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.

[Vitamin D intoxication and "milk alkali syndrome"]. / 5 minutes pour apprendre. Intoxication à la vitamine D et « milk alkali syndrome ¼.

A 80-year-old patient treated with calcium bicarbonate for a reflux developed a milk alkali syndrome after a high doses of vitamin D for a conservatively treated heel fracture. The article highlights the milk alkali syndrome as a potential complication of excessive vitamin D supplementation, emphasizing that routine vitamin D testing and supplementation should be limited to specific situations.

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.

Intravenous lipid emulsion therapy in 2 dogs and 2 cats with vitamin D toxicosis.

Vitamin D toxicosis can lead to severe and prolonged hypercalcemia resulting in multi-organ damage and even death. Current treatment often involves prolonged hospitalization and may require medications with potential for adverse effects. The objective of this case series was to describe reductions in serum ionized calcium concentrations following intravenous lipid emulsion therapy in vitamin D toxicosis. Two dogs and 2 cats with vitamin D toxicosis were treated with intravenous lipid emulsion therapy in addition to standard treatment regimens. Ionized hypercalcemia was lower following intravenous lipid emulsion therapy despite a more than 24-hour delay in initiating treatment in 3 of the 4 patients, and no adverse reactions were observed. Additionally, 2 of the 4 animals in this case series had long-term monitoring of 25-hydroxyvitamin D concentrations that revealed persistent elevations at 6 d in a dog and 5 mo in a cat, despite earlier resolution of their ionized hypercalcemia. Key clinical message: This is the first documented serial report of reduction of serum ionized calcium concentrations after administration of intravenous lipid emulsion, in addition to other standard therapies, in 2 dogs and 2 cats with vitamin D toxicosis. Furthermore, a chronically elevated plasma 25-hydroxyvitamin D concentration was documented in 2 of the 4 patients, including the first report in a cat. In these 2 cases, ionized calcium concentrations normalized despite persistently elevated 25-hydroxyvitamin D concentrations.

Thérapie par émulsion lipidique intraveineuse chez 2 chiens et 2 chats atteints de toxicose à la vitamine D. La toxicose à la vitamine D peut entraîner une hypercalcémie grave et prolongée entraînant des lésions à plusieurs organes, voire la mort. Le traitement actuel implique souvent une hospitalisation prolongée et peut nécessiter des médicaments susceptibles d'entraîner des effets indésirables. L'objectif de cette série de cas était de décrire les réductions des concentrations sériques de calcium ionisé par suite d'un traitement par émulsion lipidique intraveineuse dans le traitement de la toxicose à la vitamine D. Deux chiens et 2 chats atteints d'une toxicose à la vitamine D ont été traités par émulsion lipidique intraveineuse en plus des protocoles thérapeutiques standards. L'hypercalcémie ionisée était plus faible après un traitement par émulsion lipidique intraveineuse malgré un retard de plus de 24 heures dans le début du traitement chez 3 des 4 patients, et aucun effet indésirable n'a été observé. De plus, 2 des 4 animaux de cette série de cas ont fait l'objet d'une surveillance à long terme des concentrations de 25-hydroxyvitamine D qui ont révélé des concentrations élevées persistantes à 6 jours chez un chien et à 5 mois chez un chat, malgré une résolution plus précoce de leur hypercalcémie ionisée.Message clinique clé :Il s'agit du premier rapport documenté d'une série de réduction des concentrations sériques de calcium ionisé après l'administration d'une émulsion lipidique intraveineuse, en plus d'autres traitements standards, chez 2 chiens et 2 chats atteints de toxicose à la vitamine D. De plus, une concentration plasmatique chroniquement élevée de 25-hydroxyvitamine D a été documentée chez 2 des 4 patients, y compris le premier rapport chez un chat. Dans ces 2 cas, les concentrations de calcium ionisé se sont normalisées malgré des concentrations constamment élevées de 25-hydroxyvitamine D.(Traduit par Dr Serge Messier).

[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.

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.

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.

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.

Long-term supplementation with 3200 to 4000 IU of vitamin D daily and adverse events: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The upper tolerable intake level for vitamin D in the general population has been set at 4000 international units (IU) daily, but considerable uncertainty remains. We summarized reported harmful effects of a daily vitamin D supplement of 3200-4000 IU in trials lasting ≥ 6 months. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials in several databases and identified 22 trials reporting safety data. Parameters of calcium metabolism, falls, hospitalization, and mortality were assessed. RESULTS: The selected trials comprised a total number of 12,952 participants. All trials used supplemental vitamin D3. The relative risk (RR) of hypercalcemia in the vitamin D vs. control arm was 2.21 (95%CI: 1.26-3.87; 10 studies), with a vitamin D-induced frequency of hypercalcemia of 4 cases per 1000 individuals. Subgroup analysis in trials with > 100 and ≤ 100 study participants revealed an RR of 2.63 (95%CI: 1.30-5.30; 7 studies) and 0.80 (95%CI: 0.24-2.62; 3 studies), respectively (Pinteraction = 0.06). Risks of falls and hospitalization were also significantly increased in the vitamin D arm with an RR of 1.25 (95%CI: 1.01-1.55; 4 studies) and 1.16 (95%CI: 1.01-1.33; 7 studies), respectively. Risks of hypercalciuria, kidney stones, and mortality did not differ significantly between study arms. Quality assessment revealed high risk of incomplete reporting of safety-related outcome data. CONCLUSION: Supplemental vitamin D doses of 3200-4000 IU/d appear to increase the risk of hypercalcemia and some other adverse events in a small proportion of individuals, indicating that this dose is not completely safe. In future studies, rigorous reporting of safety-related outcomes is needed when using moderately high doses of vitamin D.

