Serum Intact Parathyroid Hormone Research Articles

Radiofrequency Ablation of Parathyroid Adenoma: Results of a Retrospective Analysis of 60 Patients.

To present the effectiveness and safety of radiofrequency ablation (RFA) in parathyroid adenoma (PTA). In this retrospective study, 60 patients with a single PTA were evaluated for changes in biochemical and ultrasonographic features up to 6months after RFA of the lesion. Adenomas were ablated with an alternative technique so called "Nik jet dissection" which incorporates full hydrodissection and polar artery coagulation. Complications as well as the variations in biochemical data and nodule volumes were analyzed between baseline measurements and at each follow-up interval data (first day, 1, 3, and 6months after ablation) were analyzed. A significant reduction in serum intact parathyroid hormone and calcium levels was observed 6 months after ablation, with a mean difference of - 83.4 ± 104.1pg/mL, p < 0.001, and - 0.29 ± 0.22mmol/L, p < 0.001, respectively. Serum phosphorus levels increased significantly with a mean difference of 0.09 ± 0.19mmol/L, p = 0.040 at the end of the follow up. We observed a significant volume reduction rate of parathyroid adenomas with 89 ± 20.8 percent, p < 0.001. Also, 51% of adenomas disappeared at the end of the follow up. In this study, two cases of hematoma and one case of transient hoarseness (grade 1 of the CIRSE classification) were encountered. Our study showed that RFA with the alternative technique, called "Nik jet dissection" is a safe and effective modality in management of PTA. Therefore, we suggest expanding the indications for RFA in PTA management, especially when surgery is not feasible. Level 3, Local non-random sample.

5-year Follow-up of Reimplanted Parathyroid Glands in Forearm Subcutaneous Tissue During Thyroidectomy. A Confirmation of Graft Vitality in a Large Series of Patients.

The aim of this study is to assess the outcomes of parathyroid gland reimplantation with PR-FaST technique in patients undergoing thyroid surgery, focusing on graft functionality over a 5-year follow-up period. We analyzed data from 131 patients who underwent parathyroid reimplantation using the PR-FaST technique during thyroid surgery due to inadvertent parathyroid removal or evident vascular damage. Postoperative evaluations included serum calcium (Ca), magnesium (Mg), and phosphorus (P) analyses on the 1st and 2nd postoperative days, at 10 days, and at 1, 3, 6months, 1 year, and 5 years of follow-up. Additionally, the mean values of serum intact parathyroid hormone (iPTH) concentration were measured from blood samples collected from both the reimplanted arm (iPTH RA) and non-reimplanted arm (iPTH NRA) within the same period. Among 131 patients, at 10 days post-surgery, only 46 patients (35.1%) out of 131 exhibited graft viability (iPTH ratio >1.5). This percentage increased to 72.8% (94 patients) after 1 month and further to 87.8% (108 patients) after 3 months post-surgery. At 1 year, 84.7% of patients showed good graft functionality. After 5 years, the percentage remained stable, with graft viability observed in 81.3% of patients. Only 91 of the initial 131 patients completed follow-up up to 5 years, with a dropout rate of 30.5 %. Parathyroid reimplantation using the PR-FaST technique is a viable option for patients undergoing thyroidectomy and has been shown to be a reproducible and effective technique in most patients, with sustained graft functionality and parathyroid hormone production over a 5-year follow-up period.

Predicting tumor volume in primary hyperparathyroidism from preoperative clinical data.

Primary hyperparathyroidism (PHPT) is an endocrine disorder that is treated surgically, and some correlation between the size of the responsible lesion and preoperative clinical data is assumed. The purpose of this study was to predict tumor volume of the lesion responsible for PHPT from preoperative clinical data. Participants comprised patients with surgically treated PHPT who underwent initial surgery in our department between January 2000 and December 2021. The volume of parathyroid gland removed was used as the primary outcome and associations with preoperative clinical data were assessed by multivariable analysis. A positive correlation was identified between parathyroid tumor volume and both preoperative intact parathyroid hormone (PTH) (Spearman's r = 0.503) and calcium values (Spearman's r = 0.338). Data for intact PTH value and tumor volume were logarithmically transformed (ln-PTH = log-transformed intact PTH value; ln-volume = log-transformed tumor volume). Multiple regression analysis revealed male sex, ln-PTH and calcium values as significant predictors of ln-volume, with standardized regression coefficients of 0.213 (95% confidence interval [CI] 0.103-0.323), 0.5018 (95%CI 0.4442-0559) and 0.322 (95%CI 0.0339-0.149), respectively. The adjusted R2 for this model is 0.320. Preoperative serum intact PTH value is associated with tumor volume of the lesion responsible for PHPT. A rough estimation of the tumor size would provide responsible physicians with opportunities to add further imaging tests or plan appropriate surgical strategies.

