An infant developing hypercalcemia and hypophosphatemia due to the use of exclusively almond milk.

OBJECTIVES: Plant-based milk alternatives are increasingly utilized in children with cow milk allergy, lactose intolerance, and personal preference. However, notable differences exist in mineral content between cow milk and plant-based alternatives. Almond milk, in particular, varies in mineral and caloric content across different brands. This case report highlights a toddler who developed hypercalcemia and hypophosphatemia attributed to almond milk consumption. CASE PRESENTATION: A fourteen-month-old girl with a history of biliary atresia underwent liver transplant at seven months of age. She was exclusively consuming almond milk for two months prior to presentation. She was admitted to the hospital for severe hypercalcemia (14.6 mg/dL) and hypophosphatemia (1.6 mg/dL). She had elevated random urine calcium to creatinine ratio (2.56 mg/g) and low urine phosphorus to creatinine ratio (<0.44 mg/g) were noted. Parathyroid hormone (PTH) level was appropriately suppressed (<6 pg/mL), while 1,25 dihydroxyvitamin D level was slightly elevated at 88 pg/mL. Initial management included intravenous fluids, followed by a switch to a formula with higher phosphorus and lower calcium concentrations. The patient was discharged after six days with normalized calcium and phosphorus levels, which remained within the normal range. CONCLUSIONS: Although plant-derived milk serves as a viable alternative to cow milk, careful consideration of mineral content, particularly in infants and toddlers, is imperative. Sole reliance on almond milk for nutritional needs in this population is not recommended. Caregivers should be informed about the potential risks associated with almond milk consumption in infants and toddlers.

[A e-Hypercalcemia]. / À propos d'une e-Hypercalcémie.

INTRODUCTION: Hypercalcemia is a common biological abnormality. The etiologies are mainly represented by hyperparathyroidism and neoplastic causes. The other causes, including poisoning, are rare, but should not be neglected. OBSERVATION: An 82-year-old female patient presented to the emergency room for repeated falls at home, confusion, drowsiness and digestive symptoms. The initial assessment showed hypercalcemia above 3mmol/L. The etiological exploration revealed a very high concentration of 25OH-vitamin D. After repeated interrogations, it appeared that the cause of this intoxication was the intake of a food supplement purchased on the internet, following a prescription from her dentist. CONCLUSION: Intoxication due to a food supplement containing vitamin D is possible and potentially serious. Raising the awareness of patients and healthcare professionals is necessary in order to prevent this type of poisoning and/or to diagnose it as soon as possible.

Nephrogenic Calciphylaxis Arising after Bariatric Surgery: A Case Series.

Nephrogenic calciphylaxis is associated with multiple risk factors including long-term dialysis dependence, hyperphosphatemia, hypercalcemia, parathyroid hormone derangements, vitamin K deficiency, obesity, diabetes mellitus, warfarin use, and female sex. Bariatric surgery is known to cause altered absorption, leading to mineral and hormonal abnormalities in addition to nutritional deficiency. Prior case reports on calciphylaxis development following bariatric surgery have been published, though are limited in number. We report a case series of five bariatric patients from a single institution who developed nephrogenic calciphylaxis between 2012 and 2018. These patients had a history of bariatric surgery, and at the time of calciphylaxis diagnosis, demonstrated laboratory abnormalities associated with surgery including hypercalcemia (n = 3), hyperparathyroidism (n = 2), hypoalbuminemia (n = 5), and vitamin D deficiency (n = 5), in addition to other medication exposures such as vitamin D supplementation (n = 2), calcium supplementation (n = 4), warfarin (n = 2), and intravenous iron (n = 1). Despite the multifactorial etiology of calciphylaxis and the many risk factors present in the subjects of this case series, we submit that bariatric surgery represents an additional potential risk factor for calciphylaxis directly stemming from the adverse impact of malabsorption and overuse of therapeutic supplementation. We draw attention to this phenomenon to encourage early consideration of calciphylaxis in the differential for painful skin lesions arising after bariatric surgery as swift intervention is essential for these high-risk patients.

[Pattern of biochemical markers of mineral and bone disorders in kidney transplant recipients: real-world data].

