Lithium-associated hypercalcemia and hyperparathyroidism: A systematic review and meta-analysis.

OBJECTIVES: We aimed to review and summarise the existing human literature on the association between lithium and hyperparathyroidism. METHODS: A systematic literature search was carried out according to PRISMA guidelines (last search 27 February 2024), using MEDLINE, Web of Science, Embase and the Cochrane Library. A meta-analysis was performed to determine the prevalence of lithium-associated hypercalcemia (LAHca) in lithium-treated patients. RESULTS: The pooled prevalence of LAHca based on total calcium and ionised calcium was comparable, at 3.17% and 4.23%, respectively. Calcium, and PTH if the patient is hypercalcaemic, is insufficiently measured in lithium-treated patients in clinical practice. Lithium use is associated with higher calcium and PTH levels, as well as a higher incidence of hyperparathyroidism. There is a high prevalence of multiglandular disease in lithium-associated hyperparathyroidism (LAH), with a pooled prevalence of 51.28%. Parathyroid surgery and cinacalcet are effective treatments for LAH. Regarding lithium discontinuation, there is anecdotal but conflicting evidence suggesting that it can result in the resolution of LAH in selected cases. CONCLUSIONS: Lithium treatment increases the risk of hyperparathyroidism, a treatable complication with a pooled prevalence of around 4%, compared to 0.5% in the healthy population.

Lithium-associated primary hyperparathyroidism:: An evaluation of screening and referral patterns in a southeastern veteran population.

BACKGROUND: Long-term lithium therapy has a well-established but under-recognized association with primary hyperparathyroidism. Rates of hypercalcemia, screening for primary hyperparathyroidism, and referral for parathyroidectomy were evaluated among United States veterans on long-term lithium therapy. METHODS: Patients undergoing chronic long-term lithium therapy (>12 months) were identified from 1999 to 2022. Demographics, long-term lithium therapy duration, post-treatment calcium, parathyroid hormone, creatinine, and vitamin D levels were abstracted. Rates of screening for hypercalcemia (calcium ≥10.2 mg/dL), primary hyperparathyroidism (parathyroid hormone ≥30 pg/mL in the setting of hypercalcemia), referral for parathyroidectomy, and outcomes were evaluated. RESULTS: A total of 1,356 patients underwent long-term lithium therapy, 514 of whom received chronic long-term lithium therapy. Baseline characteristics of patients with and without post-treatment hypercalcemia were compared. Of 148 patients with post-treatment hypercalcemia, 112 (74.7%) underwent no further evaluation for primary hyperparathyroidism, while 36 (25.3%) patients had a parathyroid hormone level recorded. Although 33 (91.7%) hypercalcemic patients screened positive for primary hyperparathyroidism, only 5 (13%) were referred for parathyroidectomy. Of the 4 patients who underwent parathyroidectomy, mean calcium was 11.2 mg/dL (range 11.1-11.4), and mean parathyroid hormone was 272 pg/mL (range 108-622). Three patients were localized on preoperative imaging, 2 of whom underwent unilateral exploration with cure, with 1 experiencing recurrence at 31 months. The remaining patient who localized preoperatively underwent bilateral exploration and had 2 ipsilateral glands resected and persistence. The patient who did not localize preoperatively underwent bilateral exploration with 3 gland resection and cure. CONCLUSIONS: Screening for primary hyperparathyroidism and referral for parathyroidectomy are underutilized in United States veterans undergoing chronic long-term lithium therapy. Institutional protocols to standardize screening, surveillance, and referrals to endocrinology/endocrine surgery could benefit this population at increased risk for primary hyperparathyroidism.

Characteristics of hospitalized patients with hypercalcemia in the province of Malaga: a longitudinal, retrospective, multicenter study.