Diabetes mellitus modifies the association between chronic kidney disease-mineral and bone disorder biomarkers and aortic stiffness in peritoneal dialysis patients.

This study aimed to investigate the relationship of four chronic kidney disease-mineral and bone disorder (CKD-MBD) biomarkers, including intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), soluble klotho, and fetuin-A, with aortic stiffness in peritoneal dialysis (PD) patients, comparing those with and without diabetes mellitus (DM). A total of 213 patients (mean age 58 ± 14years; 81 (38.0%) patients with DM) were enrolled. Their aortic pulse wave velocity (PWV) was measured using pressure applanation tonometry, while serum intact PTH, FGF23, α-klotho, and fetuin-A levels were measured using enzyme-linked immunosorbent assay. Overall, patients with DM had higher aortic PWV than those without (9.9 ± 1.8 vs. 8.6 ± 1.4m/s, p < 0.001). Among the four CKD-MBD biomarkers, FGF23 levels were significantly lower in DM group (462 [127-1790] vs. 1237 [251-3120] pg/mL, p = 0.028) and log-FGF23 independently predicted aortic PWV in DM group (β: 0.61, 95% confidence interval: 0.06-1.16, p = 0.029 in DM group; β: 0.10, 95% confidence interval: - 0.24-0.45, p = 0.546 in nonDM group; interaction p = 0.016). In conclusion, the association between FGF23 and aortic PWV was significantly modified by DM status in PD patients.

Association of Low Vitamin D and Intact Parathyroid Hormone (iPTH) in Nepalese Population: When Does iPTH Exactly Rise?

Vitamin D deficiency is a global public health concern that provokes bone demineralization and weakening. In response to the decreased vitamin D level, calcium stores wear out. The homeostatic effect of compensatory hyperparathyroidism in vitamin D deficiency incites variable discrepancies in different populations. This study intends to decipher the transition point of PTH in relation to levels of vitamin D in a Nepalese population. A cross-sectional study was carried out at Tribhuvan University Teaching Hospital, Nepal. Serum calcium, phosphorus, intact PTH, and 25-hydroxy vitamin D levels were assayed in an Abbott ARCHITECT Integrated System. A correlation plot of PTH and vitamin D was analyzed in Statistical Package for Social Sciences version 22.0. Using a locally weighted scatter plot smoothing method, the relation between these variables was presented graphically. Among 281 individuals, 30.2% had vitamin D levels below 20 ng/mL. There was an archetypical transition in the PTH levels in concert with the decrease in vitamin D level marked by 2 inflection points (ie, 18.5 and 42.0 ng/mL). Our findings suggest that to augment overall health and avert weakness due to vitamin D deficiency, the levels of vitamin D should be maintained above 42.0 ng/mL in our population.

Predictive factors for persistent hypercalcemia following parathyroidectomy in patients with persistent hyperparathyroidism after kidney transplantation: a retrospective cohort study.

