Morbidity induced by the infiltration of foreign substances into the buttocks: A systematic review.

The infiltration of substances into the buttocks for esthetic purposes can cause local or systemic damage. These infiltrated substances, known as adjuvants, foreign substances, and polymers, often lack sufficient and frequently controversial evidence. To identify the systemic complications associated with substances locally infiltrated in the buttocks for treatment, we conducted a systematic review following the PRISMA criteria. Of 275 publications, 29 met the eligibility criteria: 3 systematic reviews, 6 case series, and 20 case reports. The study comprises 463 cases, mainly women (87%), with an average age of 39.94 years. The average time between infiltrations was 7.65 years. Infiltrated substances included silicone, oils, methyl methacrylate, guaiacol, sodium gadolinium, collagen, paraffin, and other unknown substances. The complications fell into three categories: local, systemic with inflammatory-immune response, and renal damage due to hypercalcemia induced by the granulomatosis caused by the substance. Treatment lacked uniformity, mainly focusing on the main effect. Surgical resection of affected tissue resulted in local and systemic improvement (renal, hypercalcemia, or inflammatory-immune) for most patients. Patients who received comprehensive treatment based on inflammatory-immune control, control of renal involvement, and resection of the tissue area that contained large amounts of the infiltrated substance had a better prognosis than those with diffuse infiltration and delayed treatment.

Efficacy of denosumab in the treatment of hypercalcemic renal dysfunction in sarcoidosis: a case report.

A 70-year-old female patient was admitted for close examination and treatment of hypercalcemia (corrected serum calcium levels: 3.04 mmol/L) and renal dysfunction (serum creatinine levels: 254.59 µmol/L). The patient had a history of sarcoidosis, diagnosed based on epithelioid cell granulomas in subcutaneous nodule biopsies, uveitis, and bilateral hilar lymphadenopathy, which had spontaneously remitted 10 years before admission. Because the patient was diagnosed with hypercalcemia associated with recurrent sarcoidosis, prednisone (20 mg/day) was initiated, and its dose was tapered following the decrease in serum calcium and creatinine levels. However, the levels of these parameters increased again when the prednisone dose was reduced to ≤ 4 mg/day. We were concerned about glucocorticoid-induced osteoporosis in the patient but hesitated to use first-line bisphosphonates because of renal dysfunction. Therefore, denosumab was initiated to reduce the risk of hypercalcemia, renal dysfunction, and glucocorticoid-induced osteoporosis. Serum creatinine and corrected serum calcium levels subsequently decreased. The prednisone dose could be reduced following repeated denosumab administration.Thus, denosumab can be a multifaceted, beneficial option for sarcoidosis-induced hypercalcemia, as it alleviates renal dysfunction indirectly by normalizing serum calcium levels, facilitates reduction of the glucocorticoid dose, and ameliorates glucocorticoid-induced osteoporosis.

Comparison of Class-Specific Side Effects Across Preventative Pharmacologic Therapies for Kidney Stone Disease.

INTRODUCTION: Clinical guidelines recommend monitoring for metabolic derangements while on preventive pharmacologic therapy for kidney stone disease. The study objective was to compare the frequency of side effects among patients receiving alkali citrate, thiazides, and allopurinol. METHODS: Using claims data from working-age adults with kidney stone disease (2008-2019), we identified those with a new prescription for alkali citrate, thiazide, or allopurinol within 12 months after their index stone-related diagnosis or procedure. We fit multivariable logistic regression models, adjusting for cohort characteristics like comorbid illness and medication adherence, to estimate 2-year measured frequencies of claims-based outcomes of acute kidney injury, falls/hip fracture, gastritis, abnormal liver function tests/hepatitis, hypercalcemia, hyperglycemia/diabetes, hyperkalemia, hypokalemia, hyponatremia, and hypotension. RESULTS: Our cohort consisted of 1776 (34%), 2767 (53%), and 677 (13%) patients prescribed alkali citrate, thiazides, or allopurinol, respectively. Comparing unadjusted rates of incident diagnoses, thiazides compared to alkali citrate and allopurinol were associated with the highest rates of hypercalcemia (2.3% vs 1.5% and 1.0%, respectively, P = .04), hypokalemia (6% vs 3% and 2%, respectively, P < .01), and hyperglycemia/diabetes (17% vs 11% and 16%, respectively, P < .01). No other differences with the other outcomes were significant. In adjusted analyses, compared to alkali citrate, thiazides were associated with a higher odds of hypokalemia (OR=2.01, 95% CI 1.44-2.81) and hyperglycemia/diabetes (OR=1.52, 95% CI 1.26-1.83), while allopurinol was associated with a higher odds of hyperglycemia/diabetes (OR=1.34, 95% CI 1.02-1.75). CONCLUSIONS: These data provide evidence to support clinical guidelines that recommend periodic serum testing to assess for adverse effects from preventive pharmacologic therapy.

