful if the calcium levels returned to normal ranges (&amp;lt;2.6 mmol/L) according to NICE guidelines. Results 246 pHPT patients with a mean age of 61 years were included. 222 patients (90.24%) had their calcium level return to normal indicating a successful procedure. 24 cases (9.75%) had persistence or recurrence of hypercalcaemia indicating a failure of the surgery. The rate of success was significantly higher (96.84%) in the last 2 years (2019 – 2020) of the audit suggesting an improvement in outcomes. Five patients (2.03%) out of the 246 had complications related to the surgery. Two patients reported post-operative cord paresis, two had a post-operative neck haematoma and one experienced hypocalcaemia from hungry bone syndrome. Conclusions The surgical outcomes especially in the last 2 years are comparable to other specialized centres mentioned in the review. This Audit helps us demonstrate the improvement in the surgical results over the years at our centre.

Primary hyperparathyroidism after radioactive iodine therapy: Is it a distinct clinical entity?

BackgroundRadioactive iodine (RAI) treatment is considered a rare cause of primary hyperparathyroidism (pHPT). MethodA multi-institutional retrospective review of patients with pHPT who underwent parathyroidectomy from 1990 to 2020 was completed to evaluate the prevalence and latency time for development of RAI-associated pHPT and determine clinical differences in pHPT patients with or without prior RAI treatment. Results1929 patients with sporadic pHPT underwent parathyroidectomy; 48 (2.5%) had prior RAI treatment and 1881 (97.5%) did not. RAI treatment was for thyrotoxicosis in 43 (90%) patients. Average latency was 24 years (3–59 years) and inversely correlated with age. Patients with prior RAI treatment had lower preoperative calcium and PTH levels (p < 0.0001). No significant differences were observed in age, symptoms, pathology, ectopic glands and cure rate. ConclusionRAI is a potential causative factor for pHPT, accounting for 2.5% of sporadic pHPT. RAI-associated pHPT may be a less severe form of sporadic pHPT and latency inversely correlates with age.

Association of Famine Exposure on the Changing Clinical Phenotypes of Primary Hyperparathyroidism in 20 years

Background & AimsPrimary hyperparathyroidism(PHPT) has been evolving into a milder asymptomatic disease. No study has assessed the association between famine exposure and such a shift. We aim to explore the effects of China’s Great Famine exposure on the changing pattern of PHPT phenotypes.Methods750 PHPT patients diagnosed from 2000 to 2019 were studied. The clinical presentations were compared between them in recent 10 years (2010-2019) and previous 10 years (2000-2009). Participants were then categorized into fetal, childhood, adolescent, adult exposure, and unexposed groups. Logistic regression was used to estimate the odds ratios (ORs) and confidence intervals (CIs) of famine exposure as factors contributing to the changes in the clinical presentations of PHPT.ResultsSerum levels of PTH, albumin-corrected Ca, tumor size, eGFR, BMDs (all P<0.001), and clinical symptoms became milder in recent 10 years. Famine exposure (72.6% vs 58.4%, P<0.001), especially the adult exposure (18.8% vs 4.1%, P<0.001)was significant less in recent 10 years. The ORs (95%CIs) of having upper 3rd tertile PTH were 2.79(1.34,5.8), 2.07(1.04,4.11), 3.10(1.15,8.38) and 8.85(2.56,30.56) for patients with fetal, childhood, adolescent and adult famine exposure, respectively. The ORs (95%CIs) of upper 3rd tertile albumin-corrected Ca and upper 3rd tertile of tumor size was 4.78(1.39, 16.38) and 4.07(1.12,14.84) for participants with adult famine exposure, respectively. All these associations were independent of age, sex, disease duration and other confounders.ConclusionsThe clinical manifestations of PHPT in China continue to be milder. Exposure to famine is associated with PHPT. Less famine exposure might be responsible for the mile form of PHPT in recent years.