Surgery for irreversible hyperparathyroidism is the preferred management for kidney transplant patients. The authors analyzed the factors associated with persistent hypercalcemia after parathyroidectomy in kidney transplant patients and evaluated the appropriate extent of surgery. The authors retrospectively analyzed 100 patients who underwent parathyroidectomy because of persistent hyperparathyroidism after kidney transplantation at a tertiary medical center between June 2011 and February 2022. Patients were divided into two groups: 22 with persistent hypercalcemia after parathyroidectomy and 78 who achieved normocalcemia after parathyroidectomy. Persistent hypercalcemia was defined as having sustained hypercalcemia (≥10.3mg/dl) 6 months after kidney transplantation. The authors compared the biochemical and clinicopathological features between the two groups. Multivariate logistic regression analysis was used to identify potential risk factors associated with persistent hypercalcemia following parathyroidectomy. The proportion of patients with serum intact parathyroid hormone (PTH) level is greater than 65pg/ml was significantly high in the hypercalcemia group (40.9 vs. 7.7%). The proportion of patients who underwent less than subtotal parathyroidectomy was significantly high in the persistent hypercalcemia group (17.9 vs. 54.5%). Patients with a large remaining size of the preserved parathyroid gland (≥0.8cm) had a high incidence of persistent hypercalcemia (29.7 vs. 52.6%). In the multivariate logistic regression analysis, the drop rate of intact PTH is less than 88% on postoperative day 1 (odds ratio 10.3, 95% CI: 2.7-39.1, P =0.001) and the removal of less than or equal to 2 parathyroid glands (odds ratio 6.8, 95% CI: 1.8-26.7, P =0.001) were identified as risk factors for persistent hypercalcemia. The drop rate of intact PTH is less than 88% on postoperative day 1 and appropriate extent of surgery for controlling the autonomic function were independently associated with persistent hypercalcemia. Confirmation of parathyroid lesions through frozen section biopsy or intraoperative PTH monitoring can be helpful in preventing the inadvertent removal of a parathyroid gland and achieving normocalcemia after parathyroidectomy.

Ultrasound-Guided Radiofrequency Ablation in Tertiary Hyperparathyroidism: A Prospective Study.

To prospectively evaluate the outcomes of ultrasound (US)-guided radiofrequency ablation (RFA) in tertiary hyperparathyroidism (THPT). Patients with THPT underwent RFA between September 2017 and January 2022. Laboratory parameters, including serum intact parathyroid hormone (iPTH) levels, were monitored for 48 months after RFA and compared with the levels at baseline. Complications related to RFA and changes in hyperparathyroidism-related clinical symptoms were recorded before and after RFA. A total of 42 patients with THPT were recruited for this study. Ultimately, 36 patients with renal failure and 2 patients who underwent successful renal transplantation (male:female, 17:21; median age, 54.5 years) were enrolled. The follow-up time was 21.5 ± 19.0 months in the 36 patients with renal failure. In these 36 patients, iPTH levels were significantly decreased to 261.1 pg/mL at 48 months compared with the baseline value of 1284.9 pg/mL (P = 0.012). Persistent hyperparathyroidism, defined as iPTH levels maintained at > 585.0 pg/mL for 6 months after treatment, occurred in 4.0% of patients (1/25). Recurrent hyperparathyroidism, defined as iPTH levels > 585.0 pg/mL after 6 months, were 4.0% (1/25) and 0.0% (0/9) at 6 months and 4 years after treatment, respectively. In two patients with THPT after successful renal transplantation, iPTH decreased from the baseline value of 242.5 and 115.9 pg/mL to 171.0 and 62.0 pg/mL at 6 months after treatment. All complications resolved within 6 months of ablation without medical intervention, except in 10.5% (4/38) patients with permanent hypocalcemia. The overall symptom recovery rate was 58.8% (10/17). The severity scores for bone pain, arthralgia, and itchy skin associated with hyperparathyroidism improved after treatment (P < 0.05). US-guided RFA is an effective and safe alternative to surgery in the treatment of patients with TPTH and improves hyperparathyroidism-related clinical symptoms.

Decreased level of pre-operative vitamin D in a patient who is undergoing a total thyroidectomy is an early indicator of post-operative hypocalcemia.

Objective: To investigate the viability of utilizing preoperative serum vitamin D levels as a predictor of postoperative transient hypocalcemia in patients who were undergoing total thyroidectomy in our population. Study Design: Prospective Observational study. Setting: Shifa International Hospital Islamabad, Pakistan. Period: 1st July 2020 to 30th June 2022. Material &amp; Methods: All the data was collected prospectively. Patients are divided into two groups depending on the pre- operative vitamin D levels. The preoperative vitamin D levels are checked on day of admission before the surgery. After the surgery, their post-operative serum calcium levels are checked at 6 hours, 24 hours and 48 hours. Intact PTH levels are also checked after the surgery and correlation of transient hypocalcemia with intact PTH levels is also checked. Results: Our results strongly predict that serum Vitamin D levels and intact parathyroid hormone (PTH) levels are diagnostic indicators of transient hypocalcemia in post thyroidectomy patients. Conclusion: Our study shows: Pre-operative vitamin D is an early indicator of hypocalcemia in post-thyroidectomy patients. Serum intact parathyroid hormone levels is an early indicator of hypocalcemia in post-thyroidectomy patients.