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.

[A rare cause of kidney injury: vitamin D3 intoxication]. / A vesekárosodás ritka oka: D3-vitamin-intoxikáció.

The beneficial effects of vitamin D3 treatment are known, and its side effects are documented. In connection with the case presentation, we would like to sum up the dangers of excessive vitamin D supplementation, and to draw attention to the shortcomings experienced in everyday medical practice. We discuss the tests required to create a diagnosis of vitamin D intoxication, the differential diagnosis, and present the possible treatment strategies. A 57-year-old female patient was admitted to hospital in November 2020 due to complaints of nausea, vomiting, diarrhea and general weakness. Upon admission, laboratory tests confirmed new-onset kidney damage (eGFR 38 mL/min/1.73 m2), calcium metabolism was not checked. During non-invasive investigations, urinary sediment results showed leukocyturia and non-nephrotic proteinuria, but no clear underlying cause was found. Nephrology consultation suggested acute tubular injury, kidney biopsy was performed, immune serology and serum protein electrophoresis tests were ordered. Despite conservative treatment, her kidney function deteriorated further (eGFR 32 mL/d/1.73 m2). The patient arrived at our department in December 2020 with histological results in progress. Laboratory tests taken on arrival confirmed severe hypercalcemia (tCa 3.22 mmol/L, iCa 1.74 mmol/L), and kidney function was stable (eGFR 33 mL/p/1.73 m2). Intact parathyroid hormone level was below the normal range (0.54 pmol/L), 25-OH-vitamin D level was extremely high (1106.2 nmol/L). The patient then admitted that in October 2020, she received a course of "megadose" parenteral vitamin D, but she could not recall the exact dosage nor wanted to mention the department administering the treatment. We diagnosed vitamin D intoxication. Intravenous saline, furosemide and calcitonin treatment was started. The result of the treatment: serum calcium level normalized (2.52 mmol/L), and kidney functions improved (eGFR 54 mL/p/1.73 m2). Vitamin D treatment was stopped. The patients' serum tCa and vitamin D levels normalized by February 2021, and her kidney functions improved (tCa 2.54 mmol/L, 25-OH-vitamin D 125.0 ng/mL, eGFR 72 mL/p/1.73 m2). Kidney biopsy confirmed the presence of acute tubular necrosis. Granulomatous diseases and multiple myeloma were excluded. The symptoms of vitamin D intoxication are non-specific and varied, each case presents a differential diagnostic challenge. Orv Hetil. 2023; 164(47): 1871-1876.

Frequency and determinants of serum calcium monitoring during eldecalcitol therapy in patients with osteoporosis.

INTRODUCTION: Eldecalcitol (ELD) is an active vitamin D3 analog (AVD) commonly used to treat osteoporosis in Japan. Although routine monitoring of serum calcium levels during ELD therapy is recommended, little is known about the actual frequency and determinants of monitoring. MATERIALS AND METHODS: This was a descriptive cohort study using a Japanese electronic medical records database. We identified osteoporosis patients who initiated treatment with ELD or other AVDs (alfacalcidol and calcitriol) between April 1, 2011 and September 10, 2021. The index date for cohort entry was the first prescription date of ELD or other AVDs. The frequency of serum calcium monitoring was evaluated every 6 months. Determinants of serum calcium monitoring were identified using multivariable logistic regression models. We also calculated the incidence of hypercalcemia and the frequency of serum calcium monitoring within 6 months before hypercalcemia. RESULTS: We identified 12,671 ELD users and 7867 other AVD users. Within 6 months after cohort entry, 45.9% of ELD users and 58.7% of other AVD users underwent serum calcium monitoring. Female sex, no use of systemic corticosteroids, moderate-to-good renal function, treatment in smaller hospitals, and treatment in orthopedic surgery departments were associated with a lower likelihood of receiving serum calcium monitoring during ELD therapy. The incidence of hypercalcemia among ELD users was 6.36 per 100 person-years, with 20.6% of cases not receiving serum calcium monitoring before hypercalcemia. CONCLUSION: Our findings suggest that serum calcium monitoring is not given adequate attention during ELD therapy in routine clinical practice.

[Milk-alkali syndrome: a careful history is crucial in diagnosing hypercalcemia]. / Melk-alkalisyndroom.

