Severity Of Hypercalcemia Research Articles

8063 Cystic Parathyroid Adenoma: A Rare Cause Of Severe Hypercalcemia

Abstract Disclosure: M. Owrangi: None. F. Hasan: None. Introduction: Parathyroid adenomas are the most common cause of primary hyperparathyroidism, but within this category, a rare subtype exists - cystic parathyroid adenomas (CPAs). Comprising only 0.5-1% of all parathyroid lesions, CPAs present unique diagnostic and therapeutic challenges. We report a case of a female patient presenting with severe hypercalcemia caused by a CPA. Case presentation: A 44-year-old African American female with a history of nephrolithiasis presented with abdominal pain and signs of dehydration. Labs were remarkable for serum calcium 13.2 mg/dL, albumin 4.0 g/dL, phosphorus 1.8 mg/dL, iPTH 617.7 pg/mL, 25-OH vit D 12.1 ng/mL, creatinine 0.85 mg/dL. She was initially resuscitated aggressively with IV fluids resulting in an improvement in serum calcium level to 10.3 mg/dL. Thyroid US showed a cystic nodule deep to the left thyroid lobe. Sestamibi parathyroid scan was consistent with a left superior parathyroid adenoma. She underwent 2 gland parathyroidectomy 3 months after the initial presentation. Intraoperatively serum PTH decreased by 91% after resection of the 2 parathyroid adenomas. Pathology confirmed the presence of 2 parathyroid adenomas, the larger one measuring 2.8 cm and weighing 3.8 g. Discussion: We describe a case of a middle-aged female presenting with severe hypercalcemia due to CPA. Her initial presentation was concerning for parathyroid carcinoma given the severity of hypercalcemia. However, the radiologic findings, coupled with surgical pathology, indicated that she had CPA. CPAs can be either functional, causing primary hyperparathyroidism (PHPT) with elevated serum calcium levels, or non-functional, remaining asymptomatic. Clinical features of PHPT associated with CPAs are similar to those with solid adenomas and include fatigue, GI symptoms, nephrolithiasis, bone pain, and neuropsychiatric manifestations. However, CPAs may exhibit certain distinct presentations: i) higher pre-operative serum calcium levels; and ii) increased risk of symptomatic hypercalcemia. Despite their rarity, CPAs deserve special attention due to their unique presentation, challenging diagnosis, and potential for severe hypercalcemia. Surgical parathyroidectomy is the definitive treatment for functional CPAs. Accurate localization and complete excision of the adenoma are crucial to avoid recurrence. Most CPAs occur in the fourth and fifth decade of life and are more common in women (female to male ratio of 2.5:1). 65-85% of cases are located in the neck and the majority arise from the inferior parathyroid glands and are left-sided, and may very rarely be intrathyroidal. Presentation: 6/2/2024

Hypercalcemia: a practical review

Hypercalcemia, defined as an abnormal elevation of serum calcium, is a common electrolyte anomaly in primary care, affecting almost 1% of the worldwide population. Clinical manifestations concern the neuromuscular, cardiovascular, gastrointestinal, renal and skeletal systems. Among the causes, the main ones are primary hyperparathyroidism, and malignancies. Le initial workup should include the measurement of parathyroid hormone (PTH), and the discontinuation of any medication likely to be involved in iatrogenic hypercalcemia. The chosen treatments and their speed of introduction depend mainly on the severity of hypercalcemia. They include intravenous rehydration, and antiresorptive agents such as bisphosphonates, denosumab or calcitonin.

Long-term effects of primary hyperparathyroidism and parathyroidectomy on kidney function.

