Hyperparathyroidism, Serum Phosphorus and Dietary Intake in Hemodialysis Patients: Is There a Novel Relationship?

The management of hyperparathyroidism (intact parathyroid hormone (iPTH) serum levels > 585 pg/mL), frequently focuses on the appropriate control of mineral and bone markers, with the decrease in serum and dietary phosphorus as two of the targets. We aimed to investigate the association between iPTH, serum phosphorus levels and dietary intake. This was a cross-sectional, multicenter, observational study with 561 patients on hemodialysis treatment. Clinical parameters, body composition and dietary intake were assessed. For the analysis, patients were divided into three groups: (a) iPTH < 130, (b) iPTH between 130 and 585 and (c) iPTH > 585 pg/mL. The association between PTH, serum phosphorus and dietary intake was analyzed using linear regression models. In the whole sample, 23.2% of patients presented an iPTH > 585 pg/mL. Patients with higher iPTH levels were those with longer HD vintage and lower ages, higher serum phosphorus, serum calcium, Ca/P product, albumin and caffeine intake, and a lower dietary intake of phosphorus, fiber, riboflavin and folate. Higher serum phosphorus predicted higher iPTH levels, even in the adjusted model. However, lower dietary phosphorus and fiber intake were predictors of higher iPTH levels, including in the adjusted model. Our results bring new data to the relationship between dietary intake and iPTH values. Despite higher serum phosphorus being observed in patients with HPTH, an opposite association was noted regarding dietary phosphate and fiber.

Disease Manifestations and Complications in Dutch X-Linked Hypophosphatemia Patients.

X-linked hypophosphatemia (XLH) is the most common monogenetic cause of chronic hypophosphatemia, characterized by rickets and osteomalacia. Disease manifestations and treatment of XLH patients in the Netherlands are currently unknown. Characteristics of XLH patients participating in the Dutch observational registry for genetic hypophosphatemia and acquired renal phosphate wasting were analyzed. Eighty XLH patients, including 29 children, were included. Genetic testing, performed in 78.8% of patients, showed a PHEX mutation in 96.8%. Median (range) Z-score for height was - 2.5 (- 5.5; 1.0) in adults and - 1.4 (- 3.7; 1.0) in children. Many patients were overweight or obese: 64.3% of adults and 37.0% of children. All children received XLH-related medication e.g., active vitamin D, phosphate supplementation or burosumab, while 8 adults used no medication. Lower age at start of XLH-related treatment was associated with higher height at inclusion. Hearing loss was reported in 6.9% of children and 31.4% of adults. Knee deformities were observed in 75.0% of all patients and osteoarthritis in 51.0% of adult patients. Nephrocalcinosis was observed in 62.1% of children and 33.3% of adults. Earlier start of XLH-related treatment was associated with higher risk of nephrocalcinosis and detection at younger age. Hyperparathyroidism longer than six months was reported in 37.9% of children and 35.3% of adults. This nationwide study confirms the high prevalence of adiposity, hearing loss, bone deformities, osteoarthritis, nephrocalcinosis and hyperparathyroidism in Dutch XLH patients. Early start of XLH-related treatment appears to be beneficial for longitudinal growth but may increase development of nephrocalcinosis.

Feasibility of an Online Patient-Driven International Parathyroid Registry.