BACKGROUND: Milk-alkali syndrome is a rare cause of hypercalcemia in the Netherlands, due to ingestion of large amounts of calcium and absorbable alkali. CASE DESCRIPTION: A 38-year-old female patient was admitted with severe stomach pain, vomiting and weight loss. Laboratory results showed hypercalcemia and acute kidney injury. We initially suspected that the hypercalcemia was related to primary hyperparathyroidism, a malignancy with bone metastasis or a granulomatous disease. Gastroduodenoscopy, however, revealed a duodenal ulcer, which turned out to be Helicobacter pylori-related. A thorough history revealed that the patient had consumed large amounts of milk and antacids to relieve symptoms of heartburn. In light of this history, milk-alkali syndrome was diagnosed. CONCLUSION: The case aims to underline the importance of a thorough history in patients with hypercalcemia. The use of over-the-counter medications and dairy products should be evaluated in all patients presenting with hypercalcemia.

Hypercalcemia during initiation of antiretroviral therapy in human immunodeficiency virus and Leishmania coinfection: A case report.

RATIONALE: Hypercalcemia is a common complication of many granulomatous diseases but is not typically associated with leishmaniasis. Here we report an unusual case of hypercalcemia during the initiation of antiviral therapy in a patient with acquired immunodeficiency syndrome coinfected with visceral leishmaniasis. PATIENT CONCERNS: Our patient presented with malaise and altered mental status following antiretroviral therapy initiation. He was found to have de novo hypercalcemia complicated by acute kidney injury. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: An extensive workup for other etiologies of hypercalcemia was negative. The patient was ultimately thought to have hypercalcemia secondary to visceral leishmaniasis in the setting of immune reconstitution inflammatory syndrome. He was treated with intravenous volume expansion, bisphosphonates, and oral corticosteroid therapy with complete resolution. LESSONS: This case highlights an unusual presentation of immune reconstitution inflammatory syndrome, in which proinflammatory cytokine signaling during the restoration of cellular immunity may have led to increased ectopic calcitriol production by granuloma macrophages, thereby altering bone-mineral metabolism and driving hypercalcemia.

Case Report: Hypercalcemia as a manifestation of acute adrenal crisis precipitated by fluconazole use, and a review of the literature.

Acute adrenal crisis classically presents with vomiting, altered sensorium, and hypotension. We describe a unique case manifesting with severe hypercalcemia. Addisonian crisis was unusually precipitated by fluconazole use. We reviewed other reported cases and discuss the possible mechanisms of hypercalcemia in adrenal insufficiency. This 67-year-old man presented with fever, cough, and vomiting for 1 week and with anorexia and confusion for 3 weeks. He was hypotensive and clinically dehydrated. Investigations revealed left-sided lung consolidation, acute renal failure, and severe non-parathyroid hormone (PTH)-mediated hypercalcemia (calcium, 3.55mol/L; PTH, 0.81pmol/L). Initial impression was pneumonia complicated by septic shock and hypercalcemia secondary to possible malignancy. He received mechanical ventilation; treatment with intravenous fluids, inotropes, and hydrocortisone for septic shock; and continuous renal replacement therapy with low-calcium dialysate. Although hypercalcemia resolved and he was weaned off inotropes, dialysis, and hydrocortisone, his confusion persisted. When hypercalcemia recurred on day 19 of admission, early morning cortisol was <8 nmol/L, with low ACTH level (3.2 ng/L). Other pituitary hormones were normal. Hypercalcemia resolved 3 days after reinstating stress doses of hydrocortisone, and his mentation normalized. On further questioning, he recently received fluconazole for a forearm abscess. He previously consumed traditional medications but stopped several years ago, which may have contained glucocorticoids. He was discharged on oral hydrocortisone. Cortisol levels improved gradually, and glucocorticoid replacement was ceased after 8 years, without any recurrence of hypercalcemia or Addisonian crisis. Both hypercalcemia and adrenal insufficiency may present with similar non-specific symptoms. It is important to consider adrenal insufficiency in hypercalcemia of unclear etiology.

Severe hypercalcemia caused by repeated mineral oil injections: a case report.