Limited evidence supports kidney dysfunction as an indication for parathyroidectomy in asymptomatic primary hyperparathyroidism (PHPT). To investigate the natural history of kidney function in PHPT and whether parathyroidectomy alters renal outcomes. Matched control study. A vertically integrated health care system serving 4.6 million patients in Southern California. 6058 subjects with PHPT and 16 388 matched controls, studied from 2000 to 2016. Biochemically confirmed PHPT with varying serum calcium levels. Estimated glomerular filtration rate (eGFR) trajectories were compared over 10 years, with cases subdivided by severity of hypercalcemia: serum calcium 2.62-2.74 mmol/L (10.5-11 mg/dL), 2.75-2.87 (11.1-11.5), 2.88-2.99 (11.6-12), and >2.99 (>12). Interrupted time series analysis was conducted among propensity-score-matched PHPT patients with and without parathyroidectomy to compare eGFR trajectories postoperatively. Modest rates of eGFR decline were observed in PHPT patients with serum calcium 2.62-2.74 mmol/L (-1.0 mL/min/1.73 m2/year) and 2.75-2.87 mmol/L (-1.1 mL/min/1.73 m2/year), comprising 56% and 28% of cases, respectively. Compared with the control rate of -1.0 mL/min/1.73 m2/year, accelerated rates of eGFR decline were observed in patients with serum calcium 2.88-2.99 mmol/L (-1.5 mL/min/1.73 m2/year, P2.99 mmol/L (-2.1 mL/min/1.73 m2/year, P2.87 mmol/L exhibited mitigation of eGFR decline after parathyroidectomy (-2.0 [95% CI: -2.6, -1.5] to -0.9 [95% CI: -1.5, 0.4] mL/min/1.73 m2/year). Compared with matched controls, accelerated eGFR decline was observed in the minority of PHPT patients with serum calcium >2.87 mmol/L (11.5 mg/dL). Parathyroidectomy was associated with mitigation of eGFR decline in patients with serum calcium >2.87 mmol/L.

Abstract #1406955: Two Parathyroidectomies in the Third Trimester for Severe Primary Hyperparathyroidism (PHPT) Resulting in Distinct Maternal and Fetal Outcomes

Parathyroidectomy (PTX) is well-tolerated in the second trimester of pregnancy in women with severe PHPT. We present two women requiring PTX in the third trimester of pregnancy due to the severity of the disease. Case 1: 30 y.o female presented at 33 weeks’ gestation with leg pain and severe PTH-mediated hypercalcemia; serum corrected calcium 4.2mmol/L (NR: 2.15-2.6), PTH 147.9 pmol/L (NR:1.6-6.9). She was symptomatic for 2 yrs prior and had a history of nephrolithiasis; the renal US showed 10-20 non-obstructing renal calculi. Femur X-ray demonstrated an aggressive lesion, identified as a brown tumor, on histopathology with additional bone lesions on skeletal survey. Severe hypercalcemia was managed with IV fluids, calcitonin and cinacalcet 30 mg BID. Neck-CT showed a 4cm parathyroid adenoma with no overt malignant features. Subtotal PTX was performed at 33w2d, and PTH dropped to 4.7pmol/L postop. Histopathology reported atypical parathyroid adenoma. Post PTX patient went into premature rupture of membranes, c-section done at 34 weeks’ gestation. Day 8 post PTX, the patient developed hungry bone syndrome, she also had a mechanical fall and sustained a pathological fracture of the femur, the site of brown tumor. Baby was admitted to NICU with hypoparathyroidism, resolved at 3 months of age. Case 2: 32 y.o female presented at 27 weeks’ gestation with incidental hypercalcemia and high PTH. Nausea and vomiting worsened from the 18th week of gestation. No end-organ involvement. Corrected calcium 3.04 mmol/L, PTH 17.1 pmol/L. Managed with IV fluids, and remained symptomatic with no improvement in hypercalcemia. PTX for parathyroid adenoma was performed at 30 weeks’ gestation with excellent maternal and fetal outcomes. PTH dropped to 2.0 pmol/L postop. Had spontaneous vaginal delivery at 39 weeks’ gestation, no neonatal hypocalcemia. Baby has normal milestones. Biochemical workup for Multiple Endocrine Neoplasia type1 (MEN1) was unremarkable for both patients, DNA testing is outstanding. The duration of PHPT, the severity of hypercalcemia, and the involvement of end-organ damage are critical factors that may influence both maternal and fetal outcomes in women with PHPT who undergo PTX in the third trimester.

Prevalence and outcomes associated with hypocalcaemia and hypercalcaemia among pre-dialysis chronic kidney disease patients with mineral and bone disorder.