INTRODUCTION: Traditional parathyroid registries are labor-intensive and do not always capture long-term follow-up data. This study aimed to develop a patient-driven international parathyroid registry and leverage community connections to improve patient-centered care for hyperparathyroidism. METHODS: An anonymous voluntary online survey was developed using Qualtrics and posted in an international patient and advocate-run social media group affiliated with over 11,700 members. The survey was developed from a literature review, expert opinion, and discussion with the social media group managers. It consists of seven sections: patient demographics, past medical history, preoperative symptoms, laboratory evaluation, preoperative imaging studies, operative findings, and operative outcomes. RESULTS: From July 30, 2022, to October 1, 2022, 89 complete responses were received. Participants were from 12 countries, mostly (82.0%) from the United States across 31 states. Most participants were female (91.4%), White (96.7%) with a mean (±standard deviation) age of 58 ± 12 y. The most common preoperative symptoms were bone or joint pain (84.3%) and neuropsychiatric symptoms: including fatigue (82.0%), brain fog (79.8%), memory loss (79.8%), and difficulty with concentration (75.3%). The median (interquartile range) length from symptom onset to diagnosis was 40.0 (6.8-100.5) mo. Seventy-one percent of participants had elevated preoperative serum calcium, and 73.2% had elevated preoperative parathyroid hormone. All participants obtained preoperative imaging studies (88.4% ultrasound, 86.0% sestabimi scan, and 45.3% computed tomography). Among them, 48.8% of participants received two, and 34.9% had three imaging studies. The median (interquartile range) time from diagnosis to surgical intervention was 3 (2-9) mo. Twenty-two percent of participants traveled to different cities for surgical intervention. Forty-seven percent of participants underwent outpatient parathyroidectomy. Eighty-four percent of participants reported improved symptoms after parathyroidectomy, 12.4% required oral calcium supplementation for more than 6 mo, 32.6% experienced transient hoarseness after parathyroidectomy, and 14.6% required reoperation after initial parathyroidectomy. CONCLUSIONS: This international online parathyroid registry provides a valuable collection of patient-entered clinical outcomes. The high number of responses over 10 wk demonstrates that participants were willing to be involved in research on their disease. The creation of this registry allows global participation and is feasible for future studies in hyperparathyroidism.

Ultrasound-guided microwave ablation for tertiary hyperparathyroidism in patients with renal transplantation.

OBJECTIVE: To explore the safety and efficacy of ultrasound-guided microwave ablation (MWA) for tertiary hyperparathyroidism (THPT) in patients with renal transplantation (RT). METHODS: In total, fifteen patients with THPT after renal transplantation who underwent MWA were enrolled in the study. The pre- and post-MWA intact parathyroid hormone (iPTH), serum calcium, phosphorus, creatinine, urea nitrogen and estimated glomerular filtration rate (eGFR) values were compared. RESULTS: A total of 38 parathyroid hyperplastic nodules in 15 RT patients were treated with ultrasound-guided MWA. The mean (median, range) size of the hyperplastic parathyroid nodules was 11.5 mm (11 mm, 5-25 mm), and the average (median, range) ablation time was 163.5s (121 s, 44-406 s). The average levels of serum iPTH and calcium at 1 d, 7 d, 1 month, 3 months, 6 months, 1 year post-MWA and at the end of follow-up were significantly lower than those pre-MWA (all p < 0.05). Compared with the pre-MWA value (0.76 mmol/L), the serum phosphorus levels at 1 d post-MWA (0.63 mmol/L) were significantly decreased, and those at 7 d, 1 month, 3 months, 6 months, 1 year post-MWA and at the end of follow-up were significantly increased, but all were within the normal range. There was no significant difference in serum creatinine and eGFR pre-MWA and post-MWA. No major MWA-related complications occurred. CONCLUSION: Ultrasound-guided MWA shows potential as a viable treatment for THPT in RT patients. However, further studies are required to confirm its safety and effectiveness in larger cohorts of longer duration.

The association between proton pump inhibitors and hyperparathyroidism: a potential mechanism for increased fracture-results of a large observational cohort study.

Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture; however, the mechanism is unclear. PPI users taking calcium supplements were more likely to have hyperparathyroidism compared to non-users (OR 1.56, CI 1.08-2.23, p = 0.018). This highlights the importance of monitoring PPI use, especially in older adults. PURPOSE: Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture. Hyperparathyroidism may be implicated, but few studies have considered this relationship. This study evaluated the relationship between PPI use and hyperparathyroidism in older adults. METHODS: Participants were from the TUDA study, a large cross-sectional cohort of older Irish adults. Participants with an estimated glomerular filtration rate (eGFR) < 30 ml/min and serum calcium > 2.5 mmol/l were excluded to avoid hyperparathyroidism due to chronic renal disease and primary hyperparathyroidism. Hyperparathyroidism was defined as a parathyroid hormone (PTH) > 65 pg/ml. Multivariate regression models were used to analyse the relationship between PPI use and hyperparathyroidism. RESULTS: A total of 4139 participants met the inclusion criteria, of whom 37.8% (n = 1563) were taking PPI medication. PPI use was identified in 41.4% of calcium supplement users and 35.4% of non-calcium supplement users. Overall, compared to non-users of PPIs, those taking PPIs were older (74.8 vs 72.9 years, p < 0.001) and had a higher prevalence of hyperparathyroidism (17.8 vs 11.0%, p < 0.001). In those taking calcium supplements (but not in non-users), PPI use was significantly associated with hyperparathyroidism (OR 1.56, CI 1.08-2.23, p = 0.018) after adjusting for age, sex, body mass index, serum vitamin D, eGFR, timed-up-and-go, dairy intake, medications, and comorbidities. DISCUSSION: The results are consistent with the hypothesis of PPIs reducing calcium absorption, leading to a rise in PTH which could mediate increased fracture risk. No relationship of PPI use with hyperparathyroidism was observed in non-users of calcium supplements, possibly owing to lower dietary calcium intake. These results highlight the importance of monitoring PPI use, especially in older adults at risk of fracture.

Parathyroid carcinoma: impact of preoperative diagnosis on the choice of surgical procedure.

The operative procedure in the surgical treatment of parathyroid carcinoma differs from that of benign hyperparathyroidism. However, preoperative differentiation is often difficult. This study elucidated how clinicians diagnose parathyroid carcinoma and the relationship between preoperative diagnosis and the operative course. Using a retrospective chart review, twenty cases of parathyroid carcinoma from nine participating centers were examined. In 11 cases with preoperative suspicion of malignancy, at least one of these three features was found: elevated serum calcium level (>14 mg/dL), palpable mass, and irregular margin on ultrasonography. Although an intact parathyroid hormone (iPTH) threshold to suspect malignancy has not been established, six cases showed marked iPTH elevation exceeding 8.0 times the upper limit of normal. One case was excluded from analysis due to hemodialysis. Compared with the four cases that showed calcium elevation, the iPTH threshold might represent better sensitivity. Among 9 cases of benign preoperative diagnosis, six cases were performed with pericapsular resection. In three cases where malignancy was suspected in the middle of the operation, the recommended en bloc resection with ipsilateral thyroid lobectomy was not performed but a parathyroidectomy with surrounding soft tissue. In contrast, 10 preoperatively suspected cases underwent en bloc resection, and one case underwent pericapsular resection followed by supplementary ipsilateral hemithyroidectomy due to the uncertain pre- and intraoperative findings to determine the diagnosis. In conclusion, the surgical procedure for parathyroid carcinoma strongly depends on the preoperative diagnosis. The presence of excessive iPTH levels might contribute to improved preoperative diagnostic sensitivity for parathyroid carcinoma.

Pre-operative Cinacalcet Administration Reduces Immediate Post-operative Hypocalcemia Following Total Parathyroidectomy in Severe Renal Hyperparathyroidism.

BACKGROUND: In severe renal hyperparathyroidism (RHPT), whether administrating Cinacalcet before total parathyroidectomy can reduce post-operative hypocalcemia remains unclear. We compared post-operative calcium kinetics between those who took Cinacalcet before surgery (Group I) and those who did not (Group II). METHODS: Patients with severe RHPT (defined by PTH ≥ 100 pmol/L) who underwent total parathyroidectomy between 2012 and 2022 were analyzed. Standardized peri-operative protocol of calcium and vitamin D supplementation was followed. Blood tests were performed twice daily in the immediate post-operative period. Severe hypocalcemia was defined as serum albumin-adjusted calcium < 2.00 mmol/L. RESULTS: Among 159 patients who underwent parathyroidectomy, 82 patients were eligible for analysis (Group I, n = 27; Group II, n = 55). Demographics and PTH levels before Cinacalcet administration were comparable (Group I: 169 ± 49 pmol/L vs Group II: 154 ± 45, p = 0.209). Group I had significantly lower pre-operative PTH (77 ± 60 pmol/L vs 154 ± 45, p < 0.001), higher post-operative calcium (p < 0.05), and lower rate of severe hypocalcemia (33.3% vs 60.0%, p = 0.023). Longer duration of Cinacalcet use correlated with higher post-operative calcium levels (p < 0.05). Cinacalcet use for > 1 year resulted in fewer severe post-operative hypocalcemia than non-users (p = 0.022, OR 0.242, 95% CI 0.068-0.859). Higher pre-operative ALP independently correlated with severe post-operative hypocalcemia (OR 3.01, 95% CI 1.17-7.77, p = 0.022). CONCLUSION: In severe RHPT, Cinacalcet led to significant drop in pre-operative PTH, higher post-operative calcium levels, and less frequent severe hypocalcemia. Longer duration of Cinacalcet use correlated with higher post-operative calcium levels, and the use of Cinacalcet for > 1 year reduced severe post-operative hypocalcemia.