BACKGROUND AND OBJECTIVE: There are limited studies analyzing hypercalcemia in hospitalized patients. Our objectives were to describe the clinical characteristics of hospitalized patients with hypercalcemia, estimate its prevalence in the hospital setting, analyze the rate of correction of hypercalcemia, and identify prognostic variables. MATERIALS AND METHODS: Observational, longitudinal, retrospective, and bicentric study. Adult patients admitted to two hospitals in Málaga (2014-2018) with a diagnosis of hypercalcemia were included. The minimum follow-up was 2 years or until death. RESULTS: A total of 205 patients with hypercalcemia were included (incidence: 0.13%). The mean age (SD) was 68.2 (13.1) years, with a predominance of males (55.1%). The median (IQR) serum calcium at admission was 13.1 (11.8-14.6) mg/dl. The most common etiologies were neoplasms (75.1%), primary hyperparathyroidism, and medications (both 8.8%). The median (IQR) follow-up period was 5.1 (1.7-60.3) weeks. The most commonly used treatments were fluid therapy (86.8%), loop diuretics (70.9%), bisphosphonates (60.7%), and glucocorticoids (46.2%). The rate of correction of hypercalcemia was 65.2%, with a median (IQR) of 6 (3-10) days. The mortality rate was 81.5%. The median (95% CI) survival was 5.1 (3-7.3) weeks. Factors associated with higher mortality were advanced age, neoplastic etiology, serum calcium at admission, and failure to correct hypercalcemia. CONCLUSIONS: Hypercalcemia in hospitalized patients is mainly due to neoplastic processes and is associated with high mortality. We observed a low rate of adherence to recommendations for the management of hypercalcemia.

Characteristics and outcome of severe hypercalcemia on admission to the emergency department: a retrospective cohort study.

AIMS OF THE STUDY: To investigate the prevalence of hypercalcemia (>2.60 mmol/l) and severe hypercalcemia (≥2.80 mmol/l) on admission. Symptoms, causes, course of serum calcium, treatment and outcome of severe hypercalcemia were evaluated and compared to historical data from previous studies. METHODS: In this retrospective cohort study, all patients presenting to the interdisciplinary emergency department of the Buergerspital Solothurn between 01 January 2017 and 31 December 2020 with measurements of serum calcium were included. Chart reviews were performed for patients with calcium ≥2.80 mmol/l to assess clinical presentation, course of disease and treatment for severe hypercalcemia. RESULTS: Of 31,963 tested patients, 869 patients (2.7%) had hypercalcemia on the admission, of which 161 had severe hypercalcemia. Non-albumin corrected calcium was 3.07 (0.32) while albumin corrected calcium was 3.34 (0.44). Calcium was higher in patients with malignancy-related hypercalcemia (3.18 [0.34] versus 3.00 [0.3], p <0.001). Neuropsychiatric (35%) and gastrointestinal (24%) were the leading symptoms. Malignancy was the most common identifiable cause of hypercalcemia (40%), with lung cancer (20%), multiple myeloma (14%) and renal cell carcinoma (11%) being the main cancer types. 36% of patients with severe hypercalcemia took calcium supplements. Bisphosphonate treatment was an independent predictor of a fall in calcium until day 5 (regression coefficient: -0.404, standard error 0.11, p <0.001). Hypercalcemia was not mentioned in the final discharge report in 38% of cases. CONCLUSION: Severe hypercalcemia is common and malignancy-related in almost half of the cases. Neuropsychiatric and gastrointestinal symptoms were most prevalent. Awareness of hypercalcemia, particularly in cancer patients and those with known triggering factors, should be raised in order to identify and treat this harmful disorder early.

Prevalence and Clinicopathologic Characteristics of Hypercalcemia in Patients With Cholangiocarcinoma.

This cohort study investigates clinicopathologic and prognostic associations of hypercalcemia in patients with intrahepatic or extrahepatic cholangiocarcinoma.

Does Surgeon Volume Impact Morbidity Following Parathyroidectomy? A Study of 16,140 Parathyroidectomies from the UK Registry of Endocrine and Thyroid Surgery (UKRETS) Database.