Chronic kidney disease-mineral and bone disease (CKD-MBD) is a complication of chronic kidney disease (CKD) involving derangements in serum calcium and phosphate. This study aims to evaluate hypo- and hypercalcaemia and their associated outcomes among pre-dialysis CKD patients. A retrospective cohort study was performed and included all adult CKD stage 4-stage 5 patients who were on treatment for CKD-MBD between 2016 and 2017. Each patient was followed up for 3 years. Hypo- and hypercalcaemia were defined as serum corrected calcium (Ca 2+ ) <2.10 and >2.46 mmol/L, respectively. Outcomes evaluated included all-cause mortality and cardiovascular events. Multivariate Cox regression analysis was done to evaluate the association of hypocalcaemia and/or hypercalcaemia with the clinical outcomes. Severity of hypocalcaemia episode was classified as 'mild' (Ca 2+ : between 1.90 and 2.10 mmol/L) and 'severe' (Ca 2+ : <1.90 mmol/L). Severity of hypercalcaemia was classified as 'mild' (Ca 2+ : between 2.47 and 3.00 mmol/L), moderate (Ca 2+ : between 3.01 and 3.50 mmol/L) and severe (Ca 2+ : >3.50 mmol/L). Of the 400 patients, 169 (42.2%) and 94 (23.5%) patients experienced hypocalcaemia and hypercalcaemia, respectively. Severe hypocalcaemia was more prevalent in CKD stage 5 compared to CKD stage 4 (96 [40.5%] vs. 36 [25.9%], P = 0.004). Results from multivariate analyses after adjustment showed that hypocalcaemia and/or hypercalcaemia were not associated with all-cause mortality ( P > 0.05) or the occurrence of cardiovascular events ( P > 0.05). Hypocalcaemia and hypercalcaemia episodes were prevalent among pre-dialysis CKD patients. Studies with longer follow-up durations are required to assess the effects of calcium derangements on clinical outcomes.

Different treatment strategies in primary hyperparathyroidism during pregnancy.

Primary hyperparathyroidism (PHPT) in pregnancy is rare enough and can be unrecognized because of nonspecific symptoms in most cases, but life-threatening complications for mother, fetus and neonate also occurs. PHPT requires frequent monitoring of the mother and fetus by a multidisciplinary team. Diagnostics and treatment approaches are limited and require individual risk-benefit assessment. In this paper we describe 3 cases of PHPT in pregnant women with different managing approaches (surveillance, drug therapy and surgical treatment) and successful outcomes. Additionally, the most actual literature data on this problem is reviewed. The management of PHPT in pregnancy should be based on the clinical features, severity of hypercalcemia, gestational age and patient's preference. In the first case a conservative approach with low-calcium diet and oral hydration resulted in mother's reduced serum calcium level before delivery. The second patient had severe hypercalcemia and absolute indications for surgery that was successfully performed at 25 week of gestation. The third woman received cinacalcet because of severe hypercalcemia and potential perioperative risks in the third trimester with an improvement in well-being. Nowadays parathyroidectomy is the best choice for patients with symptomatic PHPT and severe hypercalcemia. This intervention should be carried out preferably in the second trimester to avoid maternal and fetal complications. Mild forms of the disease can require just a conservative management. The drug treatment of PHPT during pregnancy is still controversial.

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

BackgroundThe Covid-19 pandemic has had dramatic consequences on the progression of numerous pathologies, especially neoplastic ones. The orientation of hospital activities toward the care of patients with SARS-Cov2 infection has caused significant delays in the diagnosis and therapy of many other pathologies. What about severe hypercalcemia? The aim of this work was to determine the clinical and biological presentation, etiologies, mortality, and the impact of the Covid-19 pandemic on severe hypercalcemia.Material and methodswe conducted a retrospective study for 84 months (September 2014 to September 2021) at the Nephrology Unit in University Hospital Mohammed VI, Oujda, Morocco. Included were all adult patients diagnosed with severe hypercalcemia (defined as corrected total serum calcium of >3.5 mmol/l or > 14.0 mg/dl) and who had benefited from one or more hemodialysis sessions.Results66 episodes of severe hypercalcemia occurred in 64 patients. The mean age was 57 ± 15 years and 57.6% were female. The mean corrected serum calcium at admission was 16.9 ± 2.1 mg/dl and 33.3% had more than 18.0 mg/dl. Malignancies represented 80.4% of all etiologies. Acute kidney injury was observed in 69.7%. The delta drop in serum calcium 48 h after initiation of medical treatment was 4.64 ± 1.63 mg /dl. Mortality was noted in 14% of all cases. Electrocardiographic abnormalities were observed in 58.3%, 87.5% and 85.7%, respectively, in group 1 (14.0–16.0 mg/dl), group 2 (16.1–18.0 mg/dl), and group 3 (> 18.0 mg/dl) (p = 0.04). The mean serum potassium value was 5.1 ± 1.3, 4.0 ± 1.0, and 3.7 ± 0.7 respectively, in group 1 (14.0–16.0 mg/dl), group 2 (16.1–18.0 mg/dl), and group 3 (> 18.0 mg/dl) (p < 0.001). Newly diagnosed neoplasia, severe hypercalcemia (> 16.0 mg/dl), and mortality have been observed in 15.4% vs. 23.7% (p = 0.31), 25% vs. 50% (p = 0.03), and 35.7% vs. 52.6% (p = 0.13) respectively, in patients before and during the Covid-19 pandemic.ConclusionsThe Covid-19 pandemic caused an increase in both the incidence and severity of hypercalcemia and the hemodialysis practiced in this context remains efficient and safe.