Morbidity and long-term outcome of surgery for renal hyperparathyroidism: results from a prospective cohort.

PURPOSES: Surgery remains an important treatment option for renal hyperparathyroidism (rHPT). The number of long-term outcome studies of parathyroidectomy is limited. METHODS: All consecutive patients with a parathyroidectomy for rHPT between 09/2009 and 04/2021 in a Belgian tertiary referral hospital were prospectively enrolled. The main outcomes were (long-term) cured proportion and postoperative morbidity (hypocalcemia, recurrent laryngeal nerve (RLN) palsy, re-intervention for bleeding, and wound morbidity). RESULTS: Sixty patients with a median age of 57 years were analyzed, including 23 patients before kidney transplantation, 23 patients without kidney transplantation, and 14 patients after kidney transplantation. Median time to transplant was 15 (6-24) months after parathyroidectomy. Morbidity was low with only two non-urgent returns to theatre (wound infection and non-compressive hematoma), two temporary RLN paralyses, and no 30-day mortality. Length of hospital stay was longer in patients with parathyroidectomy before kidney transplant, due to a more severe and prolonged need for calcium supplementation. After a median follow-up of 63 months, 37 patients (62%) were still alive, and 11 patients (18%) developed a recurrence. CONCLUSIONS: This single-surgeon, single-center cohort with long-term follow-up confirms the safety and excellent 'cure' proportions of surgery for rHPT but stretches the importance of long-term follow-up.

Persistent primary hyperparathyroidism secondary to an ectopic mediastinal adenoma in a young adult: A case report / Journal of the ASEAN Federation of Endocrine Societies

@#Primary hyperparathyroidism commonly affects elderly women. When present in the young population, it is usually asymptomatic, most frequently due to a parathyroid adenoma and the definitive management is surgical excision. Uncommonly, 5-10% of patients fail to achieve long-term cure after initial parathyroidectomy and 6-16% of them is due to an ectopic parathyroid adenoma that will require focused diagnostic and surgical approaches. We report a 21-year-old male who had bilateral thigh pain. Work-up revealed bilateral femoral fractures, brown tumors on the arms and multiple lytic lesions on the skull. Serum studies showed hypercalcemia (1.83 mmol/L), elevated parathyroid hormone [(PTH) 2025.10 pg/mL], elevated alkaline phosphatase (830 U/L), normal phosphorus (0.92 mmol/L) and low vitamin D levels (18.50 ng/mL). Bone densitometry showed osteoporotic findings. Sestamibi scan showed uptake on the left superior mediastinal region consistent with an ectopic parathyroid adenoma. Vitamin D supplementation was started pre-operatively. Patient underwent parathyroidectomy with neck exploration; however, the pathologic adenoma was not visualized and PTH levels remained elevated post-operatively. Chest computed tomography with intravenous contrast was performed revealing a mediastinal location of the adenoma. A repeat parathyroidectomy was done, with successful identification of the adenoma resulting in a significant drop in PTH and calcium levels. Patient experienced hungry bone syndrome post-operatively and was managed with calcium and magnesium supplementation. A high index of suspicion for an ectopic adenoma is warranted for patients presenting with hypercalcemia and secondary osteoporosis if there is persistent PTH elevation after initial surgical intervention. Adequate follow-up and monitoring is also needed starting immediately in the post-operative period to manage possible complications such as hungry bone syndrome.

Parathyroid carcinoma: Single centre experience.