Vitamin D deficiency is associated with single gland parathyroid disease

BackgroundPrimary hyperparathyroidism (PHPT) with low preoperative vitamin D levels is thought to be related to 4-gland hyperplasia. We reviewed final parathyroid pathology in relationship to preoperative vitamin D levels. MethodsA retrospective review was performed for all PHPT patients undergoing parathyroidectomy from 2001 to 2019. Patient demographics, laboratory studies, and final pathology were reviewed. Results2230 patients were included in the analysis, 78.1% were female with a mean age of 59 years. Patients were stratified into 3 groups based on their preoperative 25-hydroxy vitamin D levels; “deficient” (<20 ng/mL) (n = 319), “insufficient” (20–30 ng/mL) (n = 1108), or “sufficient” (>30 ng/mL) (n = 803). Patients with deficient vitamin D had a higher frequency of single adenoma (71%) compared to sufficient vitamin D patients (62%) (p < 0.001) and fewer hyperplastic glands (19%) compared to sufficient vitamin D level patients (25%) (p < 0.001). ConclusionsVitamin D deficiency is more strongly associated with single-gland parathyroid disease than 4-gland hyperplasia. Further investigation into the complex interplay between vitamin D levels and autonomous parathyroid function is warranted.

Neuropsychiatric Comorbidity in Primary Hyperparathyroidism Before and After Parathyroidectomy: A Population Study

BackgroundPrimary hyperparathyroidism (PHPT) is often accompanied by neuropsychiatric symptoms. This study aimed to map out psychiatric comorbidity as reflected by medical treatment for psychiatric symptoms.MethodsA retrospective case–control analysis and a prospective cohort analysis of psychotropic drug utilization before and after PTX. A total of 8279 PHPT patients treated with parathyroidectomy in Sweden between July 1, 2008 and December 31, 2017 compared to a matched control cohort from the total population (n = 82,790). Information on filled prescriptions was collected from the Swedish Prescribed Drug Register (SDR). Socioeconomic data and diagnoses were added by linkage to national patient and population registers. Regression analyses were used to calculate relative drug utilization (OR) within 3 years prior to PTX and relative incidence of drug treatment (RR) within 3 years postoperatively.ResultsUtilization of antidepressant, anxiolytic and sleep medication was more comprehensive in PHPT patients compared with the controls prior to PTX. The most common were benzodiazepines [OR 1.40 (95% CI: 1.31–1.50)] and selective serotonin reuptake inhibitors [SSRI; OR 1.38 (95% CI: 1.30–1.47)]. Postoperatively, the excess prescription rate for anxiolytic benzodiazepines decreased within three years from a 30 to 19% excess and for benzodiazepines for sleep from 31 to 14%. No corresponding decrease in excess prescription rate was observed for SSRI.ConclusionPHPT is associated with increased utilization of antidepressive medications and benzodiazepines before PTX. This study implies that psychiatric symptoms should be considered in PHPT patients and continuous medication should be reevaluated after PTX.

Native thiol decreases in patients with asymptomatic primary hyperparathyroidism, especially in the presence of surgery indication.

Oxidative stress increases in many systemic and endocrine diseases. The effect of increased parathyroid hormone levels (PTH) and the effects of this hormone on oxidative stress in patients with primary hyperparathyroidism (pHPT) is unknown. We aimed to investigate the change of Thiol-disulfide (SH-SS), one of the oxidative stress parameters, in patients diagnosed with pHPT and the usability of this parameter in patients with pHPT. Forty-six patients who recently diagnosed with asymptomatic pHPT and 40 healthy controls were included in this prospective study. In addition to routine examinations for pHPT, serum SH-SS measurements were recorded. The pHPT patients included in the study were divided into two groups as patients with and without surgical treatment indication. It was observed that the pHPT group had lower total SH and native SH values and higher SS values compared to the control group (P<0.05 for each). Native SH values were found to be lower in pHPT patients who were indicated for surgical treatment compared to those who did not (P<0.05). An independent relationship was found between Native SH and serum calcium, urine calcium and T scores in DEXA level in asymptomatic pHPT patients with surgical treatment indication (P<0.05). In our study, native SH level decreases in patients with pHPT, especially in patients with surgical treatment indication for pHPT. The decrease in SH levels, which is a natural antioxidant that protects the body against oxidative stress, and the increase in SS levels in pHPT patients may be another metabolic effect of this disease. Native SH may be helpful in determining the indication for surgical treatment in asymptomatic pHPT patients.

