Hypercalcemia In Primary Hyperparathyroidism Research Articles

Exacerbation of hypercalcaemia in primary hyperparathyroidism following immobilisation in the elderly

Exacerbation of hypercalcaemia in primary hyperparathyroidism following immobilisation in the elderly

Hypercalcemia in Primary Hyperparathyroidism with Manifestations of Acute Pancreatitis

Background: Primary hyperparathyroidism can result in hypercalcemia and hypophosphatemia which can cause gastrointestinal symptoms, electrolyte disturbances, renal dysfunction, and acute pancreatitis. The association between pancreatitis and primary hyperparathyroidism is rarely discussed. Case Illustration: We report a 32-year-old man who presented with a history of abdominal pain, nephrolithiasis, and increasing calcium serum. Primary hyperparathyroidism was overlooked until the patient was referred due to pancreatitis. The patient had additional risk factors for pancreatitis such as a history of alcohol consumption and hypertriglyceridemia. The patient had a worsening condition and died because of a septic condition and multiple organ failure. Conclusion: Hyperparathyroidism can cause acute pancreatitis through hypercalcemia with the mechanisms of trypsinogen activation, pancreatic duct obstruction, and genetics. In patients with acute pancreatitis with hypercalcemia, further hyperparathyroidism evaluation is necessary.

SAT228 Denosumab Associated Severe Hypocalcemia Due To Vitamin D Deficiency In A Patient With Undiagnosed Primary Hyperparathyroidism

Abstract Disclosure: S. Bendaram: None. P.J. Bhatt: None. V. Kantorovich: None. Background: The Human monoclonal antibody, Denosumab is a widely used antiresorptive therapy for Osteoporosis, which in the presence of risk factors can lead to hypocalcemia. We present an interesting case of severe and prolonged hypocalcemia due to Denosumab therapy, due to Vitamin D deficiency from malabsorption, despite the presence of undiagnosed Primary Hyperparathyroidism (PHPT). Case Presentation: 74-year old white female with a history of Crohn’s disease s/p ileostomy, Osteoporosis on Denosumab, Seizure disorder on Divalproex, and Parkinson’s disease presented to the ED for worsening altered mental status and decreased oral intake for at least 2 weeks prior to admission. On presentation, she was alert, oriented to person only, complaining of body aches. She was on no vitamin D supplements. Vital signs were unremarkable except for low BMI of 17.05 kg/m2. Physical exam revealed a chronic upper extremity tremor and a new facial mouth tremor associated with bruxism. Chvostek and Trousseau signs were negative, however this was after 1 dose of IV calcium gluconate in the ED. On presentation, initial labs revealed total calcium of 5.3 mg/dL [8.7-10.5], Albumin 4.7 g/dL [3.4-4.8], Magnesium 1.2 mg/dL [1.6-2.7], creatinine 1.5 mg/dL [04-1.1] (baseline 1.0). Further testing showed ionized calcium of 0.56 mmol/L [1.17-1.33], 25 Hydroxy Vitamin D 9 ng/mL [30-100], PTH 777 pg/mL [15-65] and phosphorus 3.6 mg/dL [2.7-4.5]. She was treated with IV calcium gluconate, 50,000 IU weekly vitamin D3 and calcium citrate 950mg oral BID, followed by which her total calcium went up to 12 mg/dl, with ionized calcium elevated at 1.36 mmol/L, while herPTH levels stayed inappropriately normal at 55 pg/ml. On the day of discharge, 25-OH-Vitamin D was 15 ng/dl, PTH 222 pg/ml and ionized calcium 1.07 mmol/L, when she was alert, oriented, with resolution of bone pains. Conclusion: Hypercalcemia in PHPT is from activation of osteoclasts and when these cells are inhibited by antiresorptive therapy, intestinal absorption will remain the primary source of plasma calcium levels. This explains the severe and prolonged hypocalcemia caused by Denosumab owing to its mechanism of action and long elimination half life, in our patient with Vitamin D deficiency on the background of malabsorption, despite a combination of primary and secondary elevation of PTH. Careful baseline assessment of calcium and Vitamin D levels, along with adequate supplementation and regular monitoring should be undertaken in all patients treated with Denosumab to avoid this. Presentation: Saturday, June 17, 2023

Persistence and Recurrence of Hypercalcemia After Parathyroidectomy Over 5 Decades (1965-2010) in a Community-based Cohort.