A Case Report of Patient With Mysterious Hypercalcemia

Background: Non-parathyroid hormone related hypercalcemia has a broad differential diagnosis. One of the key diagnosis to exclude is malignancy. Case: A 41 yo male with paraplegia due to an accident at age 21, b/l BKA, stage 4 sacral pressure ulcer complicated by vesico-cutanous fistula status post ileal conduit and chronic osteomyelitis of the ischia, sacrum and pelvis was admitted with sepsis secondary to infected sacral pressure ulcer. He was noted to be hypercalcemic with corrected calcium of 13.4mg/dl. He had no previous history of hypercalcemia, kidney stones, head or neck radiation. Work up showed appropriately suppressed PTH with normal PTHrp, 1,25-dihydroxy vitamin D, 25-dihydroxy vitamin D, SPEP, UPEP and TSH. Drug induced hypercalcemia was ruled out. CT abdomen/pelvis was done and showed chronic osteomyelitis; destruction of the sacrum, ischia, pubic bones and femoral heads with enlarged inguinal lymph nodes. Review of records showed a NM bone scan done the year prior to admission to evaluate the chronic destruction of pelvic bones was negative for malignancy. Chest imaging was unremarkable. Patient underwent debridement and wash out of sacral and bilateral lower extremity wounds with bone biopsy. Pathology showed necrotic bone, chronic and acute inflammatory tissue. Calcium peaked at 17mg/dl prior to bisphosphonate, calcitonin and IVF becoming effective. Given the severity of hypercalcemia there was concern for malignancy despitethe negative work up thus Interventional Radiology was consulted for lymph node biopsy. Inguinal lymph node FNA was positive for metastatic squamous cell cancer prompting an exam under anesthesia which was negative for anal lesions. He underwent a cystoscopy which showed a large fungating mass involving the bulbar and membranous urethra with biopsies consistent with invasive and moderately differentiated keratinizing squamous cell carcinoma. Hypercalcemia resolved with treatment and he was discharged home to complete an antibiotic course prior to anticipated chemotherapy. Unfortunately, patient died prior to starting chemotherapy. Conclusion: Hypercalcemia has been found to be associated with 30% of late stage malignancies and is a marker of poor prognosis. It is most commonly associated with hematological malignancies, such as multiple myeloma and leukemias as well solid tumors like breast carcinomas. In Hypercalcemia of malignancy, PTHrp is the causal agent in over 80% of cases with 20% of cases attributed to osteolytic mechanisms mediated by inflammatory cytokines. Less than 1% of hypercalcemia of malignancy is attributed to excess 1,25-dihydroxy vitamin D. High level of suspicion for malignancy should be presentwhen patients present moderate/severe non-PTH mediated hypercalcemia. Workup for malignancy should be pursued even with normal PTHrp.

Influence of common clinical variables on intraoperative parathyroid hormone monitoring during surgery for primary hyperparathyroidism.