BACKGROUND: Outcomes in endocrine surgery have been shown to improve with surgeon volume. We aimed to study the effect of surgeon volume on morbidity following parathyroidectomy. METHODS: UKRETS data from 2004 to 2019 was studied. Parathyroidectomies for primary hyperparathyroidism with complete data were included. Exclusion criteria were age <18 or >80 years; surgeons contributing <10 cases overall; and length of stay >28 days. Multivariable analysis was performed. Primary outcome was persistent hypercalcaemia; secondary outcomes were haemorrhage, length of stay, need for re-admission, post-operative hypocalcaemia, and need for calcium/vitamin D supplements to maintain eucalcaemia at 6 months. RESULTS: 153 surgeons undertook mean 22.5 (median 17, range 2-115) parathyroidectomies/year. Persistent hypercalcaemia affected 4.8% (776/16140) overall; 5.7% (71/1242) in surgeons undertaking < 10 cases/year; 5.1% (3339/6617) for 10-30 cases/year; 5.0% (270/5397) for 30-50 cases; and 3.3% (96/2884) for >50 cases/year. High-volume (>50 parathyroidectomies/year) surgeons operated 23.4% (809/3464) of negative localisation cases compared to 16.4% (2074/12676) of positive localisation cases. Persistent hypercalcaemia was almost twice as common in image negative (7.9%) compared to image-positive (4%) cases. Persistent hypercalcaemia was significantly more likely to occur in the low volume (<10 parathyroidectomies/year) group than high volume (>50 parathyroidectomies/year), regardless of image positivity (p = 0.0006). Surgeon volume significantly reduced persistent hypercalcaemia on multivariable analysis (OR = 0.878, 95%CI 0.842-0.914, p < 0.001), along with age, sex, and positive localisation. BNE and re-operation significantly increased persistent hypercalcaemia. Post-operative hypocalcaemia occurred in 3.2% (509/16040) and was reduced with increasing surgeon volume (OR = 0.951, 95%CI 0.910-0.993, p < 0.001). Haemorrhage and length of stay were not significantly associated with surgeon volume. CONCLUSION: The incidence of persistent hypercalcaemia, post-operative hypocalcaemia, and persistent hypoparathyroidism decreased with increasing surgeon volume. The relative reduction in persistent hypercalcaemia with surgeon volume was similar in image negative and positive groups, but the absolute reduction was higher in image negative cases. Restricting image negative parathyroidectomy to high-volume surgeons could be considered.

Analysis of Time to Diagnosis and Outcomes Among Adults With Primary Hyperparathyroidism.

Importance: Despite access to routine laboratory evaluation, primary hyperparathyroidism (PHP) remains underdiagnosed and undertreated. Objective: To determine the consequences associated with missed diagnoses and prolonged time to diagnosis and treatment of PHP. Design, Setting, and Participants: This is a retrospective cohort study of patients older than 40 years with 2 instances of hypercalcemia during 2010 to 2020 and 3 years of follow-up. Patients were recruited from 63 health care organizations in the TriNetX Research Network. Data analysis was performed from January 2010 to September 2020. Exposures: Elevated serum calcium. Main Outcomes and Measures: Existing symptoms and diagnoses associated with PHP (osteoporosis, fractures, urolithiasis, major depressive disorder, anxiety, hypertension, gastroesophageal reflux disease, malaise or fatigue, joint pain or myalgias, constipation, insomnia, polyuria, weakness, abdominal pain, headache, nausea, amnesia, and gallstones) compared in patients deemed high-risk and without a diagnosis and matched controls, and those who experienced times from documented hypercalcemia to diagnosis and diagnosis to treatment within or beyond 1 year. Results: There were 135 034 patients analyzed (96 554 women [72%]; 28 892 Black patients [21%] and 88 010 White patients [65%]; 3608 Hispanic patients [3%] and 98 279 non-Hispanic patients [73%]; mean [SD] age, 63 [10] years). Two groups without a documented diagnosis of PHP were identified as high risk: 20 176 patients (14.9%) with parathyroid hormone greater than or equal to 50 pg/mL and 24 905 patients (18.4%) with no parathyroid hormone level obtained or recorded explanation for hypercalcemia. High-risk patients experienced significantly increased rates of all associated symptoms and diagnoses compared with matched controls. Just 9.7% of those with hypercalcemia (13 136 patients) had a diagnosis of PHP. Compared with individuals who received a diagnosis within 1 year of hypercalcemia, those whose workup exceeded 1 year had significantly increased rates of major depressive disorder, anxiety, hypertension, gastroesophageal reflux disease, malaise or fatigue, joint pain or myalgias, polyuria, weakness, abdominal pain, and headache at 3 years. The rate of osteoporosis increased from 17.1% (628 patients) to 25.4% (935 patients) over the study period in the group with delayed diagnosis. Among those with a diagnosis, 5280 patients (40.2%) underwent parathyroidectomy. Surgery beyond 1 year of diagnosis was associated with significantly increased rates of osteoporosis and hypertension at 3 years after diagnosis compared with those treated within 1 year. Conclusions and Relevance: Many patients were at high risk for PHP without a documented diagnosis. Complications in these patients, as well as those who received a diagnosis after prolonged workup or time to treatment, resulted in patient harm. System-level interventions are necessary to ensure proper diagnosis and prompt treatment of PHP.

Incidence of Post-denosumab Rebound Hypercalcaemia in Bony-Metastatic Breast Cancer.