The effect of parathyroidectomy compared to non-surgical surveillance on kidney function in primary hyperparathyroidism: a nationwide historic cohort study

BackgroundPatients with primary hyperparathyroidism (pHPT) and impaired kidney function (estimated glomerular filtration rate (eGFR) < 60 mL/min) are offered parathyroidectomy (PTX) to protect them from further complications. Surprisingly, two recent uncontrolled cohort studies have suggested a further decrease in kidney function following PTX. We aimed to examine the effects of PTX compared to non-surgical surveillance on kidney function in pHPT patients.MethodsHistoric cohort study. From the Danish National Patient Registry (NPR) and major medical biochemistry laboratories in Denmark, we identified 3585 patients with biochemically confirmed pHPT among whom n = 1977 (55%) were treated with PTX (PTX-group) whereas n = 1608 (45%) were followed without surgery (non-PTX group). Baseline was defined as time of diagnosis and kidney function was re-assessed 9–15 months after PTX (PTX group) or 9–15 months after diagnosis (non-PTX group).ResultsAt follow-up, eGFR had decreased significantly in the PTX- compared to the non-PTX-group (median − 4% vs. − 1%, p < 0.01). Stratification by baseline eGFR showed that the decrease was significant for those with a baseline eGFR value of 80–89 and > 90 mL/min, but not for those with lower eGFR values. Findings did not differ between patients with mild compared to moderate/severe hypercalcemia. However, after mutual adjustments, we identified baseline levels of calcium, PTH, and eGFR as well as age and treatment (PTX vs. no-PTX) as independent predictors for changes in kidney function.ConclusionCompared to non-surgical surveillance, PTX is associated with a small but significant decrease in kidney function in pHPT patients with an initial normal kidney function.

Intrathyroidal Parathyroid Adenomas in Primary Hyperparathyroidism: Clinical and Imaging Findings.

ObjectivesPrimary hyperparathyroidism (PHPT) is a common endocrine disease. Ectopic adenomas may cause a failed surgery which results in persistence or recurrence. Intrathyroidal parathyroid adenoma (ITPA) is a rare reason for PHPT and site of ectopia. Herein, we aimed to investigate the clinical and imaging features of patients with ITPAs and the effectiveness of radiological tools for localization at a tertiary reference center.MethodsThe files of 708 consecutive patients who underwent parathyroidectomy for PHPT in our department between January 2007 and December 2021 were investigated retrospectively. PHPT patients with ITPA were included in the study. Patients with missing data were excluded from the study. Clinicopathological features of the patients and radiological evaluation findings were investigated.ResultsTwenty-eight (28/708: 3.9%) patients were included in the study. The complete intrathyroidal gland and subcapsular parathyroid gland were observed in 8 (1.1%) and 20 (2.8%) patients, respectively. The ultrasound and parathyroid scintigraphy revealed the accurate localization of ITPA in 25 (89.3%) and 18 (64.3%) patients, respectively. Additional imaging modalities were applied for 10 patients in which conventional localization studies were discordant or inconclusive. ITPAs were most commonly found in the lower gland (n=20) localization. All patients had a successful parathyroidectomy and neither persistence nor recurrence was occurred in the study group.ConclusionThe ITPAs are rare in PHPT. The ultrasound has a high diagnostic rate in experienced hands. The second-line imaging methods may be favorable in the presence of negative or discordant scans. The pre-operative localization studies can detect the ITPAs in most patients, so blind thyroidectomy should be avoided.