(Epi)genetic and clinical characteristics in 84 patients with pseudohypoparathyroidism type 1B.

Pseudohypoparathyroidism type 1B (PHP1B) caused by methylation defects of differentially methylated regions (DMRs) on the GNAS locus can be categorized into groups according to etiologies and methylation defect patterns of the DMRs. The aim of this study was to clarify the clinical characteristics in each group. Comprehensive molecular analyses consisting of methylation, copy number, and microsatellite analyses. Eighty-four patients with PHP1B were included in this study. We classified them into five groups, namely, autosomal dominant inheritance-PHP1B (Group 1, G1), sporadic-PHP1B (G2), and atypical-PHP1B (G3-G5), based on the methylation defect patterns in four DMRs on the GNAS locus and etiologies and evaluated the clinical findings in each group and compared them among the groups. G2 had the youngest age and the highest serum intact parathyroid hormone levels among the five groups at the time of diagnosis. The most common symptoms at the time of diagnosis were tetany in G1, and seizures or loss of consciousness in G2. Albright's hereditary osteodystrophy and PHP-suggestive features were most frequently observed in the G2 proband. Nine patients had neurodevelopmental disorders (NDs) consisting of mild to borderline intellectual disability and/or developmental delay. There were no significant correlations between the average methylation ratios of seven CpG sites in the GNAS-A/B:TSS-DMR and hormonal and biochemical findings. This study revealed the differences in some clinical characteristics, particularly clinical features and ages at the time of diagnosis between G2 and other groups and detailed NDs observed in some patients with PHP1B.

Low serum iPTH at the end of surgery is the earliest predictor of postoperative hypocalcemia after total thyroidectomy

BackgroundThe most frequent complication of total thyroidectomy remains hypocalcemia due to low postoperative levels of serum intact parathyroid hormone (iPTH). The purpose of this study was to investigate the role of decreased iPTH at the end of surgery in predicting hypocalcemia. In addition, we examined the percentage decrease of iPTH as potential indicator of hypocalcemia.MethodsWe retrospectively collected the data of patients who underwent total thyroidectomy for benign and malignant diseases at our institution between 2010 and 2022. The iPTH level was measured before and at the end of surgery, and serum calcium levels on the first postoperative day. Demographic, clinical, and biochemical characteristics of patients with low iPTH were compared with patients with normal iPTH levels using ANOVA for continuous variables and χ2-tests for categorical variables. Multivariable logistic regression analysis evaluated the association of iPTH at the end of surgery and the relative reduction of iPTH with postoperative hypocalcemia.ResultsThe mean age of the 607 patients in this study was 55.6 years, and the female-to-male ratio was 5:1. Goiter was the most common indication for surgery (N = 382, 62.9%), followed by Graves’ disease (N = 135, 22.2%). The mean preoperative iPTH was 49.0 pg/ml, while the mean postoperative iPTH was 29.3 pg/ml. A total of 197 patients (32.5%) had an iPTH level below normal, 77 patients (39%), had iPTH levels of 10–15.0 pg/ml and 120 patients (61%) of < 10.0 pg/ml at the end of surgery. Among all patients, 124 (20.4%) developed hypocalcemia on the first postoperative day. The mean percentage of decrease of iPTH was highest among patients with iPTH < 10 pg/ml (76.9%, p < 0.01); this group of patients had also the highest rate of postoperative hypocalcemia on day one (45.0% vs. 26.0% vs 12.2%, p < 0.01).ConclusionsMeasurement of iPTH at the end of total thyroidectomy predicts patients who are at risk for postoperative hypocalcemia. The combination of low serum iPTH with a decrease in iPTH level of ≥ 50% may improve prediction of hypocalcemia compared to iPTH levels alone allowing for early calcium substitution in these patients at high risk of developing postoperative hypocalcemia.