Denosumab reduces incidence of skeletal related events in patients with bony-metastatic breast cancer, however cessation is associated with a rebound phenomenon which, rarely, has been associated with hypercalcaemia. We aimed to identify the incidence of post-denosumab cessation rebound hypercalcaemia amongst patients with breast cancer-related bony metastases. We performed a single-centre retrospective cohort analysis to determine the incident of rebound hypercalcaemia amongst patients treated with antiresorptive agents for bony metastatic breast cancer between 2016-2020. 22,320 outpatient encounters were reviewed, which identified 97 patients with bonymetastatic disease treated with antiresorptive therapy. Of the 21 patients who had denosumab ceased, six (28.6%) developed hypercalcaemia. Interval between last denosumab dose and onset of hypercalcaemia was a median 7.5 (range 2-13) months. There was a significant difference in both denosumab treatment duration as well as total treatment dose exposure between patients who developed hypercalcaemia post-denosumab cessation (median 41 months, 40 doses) and those who remained normocalcaemic (median 10 months, 5 doses), p = 0.009. In our study, hypercalcaemia occurred between two and thirteen months after denosumab cessation. Greater denosumab treatment duration as well as total denosumab dose exposure was associated with higher risk of hypercalcaemia after denosumab cessation. Hormonal therapy or previous bisphosphonate treatment was not seen to impact upon development of hypercalcaemia. Rebound hypercalcaemia is a rare but important diagnosis to consider in patients experiencing hypercalcaemia after denosumab cessation.

Risk factors for surgical failure in patients undergoing surgery for primary hyperparathyroidism.

INTRODUCTION: Primary hyperparathyroidism is the third most common endocrine disease. The aim of our study was to determine long-term outcomes and risk factors for persistence in patients undergoing parathyroidectomy for primary hyperparathyroidism. METHODS: Retrospective study including patients undergoing parathyroidectomy between 2009-2019. Cure was defined as reestablishment of normal calcium homeostasis lasting a minimum of 6 months. Persistence was defined by ongoing hypercalcemia more than 6 months after surgery. Recurrent PHTP was defined by recurrence of hypercalcemia after a normocalcemic interval at more than 6 months after surgery. A more detailed analysis was performed on patients with normocalcemia and persistently elevated PTH levels after surgery. Variables independently related to persistence were analyzed by multivariate analysis. RESULTS: We included 212 patients. Mean age was 59 years and 83% were women. Cure was observed in 204 patients (96.2%), persistence in 8 (3.8%) and recurrence in 3 (1.4%). Four patients (1.9%) presented normocalcemia and persistently elevated PTH after surgery. All presented parathyroid pathology (2 adenomas and 2 hyperplasia). In follow-up we observed that adenoma subgroup presented one patient with CKD and one with vitamin D deficiency while in the hyperplasia subgroup two patients presented CKD. Persistence was independently associated with hyperplasia (Odds ratio = 12.6, IC95% = 1.28-124, p = 0.030) and normal parathyroid tissue (Odds ratio = 188, IC95% = 9.33-379, p = 0.001) on histopathological report. CONCLUSION: Primary hyperparathyroidism is a safe procedure in terms of morbidity and long-term outcomes. Hyperplasia and normal parathyroid tissue on histopathological report are risk factors for persistence. An interdisciplinary diagnostic and therapeutic approach is required to prevent persistence.

What an endocrinologist should know for patients receiving lithium therapy.

Lithium is an efficient treatment of bipolar disorder. Besides renal insufficiency, many endocrine side effects are described such as the occurrence of thyroid disorders, hypercalcaemia and nephrogenic diabetes insipidus. Lithium inhibits the secretion of thyroid hormones. The prevalence of goiter is 4 times more common in Lithium-treated patients compared as to the general population. Hypothyroidism (8-20%) is more frequent in women and in case of pre-existing thyroid autoimmunity. Grave's disease and other hyperthyroidisms are sometimes reported. Lithium stimulates the proliferation of parathyroid cells by activating the Wnt pathway. An increase in serum calcium and PTH is described in patients treated with Lithium with a 4 to 6-fold higher risk of primary hyperparathyroidism than in the general population. Nevertheless, 24-hour urine calcium is not often increased, and the phenotype can mimic a hypercalcemia-hypocalciuria syndrome that may regress with Lithium discontinuation. Surgery should be cautious since parathyroid hyperplasia is more common than parathyroid adenoma. Nephrogenic diabetes insipidus is frequently reported and may be debilitating, sometimes intricated with severe dehydration, hypernatremia, and acute renal insufficiency. Nephrogenic diabetes insipidus is not generally reversible after Lithium discontinuation, especially in patients who have chronic kidney disease due to interstitial tubule nephritis. In conclusion, clinical assessment (goiter, diuresis) and biological monitoring of serum calcium, sodium creatinine, TSH and lithium are recommended in patients receiving Lithium therapy. The risk of Lithium discontinuation in case of side effects should be weighed against the psychological risk, and must be discussed with the psychiatrist.