OBJECTIVE: Parathyroid Carcinoma is a rare malignant neoplasm, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single centre regarding the management and outcome of patients with parathyroid carcinomas and revise relevant literature. DESIGN: Retrospective review of all patients with parathyroid carcinoma evaluated at a tertiary oncologic centre from 1991 until 2021. RESULTS: Seventeen patients were identified (10 males), with a mean age at diagnosis of 53 ± 16 years and a median follow-up of 16.5 years. Most patients presented with hypercalcemia (n = 15), with a mean serum calcium concentration of 13.5 mg/dl (9.6-16.5) and mean PTH of 1173 pg/ml (276-2500). Hyperparathyroidism-mediated organ damage was observed in most patients (n = 16), with predominant renal (n = 12) and skeletal (n = 9) complications. En bloc surgical resection was performed in nine patients. Three patients underwent adjuvant radiotherapy. Recurrence was observed in 8 cases (47.1%) after a median of 24 months following surgery and no independent predictors of recurrence were identified. The overall survival and disease specific survival at 5-year was 88% and 94%, respectively. CDC73 mutations were present in 38.5% of analysed patients and one patient was diagnosed with MEN1. CONCLUSION: Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Therefore, preoperatively high index of suspicion is paramount to optimize patient care. This is, to our knowledge, the largest Portuguese cohort published so far.

Effective long-term management of parathyromatosis-related refractory hypercalcemia with a combination of denosumab and cinacalcet treatment.

Parathyromatosis is a rare cause of persistent or recurrent primary hyperparathyroidism and hypercalcemia due to the presence of hyperfunctioning foci of parathyroid tissue in the neck and/or mediastinum. We describe the case of a male patient who presented with severe hypercalcemia and a left-sided palpable parathyroid mass. Over the course of the next 18 years, the patient underwent neck exploration surgery on multiple occasions due to recurrent primary hyperparathyroidism and refractory hypercalcemia, complicated by nephrolithiasis and impairment of renal function, while bone mineral density was preserved. Histological findings and the natural course of the disease were consistent with parathyromatosis. Medical interventions with oral bisphosphonates or high-dose cinacalcet failed to control the patient's hypercalcemia. The combination of monthly denosumab and cinacalcet was, however, successful in maintaining the patient's serum calcium in the normal/upper-normal range over a 36-month period with no significant side effects. This is the first report of off-label denosumab use in combination with cinacalcet in the long-term management of parathyromatosis-related refractory hypercalcemia.

Usefulness of PET/CT with Carbon-11-Labeled Methionine in the Diagnosis of Tertiary Hyperparathyroidism.

Introduction: Tertiary hyperparathyroidism (tHP) may develop in patients treated with hemodialysis or peritoneal dialysis. Parathyroidectomy may result in a significant reduction in the severity of symptoms. For the effective surgical treatment of hyperparathyroidism, proper localization of the parathyroid glands prior to surgery is essential. The sensitivity of scintigraphy in the diagnosis of tHP is lower than in the diagnosis of primary hyperparathyroidism. In recent years, positron emission tomography (PET/CT) has been gaining importance, usually as a complementary technique. Aim: The aim of this study was to determine the usefulness of PET/CT with [11C]MET in the preoperative localization diagnosis of patients with tertiary hyperparathyroidism caused by chronic kidney disease, in whom first-line diagnostic methods did not allow the localization of pathologically parathyroid glands. Material and methods: The study was conducted in a group of 19 adult patients with severe tHP who were resistant or intolerant to non-invasive treatment, with negative results of scintigraphy and ultrasonography of the neck. The study protocol included measurement of the concentration of calcium, phosphorus, and PTH in the blood serum and performing PET/CT with [11C]MET. Results: A positive result of PET/CT was obtained in 89.5% of the patients (17/19). Parathyroidectomy was performed in 52.9% of the patients (9/17) with positive results of PET/CT with [11C]MET, which were fully consistent with the results of the histopathological examinations of the removed parathyroid glands. On this basis, the sensitivity of PET/CT with [11C]MET in the preoperative localization diagnosis of patients with tHP was found to be 100%. Multiple lesions were visualized in 57.9% of the patients (11/19). Ectopic lesions were visualized in 21.1% of the patients (4/19). Conclusions: PET/CT with [11C]MET is a sensitive technique for the second-line preoperative imaging of parathyroid glands in patients with tertiary hyperparathyroidism in whom first-line examinations, such as ultrasound and scintigraphy, has failed.

