Primary Hyperparathyroidism Group Research Articles

6990 Vitamin D Supplementation in Primary Hyperparathyroidism: Effects on 1,25(OH)Vitamin D and FGF23 Levels

Abstract Disclosure: S.G. Pallone: None. M. Ohe: None. L.D. Santos: None. I.O. Nakaguma: None. I.S. Kunii: None. R.E. Silva: None. S.S. Maeda: None. C.M. Brandao: None. J.G. Vieira: None. M. Lazaretti-Castro: None. Background: Primary hyperparathyroidism (PHPT) is a condition characterized by high levels of PTH in the presence of hypercalcemia. Vitamin D deficiency has been associated with more severe presentations. Our aim was to evaluate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with PHPT compared to controls without PHPT. Materials and methods: Individuals with and without PHPT received 14,000 IU/week of oral vitamin D3 for 12 weeks. At baseline and endpoint, blood samples were collected to measure 1,25(OH)2 vitamin D (1,25(OH)2D), intact Fibroblast Growth Factor 23 (FGF23), 25-hydroxyvitamin D (25OHD), Parathormon (PTH), total calcium (tCa), phosphorus and other biochemical markers. The intact FGF23 was measured using an automated Diasorin LIAISON kit. The 1,25(OH)2D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS). Results: 70 PHPT patients and 75 healthy individuals (CTRL) were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. At baseline, tCa, PTH, 1,25(OH)2D, and intact FGF23 concentrations were significantly higher in PHTP, with no difference in 25OHD levels. After the intervention, the 25OHD levels increased significantly in both groups (PHPT: 22.6.9±6.1 to 31.5±6.8; CTRL: 20.3±5.7 to 32.5±6.4 ng/mL, p<0.001). There was significative increase in intact FGF23 levels in both groups (PHPT: 47.9±27.1 to 76.3±33.3; CTRL: 40.5±13.9 to 59.8±19.8 pg/mL, p<0.001). After the vitamin D replacement, the tubular reabsorption of phosphate (TRP) was significantly reduced in both groups (PHPT: 85.0±7.4% to 83.6±7.75% CTRL: 89.5±4.5% to 88.7±4.8%, p=0.031), without changes in serum phosphorus levels, possibly indicating phosphaturic response to the intervention. Moreover, this decrease of TRP was positively correlated to the increment of FGF23 in the PHPT group. A paradoxical decrease in 1,25(OH)2D levels after vitamin D supplementation was observed in both groups (PHPT: 94.8±34.6 to 68.9±25.3; CTRL: 68.7±23.5 to 56.4±20.7 pg/mL, p<0.001). The reduction of 1,25(OH) 2 D was inversely correlated with the elevation of FGF23 in both groups (r=-0.302, p=0.028). In both groups, no changes in tCa were observed (PHPT: from 11.02±0.9 to 11.1±0.8; CTRL: 9.6±0.3 to 9.6±0.3 pg/mL, p=0.153), as the same for urinary calcium (p=0.534) and PTH measurements (p=0.516). Conclusion: The weekly administration of 14,000 IU of Vitamin D3 was safe and the increase in 25OHD after supplementation did not change the serum or urinary calcium levels in adults with and without PHPT. In both groups, it was observed a paradoxical decrease in 1,25(OH)2D levels after supplementation, which was associated with significant increase in intact FGF23 levels. This effect can maybe explain the safety response on calcium levels in face of vitamin D supplementation among PHPT patients. Presentation: 6/2/2024

Fertility and pregnancy outcomes in primary hyperparathyroidism: Observations from a large insured population.

Primary hyperparathyroidism (PHPT) has initially been implicated in adverse maternal and neonatal outcomes, while subsequent population studies have failed to show an association. To compare maternal, pregnancy, and neonatal outcomes in patients with and without PHPT. Retrospective matched-cohort study (2005-2020). An integrated healthcare delivery system in Southern California. Women aged 18-44 years were included. Patients with biochemical diagnosis of PHPT were matched 1:3 with eucalcemic controls (non-PHPT). Achievement of pregnancy, pregnancy outcomes (including rates of abortion, maternal complications), and neonatal outcomes (including hypocalcemia, need for intensive care). The cohort comprised 386 women with PHPT and 1158 age-matched controls. Pregnancy rates between PHPT and control groups were similar (10.6% vs 12.8%). The adjusted rate ratio of pregnancy was 0.89 (95% CI: 0.64-1.24) (PHPT vs non-PHPT). Twenty-nine pregnancies occurred in women with co-existing PHPT and 191 pregnancies occurred in controls, resulting in 23 (79.3%) and 168 (88.0%) live births, respectively (p=0.023). Neonatal outcomes were similar. Live birth rates were similar (86.4%, 80%, 79.2%) for those undergoing parathyroidectomy prior (n=22), during (n=5), or after pregnancy/never (n=24). Among patients who underwent parathyroidectomy during pregnancy, no spontaneous abortions occurred in women entering pregnancy with peak calcium <11.5 mg/dL [2.9 mmol/L]. We observed no difference in pregnancy rates between women with or without PHPT. Performing parathyroidectomy before pregnancy or during the second trimester appears to be a safe and successful strategy, and adherence to this strategy may be most critical for patients with higher calcium levels (≥11.5 mg/dL [2.9 mmol/L]).