Biochemical markers and FokI and TaqI vitamin D receptor genes polymorphism in rheumatoid arthritis

BackgroundPrevious studies have reported the role of genes in different metabolic processes in the human body, and any variation in gene polymorphisms could lead to disturbances in these processes and different diseases.ObjectiveThis study aimed to compare vitamin D receptor (VDR) FokI and TaqI genotypes in terms of parathyroid hormone (PTH) and some biomarkers of inflammation and susceptibility to rheumatoid arthritis (RA) disease.MethodsThis study included 100 patients with rheumatoid arthritis (RA). Genotyping was performed by polymerase chain reaction (PCR) and examined by specific restriction enzymes using restriction fragment length polymorphism (RFLP). Serum intact PTH, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibodies (ACCPs) levels were measured.ResultsAn increased PTH level (> 65 pg/ml) was found in 8% of patients. No significant differences among FokI and TaqI vitamin D receptor genes polymorphism regarding positive and negative RF or ACCPs were found. A significant difference was found among FokI (p = 0.009) and none in TaqI genotypes regarding intact parathyroid hormone level categories. No significant correlation was found between the serum intact PTH level and ESR or CRP levels (P = 0.13 and 0.28, respectively). The parathyroid hormone level was not a good predictor for RF or ACCPs (P = 0.5 and 0.06, respectively).ConclusionThe FokI gene may play a role in controlling PTH levels in patients with RA. There was no significant correlation found between the serum intact PTH level and RA severity according to ESR and CRP inflammatory biomarkers. There are no differences between VDR genes FokI and TaqI polymorphism in terms of RA susceptibility (for RF and ACCPs).

Genotype phenotype correlations in pseudohypoparathyroidism type 1a patients: a systemic review.

Pseudohypoparathyroidism type 1a (PHP1a) is a rare endocrine disease caused by partial defects of the α subunit of the stimulatory GTP binding protein (Gsα) resulting from maternal GNAS gene variation. The clinical manifestations are related to PTH resistance (hypocalcemia, hyperphosphatemia, and elevated serum intact PTH) in the presence or absence of multihormone resistance, and Albright's hereditary osteodystrophy (AHO). To summarize the molecular genetics results and clinical characteristics as well as to explore the correlations between them. Articles pertaining to PHP1a until May 31, 2021 were reviewed and 527 patients with genetic diagnosis were included in the data analysis. The clinical characteristics and molecular genetics results of these patients were analyzed and compared to explore the correlations between them. A total of 258 GNAS rare variants (RVs) were identified in 527 patients. The RVs were most commonly found in exons 1 and 7 (17.6% each), with frameshift (36.8%) and missense (31.3%) being the main types of RVs. The median age of onset was 5.0 years old. The most common clinical manifestations were elevation of PTH (86.7%) and AHO (87.5%). TSH resistance was the most common hormone resistance (75.5%) other than PTH resistance. Patients with missense and in-frame RVs had lower incidence rates of round face (P = 0.001) and subcutaneous ossifications (P < 0.001) than those with loss-of-function (nonsense, frameshift, splicing site variants and large deletions) variants. This study revealed the correlation between loss-of-function RVs with round face and subcutaneous ossifications in PHP 1a patients. Further exploration on genotype phenotype correlations through more standardized and prospective studies with long-term follow-up is necessary.

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.