There is limited long-term follow-up of patients undergoing parathyroidectomy. Recurrence is described as 4% to 10%. This study evaluated persistence and recurrence of hypercalcemia in primary hyperparathyroidism after parathyroidectomy. Single-institution retrospective (1965-2010) population-based cohort from Olmsted County (MN) of patients undergoing surgery for primary hyperparathyroidism. Patients' demographic data, preoperative and postoperative laboratory values, clinical characteristics, surgical treatment, and follow-up were noted. A total of 345 patients were identified, 75.7% female, and median age 58.4 years [interquartile range (IQR): 17.6]. In all, 68% of patients were asymptomatic and the most common symptoms were musculoskeletal complaints (28.4%) and nephrolithiasis (25.6%). Preoperative median serum calcium was 11mg/dL (IQR: 10.8-11.4mg/dL), and median parathyroid hormone was 90pg/mL (IQR: 61-169 pg/dL). Bilateral cervical exploration was performed in 38% and single gland resection in 79% of cases. Median postoperative serum calcium was 9.2mg/dL (IQR: 5.5-11.3). Nine percent of patients presented persistence of hypercalcemia, and recurrence was found in 14% of patients. Highest postoperative median serum calcium was 10mg/dL (IQR: 6-12.4), and median number of postoperative calcium measurements was 10 (IQR: 0-102). Postoperative hypercalcemia was identified in 37% of patient. Fifty-three percent were attributed to secondary causes, most commonly medications, 22%. Three percent of patients required treatment for postoperative hypercalcemia. Median time to recurrence and death were 12.2 and 16.7 years, respectively. Recurrent hypercalcemia after successful parathyroidectomy is higher than previously reported. Most cases are transient and often associated to other factors with only the minority requiring treatment. Long-term follow-up of serum calcium should be considered in patients after successful parathyroidectomy.

Lower than recommended doses of cinacalcet are effective and well tolerated in the control of hypercalcaemia of primary hyperparathyroidism

Lower than recommended doses of cinacalcet are effective and well tolerated in the control of hypercalcaemia of primary hyperparathyroidism

Denosumab for management of severe hypercalcemia in primary hyperparathyroidism.

Hypercalcemic crisis is a severe but rare complication of primary hyperparathyroidism (PHPT), and data on denosumab treatment of patients with this disease is still very limited. The aim of this paper is to investigate the hypocalcemic effect of denosumab in PHPT patients with severe hypercalcemia when surgery should be delayed or is impossible for some reasons. We performed a retrospective study of 10 patients. The analysis included the use of biochemical markers of calcium-phosphorus metabolism, which were followed after the administration of 60 mg of denosumab. The trend to calcium reduction was already determined on the 3rd day after denosumab administration. In most cases the decrease in serum calcium level to the range of 2.8 mmol/L on average or lower was observed on the 7th day (P = 0.002). In addition to a significant increase in calcium levels we confirmed a significant increase in the estimated glomerular filtration rate on 7th day (P = 0.012). After that, seven patients underwent successful parathyroidectomy and achieved eucalcemia or hypocalcemia, one patient developed the recurrence of parathyroid cancer after initial surgery, while two patients with severe cardiovascular pathology refused surgery. Our study shows that denosumab is a useful tool in PHPT-associated hypercalcemia before surgery or if surgery is contraindicated.

Could there be a role of serum zonulin increase in the development of hypercalcemia in primary hyperparathyroidism.