Relationship between gut microbiome and bone deficits in primary hyperparathyroidism: A proof-of-concept pilot study.

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age-sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and 1 month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversities were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of Subdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium, and Clostridium sensu stricto_1 were significantly lower in PHPT than in controls (p < 0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, and Ruminococcus and Alloprevotella increased (p < 0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p < 0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto_1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy.

Unveiling the Hidden Stroke Threat in Patients With Atrial Fibrillation and Primary Hyperparathyroidism

Recent American College of Cardiology (ACC), American Heart Association (AHA), American College of Clinical Pharmacy (ACCP), and Heart Rhythm Society (HRS) guidelines suggest that patients with atrial fibrillation (AF) at intermediate to low annual risk of ischemic stroke can benefit from consideration of factors that might modify their risk of stroke. The role of nontraditional risk factors, such as primary hyperparathyroidism (PHPT), remains unexplored. In our study, we investigated the potential association between PHPT and the risk of ischemic stroke in patients with AF. Using data from the Nationwide Inpatient Sample Database, a retrospective cohort study focused on the adult population with AF, we stratified the participants based on PHPT presence. Demographic information, co-morbidities, and hospitalization details were extracted using International Classification of Diseases, Tenth revision codes. Propensity score matching was applied, encompassing over 20 confounding variables, including the risk factors outlined in the CHA2DS2-VASc (Congestive heart failure (C), Hypertension (H), Age ≥75 years (A₂), Diabetes Mellitus (D), Stroke/Transient Ischemic Attack (TIA)/Thromboembolism (S₂), Vascular disease (V), Age 65-74 years (A), Sex category [female] (Sc)) score. Multivariate logistic regression analysis was performed after matching to assess the independent impact of PHPT as an ischemic stroke risk factor. A total of 2,051 of the identified 395,249 patients with AF had PHPT. The PHPT group had an average age of 74 years and consisted of more women (66.1% vs 53.0%). After matching, it was observed that the PHPT group had longer hospital stays (5 vs 4 days) and higher hospitalization charges ($45,126 vs $36,644). This group exhibited higher rates of ischemic stroke (6.0% vs 4.4%) and mortality (6.3% vs 4.9%). The adjusted outcomes showed a 1.4-fold increased risk for ischemic stroke and a 1.32-fold increased risk for mortality in the PHPT cohort. The subgroup analysis showed a higher incidence of mortality in men with a high CHA2DS2-VASc score. In conclusion, this study highlights a marked association between PHPT and ischemic stroke in patients with AF, independent of the conventional CHA2DS2-VASc score. The potential mechanisms implicated include vascular changes, cardiac dysfunction, and coagulation cascade alterations. The presence of PHPT should be taken into consideration when deciding the assessment of thromboembolic risk.

Increased Prevalence of Autoimmune Rheumatologic Diseases in Patients With Primary Hyperparathyroidism.

Background Parathyroid hormone (PTH) and Dickkopf-related protein 1 (DKK-1) have been mentioned together at the intersection of autoimmune rheumatologic diseases (ARDs) and osteoimmunology. However, few studies have evaluated the association between primary hyperparathyroidism (PHPT) and ARDs. Methodology This retrospective study included 225 PHPT patients and 386 patients with thyroid nodules as a control group. The electronic hospital records of all patients were screened going back nine years for the presence of ARDs. Patients who were diagnosed at least three months ago, had complete serologic tests, and were continuing with rheumatologic follow-up were included. Results The prevalence of ARDs in the PHPT group was 9.77% (22/225), while the prevalence of ARDs in the CG was 1.04% (4/386, p < 0.001). The prevalence of rheumatoid arthritis in the PHPT group was 4.4% (10/225), ankylosing spondylitis 3.1% (7/225), systemic lupus erythematosus 0.88% (2/225), Behçet's disease 0.88% (2/225), and mixed connective tissue disease 0.44% (1/225). Of the 22 patients with ARDs, 21 (95.45%) were diagnosed before they were diagnosed with PHPT, and the median time from diagnosis with ARD to the onset of PHPT was 36 months (interquartile range = 61.5). Logistic regression analysis showed a positive correlation between the duration of PHPT and ARDs (odds ratio (OR) = 1.06; 95% confidence interval (CI) = 1.02-1.09, p < 0.001) and a negative correlation between ARDs and calcium levels (OR = 0.26; 95% CI = 0.09-0.79, p = 0.018). Conclusions The prevalence of ARDs increased in PHPT patients and PHPT accompanying ARDs developed after rheumatologic disease. ARDs with PHPT are cases with a prolonged duration of PHPT and mildly elevated calcium, probably preceded by parathyroid hyperplasia. Therefore, the factors that cause ARDs may trigger a process that leads to mild PHPT.