SAT213 Post-parathyroidectomy Acute Pseudogout Flare-up; A Case Report

Abstract Disclosure: S. Rabiei: None. V. Kantorovich: None. Introduction: Acute post-parathyroidectomy pseudogout has been reported in the early post-operative. Although the exact mechanism is unknown, accepted theories include decreased solubility of calcium pyrophosphate and unbalanced equilibrium between production and hydrolysis of inorganic phosphate. We present a patient who developed an acute pseudogout attack after parathyroidectomy. The Case: Patient is a 45-year-old male with a history of nephrolithiasis who presented to outpatient clinic with a right-sided neck mass that has been present for several years with recent increase in size. He reported unintentional weight loss (25 pounds) and night sweats. On physical examination, a right lateral neck mass measuring 6 x 4 cm was noted. CT scan of the neck demonstrated a complex mass with calcification. Serum calcium (Ca), phosphorus (P), potassium (K), and alkaline phosphatase levels were 17.2 mg/dL, 1.8 mg/dL, 2.6 mmol/L, and 1,782 U/L, respectively. Serum intact parathyroid hormone (iPTH) was 3,341 pg/mL. The patient was then admitted. He received intravenous fluid, zolindronic acid, and started on vitamin D supplementation in preparation for surgery. Pre-operative CT scan of the chest, abdomen, and pelvis was concerning for metastatic disease (retroperitoneal lymphadenopathy, multiple bilateral lung solid nodules, liver, kidney and bone lesions). The patient underwent complete resection of the tumor. Intra-operative frozen section confirmed parathyroid tumor with atypia. Twenty-minute post-excision iPTH was 476 pg/mL. In the early post-operative period, serum Ca level was reduced to 7.5-8.5 mg/dL and oral Ca and calcitriol supplementation were administered. However, serum PTH reached levels as high as 900 pg/mL. Post-operative MRI demonstrated benign liver and kidney lesion with non-visualization of the previously reported retroperitoneal lymph nodes and pulmonary nodules on the CT.A few days later, the patient complained of bilateral knee pain. Serum Ca, P, and PTH levels were 7.9 mg/dL, 3.0 mg/dL, and 861 pg/mL, respectively. The skeletal survey revealed diffuse osseous metabolic process with scattered lucent osseous lesions compatible with osteitis fibrosa cystica/brown tumors as well as chondrocalcinosis of knees and hand joints. Prednisone was started for treatment of presumed acute CPPD attack with subsequent significant resolution of patient’s joint pain. Discussion: This case demonstrated the importance of thorough evaluation of musculoskeletal complaints in patients with hyperparathyroidism. Bone and joint pain in patients with hyperparathyroidism is common and is most often the result of high bone turnover. However, other etiologies including acute pseudogout should be contemplated in order to provide the appropriate treatment. Post-parathyroidectomy acute pseudogout attack should generally be treated in the same way as in the general population. Presentation: Saturday, June 17, 2023

Elderly-onset calcinosis of hyperphosphataemic familial tumoural calcinosis/hyperostosis-hyperphosphataemia syndrome: the role of comorbid scleroderma.

A 73-year-old woman with type 2 diabetes mellitus was referred to our department for glycaemic control. Physical examination revealed two subcutaneous hard masses around the left shoulder and the right hip joint. The patient could not fully extend her fingers because of skin sclerosis in both hands. Laboratory studies showed hyperphosphataemia and a high ratio of renal tubular maximum reabsorption of phosphate to glomerular filtration rate. There were no abnormalities in serum calcium, creatinine, alkaline phosphatase, and intact parathyroid hormone levels, whereas serum fibroblast growth factor 23 was low. Hyperphosphataemic familial tumoural calcinosis/hyperostosis-hyperphosphataemia syndrome (HFTC/HHS) was diagnosed using whole genome sequencing that revealed a novel frameshift beyond the 584th threonine located in the lectin domain of UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 associated with a duplication of the 1748th thymine in the coding region of the corresponding gene. Furthermore, anti-nuclear, anti-centromere, and anti-cardiolipin antibodies were positive, implying that comorbid limited type scleroderma might play a role in tumoural calcinosis (TC) development. A low phosphate diet was prescribed with phosphate-lowering medications, including aluminium hydroxide, acetazolamide, and sevelamer hydrochloride. The patient displayed a decrease in serum phosphate levels from 6.5 to 5.5 mg/dL 10 months after the initiation of treatment, but her TC had not improved during treatment for more than 1 year. This case was interesting because the patient with HFTC/HHS exhibited TC despite being over her 60s, and subsequent scleroderma might contribute to the specific clinical course. When HFTC/HHS presents with elderly-onset TC, the involvement of comorbidities in exacerbating TC should be considered. HFTC/HHS occurs on an autosomal recessive basis, but its clinical course and manifestations differ significantly throughout the cases. HFTC/HHS may be undiagnosed until later in life because of its rarity, unfamiliarity, and phenotype diversity; therefore, HFTC/HHS should be included in the differential diagnosis of elderly patients with unexplained hyperphosphataemia or ectopic calcinosis. Comorbidities, including rheumatologic disorders, may contribute to developing HFTC/HHS-associated calcinosis.