Hypercalcemia is a frequent condition in clinical practice and when the most frequent causes are excluded, etiological diagnosis can be challenging. A rare cause of PTH-independent hypercalcemia is described in the present case report. A male adult with a history of androgenic-anabolic steroids abuse, and injection of mineral oil and oily veterinary compound containing vitamins A, D and E into muscles for local hypertrophy presented with hypercalcemia, nephrocalcinosis, and end-stage renal disease. On physical examination, the presence of calcified subcutaneous nodules and calcification of musculature previously infused with oily substances drew attention. Laboratory tests confirmed hypercalcemia of 12.62 mg/L, low levels of PTH (10 pg/mL), hyperphosphatemia (6.0 mg/dL), 25(OH)D of 23.3 ng/mL, and elevated 1,25(OH)2D (138 pg/mL). Imaging exams showed diffuse calcification of muscle tissue, subcutaneous tissue, and organs such as the heart, lung, and kidneys. The patient was diagnosed with PTH-independent hypercalcemia secondary to foreign body reaction in areas of oil injection. The patient underwent treatment with hydrocortisone for 10 days, single dose zoledronic acid and hemodialysis. He evolved with serum calcium levels of 10.4 mg/dL and phosphorus of 7.1 mg/dL. In addition, sertraline and quetiapine were prescribed to control body dysmorphic disorder. The medical community should become aware of new causes of hypercalcemia as secondary to oil injection since this should become increasingly frequent due to the regularity with which such procedures have been performed.

Hypercalcemia worsened after vitamin D supplementation in a sarcoidosis patient: A case report.

RATIONALE: There are many causes of hypercalcemia, with hyperparathyroidism and malignancy accounting for 90% of cases. Sarcoidosis and the intake of vitamin D supplements may also cause hypercalcemia, although the occurrence rate is low if only one is involved. We herein report a sarcoidosis patient who developed hypercalcemia after taking cholecalciferol (vitamin D supplement) for a year. PATIENT CONCERN: A 62-year-old Japanese man presented with hypercalcemia and acute kidney injury along with symptoms of fatigue and appetite loss while being followed up for sarcoidosis. DIAGNOSES: We determined that a combination of cholecalciferol supplementation and sarcoidosis had led to hypercalcemia for several reasons. First, hypercalcemia had not been noted when this patient had first been admitted due to sarcoidosis-related respiratory failure several years earlier, which we presumed that was the highest sarcoidosis disease activity. Second, low serum 25-OH Vit.D3 and high 1,25-(OH)2 Vit.D3 levels were noted despite cholecalciferol supplementation for a year, suggesting that 1-α-hydroxylase overexpression caused by sarcoidosis accelerated the conversion from 25-OH Vit.D3 to 1,25-(OH)2 Vit.D3. INTERVENTIONS: Although initially resistant to preservative management, the hypercalcemia promptly improved after starting corticosteroid treatment. OUTCOMES: Hypercalcemia and acute kidney injury were normalized after corticosteroid treatment. LESSONS: We should be aware of patients' medications, especially in patients with granulomatosis disease. The concomitant measurement of 25-OH Vit.D3 and 1,25-(OH)2 Vit.D3 levels is useful for determining the cause of hypercalcemia.

Atorvastatin lowers serum calcium levels in lithium-users: results from a randomized controlled trial.

BACKGROUND: Although lithium is considered the gold-standard treatment for bipolar disorder (BD), it is associated with a variety of major endocrine and metabolic side effects, including parathyroid hormone (PTH) dependent hypercalcemia. Aside from surgery and medication discontinuation, there are limited treatments for hypercalcemia. This paper will assess data from a randomized controlled trial (RCT). METHODS: This is a secondary analysis of an RCT that explored the effects of atorvastatin (n = 27) versus placebo (n = 33) on lithium-induced nephrogenic diabetes insipidus (NDI) in patients with BD and major depressive disorder (MDD) using lithium (n = 60), over a 12-week period. This secondary analysis will explore serum calcium levels and thyroid stimulating hormone (TSH) measured at baseline, week 4, and week 12. RESULTS: At 12-weeks follow-up while adjusting results for baseline, linear regression analyses found that corrected serum calcium levels were significantly lower in the treatment group (mean (M) = 2.30 mmol/L, standard deviation (SD) = 0.07) compared to the placebo group (M = 2.33 mmol/L, SD = 0.07) (ß = - 0.03 (95% C.I.; - 0.0662, - 0.0035), p = 0.03) for lithium users. There were no significant changes in TSH. CONCLUSION: In lithium users with relatively normal calcium levels, receiving atorvastatin was associated with a decrease in serum calcium levels. Although exciting, this is a preliminary finding that needs further investigation with hypercalcemic patients. Future RCTs could examine whether atorvastatin can treat PTH dependent hypercalcemia due to lithium and other causes.

Hypercalcemia Associated with the Ectopic Expression of 25-hydroxyvitamin D3-1α-hydroxylase in Diffuse Large B-cell Lymphoma.

