Patient: Male, 23
Final Diagnosis: Rabdomyolysis
Symptoms: Cardiac arrest • cardiac arrhythmia • hypercalcemia
Clinical Procedure: —
Unusual clinical course
Rhabdomyolysis is frequently complicated by multiple electrolyte abnormalities, including hyperkalemia, hyperphosphatemia, and hypo/hypercalcemia. Hypercalcemia can be severe and life-threatening.
A 23-year-old white male suffered severe trauma to his lower extremities after a motor vehicle accident, leading to severe muscle damage, cardiac arrhythmia, cardiac arrest, and oliguric acute kidney injury (AKI), requiring hemodialysis treatment. As expected, he was hypocalcemic during the oliguric phase but during the diuretic phase he developed severe symptomatic hypercalcemia requiring hemodialysis treatment in spite of volume replacement and administration of pamidronate. Hypercalcemia reached a peak of 17.1 mg/dL, corrected for serum albumin and urine output was as high as 11.9 liters daily. Hypercalcemia lasted for 3 weeks and then it returned back to normal levels. Plasma levels of 25-OH and 1–25(OH)2 vitamin D were low, intact parathyroid hormone level was appropriately suppressed, and 24-hour urine calcium was 1194 mg (normal up to 350 mg/daily). Mobilization of calcium from calcium phosphate deposits in the injured muscles seems to be the main reason for hypercalcemia and hypercalciuria in rhabdomyolysis-induced AKI.
Hypercalcemia is not uncommon during the recovery phase of ATN. Unattended, it can cause severe morbidity and even mortality. Fluid administration, pamidronate, and calcium-free dialysis are some methods used to correct severe hypercalcemia. Over time, hypercalcemia improves in almost all cases.
Acute Kidney Injury; Hypercalcemia; Rhabdomyolysis
Purpose of the review
In this review we define hypercalcemia levels, common etiologies for hypercalcemia in children, and treatment in order to aid the practicing pediatrician.
One rare cause of hypercalcemia in the child is Familial hypocalciuric hypercalcemia (FHH) [also termed familial benign hypercalcemia (FBH)]. Mutations that inactivate the Ca2+-sensing receptor gene FHH have been described as an autosomal dominant disorder, but recently milder mutations in the CASR have been shown to cause hypercalcemia when homozygous.
Normal serum levels of calcium are maintained through the interplay of parathyroid, renal, and skeletal factors. In this review, we have distinguished the neonate and infant from the older child and adolescent because the causes and clinical features of hypercalcemia can differ in these two age groups. However the initial approach to the medical treatment of severe or symptomatic hypercalcemia is to increase the urinary excretion of calcium in both groups. In most cases, hypercalcemia is due osteoclastic bone resorption, and agents that inhibit or destroy osteoclasts are therefore effective treatments. Parathyroid surgery, the conventional treatment for adults with symptomatic primary hyperparathyroidism, is recommended for all children with primary hyperparathyroidism.
hypercalcemia; pediatrics; bisphosphonates; hyperparathyroidism
Subcutaneous fat necrosis (SCFN) is a noninfectious panniculitis that occurs in term infants who experience significant distress in the 1st weeks of life, including hypoxic ischemic encephalopathy (HIE). Since the introduction of therapeutic hypothermia for HIE, there have been a few published case reports of SCFN, following this modality of treatment. Although, most cases of SCFN resolve spontaneously, SCFN may be associated with hypercalcemia, which may sometimes reach dangerous levels. Approaches used for the management of this potentially life-threatening condition, include hyperhydration, calciuric diuretics, corticosteroids, and in more resistant cases pamidronate, a bisphosphonate. We report our experience on the use of pamidronate in two cases of severe hypercalcemia associated with SCFN following therapeutic hypothermia for HIE. We believe that with increasing use of therapeutic hypothermia for HIE, clinicians are likely to encounter this condition more frequently.