BACKGROUND: There is a lack of studies providing comprehensive data on the prevalence of mineral and bone disorders (MBD) laboratory abnormalities after kidney transplantation in Russia. AIM: to obtain real-world data on the prevalence of the main mineral abnormalities among kidney transplant recipients and to revise their concomitant MBD therapy. METHOD: This cross-sectional study included 236 patients with successful kidney transplantation. Their serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were measured. RESULTS: Only 6.2% of our cohort had all laboratory parameters within the target range, whereas persistent HPT along with hypercalcemia was noted in almost one third of the patients (31%). Normal iPTH levels were observed in 13% cases; 84% of the patients had hyperparathyroidism. The fraction of patients with target iPTH did not differ between the groups with normal and decreased estimated glomerular filtration rate (eGFR) (p=0.118). Hypercalcemia was observed in 29% cases. The serum P level varied significantly in groups with different eGFR (p<0.0001), increasing with declining graft function. Furthermore, 40.7% of patients had ALP above the target range. While 123 patients received active vitamin D (alfacalcidol), 33 received monotherapy with inactive vitamin D (cholecalciferol). The control group consisted of 57 medication-naïve patients. The serum total Ca level varied significantly between the groups (p=0.0006), being higher in patients supplemented with cholecalciferol. The fraction of patients with normocalcemia was lowest in the cholecalciferol group (chi-square, р=0.0018). CONCLUSION: The prevalence of biochemical abnormalities after kidney transplantation is high. Alfacalcidol usage may be safer than using cholecalciferol to prevent hypercalcemia development.

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.

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.

Hypercalcemia: A Review.

Importance: Hypercalcemia affects approximately 1% of the worldwide population. Mild hypercalcemia, defined as total calcium of less than 12 mg/dL (<3 mmol/L) or ionized calcium of 5.6 to 8.0 mg/dL (1.4-2 mmol/L), is usually asymptomatic but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people. Hypercalcemia that is severe, defined as total calcium of 14 mg/dL or greater (>3.5 mmol/L) or ionized calcium of 10 mg/dL or greater (≥2.5 mmol/L) or that develops rapidly over days to weeks, can cause nausea, vomiting, dehydration, confusion, somnolence, and coma. Observations: Approximately 90% of people with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy. Additional causes of hypercalcemia include granulomatous disease such as sarcoidosis, endocrinopathies such as thyroid disease, immobilization, genetic disorders, and medications such as thiazide diuretics and supplements such as calcium, vitamin D, or vitamin A. Hypercalcemia has been associated with sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, but these account for less than 1% of causes. Serum intact parathyroid hormone (PTH), the most important initial test to evaluate hypercalcemia, distinguishes PTH-dependent from PTH-independent causes. In a patient with hypercalcemia, an elevated or normal PTH concentration is consistent with PHPT, while a suppressed PTH level (<20 pg/mL depending on assay) indicates another cause. Mild hypercalcemia usually does not need acute intervention. If due to PHPT, parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement. In patients older than 50 years with serum calcium levels less than 1 mg above the upper normal limit and no evidence of skeletal or kidney disease, observation may be appropriate. Initial therapy of symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate. In patients with kidney failure, denosumab and dialysis may be indicated. Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas). Treatment reduces serum calcium and improves symptoms, at least transiently. The underlying cause of hypercalcemia should be identified and treated. The prognosis for asymptomatic PHPT is excellent with either medical or surgical management. Hypercalcemia of malignancy is associated with poor survival. Conclusions and Relevance: Mild hypercalcemia is typically asymptomatic, while severe hypercalcemia is associated with nausea, vomiting, dehydration, confusion, somnolence, and coma. Asymptomatic hypercalcemia due to primary hyperparathyroidism is managed with parathyroidectomy or observation with monitoring, while severe hypercalcemia is typically treated with hydration and intravenous bisphosphonates.

Parathyroid carcinoma during pregnancy: a novel pathogenic CDC73 mutation - a case report.