Intraoperative monitoring of parathyroid hormone (IOPTH) is a reliable method of predicting the cure ofprimary hyperparathyroidism (PHPT). The aim of this study is to assess whether common clinical variables (CCV) frequently encountered in patients with PHPT may affect the magnitude of PTH drop or the likelihood of patients meeting the intraoperative cure criterion. Patients who were surgically cured from PHPT caused by single gland disease (SGD) and had full IOPTH protocol (4 measurements) were stratified according to age, gland weight, renal function, vitamin D status and severity of hypercalcemia. The percentage of IOPTH drop and the frequency of patients who had true positive IOPTH test results were compared among groups. 762 patients had surgery for PHPT, of whom 746 were (98%) cured. Of these 746 patients, 511 who had SGD and a full IOPTH protocol were included in this study. The median IOPTH drop was significantly higher among younger patients, those with severe hypercalcaemia at 5, 10, 15min after gland excision, giant glands (at 5-min only), patients with vitamin D deficiency (at 10, 15min), and those with normal renal function (at 15min only). The likelihood of the patients meeting the intraoperative cure criterion was not significantly affected among the groups except in patients with mild hypercalcaemia, who were significantly less likely to have 50% IOPTH drop than those with severe hypercalcaemia at all time points. The frequency of mildly hypercalcaemic patients who met cure criterion was significantly improved by extending measurement to 15min. IOPTH monitoring has the ability to mitigate the variability of IOPTH kinetics associated with most clinical variables. Mildly hypercalcemic patients in particular may benefit from waiting for 15-min measurement before any surgical decision is made.

Primary hyperparathyroidism: diagnostics and surgical management

Primary hyperparathyroidism is an endocrinological pathology of parathyroid glands. Its predominant form is a single parathyroid gland adenoma. We present a case of a 53-year-old patient, who was referred with primary hyperparathyroidism. She underwent ultrasound and sestamibi radionuclide scanning, and was offered surgery. The postoperative histopathological examination proved the presence of parathyroid gland adenoma. Patients managed with primary hyperparathyroidism require preoperative localization of enlarged, usually single parathyroid glands. Diagnostic modalities include ultrasounds, computed tomography scanning, and sestamibi radionuclide scanning. Parathyroidectomy is a recommended treatment modality for each stage of primary hyperparathyroidism, despite organ involvement, severity of hypercalcemia, and parathormone concentration. Significant bone remineralization is observed postoperatively. Preoperative localization of the enlarged parathyroid gland is crucial. Primary hyperparathyroidism requires surgery for definitive treatment. Surgery, although challenging, leads to a cure.

HYPERCALCEMIC CRISIS CAUSED BY CALCIUM-ALKALI SYNDROME REQUIRING URGENT HEMODIALYSIS

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Hypercalcemic crisis is a rare, life-threatening event secondary to decompensated hypercalcemia leading to renal failure and altered mental status. Primary hyperparathyroidism and hypercalcemia of malignancy are the majority of cases. However, hypercalcemia resulting from increased consumption of calcium supplement as part of the calcium-alkali syndrome should be considered. CASE PRESENTATION: An 88-year-old male presented to the ED with a history of increased confusion for 2 days. His past medical history was significant for chronic kidney disease stage 3. There was no family history of kidney stone disease, hyperparathyroidism or hypercalcemia. Vital signs were stable. Physical examination was remarkable only for dry oral mucosa and confusion. His medications did not include diuretics. His wife reported that he had been taking 10-12 tablets daily of Tums (calcium carbonate 1000mg/tablet, equivalent to 400mg of elemental calcium/tablet) recently due to worsening acid reflux. Initial electrolytes revealed serum total calcium 15.2 mg/dL, BUN 80 mg/dL, Creatinine 8.2 mg/dL, and bicarbonate 33 mmol/L. The parathyroid hormone-related peptide and 25(OH)D were normal. He had normal liver function tests, thyroid function test, Prostate-Specific Antigen, and hemoglobin. Multiple myeloma was ruled out based on normal serum and urine immunofixation studies. Electrocardiogram showed sinus bradycardia with normal corrected QT interval. A CT scan of the brain revealed no evidence of stroke. Renal ultrasound showed no renal stones or hydronephrosis. Chest x-ray did not show evidence of mass or lymphadenopathy. Hypercalcemia and renal failure failed to improve despite medical management with intravenous fluids and Calcitonin. The next day the patient received one session of hemodialysis. There was a gradual improvement in the patient’s mental status, calcium level, and renal function over the next week. DISCUSSION: The diagnosis of calcium-alkali syndrome is made based on history and metabolic abnormalities. The classic triad consists of hypercalcemia, varying degrees of renal failure, and metabolic alkalosis. The clinical presentation varies depending upon the severity of hypercalcemia. Patients may be relatively asymptomatic or may present with symptoms of nausea, vomiting, and altered mental status. In asymptomatic patients, initial management with aggressive hydration and induced diuresis with either calcitonin or bisphosphonates is recommended. However, in symptomatic or failed medical management patients, one session of hemodialysis to reduce hypercalcemia is recommended. Patients should have a close serial follow-up to rule out occult malignancy for the next 6 months. CONCLUSIONS: Due to the increasing use of calcium carbonate for dyspepsia and osteoporosis, patients should be educated and made aware of these severe, potentially life-threatening adverse effects. Reference #1: Ziegler R. Hypercalcemic crisis. J Am Soc Nephrol 2001; 12 (Suppl 17): S3–S9 Reference #2: Patel AM, Goldfarb S. Got calcium? Welcome to the calcium- alkali syndrome. J Am Soc Nephrol 2010; 21: 1440–1443 DISCLOSURES: No relevant relationships by Meily Arevalo, source=Web Response No relevant relationships by Cinthya Carrasco Barcenas, source=Web Response No relevant relationships by John Makram, source=Web Response No relevant relationships by Haneen Mallah, source=Web Response No relevant relationships by Myrian Vinan Vega, source=Web Response No relevant relationships by Wasawat Vutthikraivit, source=Web Response