Efficacy and safety of radiofrequency ablation for primary and secondary hyperparathyroidism: a retrospective study

There is now growing interest in the use of Ultrasound-guided radiofrequency ablation (RFA) to treat hyperparathyroidism. But the efficacy and limitations of this treatment have not been described in sufficient detail. Assessing and contrasting the effectiveness and safety of RFA in treating primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT). This retrospective study included 57 HPT patients (48 for PHPT and 9 for SHPT) who underwent RFA between January 2017 and April 2021. The serum intact parathyroid hormone (iPTH) and calcium, hyperplastic parathyroid volume, volume reduction rate (VRR) before and after RFA, clinical success rate, symptoms, and complications were analyzed and compared. In SHPT group, bone pain (7/9, 77.8%), skin pruritus (4/9, 44.4%), and multiple hyperplastic parathyroid glands (4/9, 44.4%) were more common compared to the PHPT group. After 12 months of follow-up, the serum iPTH, calcium, and the volume of PHPT and SHPT groups had decreased by more than 60%, 10%, and 90%, respectively (P < 0.05). In the VRR, 13 glands of SHPT (72.2%) and 42 glands of PHPT (87.5%) had achieved the clinical success. In addition, the preoperative and postoperative serum iPTH were higher in the SHPT group than in the PHPT group (P < 0.05). In terms of the serum iPTH and calcium, the PHPT group had substantially higher rates of clinical success, with 42 patients (87.5%) and 46 patients (95.8%) meeting the criteria, respectively compared to 3 patients (33.3%) and 6 patients (66.7%) of SHPT group (P < 0.05). After RFA, the clinical symptoms improved in both groups. The overall incidence of complications (hoarseness and postoperative hematoma) of RFA in the two groups was 10.5% (6/57), and hoarseness (3/9, 33.3%) of SHPT group was more common than PHPT group. All the complications were resolved spontaneously within 12 months after symptomatic treatments. In the treatment of PHPT and SHPT, ultrasound-guided RFA is both successful and safe. PHPT patients have better results in restoring normal iPTH by RFA, and have no considerable difference with the SHPT patients in terms of serum calcium, the volume of the ablation area, and the VRR.

Potential indicators for hyperparathyroidism progression: Calcium, phosphorus, alkaline phosphatase, 25 hydroxyvitamin D and hemoglobin

Purpose: To compare the differences in perioperative biochemical indices between patients with primary hyperparathyroidism (PH) and secondary hyperparathyroidism (SH).&#x0D; Methods: One hundred and ten patients with hyperparathyroidism who were treated in The Affiliated Hospital of Chengde Medical University, from June 2016 to April 2021, were enrolled and divided into two groups, viz, PH group (50 patients) and SH group (60 patients). Automatic biochemical analyzer was used to determine the levels of calcium, phosphorus, alkaline phosphatase and 25-hydroxyvitamin D, while hemoglobin was determined by liquid chromatography coupled with tandem mass spectrometry in the perioperative period.&#x0D; Results: Compared to PH group, SH group had higher levels of indicators (p &lt; 0.05). There were significant differences in body mass index (BMI), somatic cell index and blood albumin in patients from 18 to 70 years (p &lt; 0.05). BMI and blood albumin increased significantly with age (p &lt; 0.05). The complication rate was higher in SH than PH group (p &lt; 0.05). The scores of pruritus and bone pain of patients after surgery were lower than those before the operation (p &lt; 0.05). Blood calcium levels increased significantly with age, while ALP and iPTH levels decreased significantly (p &lt; 0.05). SH group showed lower scores of physiological, emotional, social, and cognitive functions than PH group (p &lt; 0.05).&#x0D; Conclusion: Patients with PH and SH have differences in perioperative biochemical indicators. Furthermore, the levels of calcium, phosphorus, alkaline phosphatase, 25 hydroxyvitamin D, and hemoglobin may be used as indicators of disease progression, and this may facilitate the development of suitable therapeutic measures.

Denosumab for osteoporosis in patients with primary hyperparathyroidism and mild-to-moderate renal insufficiency.

We aimed to assess the efficacy and safety of denosumab in postmenopausal women with primary hyperparathyroidism (PHPT)-related osteoporosis and chronic kidney disease (CKD). Women over 50 years of age with PHPT or postmenopausal osteoporosis (PMO) were retrospectively recruited into this longitudinal study. These PHPT and PMO groups were further categorized into subgroups based on the presence of CKD (Glomerular filtration rate (GFR) < 60 mL/min/1.73 m2). All patients were given denosumab over 24 months due to verified osteoporosis. The primary outcomes were changes in bone mineral density (BMD) and serum calcium levels. 145 postmenopausal women median age 69 [63;77] were recruited and assigned to one of the subgroups: PHPT patients with CKD (n = 22), PHPT patients without CKD (n = 38), PMO patients with CKD (n = 17) and PMO patients without CKD (n = 68). Denosumab treatment significantly increased BMD in patients with PHPT-related osteoporosis and CKD: median T-score L1-L4 from -2.0 to -1.35 (p < 0.001), femur neck from -2.4 to -2.1 (p = 0.012), radius 33% from -3.2 to -3 (p < 0.05)) at 24 months. Changes in BMD were similar in all four studied groups compared to baseline. A marked decline in calcium was noted in the primary study group of PHPT with CKD (median ΔCa = -0.24 mmol/L p < 0.001), compared to PHPT without CKD (median ΔCa = -0.08 mmol/L p < 0.001) and PMO with or without CKD. Denosumab treatment was well-tolerated with no serious adverse events. Denosumab treatment was similarly effective at increasing BMD in patients with PHPT and PMO with and without renal insufficiency. The calcium lowering effects of denosumab were most significant in patients with PHPT and CKD. The safety of denosumab did not differ among participants with and without CKD.