Radiofrequency ablation for patients with recurrent or persistent secondary hyperparathyroidism after parathyroidectomy: initial experience.

Reoperation for recurrent or persistent secondary hyperparathyroidism (SHPT) after parathyroidectomy is challenging due to surgical scars and postoperative adhesions. Therefore, there is an increasing need to develop a new minimally invasive therapy. To analyze the efficacy of ultrasound (US)-guided radiofrequency ablation (RFA) in patients with recurrent or persistent SHPT after parathyroidectomy. From March 2013 to January 2022, 20 enlarged parathyroid glands in 10 patients with recurrent or persistent SHPT were treated with US-guided RFA. The levels of serum intact parathyroid hormone (iPTH), calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP), as well as clinical symptoms, were compared before and after RFA. The ablation procedure-related complications were also evaluated. The target range for iPTH levels was approximately 2-9 times the upper limit of normal (130-585 pg/mL). The mean follow-up time was 49.6 ± 34.5 months (range from 6 to101 months). The levels of serum iPTH, Ca, and P decreased significantly one day post-ablation. Six months after RFA, 70% of patients reached the targets for iPTH, and 50% of patients reached targets at the end of follow-up. Two patients underwent repeat ablation at 9 months and 6 years after RFA, respectively, due to persistently elevated iPTH levels, and both had serum iPTH concentrations in the recommended range at the recent follow-up visit. The patients' clinical symptoms significantly improved after ablation. Major complications after RFA included hoarseness (2/10) and permanent hypoparathyroidism (1/10). Severe hypocalcemia occurred in four patients (4/10) after ablation. US-guided percutaneous RFA for recurrent or persistent SHPT is safe, efficacious, and repeatable, and can significantly improve hyperparathyroidism-related symptoms.

Phase 2 study of upacicalcet in Japanese haemodialysis patients with secondary hyperparathyroidism: an intraindividual dose-adjustment study.

Upacicalcet is a novel small-molecule calcimimetic agent developed for intravenous injection. Here, we evaluated the long-term efficacy and safety of upacicalcet treatment via intraindividual dose adjustment in haemodialysis patients with secondary hyperparathyroidism (SHPT). A phase 2, multicentre, open-label, single-arm study was conducted. Upacicalcet was administered for 52weeks; the starting dose was 50μg thrice a week, and then adjusted to 25, 50, 100, 150, 200, 250, or 300μg, according to the dose-adjustment method set in the protocol. The primary endpoint was the percentage of patients with serum intact parathyroid hormone (iPTH) level achieving a target range of 60-240pg/mL (target achievement rate) at week 18. A total of 58 patients were administered upacicalcet. The target achievement rate of serum iPTH level at week 18 was 57.9%, which increased to 80.8% at week 52. The serum-corrected calcium (cCa) level decreased immediately after upacicalcet administration, but no further decrease was observed. Adverse events were observed in 94.8% of patients, and adverse drug reactions (ADRs) occurred in 20.7% of patients. The most common ADR was decreased adjusted calcium in eight patients; dizziness occurred as a serious ADR in one patient. The serum cCa level of patients who interrupted upacicalcet treatment at a serum cCa level of <7.5mg/dL recovered to ≥7.5mg/dL immediately after the interruption. In haemodialysis patients with SHPT, upacicalcet doses of 25-300μg for 52 weeks were found to be highly effective and well-tolerated, with minor safety concerns.

Aldosterone-producing adenoma is associated with urolithiasis in primary aldosteronism.