An 82-year-old man was transferred to our hospital due to impaired consciousness. His albumin-corrected calcium level was 14.2 mg/dL, intact parathyroid hormone (PTH) and PTH-related protein levels were reduced, and his 1,25-dihydroxyvitamin D [1,25 (OH) 2VitD] level was elevated at 71.5 pg/mL. Computed tomography revealed masses on the bilateral ribs. The mass on the rib was biopsied and diagnosed as diffuse large B-cell lymphoma (DLBCL). Immunostaining of the biopsy sample with the anti-CYP27B1 antibody revealed the ectopic expression of 1α-hydroxylase in the lesion. We herein report a rare case of hypercalcemia induced by the overproduction of 1,25 (OH) 2VitD in DLBCL ectopically expressing 1α-hydroxylase.

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.

[Oncological emergencies with special consideration of the side effects of checkpoint inhibitors]. / Onkologische Notfälle mit besonderer Berücksichtigung der Nebenwirkungen von Checkpoint-Inhibitoren.

Oncological patients are already exceedingly burdened due to their underlying disease, so that another complication can quickly cause significant deterioration of the state of health. Febrile neutropenia should be rapidly treated with anti-infective agents and malignant hypercalcemia requires a rapid diagnosis. In the case of suspected checkpoint inhibitor-associated toxicity, an interdisciplinary consultation is often necessary.

Profound Hypercalcemia Associated with Acute Toxic-Metabolic Encephalopathy After Calcium Sulfate Bead Use: A Case Report.

CASE: We present the case of an 81-year-old woman who developed profound hypercalcemia requiring admission to the intensive care unit after calcium sulfate bead use during revision hip arthroplasty. The patient's serum calcium level peaked at 21.0 mg/dL and was associated with acute encephalopathy. After treatment with calcitonin and bisphosphonates, her serum calcium level normalized and her mentation improved. CONCLUSION: The risk of clinically significant hypercalcemia should be considered when using calcium sulfate during orthopaedic surgery.

Rebound hypercalcemia post-denosumab cessation in metastatic breast cancer.

Denosumab delays and prevents skeletal related events in patients with malignancy-related bony metastases. Rarely, denosumab discontinuation can lead to rebound hypercalcemia in the setting of increased bone resorption. We describe the case of a 49-year-old breast cancer survivor who developed rebound hypercalcemia after cessation of long-term denosumab. She had been treated with 42 doses of denosumab between August 2013 and March 2020 and 8 months after her last dose of denosumab developed symptomatic hypercalcemia. Parathyroid hormone levels were suppressed, and active malignancy was excluded based on biochemical and radiological testing. She required treatment with intravenous bisphosphonates on three separate occasions in order to achieve long-term normalization of her hypercalcemia. Rebound hypercalcemia post-denosumab cessation is a rare but serious complication that clinicians should be aware of.

Hyperprogression and hypercalcemia after nivolumab treatment in three cases with renal cell carcinoma.

INTRODUCTION: Hyperprogression is a specific type of response seen with immunotherapy that is observed in all malignancies with a frequency of 9% - 29%, characterized by a rapid increase in tumor burden. Many possible related factors and possible markers have been evaluated but a clinical or laboratory parameter associated with hyperprogression has not yet been established. For renal cell carcinoma, hypercalcemia is known to be a poor prognostic factor but it has not been linked to hyperprogression. CASE REPORT: We retrospectively evaluated 52 patients diagnosed with renal cell carcinoma who had nivolumab treatment in any line. 3 of 9 patients who had hyperprogression were noticed to have hypercalcemia preceding hyperprogression. Here we present those 3 cases who developed hypercalcemia after nivolumab and had hyperprogression at follow-up. MANAGEMENT AND OUTCOME: All cases had less than 4 courses of nivolumab and showed hyperprogression in assessment. Nivolumab was discontinued. However, patients' survival was extremely poor, as expected. DISCUSSION: The development of hypercalcemia may help predict hyperprogression in patients with renal cell carcinoma who receive immunotherapy. In such cases, early evaluation of progression and cessation of nivolumab may be considered.

Clopidogrel-induced Eosinophilia with Hypercalcemia.

There are few cases describing the association of eosinophilia with hypercalcemia, and drug-induced eosinophilia with hypercalcemia has not been reported. A 74-year-old man had been diagnosed with asthma 4 months earlier. He was admitted due to eosinophilia with hypercalcemia. Chest computed tomography showed a nodule in the left lung and mediastinal lymphadenopathy. By obtaining a detailed medical history, clopidogrel was suspected as the prime cause of eosinophilia. After the discontinuation of clopidogrel, the eosinophilia with hypercalcemia, lung nodule and mediastinal lymphadenopathy improved. Clopidogrel-induced eosinophilia can potentially cause hypercalcemia. Obtaining a detailed clinical history is important in diagnosing the cause of eosinophilia.

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.