Concentrations of total, bioavailable, and free 25OHD in individuals with and without primary hyperparathyroidism and their correlations to DXA and trabecular bone score.

This study aimed to investigate the association between 25OHD (total, bioavailable and free) with bone mass and microarchitecture among primary hyperparathyroidism (PHPT) patients and controls. Sixty-four patients in the preoperative period of PHPT and 63 matched controls, who had not taken vitamin D in the last three months. To calculate the bioavailable and free 25OHD, the genetic variants of the vitamin D-binding protein (DBP) were determined. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry (DXA). The distributions of total, bioavailable and free 25OHD and their correlation with TBS and DXA were evaluated. PHPT showed BMD and TBS values lower than CTRL in all locations (p < 0.05). There were no statistical differences in the levels of free, bioavailable and total 25OHD between the PHPT and CTRL groups [mean, min-max: 3.4 (1.4-8.6) vs. 3.1 (1.0- 9.8) pg/mL, 1.51 (0.43-3.58) vs. 1.41 (0.38-3.48) ng/mL, 22.6 (11.0-39.9) vs. 20.6 (8.9-35.3) ng/dL, respectively; (p > 0.05). The distribution of DBP haplotypes was similar between groups. DXA showed no correlation with any form of 25OHD in both groups. TBS presented a weak correlation with the total 25OHD in PHPT (r = 0.28; p = 0.02) and a moderate correlation with the total, free and bioavailable 25OHD in CTRL (r = 0.42; r = 0.42; r = 0.43; respectively, p < 0.01). The concentrations of total, free and bioavailable 25OHD were similar in both the PHPT and control groups. 25OHD concentrations correlated positively with TBS and not with DXA, especially in controls, suggesting that this method may be more sensitive to assessing the consequences of vitamin D deficiency on bone quality in individuals without PHPT.

Impairment in muscle strength and its determinants in primary hyperparathyroidism: A study in postmenopausal women

Neuromuscular impairment is described among the non-classical complications of primary hyperparathyroidism (PHPT). However, the extent of this complications and related mechanisms have not been fully addressed. The study aimed at assessing muscle strength and its main determinants in postmenopausal women with PHPT. We studied 48 postmenopausal women with PHPT (mean age 60.8±5.6 SD years; BMI 25.6±5.5kg/m2) and 38 healthy postmenopausal women (mean age 58.6±5.9; BMI 25.2±3.5). In all subjects, the maximum voluntary contraction (MVC, Newton, N) was measured by Hand held Dynamometer (Kayser Italia srl, Livorno, Italy) and the lumbar spine, total hip, femoral neck, and non dominant distal one-third radius areal BMD (aBMD) by dual X-ray absorptiometry (DXA) (Hologic, Waltham, MA). Serum ionized calcium (Ca++), parathyroid hormone (PTH), phosphorus (P), and 25-hydroxyvitaminD [25(OH)D] levels were measured in both groups. A subgroup of 30 PHPT women agreed to participate to the follow-up sub-study and were re-assessed 24months after parathyroidectomy (n=15) or after baseline evaluation (n=15). Patients with PHPT had significant lower MVC values compared to healthy women (p<0.001). As expected, serum Ca++ and PTH levels were higher and P lower in PHPT compared to controls. We observed a significant association between MVC and total hip and one-third radius aBMD (R=0.320 and 0.370, p<0.05) and negative association with Ca++ (R=-0.340, p<0.05) in the PHPT group; MVC was positively associated with one-third radius aBMD (R=0.360, p<0.05) and negatively with age, BMI and myostatin (R=-0.390, -0.340 and -0.450, p<0.05) in the group of healthy women. The linear model using BMI, Ca++, P, 25(OH)D, PTH, myostatin, and aBMD as covariates showed that one-third radius aBMD was positively associated with MVC in PHPT patients (p<0.02) and in healthy subjects (p<0.001). Additionally, serum PTH and myostatin were negatively associated with MVC in healthy subjects (p<0.03 and p<0.01). The linear model showed that surgery was associated with an increase in MVC (p<0.05) in PHPT patients after 24months, all other variables being equal and by controlling for baseline values of MVC. Handgrip strength is significantly impaired in postmenopausal women with PHPT. Some common mechanisms influencing muscle function exist in PHPT and in healthy subjects; they are associated with the reduced aBMD at cortical sites. Hypercalcemia seems to be one of the main determinants of impairment in muscle strength in PHPT, while no role is played by myostatin.