Primary aldosteronism (PA) is associated with urolithiasis as it causes hypercalciuria and hypocitraturia. However, the influence of different subtypes of PA on urinary stone formation remains unclear. This study aimed to evaluate the association between aldosterone-producing adenoma (APA) and the burden of urolithiasis in patients with PA. In the present study, we enrolled 312 patients with PA from a prospectively maintained database, of whom 179 had APA. Clinical, biochemical, and imaging data (including the presence, volume, and density of urinary stones on abdominal computed tomography) were compared between groups, with employment of propensity score matching (PSM) analysis to balance possible confounding factors. Kaplan-Meier analysis was used to estimate the acute renal colic event during follow-up. After PSM for age, sex, serum calcium, phosphate, blood urea nitrogen, creatinine, and uric acid, the APA and non-APA groups had 106 patients each. Patients with APA had higher serum intact parathyroid hormone (iPTH) (79.1 ± 45.0 vs 56.1 ± 30.3, P < 0.001) and a higher prevalence of urolithiasis (27.4% vs 12.3%, P = 0.006) than non-APA patients. During follow-up, a higher incidence of acute renal colic events was noted in the APA group than the non-APA group (P = 0.011); this association remained significant (P = 0.038) after adjustment for age and sex in Cox-regression analysis. Our data suggest that APA is associated with a heavier burden of urolithiasis and higher incidence of renal colic events compared to the non-APA subtype of PA.

Incidence and risk factors of hypoparathyroidism and hypocalcemia after hemithyroidectomy.

The incidence and risk factors for hypoparathyroidism after total thyroidectomy is well-known. However, the characteristics of hypoparathyroidism and hypocalcemia after hemithyroidectomy have not been investigated well. In this study, we aimed to evaluate the incidence, characteristics, and risk factors of hypoparathyroidism and hypocalcemia after hemithyroidectomy. We retrospectively analyzed the medical data of 321 patients who underwent hemithyroidectomy, with or without central neck dissection, from January 2012 to April 2019. We analyzed the serum intact parathyroid hormone (iPTH), calcium, and ionized calcium (iCa) levels serially (preoperatively and postoperatively on the operation day; days 1 and 3; and months 1, 3, 6, and 12) and evaluated risk factors for postoperative hypoparathyroidism and hypocalcemia. The mean iPTH and calcium levels decreased significantly after hemithyroidectomy on the operation day and postoperative days 1 and 3, and returned to the preoperative level at the postoperative 1-month follow-up. The mean iCa level decreased significantly on the operation day and postoperative day 1. Transient hypoparathyroidism and transient hypocalcemia occurred in 16 (5%) and 250 (78%) participants, and they recovered to normal levels postoperatively by 1month. Eight (2.5%) patients had mild symptoms of hypocalcemia necessitating oral calcium supplementation. No permanent hypoparathyroidism or hypocalcemia was observed. Preoperatively low serum iPTH and calcium levels were associated with transient hypoparathyroidism and hypocalcemia after hemithyroidectomy. Approximately 5% and 2.5% of participants showed transient hypoparathyroidism and mild symptomatic hypocalcemia after hemithyroidectomy. The risk factors for transient hypoparathyroidism and hypocalcemia include preoperative low serum iPTH and calcium levels.

Pharmacological profile of upacicalcet, a novel positive allosteric modulator of calcium-sensing receptor, in vitro and in vivo

Upacicalcet (formerly SK-1403/AJT240) is a novel non-peptide calcimimetic agent that acts as a calcium-sensing receptor (CaSR) agonist for the treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). We compared upacicalcet with other calcimimetics (etelcalcetide or cinacalcet) and examined its in vitro and in vivo characteristics in terms of its human CaSR agonistic activity, its efficacy in normal and CKD rats after a single administration, and its effect on gastric emptying in rats. Upacicalcet activated human CaSR depending on the extracellular calcium (Ca2+) concentration without exhibiting an agonistic action when the extracellular Ca2+ level was below the physiological level. On the other hand, etelcalcetide had an agonistic activity even in the absence of physiological levels of extracellular Ca2+. The intravenous administration of upacicalcet to normal and double-nephrectomized rats dose-dependently (0.03–3mg/kg and 0.3–30mg/kg, respectively) decreased the serum intact parathyroid hormone (iPTH) and serum Ca2+ levels; however, the effect of upacicalcet on the reduction in serum Ca2+ disappeared at extracellular Ca2+ levels below the physiologically range, even when administered at a dose higher (100-fold) than the effective dose. Furthermore, upacicalcet did not affect gastric emptying in normal rats when administered up to a dose of 10mg/kg (300-fold higher than the dose affecting serum iPTH levels), while the administration of cinacalcet significantly slowed gastric emptying by approximately 50%. These findings suggest that upacicalcet has potential as an alternative calcimimetic agent with good pharmacological properties and a lower risk of hypocalcemia and gastrointestinal complications.