Severe hypercalcemia requiring acute hemodialysis: A retrospective cohort study with increased incidence during the Covid-19 pandemic.

BACKGROUND: The Covid-19 pandemic has had dramatic consequences on the progression of numerous pathologies, especially neoplastic ones. The orientation of hospital activities toward the care of patients with SARS-Cov2 infection has caused significant delays in the diagnosis and therapy of many other pathologies. What about severe hypercalcemia? The aim of this work was to determine the clinical and biological presentation, etiologies, mortality, and the impact of the Covid-19 pandemic on severe hypercalcemia. MATERIAL AND METHODS: we conducted a retrospective study for 84 months (September 2014 to September 2021) at the Nephrology Unit in University Hospital Mohammed VI, Oujda, Morocco. Included were all adult patients diagnosed with severe hypercalcemia (defined as corrected total serum calcium of >3.5 mmol/l or > 14.0 mg/dl) and who had benefited from one or more hemodialysis sessions. RESULTS: 66 episodes of severe hypercalcemia occurred in 64 patients. The mean age was 57 ± 15 years and 57.6% were female. The mean corrected serum calcium at admission was 16.9 ± 2.1 mg/dl and 33.3% had more than 18.0 mg/dl. Malignancies represented 80.4% of all etiologies. Acute kidney injury was observed in 69.7%. The delta drop in serum calcium 48 h after initiation of medical treatment was 4.64 ± 1.63 mg /dl. Mortality was noted in 14% of all cases. Electrocardiographic abnormalities were observed in 58.3%, 87.5% and 85.7%, respectively, in group 1 (14.0-16.0 mg/dl), group 2 (16.1-18.0 mg/dl), and group 3 (> 18.0 mg/dl) (p = 0.04). The mean serum potassium value was 5.1 ± 1.3, 4.0 ± 1.0, and 3.7 ± 0.7 respectively, in group 1 (14.0-16.0 mg/dl), group 2 (16.1-18.0 mg/dl), and group 3 (> 18.0 mg/dl) (p < 0.001). Newly diagnosed neoplasia, severe hypercalcemia (> 16.0 mg/dl), and mortality have been observed in 15.4% vs. 23.7% (p = 0.31), 25% vs. 50% (p = 0.03), and 35.7% vs. 52.6% (p = 0.13) respectively, in patients before and during the Covid-19 pandemic. CONCLUSIONS: The Covid-19 pandemic caused an increase in both the incidence and severity of hypercalcemia and the hemodialysis practiced in this context remains efficient and safe.

Underdiagnosis of primary hyperparathyroidism in patients with osteoarthritis undergoing arthroplasty.

BACKGROUND: Primary hyperparathyroidism (HPT) is commonly underdiagnosed and undertreated. Joint pain is a nonspecific symptom associated with osteoarthritis or primary HPT. We hypothesize that patients treated for osteoarthritis are underdiagnosed with primary HPT. METHODS: Adult patients diagnosed with hip/knee osteoarthritis at the Medical College of Wisconsin from January 2000 to October 2020 were queried. Patients with a calcium level drawn within 1 year of diagnosis of osteoarthritis were included. Patients who had undergone prior parathyroidectomy were excluded. Patients were stratified by serum calcium level, HPT diagnosis, and PTH level. Arthroplasty rates were compared between groups. RESULTS: Of 54,788 patients, 9,967 patients (18.2%) had a high serum calcium level, of whom 1,089 (10.9%) had a diagnosis of HPT. Only 76 (7.0%) patients with HPT underwent parathyroidectomy, 208 (19.1%) underwent knee/hip arthroplasty, and 14 (1.3%) underwent both. Arthroplasty was performed in 1,793 patients without evaluation and/or definitive treatment for HPT. There were higher rates of arthroplasty performed in patients with a high serum calcium level compared with those without (21.2% vs 17.4%, P < .001). CONCLUSION: Patients with high serum calcium levels were more likely to undergo arthroplasty than those with normocalcemia. Hypercalcemia in the setting of hip or knee osteoarthritis should prompt a full evaluation for primary HPT.