Vitamin D-induced hypercalcaemia and acute kidney injury in sarcoidosis.

Vitamin D deficiency is relatively common, and its management in patients with sarcoidosis is challenging due to the risk of hypercalcaemia. Our patient had an autologous stem cell transplant for multiple sclerosis and was given high-dose vitamin D concurrently with immunosuppressive therapy. The patient subsequently presented with symptomatic hypercalcaemia and an acute kidney injury. A clinical and biochemical recovery was reached by withdrawing vitamin D and administering intravenous fluids. Interestingly, new evidence suggests that activated vitamin D can actually dampen the inflammatory process in sarcoidosis, and this was reflected in a reduction of our patient's serological markers of sarcoidosis activity. One large study found no significant risk of hypercalcaemia when low doses of vitamin D were used in sarcoidosis. Where indicated, and until clear guidelines are established, we suggest using low doses of vitamin D with cautious monitoring of calcium and renal function.

Vitamin D Toxicity from an Unusual and Unexpected Source: A Report of 2 Cases.

INTRODUCTION: Hypervitaminosis D is a relatively uncommon etiology of hypercalcemia. Toxicity is usually caused by very high doses, mostly secondary to erroneous prescription or administration of vitamin D, and less commonly, contaminated foods or manufacturing errors of vitamin D-containing supplements. CASE PRESENTATION: A 16-year-old male, previously healthy, presented with 2-week history of nonspecific symptoms (fatigue, gastrointestinal complaints). Investigations showed acute kidney injury and hypercalcemia (total calcium 3.81 mmol/L). Further diagnostic workup revealed markedly elevated 25-hydroxyvitamin D levels (1,910 nmol/L). He denied taking any vitamin D supplements; however, he reported consumption of creatine and protein supplements. Mass spectrometry analysis of the creatine supplement estimated a vitamin D content of 425,000 IU per serving (100 times the upper tolerable daily dose). A few months later, another previously healthy adolescent presented with severe hypercalcemia and acute kidney injury secondary to hypervitaminosis D. He was also using a creatine supplement, from the same manufacturer brand and lot. Both patients were treated with intravenous hydration, calcitonin, and pamidronate. They maintained normocalcemia after their initial presentation but required low-calcium diets and laboratory testing for months after this exposure. DISCUSSION/CONCLUSION: We present 2 cases of hypervitaminosis D caused by a manufacturing error of a natural health product which did not claim to contain vitamin D. The use of dietary supplements is highly prevalent; this should be incorporated while taking medical history, and considered a potential source of toxicity when an alternative source cannot be found, regardless of the product label.

Two cases of severe vitamin D3 intoxication treated with therapeutic plasma exchange and high cut-off hemodialysis.

We report on a 53-year-old female patient and a 33-year-old male patient presenting with life-threatening hypercalcemic crisis caused by self-induced vitamin-D intoxication. Both patients took high doses of vitamin D3 supplements, cumulatively up to 2,500,000-10,000,000 I.U. over several months. Accordingly, serum 25-OH-vitamin D concentrations were increased to 663 and 1289 nmol/L (reference 50-175 nmol/L), respectively. As forced diuresis and bisphosphonates failed to correct recurrent hypercalcemia, we hypothesized that add-on extracorporeal treatments might help overcome the refractory situation. Considering the binding of vitamin D3 metabolites to vitamin D-binding protein (VDBP, 59 kDa), we started extracorporeal treatments involving total plasma exchange with replacement by human albumin and by fresh frozen plasma, online hemodiafiltration and high cut-off hemodialysis. We found that in the former case, total plasma exchange with albumin and fresh frozen plasma and high cut-off hemodialysis lowered both 25-OH-vitamin D3 and 1,25-OH-vitamin D3, whereas in the latter case total plasma exchange with albumin was found to more effectively remove vitamin D metabolites compared to high cut-off hemodialysis. In contrast, the amount of total plasma calcium removed by high cut-off hemodialysis was higher compared to total plasma exchange with albumin. During follow up, patients 1 and 2 achieved almost normal total plasma calcium and vitamin D concentrations after 355 and 109 days, respectively. These two cases suggest that extracorporeal treatments with high cut-off hemodialysis and total plasma exchange with albumin may be considered as add-on treatment in refractory cases of vitamin D3-induced hypercalcemia to lower plasma 25-OH-vitamin D3 concentrations.

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.

Hypercalcaemia caused by calcium sulfate beads.

Hypercalcaemia is a relatively common metabolic disturbance seen in hospitalised patients; however, given the complicated systems of calcium regulation, it can take a significant amount of time and testing to pinpoint the aetiology. This case discusses a patient who developed acute hypercalcaemia from calcium sulfate-containing antibiotic beads placed during an orthopaedic procedure. These beads are used in surgical procedures to fill gaps/voids in bony structures and for local delivery of antibiotics. The case highlights the importance of careful review of a patient's hospital course, including the administration of medical products that may not be clearly documented on a patient's medicine administration record when working up an unexplained finding.