Perioperative changes of FGF23 in patients undergoing surgery for primary hyperparathyroidism

BackgroundFibroblast growth factor 23 (FGF23) is a key regulator of urine phosphate excretion. The aim of the study was to investigate the perioperative (intraoperative and postoperative) changes of plasma intact and C-terminal FGF23 (iFGF23, cFGF23) concentrations in patients with primary hyperparathyroidism (pHPT) submitted to surgery.Materials and methodsThe study involved 38 adult patients with pHPT caused by adenoma. Parathyroid hormone (PTH) levels were investigated intraoperatively (just before the incision and 10 min after adenoma excision). cFGF23, iFGF23, phosphate, estimated glomerular filtration rate (eGFR), and procollagen type 1 N-terminal propetide (P1NP) were measured intraoperatively and postoperatively (next day after the surgery).ResultsPTH levels decreased intraoperatively (13.10 pmol/L vs 4.17 pmol/L, P< 0.0001). FGF23 levels measured intraoperatively were at the upper level of reference interval. cFGF23 decreased postoperatively compared with the values measured just before the incision (cFGF23: 89.17 RU/mL vs 22.23 RU/mL, P< 0.0001). iFGF23 decreased as well, but the postoperative values were low. Postoperative inorganic phosphate values increased (1.03 mmol/L vs 0.8 mmol/L, P= 0.0025). We proved significant negative correlation of perioperative FGF23 with inorganic phosphate (cFGF23: Spearman’s r = −0.253, P= 0.0065; iFGF23: Spearman’s r = −0.245, P= 0.0085). We also found that FGF23 values just before incision correlated with eGFR (cystatin C) (cFGF23: Spearman’s r = −0.499, P= 0.0014; iFGF23: Spearman’s r = −0.413, P= 0.01).ConclusionIntraoperative iFGF23 and cFGF23 did not change despite PTH decreased significantly. cFGF23 and iFGF23 significantly decreased 1 day after parathyroidectomy and are associated with increase of inorganic phosphate in pHPT patients. cFGF23 and iFGF23 just before incision correlated with eGFR (cystatin C). Similar results found in both iFGF23 and cFGF23 suggest that each could substitute the other.

Primary Hyperparathyroidism Is Associated With Shorter QTc Intervals, but Not Arrhythmia.

Primary hyperparathyroidism (PHPT) is associated with subclinical cardiovascular disease, but data regarding cardiac conduction abnormalities are limited. Retrospective cross-sectional comparison of cardiac conduction in patients with PHPT or thyroid disease (TD). Patients ≥40 years old who underwent parathyroidectomy or thyroidectomy at a single tertiary institution from 2013 to 2018. Demographics and preoperative electrocardiogram (EKG) parameters were compared using the Mann-Whitney U, chi-square test, and linear regression. A total of 1242 patients were included: 49.8% PHPT (n = 619) and 50.2% TD (n = 623). Median age was 60.5 years [interquartile range (IQR) 53.6-67.9]. Compared to controls, PHPT patients had higher median serum calcium [10.7 mg/dL (IQR 10.4-11.1) vs 9.5 mg/dL (IQR 9.3-9.8), P < 0.001] as expected, as well as, a higher prevalence of hyperlipidemia (49% vs 36%, P < 0.001) and hypertension (50.1% vs 42.2%, P < 0.01). Based on EKG, there was no difference in PR interval or the prevalence of arrhythmia, atrioventricular block, ST segment/T wave changes, premature ventricular complexes, right bundle branch block, or left bundle branch block after adjusting for covariates. The PHPT group had a lower mean corrected QT interval (414 ± 24) ms vs 422 ± 24 ms, P < 0.01), adjusted for covariates. Serum calcium predicted QTc independently of age, sex, and other covariates. In the largest study to date, PHPT patients had shorter QTc intervals compared to TD controls but no increased prevalence of arrhythmia based on preoperative EKG.

Primary Hyperparathyroidism in Homozygous Sickle Cell Patients: A Hemolysis-Mediated Hypocalciuric Hypercalcemia Phenotype?