Hypercalcemia associated with cosmetic injections: a systematic review.

Cosmetic injections with silicone and polymethylmethacrylate are not FDA approved for augmentation of body parts such as breast, buttock or legs, but they have been widely used for decades. Cosmetic injections can cause foreign body granulomas and occasionally severe and life-threatening hypercalcemia. We aimed to systematically analyze the published literature on cosmetic injection-associated hypercalcemia. We searched relevant articles on hypercalcemia associated with various cosmetic injections and extracted relevant data on demographics, cosmetic injections used, severity of hypercalcemia, management and outcomes. We identified 23 eligible patients from 20 articles. Mean age was 49.83 ± 14.70 years with a female preponderance (78.26% including transgender females). Silicone was most commonly used, followed by polymethylmethacrylate and paraffin oil (43.48, 30.43, and 8.70% respectively). The buttock was the most common site followed by the breast (69.57% and 39.13% respectively). Hypercalcemia developed at mean duration of 7.96 ± 7.19 years from the initial procedure. Mean ionized calcium at presentation was 2.19 ± 0.61 mmol/L and mean corrected calcium at presentation was 3.43 ± 0.31 mmol/L. 1,25-Dihydroxyvitamin D (1,25(OH)2D or calcitriol) was elevated while 25-hydroxyvitamin D (25(OH)D) and PTH were low in majority of cases. Hypercalcemia was managed conservatively with hydration, corticosteroids and bisphosphonates in majority of cases. Surgery was attempted in 2 cases but was unsuccessful. Renal failure was the most common complication (82.35% cases) and 2 patients died. Hypercalcemia from cosmetic injections can be severe and life threatening and can present years after the initial procedure. Cosmetic injection-associated granuloma should be considered a cause of hypercalcemia, especially in middle-aged females presenting with non-PTH-mediated, non-malignant hypercalcemia, which is often associated with elevated calcitriol; however, it should be noted that calcitriol level may be normal as well.

Cinacalcet: A Viable Therapeutic Option for Primary Hyperparathyroidism in the Elderly.