Degraded Bone Microarchitecture in Women with PHPT–Significant Predictor of Fracture Probability

Patients with primary hyperparathyroidism (PHPT) experience bone mineral density (BMD) loss and trabecular bone score (TBS) alteration, which current guidelines recommend assessing. Considering TBS alongside BMD for a 10-year fracture risk assessment (FRAX) may improve PHPT management. Retrospective, cross-sectional study composed of 49 Caucasian females (62 ± 10.6 years, 27.7 ± 0.87 kg/m2) with PHPT and 132 matched control subjects (61.3 ± 10.5 years, 27.5 ± 0.49 kg/m2) evaluated in 3 years. We assessed lumbar spine (LS) and femoral neck (FN) BMD, T and Z scores (GE Healthcare Lunar Osteodensitometer) and TBS (iNsight 1.8), major osteoporotic fracture (MOF), and hip FRAX. Patients with PHPT had statistically lower mean values for lumbar spine bone mineral density (LS BMD) (0.95 ± 0.25 vs 1.01 ± 0.14 g/cm2, P = .01), LS T-scores (-2 ± 0.2 vs -1.4 ± 0.1 SD, P = .009), LS Z scores (-0.9 ± 0.19 vs -0.1 ± 0.11 SD, P = .009), femoral neck bone mineral density (FN BMD) (0.79 ± 0.02 vs 0.83 ± 0.01 g/cm2, P = .02), FN T-scores (-1.8 ± 0.13 vs -1.5 ± 0.07 SD, P = .017), FN Z scores (-0.51 ± 0.87 vs -0.1 ± 0.82 SD, P = .006), and TBS (0.95 ± 0.25 vs 1.01 ± 0.14 g/cm2, P = .01) compared with control subjects. 22.4% of patients with PHPT had degraded microarchitecture (TBS < 1.2) vs. 7.6% in control group (χ2 = 0.008). PHPT proved to be a covariate with unique contribution (P = .031) alongside LS BMD (P = .040) in a linear regression model [R 2 = 0.532, F(4,16) = 4.543] for TBS < 1.2. TBS adjustment elevated MOF FRAX both for PHPT (4.35 ± 0.6% vs 5.25% ± 0.73%, P < .001) and control groups (4.5 ± 0.24% vs 4.7% ± 0.26%, P < .001) compared with BMD-bases FRAX, but also increased differently between the 2 study groups (1.1-folds for PHPT patients and 1.04 for control subjects, P = .034). Compared with control, TBS-adjusted FRAX provides significantly higher MOF risk than BMD-based FRAX in PHPT women.

Levels of bioavailable, and free forms of 25(OH)D after supplementation with vitamin D3 in primary hyperparathyroidism.

The 25 hydroxyvitamin D [25(OH)D] is the major metabolite for ascertaining vitamin D status, which circulates bound to a specific carrier (vitamin D-binding protein - VDBP). A portion that circulates unbound vary according to the VDBP genotype. This study evaluates the behavior of different forms of 25(OH)D, before and after supplementation with 14,000 IU of vitamin D3, weekly for 12 weeks, in individuals with primary hyperparathyroidism and controls. Fifty-six patients with active primary hyperparathyroidism (PHPT) and 64 paired controls (CTRL), not taking vitamin D3 for the last three months, were enrolled. The genetic isotypes of VDBP were determined to calculate bioavailable and free 25(OH)D. A p < 0.05 was considered significant. There were no statistical differences in free, bioavailable, and total 25(OH)D levels between PHPT and CTRL groups at baseline. The distribution of VDBP haplotypes 1s/1s, 1f/1f, 1s/1f, 2/2, 1s/2, and 1f/2 was similar between groups. After supplementation, all three forms of 25(OH)D proportionally increased within each group, although the percentage increment was lower in the PHPT group (p < 0.05). Total 25(OH)D is better correlated with PTH in the PHPT group than bioavailable and free 25(OH)D (r = -0.41; p < 0.05). The concentrations of total, free, and bioavailable 25(OH)D were similar in both PHPT and CTRL groups, and all forms increased proportionally after supplementation, although this increment percentage was higher in the CTRL group, with a subsequent reduction of PTH and AP. Total 25(OH)D correlated better with PTH than other forms, suggesting no advantages in measuring free or bioavailable 25(OH)D in these situations.

PSAT173 Weekly Supplementation with Vitamin D3 reduces 1,25(OH)2 vitamin D3 Measured by Mass Spectrometry, and increases Fibroblast-like growth factor 23 (FGF23) in Individuals with and without Primary Hyperparathyroidism (PHPT)