Drug-Related Hypercalcemia.

This review focuses on the commonly prescribed medicaments that can be responsible for hypercalcemia, considering the prevalence, the predominant pathophysiological mechanisms, and the optimal medical management of each drug-induced hypercalcemia. Vitamin D supplements and 1α-hydroxylated vitamin D analogues increase intestinal calcium absorption, renal calcium reabsorption as well as bone resorption. In patients with hypoparathyroidism receiving recombinant human PTH, transient hypercalcemia can occur because of overtreatment, usually during acute illness. Thiazide-induced hypercalcemia is mainly explained by enhanced renal proximal calcium reabsorption, changing preexistent asymptomatic normocalcemic or intermittently hypercalcemic hyperparathyroidism into the classic hypercalcemic hyperparathyroidism. Lithium causes hypercalcemia mainly by drug-induced hyperparathyroidism.

Denosumab-Induced Hypocalcemia and Hyperparathyroidism in de novo Kidney Transplant Recipients.

INTRODUCTION: Denosumab represents a realistic treatment option to increase bone mineral density in kidney transplant recipients (KTRs). It is still unknown how and at what extent posttransplantation bone disease and graft function influence the effects of denosumab on mineral metabolism indexes. In this study, we analyze risk factors of hypocalcemia and parathyroid hormone (PTH) increase after denosumab administration in eighteen de novo KTRs and its management before and after this treatment. METHODS: We conducted a monocentric, observational, prospective study on de novo KTRs. All KTRs enrolled received a single 60 mg subcutaneous dose of denosumab every 6 months. Before kidney transplantation, no patients were treated with calcio-mimetic. After kidney transplantation and before antiresorptive therapy, no patients were treated with calcio-mimetic drugs and/or vitamin D receptor agonists, while all patients received nutritional vitamin D supplementation (from 1,000 IU to 1,500 IU daily). RESULTS: Hypocalcemia was related to the degree of lumbar osteoporosis (p = 0.047); the increase in the PTH level was correlated to baseline bone turnover markers (bone alkaline phosphatase, serum osteocalcin, and ß-C-terminal telopeptide), the 25 OH status, and eGFR. The introduction of calcitriol, after the PTH increase, in addition to cholecalciferol was necessary to ensure an adequate control of serum calcium and PTH during a follow-up of 15 months. Following the treatment with denosumab, it was observed an improvement of areal bone mineral density both at lumbar and femoral sites with a mean percentual increase of 1.74% and 0.25%, respectively. CONCLUSIONS: Denosumab is an effective treatment for bone disease in KTRs. In our study, the increase in PTH is not a transient event but prolonged throughout the follow-up period and requires continuous supplementation therapy with calcitriol.

Intensive calcium monitoring improves outcomes on hungry bone syndrome in hyperparathyroidism.

Objectives. Hungry bone syndrome (HBS) is a severe and underdiagnosed complication of parathyroidectomy in the treatment of primary hyperparathyroidism (PHP) and secondary hyper-parathyroidism to chronic kidney disease (SHP-CKD).Methods. A longitudinal study was conducted to compare the postoperative outcomes of patients who developed HBS in two different time frames: before and after implementing a protocol with an intensive electrolytic monitoring and an algorithm regarding electrolytic supplementation.Results. Overall, 77 parathyroidectomies were included. In PHP, a protocol implementation led to an increased admission of patients in the Intermediate Care Unit for intensive electrolytic monitoring (p<0.001) and an increased rate of oral calcium replacement during hospital stay (p=0.013) compared to pre-protocol era. In SHP-CKD, duration of intravenous calcium replacement was reduced (p=0.010). The prevalence of HBS (9.8% in PHP and 58.3% in SHP-CKD) was similar between the two periods, although its diagnosis had an increased trend in PHP since the protocol implementation. None of the diagnosis of HBS was established due to hypocalcemic symptoms in the post-protocol era (contrary to pre-protocol period, p=0.021). Both hypocalcemia length and duration of surgical ward hospitalization were reduced (p=0.047 and p=0.042, respectively).Conclusions. An improved assessment of hyperparathyroidism and a decrease in HBS severity were noted in the post-protocol era. We strongly recommend the implementation of a standardized protocol with an intensive phosphocalcium monitoring in the high-risk patients who undergo parathyroidectomy due to hyperparathyroidism as it improves the health care and management of HBS.