Primary hyperparathyroidism (pHPT) has been reported to have a higher prevalence in sickle cell disease (SCD) patients, including a high rate of recurrence following surgery. However, most patients are asymptomatic at the time of diagnosis, with surprisingly infrequent hypercalciuria, raising the issue of renal calcium handling in SCD patients. We conducted a retrospective study including (1) 64 hypercalcemic pHPT non-SCD patients; (2) 177 SCD patients, divided into two groups of 12 hypercalcemic pHPT and 165 non-pHPT; (3) eight patients with a diagnosis of familial hypocalciuric hypercalcemia (FHH). Demographic and biological parameters at the time of diagnosis were collected and compared between the different groups. Determinants of fasting fractional excretion of calcium (FeCa2+) were also analyzed in non-pHPT SCD patients. Compared to non-SCD pHPT patients, our data show a similar ionized calcium and PTH concentration, with a lower plasmatic calcitriol concentration and a lower daily urinary calcium excretion in pHPT SCD patients (p < 0.0001 in both cases). Fasting FeCa2+ is also surprisingly low in pHPT SCD patients, and thus inadequate to be considered hypercalcemia, recalling the FHH phenotype. FeCa2+ is also low in the non-pHPT SCD control group, and negatively associated with PTH and hemolytic biomarkers such as LDH and low hemoglobin. Our data suggest that the pHPT biochemical phenotype in SCD patients resembles the FHH phenotype, and the fasting FeCa2+ association with chronic hemolysis biomarkers strengthens the view of a potential pharmacological link between hemolytic by-products and calcium reabsorption, potentially through a decreased calcium-sensing receptor (CaSR) activity.

Dual-Time-Point 18F-Fluorocholine PET/CT Improves Characterization of Thyroid Nodules in Patients Referred for Primary Hyperparathyroidism: A Proof of Concept Study.

Thyroid nodules frequently coexist with primary hyperparathyroidism (pHPT). Because of the increasing use of 18F-fluorocholine (18F-FCH) PET/CT in patients with pHPT, evaluation of its clinical utility for thyroid nodules characterization in this population is of paramount importance. Herein, we investigate the value of dual-point 18F-FCH PET/CT in the diagnosis of thyroid cancer in patients referred for pHPT imaging who have thyroid nodules. All pHPT patients who underwent a dual-time point 18F-FCH PET/CT (at 5 and 60 minutes postinjection) between July 2019 and December 2020 were analyzed. Only those with a thyroid nodule greater than 10-mm and pathological analysis (criterion standard) were included. Nodule-to-thyroid SUVmax ratio was calculated at the 2 study points, as well as the 18F-FCH washout index (WO%). Twenty-seven patients (32 nodules) were included in this study. The final diagnoses were as follows: 27 benign nodules including 2 NIFTPs (noninvasive follicular thyroid neoplasm with papillary-like nuclear features) and 5 cancers of follicular origin. Early uptake ratio was significantly higher in malignant lesions than in benign nodules (P = 0.0008). Thyroid cancers were also characterized by a marked 18F-FCH washout index (WO% benign vs cancer: 2.9% ± 4.1% vs 45.5% ± 13.4%, P = 0.0001). Using a WO% threshold of 22.1%, 25/27 benign nodules and 5/5 malignant lesions were accurately classified (sensitivity of 100%, specificity of 92.6%, positive predictive value of 71.4%, and negative predictive value of 100%). The false-positive findings were related to the 2 NIFTPs that share similarities with thyroid cancer. Our preliminary results suggest to perform a dual-time-point PET/CT acquisition protocol in pHPT patients with uncharacterized centimeter thyroid nodules. However, the real impact of these promising results should be assessed by prospective studies on a larger cohort of patients.