Objective:Parathyroidectomy is usually curative in primary hyperparathyroidism (PHPT), but its utility would be limited if patients are elderly who may either refuse surgery or may have advanced frailty and multimorbidity. We evaluated the effectiveness of cinacalcet, an allosteric modulator of calcium-sensing receptor in PHPT in an elderly cohort of patients.Methods:A prospective analysis of 29 patients who had PHPT and despite fulfilling criteria for surgery were unable to undergo parathyroidectomy either due to self-refusal (n = 12) or due to advanced multimorbidity (n = 17). All patients completed treatment with cinacalcet for at least for 6 months. Analysis were performed as per age (<75 and ≥75 years) and Charlson comorbidity index (CCI) score (≤5 and >5).Results:Our patients were the elderly (77 ± 12.7 years). In the whole group, complete normocalcemia was observed in 72.4% of patients (mean reduction: −0.55 mmol/l [confidence interval (CI) 0.4–−0.7; P < 0.0001]) and parathormone (PTH) normalized (≤6.9 pmol/l) in 33.4% of patients [mean reduction: −5.5 pmol/l (CI −11.6–0.6; P = 0.0015)]. In subgroup analysis, the severity of hypercalcemia was found to be higher patients with age <75 years and also in patients with CCI score >5. Cinacalcet lowered adjusted calcium in both age groups (P < 0.0001) with a greater reduction (20.5% vs. 16.2%; P < 0.0001 for both) in patients with CCI score >5. PTH fell in both age groups but significantly (−6.7 pmol/l [CI −14.9–1.5]; P = 0.008) in ≥ 75 years category and likewise, the drop was greater in patients with higher CCI scores (−7.1 pmol/l [CI −15.8–1.6); P = 0.009] vs. [−4.5 pmol/l [CI −3.9–−5.10]; P = 0.001). Patients with age <75 years and with CCI score ≤5 needed higher doses of cinacalcet to achieve biochemical targets.Conclusion:Cinacalcet is a viable and valuable treatment strategy for elderly patients with multiple comorbidities who suffer from PHPT but either cannot or refuse to undergo parathyroidectomy.

Primary hyperparathyroidism in pregnancy

Primary hyperparathyroidism (PHPT) is one of the most common endocrine disorders in the general population but is rarely diagnosed during pregnancy. Symptoms of gestational PHPT may be unrecognized, or masked by physiological changes in calcium homeostasis associated with pregnancy. Gestational PHPT may have severe consequences for both mother and fetus. However, nowadays, gestational PHPT is usually diagnosed in earlier stages and milder forms, with low complication rates. Treatment should be individually tailored according to gestational age, the severity of hypercalcemia, and the risk-benefit balance. The conservative approach is preferred in mild forms, whereas surgery, usually performed during the second trimester, is reserved for symptomatic hypercalcemic PHPT. Given the young age of the patients, genetic causes should be considered.

Primary hyperparathyroidism in pregnancy: a two-case report and literature review.

Primary hyperparathyroidism (PHPT) in pregnant women is an uncommon disease. It could be easily misdiagnosed because of physiologic changes during pregnancy; in some cases, patients could remain asymptomatic maintaining elevated calcium serum levels, and this situation represents a threat to the health of both mother and fetus. We present two cases of PHPT during pregnancy and their evolution after surgical treatment in the second trimester; there were no observed complications during pregnancy or delivery in our patients. Early diagnosis and medical/surgical treatment in PHPT are necessary for avoiding maternal and fetal complications which could not be predicted based on duration or severity of hypercalcemia. An appropriate management of PHPT during pregnancy is necessary for preserving the health of both the woman and the fetus.

Management of Neonatal Hypercalcemia: A Case Report and Review of Literature

Hypercalcemia in the newborn is relatively uncommon but its causes are numerous. Frequently the newborn infant may have no symptoms but severe hypercalcemia may present dramatically with multiorgan involvement and maybe potentially fatal. Treatment generally depends upon whether the hypercalcemia is mild or moderate/severe. The best treatment option depends on rectifying the underlying cause such as iatrogenic excessive calcium supplementation. However severity of hypercalcemia and clinical presentation may dictate a need to reduce the high serum calcium level emergently. There are no standardized guidelines for the management of neonatal hypercalcemia. We report a case of severe neonatal hypercalcemia which was particularly difficult to treat and also present pertinent review of literature.

Letter to the Editor Hypercalcemia and acute renal failure associated with calcium carbonate consumption in a patient with hypoparathyroidism

Letter to the Editor Hypercalcemia and acute renal failure associated with calcium carbonate consumption in a patient with hypoparathyroidism