BACKGROUND: Parathyroid carcinoma is an uncommon cause of PTH-dependent hypercalcemia. Only a handful of cases have been reported of parathyroid carcinoma during pregnancy. CASE PRESENTATION: Twenty-four - Year - old female presented with proximal myopathy was found to have hypercalcemia. Her serum corrected total calcium was - 15 mg/dl (8.5 - 10.3), serum phosphate - 2.3 mg/dl (2.5 - 4.5), intact PTH - 118 pg/ml (20 - 80), Vitamin D - 15 ng/ml and Urine Ca/Cr ratio - 2.1 (0.1 - 0.2). Her CECT-neck revealed a well-defined mass lesion posterior to the right lobe of the thyroid - 2.6 cm × 2.5 cm × 2.9 cm in size. She was started on vitamin D supplementation, and she underwent right lower focal parathyroidectomy. Her PTH levels normalized following surgery. Her histology revealed an atypical parathyroid adenoma. She was treated with calcium and vitamin D. Her follow up was uneventful. One year following initial surgery the patient became pregnant and at 16 weeks of POA, the patient presented with a rapidly enhancing neck mass for one week duration. Her biochemical investigations were suggestive of a recurrence of primary hyperparathyroidism. Her ultrasound scan of the neck revealed a well-defined discreate hypoechoic nodule, superior to the thyroid isthmus which was confirmed by a non-contrast MRI scan of the neck. She underwent an uncomplicated second trimester parathyroid tumour excision with normalization of post op PTH. Her histology revealed a parathyroid carcinoma with vascular and capsular invasion. Her genetic studies revealed a novel frameshift mutation of the CDC73 gene. She was treated with calcium and vitamin D supplementation and closely followed up with ionized calcium and PTH levels which were normal throughout the pregnancy. She had an uncomplicated caesarean section at a POA of 37 weeks. Currently she is twelve weeks post-partum, in remission of disease. CONCLUSION: This case shows the importance of stringent follow up of atypical parathyroid adenoma patients, the benefit of second trimester surgery in management of hypercalcemia due to parathyroid carcinoma during pregnancy and the importance of identifying the novel CDC73 gene mutation.

Too much of a good thing: A case series of rare yet pertinent causes of hypercalcaemia and acute kidney injury.

Calcium compounds and vitamin D supplements are readily available as over-the-counter preparations. Whilst integral in maintaining calcium homeostasis in certain patients, excess exogenous intake of these preparations can have deleterious effects, particularly in terms of renal function. We look at the cases of two patients, aged 52 and 34, who were referred into hospital with hypercalcaemia and acute kidney injury (AKI). Both individuals reported regular and prolonged self-medication with unregulated over-the-counter supplements containing calcium carbonate and vitamin D, respectively. Prompt investigation and treatment enabled an element of reversibility of the AKI in both the cases, with further improvement in renal function over time. We emphasise the importance of recognising the overuse of exogenous vitamin D supplements and calcium compounds as rare yet treatable causes of AKI associated with hypercalcaemia and discuss how raising public awareness into the risks posed by self-medication of over-the-counter medicines is paramount.

[Long-term efficacy and safety of treatment with cinacalcet in hypercalcemic persistent secondary hyperparathyroidism in renal transplant].

Introduction: persistent hypercalcemic secondary hyperparathyroidism (PSHPT) in kidney transplantation (KTx) can expose renal transplant recipients (RTRs) to a series of complications. Cinacalcet has been shown to be effective in controlling hypercalcemic PSHPT. Therefore, we evaluated the efficacy and tolerability of cinacalcet, over a period of 3 years, in the treatment of hypercalcemic PSHPT in a group of RTRs. Patients and Methods: eight patients with a kidney transplant age > 12 months, parathyroid hormone (PTH) levels > 120 pg/ml and total serum calcium (TCa) levels > 10.5 mg/dl, were treated with cinacalcet at an initial dose of 30 mg/day. Hypercalcemic PSHPT picture must have been present for at least 6 months before the start of treatment with cinacalcet. Every 6-8 weeks were determined: estimated glomerular filtration rate (eGFR), PTH, TCa, serum phosphorus, fractional excretion of calcium (FECa), tubular maximum reabsorption rate of phosphate (TmP/GFR), serum tacrolimus. Annually all patients underwent to ultrasound control of the transplanted kidney. The main endpoints of the study were the reduction of PTH levels > 30% from baseline and the normalization of TCa levels (<10.2 mg/dl). Results: the results are shown as median ± interquartile range (IQR). At follow-up PTH levels decreased from 223 (202-440) to 135 pg/ml (82-156) (P < 0.01), with a percentage decrease of -54 (-68;-44), TCa levels decreased from 11.0 (10.7-11.7) to 9.3 mg/dl (8.8-9.5) (P < 0.001). Serum phosphorus levels increased from 2.7 (2.0-3.0) to 3.2 mg/dl (2.9-3.5) (P < 0.05). Fractional excretion of calcium did not change, while TmPO4/GFR increased even not significantly. Renal function and serum levels of tacrolimus did not change throughout the observation period. At end of the study the average cinacalcet dosages were 30 mg/day (30-30). Ultrasound scans of the transplanted kidney showed no development of nephrocalcinosis and/or nephrolithiasis. Conclusions: cinacalcet has proved effective and well tolerated in the treatment of hypercalcemic PSHPT in RTRs.

[Hypercalcemia after hyperkalemia]. / Hypercalciëmie na een hyperkaliëmie.