Anesthetic considerations in hyperparathyroid crisis: A case report.

INTRODUCTION: Hyperparathyroid crisis is a rare and potentially life-threatening complication of severe calcium intoxication. Parathyroidectomy is the only curative method for hyperparathyroid crisis. Several case reports and case series have been published on the medical and surgical treatments for hyperparathyroid crisis, however, few reports have focused on the associated perioperative anesthetic management. PATIENT CONCERNS: A 48-year-old Chinese woman presented with a 2-week history of nausea and vomiting and complained of mental status alteration including confusion and agitation in the 24 hours prior to her admission. She denied any history of past illness. Laboratory tests showed severe hypercalcemia crisis with a serum calcium level of 5.21 mmol/L and a serum intact parathyroid hormone level of > 5000 pg/mL. DIAGNOSIS: The diagnosis was hyperparathyroid crisis, acute kidney injury, acute liver injury, rhabdomyolysis, infection, and shock. INTERVENTIONS: She underwent initial management with aggressive intravenous fluid resuscitation, loop diuretic treatment, vitamin D supplement, intravenous bisphosphonates, and calcitonin therapy. However, her condition worsened, and she was transferred to the operating theater for a parathyroidectomy under general anesthesia. She was under general anesthesia and monitored with electrocardiogram, pulse oxygen saturation, continuous arterial blood pressure, central venous pressure and nasopharyngeal temperature. Cardiac output and stroke volume variation were monitored from the FloTrac system. After liberal fluid rehydration, circulatory support, cooling treatment and calcium supplement after tumor removal, her unstable vital signs gradually improved. OUTCOMES: After meticulous anesthetic management by the anesthesiologist and complete tumor resection by the surgeon, she survived this fatal disease. The patients was discharged on postoperative day 37 without any sequelae. LESSONS: Patients with hyperparathyroid crisis should undergo a thorough preoperative evaluation. Difficult airway, fluid depletion, multiple organ dysfunction, hypercoagulability, and concomitant diseases are the primary challenges in anesthetic management. After tumor removal, the serum calcium level should be monitored closely and calcium should be supplemented in a timely manner to prevent serious complications.

Intra-operative parathyroid hormone evaluation is superior to frozen section analysis in parathyroid surgery.

BACKGROUND: Surgery is currently the only treatment option for patients with primary hyperparathyroidism (PHPT). Recently, minimally invasive parathyroidectomy (MIP) has begun to replace traditional bilateral neck exploration (BNE). OBJECTIVE: The aim of this study is to compare the results of parathyroidectomies performed in our hospital over the past decade that were guided by intra-operative parathyroid hormone (IOPTH) sampling or frozen section (FS) analysis. MATERIAL AND METHODS: Data on 697 patients who underwent parathyroidectomies in the Department of Endocrine Surgery, Dokuz Eylul University between January 2005 and 2018 were included in this study. Patients with malignancies other than thyroid papillary microcarcinoma and parathyroid cancer were excluded from the study. RESULTS: The concomitant use of neck ultrasound (US) and technetium 99m Sestamibi (99mTc MIBI) scintigraphy successfully localized the hyperfunctioning parathyroid glands in nearly 96% of cases. As compared with the IOPTH group, the operation time was longer in the FS group (p < 0.001), and the need for postoperative calcium (Ca) supplementation was higher (p < 0.001). The duration of hospitalization (days) was significantly higher in the FS group (4.2 ± 3.4 vs. 2.6 ± 1.9) as compared with that in the IOPTH group (p < 0.001). In addition, the recurrence rate in the FS group was significantly higher than that in the IPOTH group (p = 0.002). CONCLUSION: IOPTH sampling is a safe and effective method when performed by experienced surgeons and with appropriate preoperative screening. This study emphasizes that IOPTH sampling. We believe that the success in parathyroid surgery is due to three factors: correct indication, accurate localization and experienced surgeon.