To evaluate the serum level of zonulin, which is an intestinal permeability (IP) biomarker, in primary hyperparathyroidism (PHPT) and to investigate the relationship between zonulin, calcium, and parathormone (PTH) levels. The study included 34 healthy control (HC) and 39 patients with PHPT. Serum calcium, phosphorus, magnesium, creatinine, albumin, and 24 h urine calcium levels were measured in all groups. Serum levels of zonulin were measured quantitatively by enzyme-linked immunosorbent assay (ELISA). Urinary ultrasonography (to assess the presence of nephrolithiasis) and dual energy X-ray absorptiometry (to assess the presence of osteoporosis) were used to evaluate complications related to PTHP. Serum zonulin levels were significantly higher in the PHPT group than the HC group (p < 0.001). Zonulin levels were significantly positively correlated with plasma PTH and serum calcium levels (r = 0.600, p < 0.001 and r = 0.610, p < 0.001; respectively). There was no correlation between serum zonulin levels and adenoma volume. Serum zonulin level increases in patients with PHPT. Serum zonulin levels show a moderate/strong positive correlation with serum calcium and plasma PTH levels. This suggests that IP increase may play a role in the development of hypercalcemia in patients with PHPT.

Short-term medical treatment of hypercalcaemia in primary hyperparathyroidism predicts symptomatic response after parathyroidectomy.

Primary hyperparathyroidism is often associated with non-disease-specific symptoms. The aim of this study was to evaluate whether normalization of hypercalcaemia with short-term medical treatment can be used to predict the effects of parathyroidectomy and guide in surgical decision-making. This observational study included patients who received calcimimetic treatment for 4 weeks before parathyroidectomy (30-60 mg daily). A panel of tests was used to assess various aspects of quality of life (European Organisation and Treatment of Cancer QLQ-C30 core questionnaire, Hospital Anxiety and Depression Scale and Positive State of Mind questionnaire), cognitive function (Montreal Cognitive Assessment) and muscle strength (timed-stands test). The tests were carried out at baseline, after 4 weeks of calcimimetic treatment, and at 6 weeks and 6 months after parathyroidectomy. The predictive values of changes during calcimimetic treatment were determined for each test. The study included 110 patients of median age 62 years (91 women). Calcimimetic treatment resulted in normalization of calcium levels and improvements in quality-of-life parameters. The time spent on the timed-stands test was significantly shortened. Eleven of 38 participants with a baseline Montreal Cognitive Assessment score below 26, indicating mild cognitive impairment, reached scores of at least 26 during treatment with calcimimetic. Improvements during treatment with calcimimetic correlated well with postoperative outcomes (positive predictive values 74-96 per cent). The method described in this study may be used to aid surgical decision-making for patients with primary hyperparathyroidism and non-disease-specific symptoms by predicting the effects of normalization of hypercalcaemia.

SUN-496 A Perioperative Risk For Exacerbation of Hypercalcemia in Primary Hyperparathyroidism

[Introduction] Primary hyperparathyroidism (PHPT) occasionally presents a hyperparathyroid crisis which provides a pivotal cue for its diagnosis. However, the perioperative risk for exacerbation of hypercalcemia has been unknown in PHPT. We herein report 2 cases of PHPT which presented a hyperparathyroid crisis during the perioperative period for other complications. [Case presentaion] Case 1; A 81-year-old man was referred to our center due to urinary stone and hypercalcemia. Baseline laboratory data were as follows; corrected serum Ca 11.2 mg/dl; serum P 2.0 mg/dl; whole PTH 89.6 pg/ml, eGFR 49 ml/min/1.73m2. CT revealed a neck tumor of 10 mm with 99mTc-MIBI uptake, which was considered as a cause of PHPT. Simultaneously, CT also pointed out thoracic aortic aneurysm of 70 mm. Therefore, he underwent endovascular stent graft therapy prior to tumorectomy of PHPT. The procedure of stent graft was successfully performed but also caused subarachnoid hemorrhage and acute kidney injury (AKI). Corrected Ca level was subsequently elevated to 12.4 mg/dl, implying an exacerbation of PHPT. He received 60 mg denosumab administration in order to control Ca level complicated with AKI, resulted in improvement of hypercalcemia. However, PTH level was not significantly changed (57.4 pg/ml) during the period, indicated that lower urinary excretion of calcium due to AKI was the main cause of Ca level elevation. Case 2; A 57-year-old woman was admitted to our center due to incidental hypercalcemia. Baseline laboratory data were as follows; corrected serum Ca 12.5 mg/dl; serum P 2.1 mg/dl; whole PTH 140 pg/ml, eGFR 74 ml/min/1.73m2. CT revealed a neck tumor of 17 mm with 99mTc-MIBI uptake, considered as a cause of PHPT. Unexpectedly, MR imaging revealed meningioma of 48 mm on the Turkish saddle. She underwent embolization and removal of meningioma prior to tumorectomy of PHPT. After surgery, she had a persistent disturbance of consciousness because of hypernatremia (over 160 mM) and hypercalcemia (17.2 mg/dl) complicated with AKI. As a hyperparathyroid crisis, we administered 60 mg denosumab and continued fluid replacement therapy, leading to gradual improvement of electrolyte imbalances. PTH level was significantly elevated to 443 pg/ml compatible with a hyperparathyroid crisis. Her serum Ca level was kept lower than 12 mg/dl by denosumab for more than 3 months. [Conclusion] Our cases suggested that serum Ca level in PHPT could be influenced by perioperative conditions, although the trigger for exacerbation of PHPT remains unclear. Management of PHPT should be considered before surgery for other complications. Denosumab is useful for management of PHPT regardless of renal function.