Prevalence, causes and associated mortality of hypercalcaemia in modern hospital care.

BACKGROUND: Studies examining hypercalcaemia in inpatients were largely published over 20 years ago, and it is likely the epidemiology of hypercalcaemia has changed related to increased lifespan and changes in the prevalence of the underlying causes such as malignancy. AIM: To explore the epidemiology of hypercalcaemia in a modern tertiary hospital setting in Australia and evaluate the risk of mortality associated with hypercalcaemia. METHODS: A retrospective study was performed in all inpatients with elevated blood calcium levels admitted from July 2013 to June 2018. ICD coding data identified primary diagnoses and mortality. Electronic medical records were reviewed in n = 292 patients admitted across 12 months from January to December 2017, to determine the causes of hypercalcaemia. RESULTS: Hypercalcaemia occurred in 1819 admissions (0.93% of all hospital admissions), during the 5-year period. The admission primary diagnoses were: malignancy (20% of cases), cardiovascular disease (17%) and gastrointestinal disease (11%). The top causes of hypercalcaemia among the 292 cases where electronic records were reviewed were malignancy (26%), primary hyperparathyroidism (25%) and hyperparathyroidism in the setting of chronic kidney disease (12%). Mortality occurred in 17% of these admissions. Non-survivors had significantly higher calcium levels, phosphate and white cell count, and had lower haemoglobin and albumin levels. CONCLUSION: Hypercalcaemia occurred in ~1% of admissions with main causes being malignancy and primary hyperparathyroidism, similar to historical studies. Hypercalcaemia in hospitalised patients is associated with high mortality and higher levels may be a marker for more severe underlying disease.

Prevalence and risk factors for tertiary hyperparathyroidism in kidney transplant recipients.

BACKGROUND: Tertiary hyperparathyroidism after kidney transplantation has been associated with graft dysfunction, cardiovascular morbidity, and osteopenia; however, its true prevalence is unclear. The objective of our study was to evaluate the prevalence of and risk factors for tertiary hyperparathyroidism. METHODS: A prospective cohort of 849 adult kidney transplantation recipients (December 2008-February 2020) was used to estimate the prevalence of hyperparathyroidism 1-year post-kidney transplant. Tertiary hyperparathyroidism was defined as hypercalcemia (≥10mg/dL) and hyperparathyroidism (parathyroid hormone≥70pg/mL) 1-year post-kidney transplantation. Modified Poisson regression models were used to evaluate risk factors associated with the development of both persistent hyperparathyroidism and tertiary hyperparathyroidism. RESULTS: Among kidney transplantation recipients, 524 (61.7%) had persistent hyperparathyroidism and 182 (21.5%) had tertiary hyperparathyroidism at 1-year post-kidney transplantation. Calcimimetic use before kidney transplantation was associated with 1.30-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.30, 95% CI: 1.12-1.51) and 1.84-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 1.84, 95% CI: 1.25-2.72). Pre-kidney transplantation parathyroid hormone ≥300 pg/mL was associated with 1.49-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.49, 95% CI = 1.19-1.85) and 2.21-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 2.21, 95% CI = 1.25-3.90). Pre-kidney transplantation tertiary hyperparathyroidism was associated with an increased risk of post-kidney transplantation tertiary hyperparathyroidism (adjusted prevalence ratio = 1.71, 95% CI = 1.29-2.27), but not persistent hyperparathyroidism. Furthermore, 73.0% of patients with persistent hyperparathyroidism and 61.5% with tertiary hyperparathyroidism did not receive any treatment at 1-year post-kidney transplantation. CONCLUSION: Persistent hyperparathyroidism affected 61.7% and tertiary hyperparathyroidism affected 21.5% of kidney transplantation recipients; however, the majority of patients were not treated. Pre-kidney transplantation parathyroid hormone levels ≥300pg/mL and the use of calcimimetics are associated with the development of tertiary hyperparathyroidism. These findings encourage the re-evaluation of recommended pre-kidney transplantation parathyroid hormone thresholds and reconsideration of pre-kidney transplantation secondary hyperparathyroidism treatments to avoid the adverse sequelae of tertiary hyperparathyroidism in kidney transplantation recipients.

Recurrence after successful parathyroidectomy-Who should we worry about?