Effect of Parathyroidectomy Timing in Kidney Transplant Recipients on Graft Function.

OBJECTIVES: Persistent hyperparathyroidism can have a deleterious effect on graft function in kidney transplant recipients, although serum calcium, phosphorus, and parathyroid hormone levels tend to normalize after successful transplant. Parathyroidectomy can result in sustained amelioration of persistent hyperparathyroidism despite graft failure risk and unfavorable graft outcomes. Data on this issue are limited and conflicting. Here, we evaluated the effects of parathyroidectomy on graft function in kidney transplant recipients. MATERIALS AND METHODS: This retrospective study included 249 adult kidney transplant recipients (121 deceased-donor/128 living-donor; 142 males/107 females; mean age of 39.3 ± 11.6 y; mean follow-up of 46.5 ± 23.5 mo). Participants were grouped as those without (n = 222), those with pretransplant (n = 12), and those with posttransplant (n = 15) parathyroidectomy. Graft outcomes and serum calcium, phosphorus, and parathyroid hormone levels were studied. RESULTS: Serum calcium levels at baseline and at 1, 3, 6, and 12 months and parathyroid hormone levels at baseline and at 6 and 12 months were higher and serum phosphorus levels at 3, 6, and 12 months were lower in the posttransplant parathyroidectomy group versus the other groups (P < .001). We observed no significant differences between groups regarding serum calcium, phosphorus, and parathyroid hormone levels at last visit. Estimated glomerular filtration rates at 3, 6, and 12 months and at last visit in the pretransplant parathyroidectomy group were higher than in those without parathyroidectomy (P < .05) and higher at 6 and 12 months than in the posttransplant parathyroidectomy group (P < .05). No significant differences regarding graft loss and patient mortality were observed among the 3 groups (P > .05). CONCLUSIONS: Parathyroidectomy resulted in sustained decreased levels of serum calcium and parathyroid hormone. We observed no graft failure risk associated with parathyroidectomy in our study. Parathyroidectomy before transplant is advantageous with better graft function.

Successful Use of Denosumab for Life-Threatening Hypercalcemia in a Pediatric Patient with Primary Hyperparathyroidism.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is rare and usually symptomatic in children. There is no approved medication to lower serum calcium levels in this patient group. Denosumab is used in adult patients with osteoporosis and hyperparathyroidism. To our knowledge, only 1 case of denosumab treatment in a child with severe PHPT has been reported to date. CASE PRESENTATION: A 16-year-old female was referred to our clinic with symptoms including pathologic fractures, nausea, emesis, and progressive weight loss. At admission, her serum total calcium was 4.17 mmol/L (reference range 2.15-2.55), parathyroid hormone 2,151 pg/mL (15-65), and phosphate 1.07 mmol/L (1.45-1.78). Due to potentially life-threatening hypercalcemia, denosumab 60 mg subcutaneously was administered after obtaining informed consent. Serum calcium levels were reduced within 12 h of injection and the patient's condition rapidly improved, which allowed genetic testing to be done prior to surgery. A heterozygous mutation in the CDC73 gene was revealed, and a parathyroidectomy was performed on day 22 after denosumab administration. Morphological examination revealed solitary parathyroid adenoma. After surgery, hypocalcemia developed requiring high doses of alfacalcidol and calcium supplements. CONCLUSION: Our case supports the previous observations in adults that denosumab can be safely and effectively used as a preoperative treatment in patients with PHPT and severe hypercalcemia and shows that it may be used in pediatric patients.

Microsatellite instability driven metastatic parathyroid carcinoma managed with the anti-PD1 immunotherapy, pembrolizumab.

The present case report describes a 65-year-old man with Lynch syndrome and hypercalcaemia associated with hyperparathyroidism. Parathyroid surgery confirmed the diagnosis of parathyroid carcinoma. Serum calcium and parathyroid hormone (PTH) concentrations serially increased after initial surgery. Imaging study and subsequent biopsy confirmed lung metastases with mismatch repair deficiency. Pembrolizumab was initiated achieving 60% reduction in tumour burden.