The effect of primary hyperparathyroidism on pancreatic exocrine function.

Elastase-1 is a proteolytic enzyme secreted by pancreatic acinar cells, and measurements of the concentration this enzyme are used to evaluate pancreatic exocrine function. We aimed to determine whether pancreatic exocrine function declines due to chronic hypercalcemia by measuring fecal elastase levels. 75 patients with primary hyperparathyroidism (18 men and 47 women) and 30 healthy subjects (11 men and 19 women) participated in this study. Renal function tests, lipid parameters, bone mineral density, and serum calcium, phosphorus, vitamin D, parathormone, glucose, and thyroid stimulating hormone levels as well as fecal elastase concentrations, were determined in these patients and controls. The mean fecal elastase level was 335.3±181.4μg/g in the PHPT group and 317.4±157.3μg/g in the control group. There was no significant difference in fecal elastase levels between the two groups (p=0.5). Chronic hypercalcemia in primary hyperparathyroidism did not decrease the fecal elastase level, which is an indirect indicator of chronic pancreatitis; therefore, chronic hypercalcemia in PHPT may not cause chronic pancreatitis.

Diagnostische Aufarbeitung und Management der Hyperkalzämie des Hundes am Beispiel des primären Hyperparathyreoidismus

Hypercalcaemia can be caused by many different diseases. This article summarizes the causes, pathophysiologic mechanisms and diagnostic procedures as well as treatment recommendations. The main focus is on hypercalcaemia in primary hyperparathyroidism (PH), complemented by a case report. An elevated total calcium level should generally be investigated and verified by measurement of ionized calcium concentration. The further diagnostic approach depends on the phosphate level. Tumour screening, measurement of parathormone and parathromone-related protein and sonography of parathyroid glands may be necessary. If the calcium-phosphate-product exceeds 60 mg/dl, there is a risk of tissue mineralisation and a rapid treatment of hypercalcaemia is required. For acute therapy, sodium chloride infusion, furosemide and glucocorticoids can be used. Glucocorticoids should only be given after strict indication and after a definite diagnosis. For long-term management, bisphosphates, particularly alendronate, are increasingly used successfully. Causal therapy of PH can be performed by parathyreoidectomy, heat ablation or ethanol ablation. Thereafter, particularly in cases of severe preoperative hypercalcaemia, hypocalcaemia can occur. Treatment is performed using vitamin D3 (calcitriol), which may also be given preoperatively in cases of severe hypercalcaemia. A concomitant oral calcium supplementation using calcium carbonate as medication of choice is contentious. Due to a potential relapse after successful excision of the affected parathyroid gland in PH, the serum calcium level should be monitored periodically.