Abstract Introduction Vitamin D deficiency is a very common condition, which has been associated with more severe presentations of PHPT. It has been suggested that the Vitamin D replacement improves this prognosis, but there are few data regarding its effect on mineral homeostasis. The aim of this research was to evaluate the effects of weekly Vitamin D supplementation on the mineral metabolism in this population.Material and methods: In this prospective case-control trial, we evaluated the effects of 14,000 IU/week of oral Vitamin D3, for 12 weeks, on albumin-adjusted total Calcium (TCa), Parathormone (PTH), 25 hydroxyvitamin D3 (25OHD), intact FGF23 and 1,25dihydroxyvitamin D3 (1,25(OH)2D), in addition to other biochemical markers. Volunteers with active PHPT (n=55) and paired controls (n=64) collected fasting blood samples before and after 12 weeks of the Vitamin D supplementation. 1,25(OH)2D was measured by liquid chromatography and mass spectrometry, and other hormones by commercial immunometric assays. P&amp;lt;0.05 was considered significant. Results At baseline there were no differences between groups regarding 25OHD, FGF23 and clearance of creatinine. As expected, the concentrations of TCa, PTH, 1,25(OH)2D were higher in the PHPT. After supplementation, TCa and PTH did not change despite the significant increase on 25OHD in both groups, more markedly in the controls (from 22.7±6.1 to 31.5±6.8 ng/mL in PHPT; and from 20.4±5.8 to 32.5±6.4 ng/mL in controls). FGF23 levels significantly increased after supplementation in both groups, more markedly in the PHPT. (from 47.9 ± 27.1 to 76.3 ± 33.3 pg/mL in PHPT and from 40.5 ± 13.9 to 59.8±19.8 pg/mL in controls). A significant reduction in the concentrations of 1,25(OH)2D was seen in both groups, (time effect p-value&amp;lt;0.001), with more intensity in the PHPT group (time x group effect p-value=0.015) (from 94.8±34.6 to 68.9±25.3 pg/mL in PHPT and from 68.7±23.5 to 56.4±20.7pg/mL in controls). The delta of 1,25(OH)2D was inversely correlated with the delta of FGF23 in both the PHPT (r=-0.302, p-value=0.028) and control (r=-0.278, p-value=0.027) groups. Conclusion In both patient groups (with and without PHPT), weekly administration of 14,000IU of Vitamin D3 reduced 1,25(OH)2D concentrations measured by mass spectrometry, probably due to the inhibition of 1α-hydroxylase induced by the increase in FGF23. This phenomenon could explain the absence of hypercalcemia after supplementation, even in individuals with active PHPT, appearing to be a protective mechanism against Vitamin D excess. Future studies are needed to see if this increase in FGF23 could explain the paradoxical effects observed with the high bolus doses of vitamin D described by others.*This research received public grants from FAPESP (Fundação de Amparo a Pesquisa do Estado de Sao Paulo), with technical support from Laboratorio Fleury Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

RF25 | PMON147 Plasma MicroRNA Expression in Phenocopy of Multiple Endocrine Neoplasia Type 1 Compared to Patients with Acromegaly and Primary Hyperparathyroidism: Potential Biomarkers of Multiple Endocrine Tumor Growth

Abstract Introduction Changes in the expression of microRNA facilitate in the formation of various tumors. MEN1 is a rare disease caused by mutations in MEN1 gene encoding the menin protein and characterize by the occurrence of parathyroid, pituitary, gastroenteropancreatic and other tumors. If a patient with the MEN1 phenotype carry no mutations in the MEN1 gene, the condition considers a phenocopy of syndrome (phMEN1). We hypothesize that the pathogenic link among the above sporadic tumors might be represented by molecular pathways involving the MEN1 gene and epigenetic regulations — particularly microRNAs. Materials &amp; methods Single-center, case-control study: assessment of plasma microRNA expression in patients with phMEN1, acromegaly (AM), primary hyperparathyroidism (PHPT) and healthy controls. Morning plasma samples were collected from fasting patients and age- and sex-matched controls and stored at –80°C. Total RNA isolation: miRNeasy Mini Kit with QIAcube. The libraries were prepared by the QIAseq miRNA Library Kit following the manufacturer. Circulating miRNA sequencing was done on Illumina NextSeq 500 (Illumina). Subsequent data processing was performed using the DESeq2 bioinformatics algorithm. Results We enrolled 36 consecutive patients (12 patients in each group) with phMEN1, AM, PHPT, along with 12 age and gender matched controls. Median age of phMEN1 group — 59 [52; 60.5]; AM — 59 [52; 63]; PHPT — 60.5 [54; 62.5]; control — 59 [51.5; 62.5]. The groups did not differ in age (p=0.88) and gender – in all groups were 11 women and 1 man (p=1.00). We divided all assessed microRNAs into 3 groups based on the significance of the results; the first group consisted of samples with the highest levels of detected microRNAs (&amp;gt;50), the second group — moderate (10–50), the third group — the lowest (&amp;lt;10). The microRNA expression pattern was almost the same between AM and phMEN1 groups (15 microRNAs upregulated, 10 — downregulated), we found slightly decreased hsa-miR-4301 (padj=0.038); it is interesting that phMEN group when compared to PHPT and control groups showed decline in hsa-miR-4301 too. PHPT and control groups had also quite similar expression profile (4 microRNAs upregulated, 19 — downregulated). 607 microRNA were differently expressed in groups phMEN1 and PHPT (473 upregulated microRNAs, 134 — downregulated). We found increased expression of some microRNAs that interferes with menin: hsa-miR-24-1-5p (padj=0.0008), hsa-miR-24-3p (padj=0.034), hsa-miR-26a-5p (padj=0.0005), hsa-miR-421 (padj=0.018), hsa-miR-762 (padj=0.027). In addition, we found decreased microRNAs with oncogene potential: miR-3182 (padj=0.007), hsa-miR-875-5p (padj&amp;lt;0.001), hsa-miR-6749-5p (padj&amp;lt;0.001). 173 microRNA differed in phMEN1 and control groups (11 microRNAs upregulated, 162 — downregulated). We detected several decreased microRNAs in phMEN1 that participate in tumor genesis: hsa-miR-625-3p (padj&amp;lt;0.005), hsa-miR-3168 (padj=0,028), hsa-miR-302b-3p (padj&amp;lt;0.001). Conclusion We found microRNAs, which could potentially become biomarkers in phMEN1 diagnosis. The results need to be validated using different measurement method with larger sample size. Likewise further assessment of plasma microRNA expression in genetically confirmed MEN1 patients is needed. Presentation: Monday, June 13, 2022 12:30 p.m. - 12:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Full-length versus intact PTH concentrations in pseudohypoparathyroidism type 1 and primary hyperparathyroidism: clinical evaluation of immunoassays in individuals from China.