hypercalcemia; therapeutic hypothermia; newborn; pamidronate; subcutaneous fat necrosis
Neonatal severe hyperparathyroidism is a rare life-threatening disorder characterized by very high serum calcium concentrations (> 15 mg/dl). Many cases have occurred in families with familial hypocalciuric hypercalcemia, a benign condition transmitted as a dominant trait. Among several hypothesized relationships between the two syndromes is the suggestion that neonatal severe hyperparathyroidism is the homozygous form of familial hypocalciuric hypercalcemia. To test this hypothesis, we refined the map location of the gene responsible for familial hypocalciuric hypercalcemia on chromosome 3q. Analyses in 11 families defined marker loci closely linked to the gene responsible for familial hypocalciuric hypercalcemia. These loci were then analyzed in four families with parental consanguinity and offspring with neonatal severe hyperparathyroidism. Each individual who was homozygous for loci that are closely linked to the gene responsible for familial hypocalciuric hypercalcemia had neonatal severe hyperparathyroidism. The calculated odds of linkage between these disorders of > 350,000:1 (lod score = 5.56). We conclude that dosage of the gene defect accounts for these widely disparate clinical phenotypes; a single defective allele causes familial hypocalciuric hypercalcemia, while two defective alleles causes neonatal severe hyperparathyroidism.
The most common cause of hypercalcemia in hospitalized patients is malignancy. Primary hyperparathyroidism most commonly causes hypercalcemia in the outpatient setting. These two account for over 90% of all cases of hypercalcemia. Hypercalcemia can be divided into PTH-mediated and PTH-independent variants. Primary hyperparathyroidism, familial hypocalciuric hypercalcemia, familial hyperparathyroidism, and secondary hyperparathyroidism are PTH mediated. The most common PTH-independent type of hypercalcemia is malignancy related. Several mechanisms lead to hypercalcemia in malignancy-direct osteolysis by metastatic disease or, more commonly, production of humoral factors by the primary tumor also known as humoral hypercalcemia of malignancy that accounts for about 80% of malignancy-related hypercalcemia. The majority of HHM is caused by tumor-produced parathyroid hormone-related protein and less frequently production of 1,25-dihydroxyvitamin D or parathyroid hormone by the tumor. We report the rare case of a patient with hypercalcemia and diagnosed primary hyperparathyroidism. The patient had persistent hypercalcemia after surgical removal of parathyroid adenoma with recorded significant decrease in PTH level. After continued investigation it was found that the patient also had elevated 1,25-dihydroxyvitamin D and further studies confirmed a large spleen mass that was later confirmed to be a lymphoma. This is a rare example of two concomitant causes of hypercalcemia requiring therapy.
Subcutaneous fat necrosis (SCFN) is a rare form of panniculitis in infants that generally occurs following birth trauma, meconium aspiration, or therapeutic cooling. Severe hypercalcemia occurs in a subset of patients, but data on its presentation, management, and outcomes are limited. This report details the clinical course and complications of infants treated for severe hypercalcemia (peak serum calcium ≥3.0 mmol/L) due to SCFN.
Chart review of all infants with SCFN seen at a single pediatric center over a 13-year period.
Seven infants with SCFN developed severe hypercalcemia, with median peak serum calcium 4.1 mmol/L (range 3.3–5.1).
Severe hypercalcemia occurred before 6 weeks of age, and was asymptomatic in 3/7 patients (43%). Most patients were treated with intravenous hydration, furosemide, glucocorticoids, and low-calcium formula, which restored normocalcemia in a median of 9 days (range 2–42). Fever developed during treatment in 4/7 infants (57%): two patients had bacterial infections and two had no infectious source identified. Nephrocalcinosis was present in 5/6 patients (83%) who were evaluated by renal ultrasound. Nephrocalcinosis failed to resolve in all cases over a median follow up of 20 months (range 8–48), but no renal dysfunction was observed. Eosinophilia, which has not been reported previously in SCFN, was present in 6/7 patients (86%).
In this largest series to date of infants with severe hypercalcemia due to SCFN, novel findings include the common occurrence of fever and a high incidence of persistent nephrocalcinosis without evidence of adverse renal outcomes.
subcutaneous fat necrosis; infant; hypercalcemia; fever; nephrocalcinosis
The hypercalcemias are a common and heterogeneous group of disorders, ranging from the occasional detection of a high level of serum calcium to a life-treating condition. In a patient presenting with hypercalcemia, a differential diagnosis can be established easily by measuring serum calcium and parathyroid hormone (PTH) concentrations. We describe the case of an 83-year-old man presenting with a severe symptomatic hypercalcemia with high-normal PTH level due to the coexistence of primary hyperparathyroidism and malignancy-associated hypercalcemia. The presence of two conditions producing hypercalcemia was revealed only during in-hospital stay and after the administration of an intravenous bisphosphonate, when the PTH concentration increased rapidly after bisphosphonate treatment with a decrease in serum calcium. The occurrence of two conditions producing hypercalcemia is a rare event in the literature, and should be considered in the presence of an abnormally high serum calcium level associated with normal or high-normal PTH, in order to establish a correct diagnosis and appropriate interventions.