BACKGROUND: Preventing cervical reoperations is important-especially after parathyroidectomy. We sought to examine early predictors of recurrence of primary hyperparathyroidism after surgical cure. METHODS: Adult patients with sporadic primary hyperparathyroidism treated with parathyroidectomy between September 1, 1997, and September 1, 2019, with confirmed eucalcemia at 6 months postoperatively were identified. Recurrence was defined as hypercalcemia (>10.2 mg/dL) with an elevated or nonsuppressed parathyroid hormone level on subsequent follow-up. RESULTS: Parathyroidectomy was performed in 522 patients (median age, 62.1 years, 77% female) with the majority undergoing planned minimally invasive parathyroidectomy (85.4%, n = 446). After a median follow-up of 30.9 months, 13 patients (2.5%) recurred (median time to recurrence 50.2 months, interquartile range 27.9-66.5), all of whom underwent planned minimally invasive parathyroidectomy (n = 13/446, 2.9%). Recurrence was more common in those with higher (but still normal) 6-month calcium (10.1 vs 9.3 mg/dL, P < .001) or parathyroid hormone values (64 vs 46 pg/mL, P < .01). Multivariate analysis revealed that age >66.5 years, calcium ≥9.8mg/dL and parathyroid hormone ≥80 pg/mL at 6 months were associated with increased risk of recurrence. In addition, the presence of at least 1 preoperative imaging study that conflicted with intraoperative findings among minimally invasive parathyroidectomy patients (n = 446) was associated with increased risk of recurrence (hazard ratio 4.93, 95% confidence interval 1.25-16.53, P = .016). CONCLUSION: Recurrence of sporadic primary hyperparathyroidism after initial surgical cure in the era of minimally invasive parathyroidectomy is 2.5%. Identification of those at risk for recurrence using 6-month serum calcium ≥9.8 mg/dL, parathyroid hormone ≥80 pg/mL, and/or potentially conflicting localization studies may inform surveillance strategies.

Causes of hypercalcemia in renal transplant recipients: persistent hyperparathyroidism and others.

Hypercalcemia is common in patients after kidney transplantation (KTx) and is associated with persistent hyperparathyroidism in the majority of cases. This retrospective, single-center study evaluated the prevalence of hypercalcemia after KTx. KTx recipients were evaluated for 7 years after receiving kidneys from living or deceased donors. A total of 301 patients were evaluated; 67 patients had hypercalcemia at some point during the follow-up period. The median follow-up time for all 67 patients was 62 months (44; 80). Overall, 45 cases of hypercalcemia were classified as related to persistent post-transplant hyperparathyroidism (group A), 16 were classified as "transient post-transplant hypercalcemia" (group B), and 3 had causes secondary to other diseases (1 related to tuberculosis, 1 related to histoplasmosis, and 1 related to lymphoma). The other 3 patients had hypercalcemia of unknown etiology, which is still under investigation. In group A, the onset of hypercalcemia after KTx was not significantly different from that of the other groups, but the median duration of hypercalcemia in group A was 25 months (12.5; 53), longer than in group B, where the median duration of hypercalcemia was only 12 months (10; 15) (P<0.002). The median parathyroid hormone blood levels around 12 months after KTx were 210 pg/mL (141; 352) in group A and 72.5 pg/mL (54; 95) in group B (P<0.0001). Hypercalcemia post-KTx is not infrequent and its prevalence in this center was 22.2%. Persistent hyperparathyroidism was the most frequent cause, but other important etiologies must not be forgotten, especially granulomatous diseases and malignancies.

Hypercalcemia in the nephrology department patients - incidence, etiology and impact on renal function.