BACKGROUND: Hyperkalemia is a common yet dangerous phenomenon in patients with chronic kidney disease (CKD). Patients suffering from CKD are therefore often treated with potassium-binding supplements such as calcium polystyrene sulfonate (CPS). Hypercalcemia is a known side effect of CPS. However, the increase in serum calcium is usually small. CASE DESCRIPTION: A 68 year old male patient suffering from CKD was treated with a daily administration of 80mg CPS. He presented with complaints of a dry mouth, thirst and malaise. Blood tests showed an elevated serum calcium of 3,25 mmol/L (2,15- 2,55 mmol/L). Additional diagnostics revealed no abnormalities. The hypercalcemia was attributed to the use of CPS only after the exclusion of a wide differential diagnosis. CONCLUSION: Although CPS induced hypercalcemia is usually mild, a more severe course is possible. Knowledge about the composition of medication is paramount to prevent such side effects.

Vitamin D3 supplementation during pregnancy and lactation for women living with HIV in Tanzania: A randomized controlled trial.

BACKGROUND: Observational studies suggest that vitamin D deficiency among people living with HIV is associated with a greater risk of disease progression and death. Low levels of vitamin D in pregnancy are also associated with poor fetal and infant growth. Therefore, vitamin D supplementation may improve clinical outcomes for pregnant women living with HIV and improve fetal and postnatal growth for their infants. METHODS AND FINDINGS: We conducted a randomized, triple-blind, placebo-controlled trial of vitamin D3 supplementation among pregnant and lactating women living with HIV in Dar es Salaam, Tanzania (ClinicalTrials.gov NCT02305927). Participants were randomized with 1:1 allocation stratified by study clinic to receive either daily 3,000 IU vitamin D3 supplements or matching placebo supplements from the second trimester of pregnancy (12-27 weeks) until 1 year postpartum. The primary outcomes were (i) maternal HIV progression or death, (ii) small-for-gestational-age (SGA) live births (<10th percentile), and (iii) infant stunting at 1 year of age (length-for-age z-score < -2). We also examined the effect of vitamin D3 supplementation on secondary maternal and infant health outcomes, maternal and infant serum 25-hydroxyvitamin D (25[OH]D) concentrations, and maternal hypercalcemia. An intent-to-treat analysis was used as the primary analytic approach. We enrolled 2,300 pregnant women between June 15, 2015, and April 17, 2018, and follow-up of mothers and infants was completed on October 20, 2019. There were 1,148 pregnant women randomly assigned to the vitamin D3 group, and 1,152 to the placebo group. The proportion of mothers lost to follow-up at 1 year postpartum was 6.6% in the vitamin D3 group (83 of 1,148) and 6.6% in the placebo group (76 of 1,152). The proportion of children lost to follow-up at 1 year of age was 5.5% in the vitamin D3 group (59 of 1,074 live births) and 5.2% in the placebo group (57 of 1,093 live births). There was no difference in the risk of maternal HIV progression or death, with 166 events during 1,461 person-years of follow-up in the vitamin D3 group and 141 events during 1,469 person-years of follow-up in the placebo group (hazard ratio 1.21, 95% CI 0.97 to 1.52, p = 0.09). There was no difference in the risk of SGA birth between the vitamin D3 (229 SGA births among 1,070 live births) and placebo groups (236 SGA births among 1,091 live births) (relative risk 1.03, 95% CI 0.87 to 1.22, p = 0.70). There was also no difference in the risk of infant stunting at 1 year of age between the vitamin D3 (407 events among 867 infants) and placebo groups (413 events among 873 infants) (relative risk 1.00, 95% CI 0.92 to 1.10, p = 0.95). In terms of adverse events, no cases of maternal hypercalcemia were identified. One hypersensitivity reaction to the trial supplements occurred for a pregnant woman in the placebo group. A limitation of our study is that our findings may not be generalizable to HIV-negative pregnant women or contexts where severe vitamin D deficiency is prevalent. CONCLUSIONS: The trial findings do not support routine vitamin D supplementation for pregnant and lactating women living with HIV in Tanzania. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02305927.

Successful Control of Hypercalcemia with Sorafenib, Evocalcet, and Denosumab Combination Therapy for Recurrent Parathyroid Carcinoma.