PurposeThe application of the third-generation parathyroid hormone (PTH) assay [PTH(1–84) assay] for evaluating PTH levels in patients with pseudohypoparathyroidism type-1 (PHP1) is less popular than the second-generation assay. Therefore, we aimed at examining the conformity between the PTH(1–84) assay and the intact PTH (iPTH) assay, specifically examining their performance in individuals with PHP1 versus individuals with primary hyperparathyroidism (PHPT), compared to healthy controls.MethodsPTH(1–84) and iPTH assay were performed in patients with PHP1, patients with PHPT, and healthy volunteers. ∆PTH%, PTH(1–84)/iPTH (3rd/2nd ratio), iPTH/upper limit of normal (ULN), and PTH (1–84)/ULN of each group were calculated for comparison. Linear regression, Kappa conformity test, and Bland–Altman analysis of ∆PTH/mean of iPTH and PTH(1–84) (percent bias) plotted against the mean of iPTH and PTH(1–84) were performed to determine the conformance of PTH(1–84) assay with iPTH assay.ResultsA total of 54 patients with PHP1, 127 patients with PHPT, and 65 healthy volunteers were enrolled in this study. All the three groups showed strong linear relationship between iPTH and PTH (1–84) (r2 = 0.9661, 0.7733, and 0.9575, respectively). No significant differences were noted in 3rd/2nd ratio (median 0.76 vs. 0.72) between the PHP1 and PHPT groups (p > 0.05). Conformity examination showed the Kappa value was 0.778 and 0.395 for PHP1 and PHPT groups respectively. No difference in the Kappa values was found between PHP1A and PHP1B subgroups. Bland–Altman plot demonstrated that the proportion of data points that were plotted within mean ± 1.96 SD in PHP1, PHPT and normal control groups were 96.3%, 93.7%, and 98.5%, respectively. The mean percent bias of the three groups were 26.1%, 31.2%, and 17.0%, respectively. The range of mean ± 1.96 SD of percent bias of the three groups were 2.2%–50.0%, −14.3%–76.6%, and 6.7%–27.2%, respectively.ConclusionAlthough iPTH and PTH(1–84) values were both lower in the present PHP1 cohort than in the PHPT cohort, there appear to be differences in the relative agreement between both immunoassays, and in the relationship between the two values, especially in comparison to healthy controls. Whether these differences are due to differential accumulation of C-terminal fragments or other factors requires further study.

Using QCT to evaluate bone mineral and abdominal adipose changes in patients with primary hyperparathyroidism and comparing it to DXA for bone status assessment: a retrospective case-control study.

BackgroundPatients with primary hyperparathyroidism (PHPT) show changes in bone metabolism and adipose tissue, but the results are inconsistent. Quantitative computed tomography (QCT) was reported useful for detecting bone mineral and adipose tissue change, but information on the role of QCT in PHPT is limited. We aimed to explore the changes of lumbar bone mineral density (BMD) and abdominal adipose tissue in patients with PHPT using QCT based on existed CT images, and to assess the consistency between QCT and dual-energy X-ray absorptiometry (DXA) in assessing bone status.MethodsThis retrospective case-control study was conducted on 48 PHPT patients, with healthy controls (HCs) matched by their age (±3 years) and gender, and the case-to-control ratio was approximately 1:3. Volumetric bone mineral density (vBMD), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT) were measured by QCT in both PHPT and control groups and compared with the independent samples T-test. In the PHPT group, areal bone mineral density (aBMD) was measured by DXA. Pearson correlation analysis was used to investigate the association between QCT-derived vBMD and DXA-derived aBMD. Weighted kappa consistency analysis was used to clarify the agreement between QCT and DXA.ResultsCompared with HCs, the PHPT group had significantly lower vBMD (114.30±41.71 vs. 136.92±42.23 mg/cm3; P=0.002) and higher TAT (261.98±74.65 vs. 236.69±69.00 cm2; P=0.033); however, differences in SAT (120.81±40.19 vs. 109.94±36.83 cm2; P=0.085) and VAT (141.17±48.11 vs. 126.75±50.50 cm2; P=0.085) were not statistically significant. There was a strong correlation between QCT-derived vBMD and DXA-derived aBMD (all r>0.68; P<0.001), and a moderate consistency [kappa(w) =0.48; 95% CI: 0.29 to 0.68; P<0.001] was presented when defining bone status according to the respective diagnostic criteria.ConclusionsOur study may provide useful information regarding bone status and abdominal adipose tissue change in patients with PHPT without requiring additional scan and may further extend the clinical application value of QCT.