Severe Hypercalcemia Secondary to Primary Hyperparathyroidism

Primary hyperparathyroidism is usually asymptomatic or paucisymptomatic, however, in rare cases threatening hypercalcemia is the presenting symptom. The aim of our study is to analyze cases of severe hypercalcemia in primary hyperparathyroidism. Subjects and Methods: 5 patients (3M/2F, mean age = 48 years) with primary hyperparathyroidism (2 carcinomas, 3 adenomas) with serum calcium level ≥ 14 mg/dl. Results: Serum calcium levels varied between 14 and 18 mg/dl and parathormone (PTH) levels between 840 and 1631 pg/ml. Non-specific symptoms such as anorexia, nausea, vomiting, polyuria, dehydration, abdominal pain, weight loss, fatigue, muscular weakness, pruritus, irritability and lethargy were present in all patients. Bone fracture and brown tumors were present in 4 patients. Parathyroid nodule size varied between 20 and 46 mm and was clinically palpable in three patients. All patients received symptomatic treatment of hypercalcemia before parathyroid surgery: rehydration with saline in all cases, hemodialysis in one case and bisphosphonates in three patients. In the postoperative period, all patients had hypocalcaemia, which was severe, requiring high amounts of calcium in two patients. Conclusion: Severe hypercalcemia is a rare but potentially fatal endocrine emergency if unrecognized and untreated. Appropriate diagnosis and adequate management are important to improve its prognosis.

Long Term Outcome of Bisphosphonate Therapy in Patients with Primary Hyperparathyroidism

Context: Primary hyperparathyroidism (PHPT) is commonly associated with reduced bone mineral density (BMD) presenting with osteoporosis, increasing the risk of bone fragility fractures in these patients. Bisphosphonates, due to their anti-resorptive action, are known to improve the BMD and reduce the risk of bone fragility fractures. Therefore, bisphosphonates are considered as an alternative to surgical treatment in managing osteoporosis in PHPT patients. Aim: The aim of this observational study was to assess the effect of long term bisphosphonate therapy on BMD, bone fragility fracture and biochemical markers of bone metabolism in patients with PHPT. Methodology: Fifty patients (mean age 74 years) with PHPT who were treated with long term bisphosphonate therapy were studied retrospectively. The mean baseline (before commencing bisphosphonate therapy) BMD T-scores for lumbar spine (L2-L4) and left femoral neck were -2.5 and -2.1, respectively. Fourteen patients had bone fragility fractures before initiation of bisphosphonate therapy. Results: After an average of 5 years of bisphosphonate treatment, there was a significant increase in lumbar BMD T-score (-2.5 to -2.1, p = 0.013) and a non-significant change in left femoral neck BMD T-score (-2.1 to -2.2, p = 0.497). There was no increase in bone fragility fracture rate (p = 0.167). Serum corrected calcium reduced from 2.74 mmol/L to 2.60 mmol/L (p 0.001) and urine calcium to creatinine ratio from 0.70 to 0.55 (p 0.0001), both within the reference range. Conclusions: Our study suggests that long term bisphosphonate therapy improves lumbar BMD and prevents increase in bone fragility fracture rate. Additionally it improves hypercalcaemia in PHPT.

Cinacalcet treatment for hypercalcaemia in primary hyperparathyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Cinacalcet HCl Reduces Hypercalcemia in Primary Hyperparathyroidism across a Wide Spectrum of Disease Severity

Cinacalcet HCl Reduces Hypercalcemia in Primary Hyperparathyroidism across a Wide Spectrum of Disease Severity

Cinacalcet HCl Reduces Hypercalcemia in Primary Hyperparathyroidism across a Wide Spectrum of Disease Severity

Cinacalcet HCl Reduces Hypercalcemia in Primary Hyperparathyroidism across a Wide Spectrum of Disease Severity

Cinacalcet HCl Reduces Hypercalcemia in Primary Hyperparathyroidism across a Wide Spectrum of Disease Severity