Parathyroid carcinoma (PC) is a rare type of endocrine cancer. Recurrence and metastasis are common after surgery, and refractory hypercalcemia often leads to a poor prognosis. However, there are currently no specific strategies for PC recurrence. We herein report a 61-year-old Japanese man with metastatic PC who was treated with sorafenib, a multikinase inhibitor. In this case, the serum calcium level was under control for 10 months after the initiation of sorafenib. This case suggests that combination therapy with sorafenib, evocalcet, and denosumab may be an alternative, stronger management option for refractory hypercalcemia in recurrent PC.

Hypercalcemia and vitamin A: A vitamin to keep in mind.

Vitamin A, like many things in life, should be consumed in appropriate amounts. Excessive intake of preformed vitamin A, such as that found in supplements and animal sources (animal liver, fish liver oil, dairy, and eggs), is associated with multisystem effects that can include bone resorption and hypercalcemia. Hence, vitamin A toxicity should be explored in unexplained cases of parathyroid hormone-independent hypercalcemia. Serum retinol levels can be helpful in the diagnosis, but the results must be interpreted with caution since they do not always reflect total body levels. Treatment involves supportive care and withdrawal of vitamin A sources, especially preformed ones. Given the long half-life of retinol, normalization of serum levels can take several months.

Parathyroid carcinoma: Single centre experience.

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

Hypercalcemia: An Underestimated Value Always Good for a Surprise.

We present the unusual case of a 62-year-old male with profound asthenia and dyspnea for the last two months. Blood exams showed a severe hypercalcemia. Suspecting an underlying malignancy, we performed a 18F-FDG PET-CT, revealing widespread metabolic uptakes in muscles, consistent with an inflammatory process. The muscular biopsy showed a non-necrotising granuloma with multinucleated giant cells, pathognomonic for the diagnosis of acute isolated muscular sarcoidosis. A high-dose steroid therapy was started with clinical improvement and serum calcium normalization.

Atypical manifestations of infantile-onset nephropathic cystinosis: a diagnostic challenge.

A 7-month-old male infant was referred to us for evaluation of hypercalcemia and failure to thrive. He was the second-born child to third-degree consanguineous parents with a birth weight of 3.5 kg. The index child was severely underweight. Initial laboratory investigations showed hypercalcemia (13.6 mg/dL), hypophosphatemia, hyponatremia, hypokalemia and hypochloremia. The initial serum bicarbonate level was 20.9 mEq/L. The urine calcium: creatinine ratio (0.05) was normal. He was noted to have polyuria (6 mL/kg/hr) and required intravenous fluids to maintain intravascular volume and manage hypercalcemia, along with potassium chloride supplements. The serum calcium decreased to 9.7 mg/dL after hydration for 48 h. At this juncture, the child was noted to exhibit metabolic acidosis (serum bicarbonate 16 mEq/L) for the first time. Thereafter, fractional excretion of bicarbonate was estimated to be 16.5% while the tubular threshold maximum for phosphorus per glomerular filtration rate was 1.2 mg/dL; indicating bicarbonaturia and phosphaturia, respectively. Glycosuria with aminoaciduria were also noted. Clinical exome sequencing revealed a NM_004937.3:c.809_811del in exon 10 of the CTNS gene that resulted in in-frame deletion of amino acids [NP_004928.2:p.Ser270del] at the protein level. The child is now growing well on oral potassium citrate, neutral phosphate and sodium bicarbonate supplements. This case was notable for absence of metabolic acidosis at admission. Instead, severe hypercalcemia was a striking presenting manifestation, that has not been reported previously in literature. Cystinosis has been earlier described in association with metabolic acidosis, hypocalcemia and hypomagnesemia. However, typical features like metabolic acidosis were masked in early stages of the disease in our case posing a diagnostic challenge. This atypical initial presentation adds to the constellation of clinical features in this condition.

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

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

Severe neonatal hypercalcemia revealing congenital mesoblastic nephroma: A case report and management of neonatal hypercalcemia: Severe neonatal hypercalcemia revealing congenital mesoblastic nephroma.

Congenital mesoblastic nephroma is a rare pediatric renal tumor and has been reported in patients presenting with palpable abdominal mass, arterial hypertension, hematuria, polyuria, or hypercalcemia. Here we present the case of a 1-month-old neonate with suspected parathyroid hormone (PTH)-related peptide (PTH-rp)-mediated severe hypercalcemia revealing congenital mesoblastic nephroma. Preoperatively, hypercalcemia was corrected with hydration, furosemide, pamidronate, and low-calcium infant formula. Unilateral nephrectomy led to the resolution of hypercalcemia, transient hyperparathyroidism, and transient vitamin D and mineral supplementation. We conclude that congenital mesoblastic nephroma can secrete PTH-rp that can cause severe hypercalcemia.