DXA-Based Bone Strain Index: A New Tool to Evaluate Bone Quality in Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is associated with impaired bone quality and increased fracture risk. Reliable tools for the evaluation of bone quality parameters are not yet clinically available. Bone Strain Index (BSI) is a new metric for bone strength based on Finite Element Analysis from lumbar spine and femoral neck dual-energy x-ray absorptiometry (DXA) images. To assess the lumbar spine (LS), femoral neck (FN), and total hip (TH) BSI in PHPT patients compared with controls and to investigate the association of BSI with vertebral fractures (VFs) in PHPT. This case-control study enrolled 50 PHPT patients and 100 age- and sex-matched control subjects from an outpatient clinic. The main outcome measures were LS-BSI, FN-BSI, and TH-BSI. FN bone mineral density (BMD) and one-third distal radius BMD were lower in the PHPT group than in controls (FN 0.633 ± 0.112 vs 0.666 ± 0.081, P = 0.042; radius 0.566 ± 0.07 vs 0.625 ± 0.06, P < 0.001). PHPT group has significant lower TBS score compared with controls (1.24 ± 0.09 vs 1.30 ± 0.10, P < 0.001). BSI was significantly higher at LS (2.28 ± 0.59 vs 2.02 ± 0.43, P = 0.009), FN (1.72 ± 0.41 vs 1.49 ± 0.35, P = 0.001), and TH (1.51 ± 0.33 vs 1.36 ± 0.25, P = 0.002) in PHPT. LS-BSI showed moderate accuracy for discriminating VFs (AUC 0.667; 95% CI, 0.513-0.820). LS-BSI ≥ 2.2 and was a statistically significant independent predictor of VFs, with an adjusted odds ratio ranging from 5.7 to 15.1. BSI, a DXA-derived bone quality index, is impaired in PHPT and may help to identify PHPT subjects at high risk of fractures.

Diabetes and Bone Involvement in Primary Hyperparathyroidism: Literature Review and Our Personal Experience.

BackgroundPrimary hyperparathyroidism (PHPT) and type 2 diabetes mellitus (T2DM) are common endocrine disorders impacting on skeletal health, whose concomitant occurrence is becoming more frequent.Patients and MethodsWe searched the PubMed database from the National Library of Medicine about the relationship between T2DM and its treatment and bone manifestations of PHPT. Thereafter, we retrospectively evaluated a consecutive series of 472 PHPT patients. Among them 55 were also affected by T2DM. At the diagnosis of PHPT we compared bone turnover markers and bone densitometry between 55 patients with and 417 without T2DM and in the former group according to antidiabetic treatment.ResultsFew data are available about T2DM and PHPT bone involvement, studies about T2DM treatments and PHPT bone manifestations are lacking. Among patients with PHPT of our series, those with T2DM were older, had a lower prevalence of osteitis fibrosa cystica, higher lumbar and femoral T-scores than the remaining patients. No difference was disclosed among the diabetic patients according to ongoing antidiabetic treatment, even though modern treatments were under-represented.ConclusionsNo clinical study specifically evaluated the impact of T2DM on bone involvement in PHPT. In our experience, diabetic patients resulted more frequently “mild asymptomatic” than non-diabetic patients and showed a lower prevalence of radiological PHPT bone manifestations. The treatment of T2DM does not seem to affect the biochemical or clinical features of PHPT in our series. Further studies are needed to fully disclose the influence of T2DM and antidiabetic treatment on bone health in patients with PHPT.

Minimally invasive video-assisted parathyroidectomy (MIVAP) without intraoperative PTH determination.

Minimally invasive video-assisted parathyroidectomy (MIVAP) has become a standard approach to primary hyperparathyroidism (pHPT) since described. Although intraoperative parathyroid hormone assay (IOPTH) has been generalized as a complementary technique to MIVAP, its actual impact on the surgical success of this technique is not without controversy. The aim of this study was to describe our results in the management of pHPT with successful preoperative localization, by MIVAP technique, without IOPTH determination, confirming in a larger series our preliminary results. A retrospective descriptive study was conducted in pHPT patients treated by MIVAP with no IOPTH determination in a tertiary hospital between 2007 and 2019. A total of 167 patients were included in the study. Biochemical cure was achieved in 96.4%, and 94.1% did not present any surgical complication. The mean duration of surgery was 61min, and the mean length of hospital stay was 1.8days CONCLUSIONS: In case of positive preoperative localization studies, MIVAP is a safe and effective technique for the surgical treatment of pHPT due to a parathyroid adenoma, regardless of IOPTH determination, with a success rate > 95% and a low complication rate.