Excessive proliferation and apoptosis of parathyroid cells contribute to primary hyperparathyroidism in rabbit model

To explore the molecular pathogenesis of primary hyperparathyroidism (PHPT), we investigated the proliferation and apoptosis of parathyroid cells in a rabbit model of diet-induced PHPT. A total of 120 adult...

Use of Parathyroid Function Index and Wisconsin Index to Differentiate Primary Hyperparathyroidism From Secondary Hyperparathyroidism: A Case-Control Study.

Introduction: Patients with primary hyperparathyroidism (PHPT) can be asymptomatic or have a normal calcium level (NHPT). Patients with 25(OH) vitamin D insufficiency, on the other hand, may present with a similar presentation. In regions where 25(OH) vitamin D deficiency is common, patients are usually diagnosed with secondary hyperparathyroidism (SHPT). Therefore, it is necessary to separate PHPT and NHPT from SHPT. Parathormone and calcium values are used for differentiation in the clinic. The predictive value of the newly developed parathyroid function test (PFindex), which previously had a high diagnostic value, was evaluated in this patient population in our investigation.Methods: The study comprised 163 PHPT and NHPT patients with pathological confirmation and 56 SHPT patients. The PHPT, NHPT, and SHPT properties were defined using PFindex. The diagnostic power of PFindex was investigated using a receiver operating characteristic (ROC) curve of the results assessed in three groups.Results: The PHPT group had the highest PFindex (1365.4±784.6) compared to the other two groups (NHPT: 723.5±509.4; SHPT:227.2±49.9, all p < 0.001). A PFindex threshold of 327.8 yielded 91.9% and 90.9% sensitivity and specificity rates for distinguishing PHPT and NHPT from SHPT, respectively.Conclusion: PFindex gave the outstanding diagnostic capacity to distinguish PHPT from SHPT due to our research. This straightforward tool can assist in making quick decisions about vitamin D therapy or surgery for PHPT.

Serum Calcium/Phosphorus Ratio in Biochemical Screening of Primary Hyperparathyroidism.

Primary hyperparathyroidism is a common endocrine disease and most cases are asymptomatic. Currently, in a hypercalcemic patient, the first laboratory investigation is serum primary hyperparathyroidism measurement. However, the primary hyperparathyroidism level cannot be measured in many primary healthcare centers in our country. In addition, serum calcium levels are normal in normocalcemic primary hyperparathyroidism patients, even if most centers have serum calcium levels measured. Therefore, a simple and inexpensive laboratory biochemical marker is required for the diagnosis of primary hyperparathyroidism. Recently, the calcium/phosphorus ratio has been proposed as a suitable tool for diagnosing primary hyperparathyroidism. This study aimed to investigate the diagnostic value of serum calcium/phosphorus ratio in primary hyperparathyroidism screening. A total of 462 patients followed in our clinic with a diagnosis of primary hyperparathyroidism were reviewed in this retrospective study. Out of these patients, 148 with normal levels of serum parathyroid hormone, calcium, and phosphorus were selected as the control group. Serum calcium, corrected calcium, phosphorus, albumin, parathyroid hormone, 25-hydroxyvitamin D, and creatinine were evaluated. The diagnostic accuracy of the calcium/phosphorus ratio was investigated using receiver operating characteristic curve analysis. There were 404 (87.4%) females and 58 (12.6%) males in the primary hyperparathyroidism group. Calcium, parathyroid hormone, and calcium/phosphorus ratio were significantly higher in primary hyperparathyroidism than in controls (p<0.001 for each). Receiver operating characteristic curve analyses identified a cutoff value of 2.59 (3.35 if calcium and phosphorus are measured in mg/dL) for the calcium/phosphorus ratio, with a sensitivity of 90.5% and specificity of 93.2% (p<0.001). The calcium/phosphorus ratio is a simple and inexpensive method for primary hyperparathyroidism screening when a cutoff value of 2.59 is used.

Evaluation of subclinical cardiovascular disease by carotid intima media thickness, epicardial adipose tissue thickness, serum endocan, and nesfatin-1 levels in patients with primary hyperparathyroidism.

Data on the presence and extent of cardiovascular disease (CVD) risk in primary hyperparathyroidism (PHPT) are conflicting. In our study, we aimed to investigate the increased CVD risk in patients with PHPT by carotid intima-media thickness (CIMT), epicardial adipose tissue (EAT) thickness, and serum levels of endocan and nesfatin-1. Patients with PHPT (n = 44) and age- and sex-matched healthy control subjects (n = 40) were enrolled in this study. Demographic data of the participants were questioned. Serum endocan and nesfatin-1 concentrations were assessed using commercially available ELISA kits. Noninvasive measurements of CIMT and EAT thickness were made with high-resolution ultrasonography and B-mode echocardiography. There was no statistically significant difference in serum endocan and nesfatin-1 levels and EAT thickness in the PHPT group compared to controls. CIMT was statistically significantly higher in the PHPT group compared to controls (p = 0.001). A negative correlation was found between PTH and low-density lipoprotein cholesterol level (p = 0.001) but no significant relationship was found between other parameters. We found that CIMT is increased in patients with PHPT and consequently, CVD risk is high in these patients. More comprehensive studies are needed to identify other markers that predict increased CVD risk in patients with PHPT.