Primary hyperparathyroidism in pregnancy

Primary hyperparathyroidism (PHPT) is rarely diagnosed during pregnancy but is associated with significant maternal and fetal morbidity and mortality. Information on appropriate management is limited. We reviewed the medical literature through December 2012 for key articles on PHPT during pregnancy, focusing on large series. Clinical knowledge in this area is restricted to isolated case reports and a few retrospective studies. Diagnosis can be difficult, owing to the non-specific nature of signs and symptoms of hypercalcemia during pregnancy. Pregnant women with a calcium level over 2.85 mmol/L (11.4 mg/dL) and prior pregnancy loss are at a particularly high risk of maternal complications (hypercalcemic crisis, nephrolithiasis, pancreatitis, etc.) and fetal loss. Around one-half of neonates born to mothers with untreated PHPT have hypocalcemia and tetany. Algorithms proposed for the management of the pregnant woman with PHPT are not evidence based, reflecting the paucity of data. Treatment should thus be individually tailored. Gestational age and the severity of hypercalcemia should be taken into account when assessing the risk-benefit balance of a conservative approach (hyperhydration and vitamin D supplementation) versus parathyroid surgery. Current evidence supports parathyroidectomy as the main treatment, performed preferably during the second trimester, when the serum calcium is above 2.75 mmol/L (11 mg/dL). In the patients with mild forms of PHPT, which are nowadays the most frequent, a conservative management is generally preferred.

A homozygous inactivating calcium‐sensing receptor mutation, Pro339Thr, is associated with isolated primary hyperparathyroidism: correlation between location of mutations and severity of hypercalcaemia

Inactivating mutations of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor with extracellular (ECD), transmembrane (TMD) and intracellular (ICD) domains, cause familial hypocalciuric hypercalcaemia, neonatal severe primary hyperparathyroidism and occasionally primary hyperparathyroidism in adults. To investigate a patient with typical symptomatic primary hyperparathyroidism for CaSR abnormalities. PATIENT AND DESIGN: A 51-year-old woman with primary hyperparathyroidism was investigated for CaSR abnormalities as her severe hypercalcaemia (3·75 mm) persisted after the removal of two large parathyroid adenomas and she was the daughter of normocalcaemic consanguineous parents. Following informed consent, CASR mutational analysis was undertaken using leucocyte DNA. Wild-type and mutant CaSR constructs were expressed in human embryonic kidney (HEK) 293 cells and assessed by measuring their intracellular calcium responses to changes in extracellular calcium. Clinical data were pooled with previous studies to search for genotype-phenotype correlations. The proband was homozygous for a Pro339Thr CaSR missense mutation, located in the ECD, and her normocalcaemic relatives were heterozygous. The mutant Thr339 CaSR had a rightward shift in its dose-response curve with a significantly higher EC(50) = 3·18 mm ± 0·19 compared to the wild-type EC(50) = 2·16 mm ± 0·1 (P < 0·01), consistent with a loss-of-function mutation. An analysis of CaSR mutations in patients with primary hyperparathyroidism revealed that those of the ECD were associated with a significantly greater hypercalcaemia that was less likely to be corrected after removal of the parathyroid tumours. A CaSR missense mutation causing a loss-of-receptor-function can cause symptomatic primary hyperparathyroidism in adulthood.

Persistent symptomatic improvement in the majority of patients undergoing parathyroidectomy for primary hyperparathyroidism

Parathyroidectomy for primary hyperparathyroidism (PHPT) is followed by a decrease in the severity of symptoms reported on the Pasieka's parathyroid symptoms score (PPSS) and SF-36 questionnaires. Some argue that such benefits are short-lived. This study investigates the severity of symptoms at more than 12 months after parathyroidectomy. A prospective database collected clinical/operative data on consecutive patients with PHPT. PPSS was calculated as the sum of the 13 parameters self-assessed using a visual analog scale. SF-36(v2) was analyzed using commercially available software (QualityMetric Inc., Lincoln, USA). Over 3-year interval, 166 patients (119 F/47 M, age 15-89 years) were operated for with PHPT (Ca 2.90 ± 0.25 mmol/L, PTH 21.64 ± 23.05 pmol/L). Their preoperative PPSS ranged 0-1,260 (median 413) and did not correlate with the severity of hypercalcemia. One hundred and seven patients responded when contacted by post at 18 ± 6 months postoperatively. Their postoperative PPSS was significantly lower (398 ± 226 to 231 ± 203, p < 0.001) and in 55 of 107 patients the severity of symptoms reduced by at least 50%. Most significant improvements were for mood (36 ± 33 vs. 16 ± 23), weakness/tiredness (37 ± 32 vs. 17 ± 23), irritability (35 ± 31 vs. 17 ± 21), and thirst (37 ± 32 vs. 18 ± 25; p < 0.0001). Physical and mental component scores of SF-36 questionnaire improved in patients whose PPSS decreased postoperatively. Symptomatic benefits persist for at least 1 year after parathyroidectomy in the majority of patients with PHPT.