A study on the causes of operative failures after microwave ablation for primary hyperparathyroidism

ObjectiveTo summarize the occurrence of operative failures after microwave ablation (MWA) in patients with primary hyperparathyroidism (pHPT), analyze the possible reasons, and explore strategies for preventing and managing these situations.MethodsThis retrospective study reviewed 91 pHPT patients who underwent MWA from April 2015 to November 2019. A cure was defined as the reestablishment of normal calcium homeostasis lasting a minimum of 6 months. An operative failure was defined as a failure to normalize serum intact parathyroid hormone (iPTH) and/or calcium levels at 6 months or longer. Patients who encountered operative failures were compared with patients who were successfully cured.ResultsEighty-eight pHPT patients, consisting of 29 men and 59 women, were finally enrolled. The median follow-up duration was 15.9 months (IQR, 6.1–31.5 months). Seventy-eight patients (78/88, 88.6%) were cured. Ten (10/88, 11.4%) patients experienced operative failure, including 9 persistent pHPT (10.2%) and 1 (1.1%) recurrent pHPT. Small parathyroid nodules (maximum diameter < 0.6 cm) and incomplete ablation were the two key factors leading to operative failure. Of the 9 patients with a maximum nodule diameter less than 0.6 cm, 77.8% (7/9) of them encountered operative failure.ConclusionOperative failure occurred in 11.4% of the pHPT patients who underwent MWA. The possibility of operative failure was increased when the maximum diameter of parathyroid nodule was less than 0.6 cm. Complete ablation could help avoid operative failure.Key Points• Failed to ablate the target lesion and incomplete ablation were the key factors attributed to operative failures.• When the maximum diameter of the parathyroid nodules is less than 0.6 cm, the possibility of operative failure was higher.

Clinical Characteristics of Primary Hyperparathyroidism: 15-Year Experience of 457 Patients in a Single Center in China.

ObjectivePrimary hyperparathyroidism (PHPT) is a common endocrine disorder of calcium metabolism. However, data concerning a large cohort of PHPT patients in the Chinese population are scarce. Thus, the objective of this study was to determine the general clinical signatures of 457 Chinese PHPT patients and explore the clinical characteristic differences between benign and malignant PHPT.MethodsA single-center retrospective study was designed. Medical records between preoperation and postoperative follow-up, were assessed and statistical analysis of the clinical data was performed.ResultsPatients with PHPT aged 12–87 years, with a mean onset age of 56.16 ± 14.60 years, were included. Most patients (68.7%) in our center had symptomatic patterns described as bone pain (74.8%), urolithiasis (25.5%), fatigue (17.5%), and pathological fracture (13.1%), but an increasing tendency has been established in the proportion of patients with asymptomatic forms. Correlation analysis revealed that patients with higher serum levels of parathyroid hormone (PTH) and calcium presented higher serum levels of bone turnover markers (BTMs) and lower 25-hydroxy-vitamin D (25OHD) values (P<0.001). Gains in bone mineral density (BMD) at L1–4, the femoral neck and the total hip were observed 1–2 years after parathyroidectomy (9.6, 5.9, and 6.8%). Parathyroid carcinoma patients presented prominently higher serum PTH and calcium levels and BTMs and lower BMD at femoral neck and total hip than benign PHPT patients (P<0.05), while no significant differences in age, sex, and serum 25OHD concentration were observed between benign and malignant PHPT patients.ConclusionsPHPT should be paid attention to in the patients with bone pain. While, BMD and BTMs can differentiate parathyroid carcinoma from parathyroid adenoma and hyperplasia to some extent. In addition, anti-osteoporosis drugs could be used when necessary to avoid hip fractures in patients with parathyroid carcinoma.