Primary hyperparathyroidism (PHPT) is characterized by elevated serum calcium (Ca) and increased PTH concentrations. The objective of the investigation was to establish the efficacy of cinacalcet in reducing serum Ca in patients with PHPT across a wide spectrum of disease severity. The study was a pooled analysis of data from three multicenter clinical trials of cinacalcet in PHPT. Patients were grouped into three disease categories for analysis based on the following: 1) history of failed parathyroidectomy (n = 29); 2) meeting one or more criteria for parathyroidectomy but without prior surgery (n = 37); and 3) mild asymptomatic PHPT without meeting criteria for either above category (n = 15). The intervention in this study was treatment with cinacalcet for up to 4.5 yr. Measurements in the study included serum Ca, PTH, phosphate, and bone-specific alkaline phosphatase, and areal bone mineral density (aBMD). Vital signs, safety biochemical and hematological indices, and adverse events were monitored throughout the study period. The extent of cinacalcet-induced serum Ca reduction, proportion of patients achieving normal serum Ca (≤10.3 mg/dl), reduction in serum PTH, and increase in serum phosphate were similar across all three categories. Except for decreased aBMD at the total femur indicated for parathyroidectomy group at 1 yr, no significant changes in aBMD occurred. The efficacy of cinacalcet was maintained for up to 4.5 yr of follow-up. AEs were mild and similar across the three categories. Cinacalcet is equally effective in the medical management of PHPT patients across a broad spectrum of disease severity, and overall cinacalcet is well tolerated.

Hypercalcemia of Primary Hyperparathyroidism was Treated by Cinacalcet in a Patient with Liver Cirrhosis

Cinacalcet is a type II calcimimetic agent which is an allosteric modulator of the calcium-sensing receptor (CaR) located on the surface of the parathyroid cells. Cinacalcet increases the sensitivity of CaR via binding to the transmembrane region of CaR. Increasing sensitivity of CaR causes reduced secretion of parathyroid hormone (PTH) and suppression of serum calcium levels. Cinacalcet has recently been approved by Federal Drug Administration (FDA) for the treatment of patients with secondary hyperparathyroidism on maintenance dialysis and hypercalcemia in patients with parathyroid cancer. It is used also in Europe for both indications. Several controlled studies have shown that cinacalcet is effective in normalizing serum calcium levels also in primary hyperparathyroidism. Cinacalcet is metabolized primarily in the liver by N-dealkylation leading to carboxylic acid and oxidation of naphthalene ring to form dihydrodiols. The safety and optimal dosage of the drug in hypercalcemic patients with liver impairment remains unclear. We present a patient with Child-Pugh B class primary biliary cirrhosis who presented with moderate hypercalcemia and was diagnosed as primary hyperparathyroidism. As she refused having parathyroid surgery for her parathyroid adenoma at first, her hypercalcemia was treated successfully with 30 mg/day cinacalcet for 6 months. Cinacalcet was discontinued after 6 months. Her calcium level increased gradually. As she accepted surgery this time, her parathyroid adenoma was removed by minimally invasive parathyroidectomy. Parathyroid adenoma was confirmed pathologically. Her calcium levels maintained within the normal ranges after surgery.

Chloride/Phosphate Ratio in Primary Hyperparathyroidism

The chloride/phosphate (Cl:PO4) ratio is known to help distinguish between the hypercalcemia of primary hyperparathyroidism (HPT) and hypercalcemia from other causes. The Cl:PO4 ratio of 106 patients with surgically proven primary HPT was compared with that of 126 normocalcemic healthy outpatients to examine its usefulness as a confirmatory test for primary HPT. The Cl:PO4 ratio was significantly higher in patients with HPT (42.5 +/- 7.0) compared with healthy controls (28.7 +/- 4.6). Patients with HPT and mild renal insufficiency (serum creatinine, 1.5-2.4 mg/dL) also showed a significant increase in the Cl:PO4 ratio (37.3 +/- 6.6) as did those with HPT with borderline elevations in serum calcium (calcium < 11; Cl:PO4, 40.3 +/- 5.6). A Cl:PO4 ratio > or = 33 is a reliable diagnostic test for primary HPT when compared with a normal population. The Cl:PO4 ratio is also of value in the evaluation of the patient with suspected HPT and borderline calcium elevation and those with mild renal impairment. These data suggest that an inexpensive Cl:PO4 ratio might replace serum parathormone assay as a confirmatory test in the evaluation of suspected primary HPT, especially for those patients in whom a localizing study (sestamibi scan) is obtained before neck exploration.

Effectiveness of pamidronate in the control of hypercalcemia in primary hyperpara thyroidism

Effectiveness of pamidronate in the control of hypercalcemia in primary hyperpara thyroidism