Hypercalcemia (HCM) is predominantly caused by primary hyperparathyroidism (PHPT) or malignancy. It's incidence varies from 0.17% to 4.74%. Its numerous manifestations include renal symptoms. AIM: The aim of the study was to assess the incidence and etiology of hypercalcemia in patients hospitalized at the Department of Nephrology of the Warsaw Military Institute, as well as to evaluate its impact on renal function. MATERIALS AND METHODS: In this cross-sectional study patients admitted to the Nephrology Department of the Warsaw Military Institute between January 2017 and December 2018 were retrospectively screened for presence of HCM, defined as total calcium level or corrected calcium level in case of hypoalbuminemia >10.2 mg/dl, measured at least twice. Each patient's medical history as well as other laboratory findings were subsequently analyzed in order to establish the etiology of hypercalcemia. RESULTS: Among 3062 hospitalisations (1993 patients) at The Department, 96 patients had elevated calcium level of which 36 were identified as hypercalcemic (1,81%). Median calcium level was 11.9 mg/dl (IQR: 11.25-13.46) with 22.24 mg/dl being the maximum observed value. Malignancy and drugs having hypercalcemizing effect were the most common etiologies identified, both being found in 9 cases (25%). Other causes of HCM included sarcoidosis, multiple myeloma (analyzed separately from other malignancies), PHPT and hypercalcemic hypocalciuria. In 7 cases HCM etiology could not be established, it therefore remained idiopathic. Acute kidney injury (AKI) developed in 20 patients (56%), in this group serum calcium levels were significantly higher than in non-AKI patients (median: 12.85 mg/dl (IQR:11.82-14.65) vs 11.25 mg/dl (IQR:10.75-11.93); p=0.0039). Additionally, chronic kidney disease (CKD) patients presented significantly lower calcium values than non-CKD patients (median: 11.47 mg/dl (IQR: 10.8-12.6) vs 13.01 mg/dl (IQR:11.9-16.08; p=0.0131). CONCLUSIONS: Hypercalcemia is a rare disorder among Nephrology Department patients, which primary etiology is malignancy and medications having hypercalcemizing effect. Kidney injury is dependent on the severity of hypercalcemia.

The evaluation of the effect of hypercalcemia in oral pathologies.

OBJECTIVE: Hypercalcemia is determined as an increase in the serum calcium level (above 10.5 mg/dL or ionized calcium is above 1.5 mmol/L). It was aimed to evaluate the effect of the increased serum calcium levels in dental panoramic radiographs with oral pathologies. MATERIALS & METHODS: The final sample number of the present study was determined as 143. 61 patients with hypercalcemic calcium levels were grouped in Hypercalcemia Group (HPEG) whereas 82 patients were grouped in Normal Group. (NG) Measurements were performed only on the panoramic radiographs. The evaluated parameters were cyst-tumor or granuloma existence, sinus pneumatization, stylohyoid ligament calcifications, lamina dura loss, bone loss existence, etc. Statistical tests were carried out at p < 0.05 significance level. RESULTS: The cyst-tumor formation (p = 0.03) and stylohyoid ligament calcification (p = 0.009) and increased radiopacity (p = 0.03) were significantly more common in NG than the HPEG group. Alveolar bone loss (p = 0.001) and periodontal defects (p = 0.01) were significantly more common in HPEG than the NG group. There was no significant relationship between other examined parameters. (p > 0.05) CONCLUSION: The serum calcium level revealed statistically significant outcomes and a close relationship with the pathologies occurring in the alveolar bone in the oral and maxillofacial region. However, it is highly recommended to include more patients in the newly planned studies and another bone-related biomarker should be evaluated simultaneously.

Causes of hypercalcemia in renal transplant recipients: persistent hyperparathyroidism and others

Hypercalcemia is common in patients after kidney transplantation (KTx) and is associated with persistent hyperparathyroidism in the majority of cases. This retrospective, single-center study evaluated the prevalence of hypercalcemia after KTx. KTx recipients were evaluated for 7 years after receiving kidneys from living or deceased donors. A total of 301 patients were evaluated; 67 patients had hypercalcemia at some point during the follow-up period. The median follow-up time for all 67 patients was 62 months (44; 80). Overall, 45 cases of hypercalcemia were classified as related to persistent post-transplant hyperparathyroidism (group A), 16 were classified as "transient post-transplant hypercalcemia" (group B), and 3 had causes secondary to other diseases (1 related to tuberculosis, 1 related to histoplasmosis, and 1 related to lymphoma). The other 3 patients had hypercalcemia of unknown etiology, which is still under investigation. In group A, the onset of hypercalcemia after KTx was not significantly different from that of the other groups, but the median duration of hypercalcemia in group A was 25 months (12.5; 53), longer than in group B, where the median duration of hypercalcemia was only 12 months (10; 15) (P<0.002). The median parathyroid hormone blood levels around 12 months after KTx were 210 pg/mL (141; 352) in group A and 72.5 pg/mL (54; 95) in group B (P<0.0001). Hypercalcemia post-KTx is not infrequent and its prevalence in this center was 22.2%. Persistent hyperparathyroidism was the most frequent cause, but other important etiologies must not be forgotten, especially granulomatous diseases and malignancies.