Bisphosphonates; Hypercalcemia; Malignancy-associated hypercalcemia; Parathyroid hormone; Primary hyperparathyroidism
To present a case of hypercalcemia associated with thyrotoxicosis in a patient with vitamin D deficiency and review biochemical changes during the course of treatment.
We report a case, describe the changes in serum calcium, phosphorus, parathyroid hormone in Graves’ disease and concomitant Vitamin D deficiency. We compare our findings to those reported in literature.
Our patient had hypercalcemia secondary to thyrotoxicosis alone, which was confirmed by low parathyroid hormone level and resolution of hypercalcemia with treatment of thyrotoxicosis. The case was complicated by a concomitant vitamin D deficiency. Serum calcium elevation in patients with thyrotoxicosis occurs secondary to hyperthyroidism alone or due to concurrent hyperparathyroidism. Hypercalcemia from thyrotoxicosis is usually asymptomatic and is related to bone resorption. Vitamin D deficiency can be seen in patients with thyrotoxicosis because of accelerated metabolism, poor intestinal absorption and increased demand during bone restoration phase. Coexistence of hypercalcemia and Vitamin D deficiency in patients with thyrotoxicosis is rare, but possible, and 25-hydroxyvitamin D levels should be checked. The definite treatment for hypercalcemia in thyrotoxicosis is correction of thyroid function.
Hypercalcemia in thyrotoxicosis should be distinguished from concomitant hyperparathyroidism and confirmed by resolution of hypercalcemia with control of thyrotoxicosis. Patients with hypercalcemia and thyrotoxicosis may also have vitamin D deficiency and 25-OH Vitamin D levels should be checked.
hypercalcemia; thyrotoxicosis; vitamin D deficiency
Disaccharide Intolerance Type I (Mendelian Interance in Man database: *222900) is a rare inborn error of metabolism resulting from mutation in sucrase-isomaltase (Enzyme Catalyzed 184.108.40.206). Usually, infants with SI deficiency come to attention because of chronic diarrhea and nutritional evidence of malabsorption.
We describe an atypical presentation of this disorder in a 10-month-old infant. In addition to chronic diarrhea, the child displayed severe and chronic hypercalcemia, the evaluation of which was negative. An apparently coincidental right orbital hemangioma was detected. Following identification of the SI deficiency, an appropriately sucrose-restricted, but normal calcium diet regimen was instituted which led to cessation of diarrhea, substantial weight gain, and resolution of hypercalcemia.
This case illustrates that, similar to congenital lactase deficiency (Mendelian Interance in Man database: *223000, Alactasia, Hereditary Disaccharide Intolerance Type II), hypercalcemia may complicate neonatal Sucrase-Isomaltase deficiency. Hypercalcemia in the presence of chronic diarrhea should suggest disaccharide intolerance in young infants.
Clear cell sarcoma of the kidney (CCSK) is a rare renal neoplasm of paediatrics, making up about 3% of all renal tumours in paediatrics, with a high tendency for developing bone metastasis. A seven year-old boy was referred to our clinic with two firm, large masses over the manubrium of the sternum and right frontal area, which pathologically were confirmed as a metastatic CCSK. The patient had a history of a renal mass three years earlier, for which radical nephrectomy had been performed, and histopathologic diagnosis was compatible with mesoblastic nephroma. Thus, no further investigation and therapy had been applied for the patient. CCSK is a rare but malignant and aggressive paediatric renal tumour, with a high tendency for developing distant bone metastases, leading to its poor prognosis. CCSK could be misdiagnosed as several other renal tumours such as mesoblastic nephroma, and thus CCSK should be taken carefully into consideration in the diagnosis of renal tumours.
clear cell sarcoma of the kidney; sternum; frontal bone; mesoblastic nephroma; bone metastasis
Hypercalcemia is well described in various granulomatous disorders, such as sarcoidosis, tuberculosis, berylliosis, leprosy and fungal infections. However, the association of Paracoccidioides brasiliensis and hypercalcemia is rare: to the best of our knowledge, only two cases have previously been reported, and neither had a clear documentation of the etiology of the hypercalcemia.
We report the case of a 22-year-old man in whom disseminated infection with paracoccidioidomycosis was associated with hypercalcemia. The patient had a high normal serum level of 1,25-dihydroxyvitamin D and a suppressed parathyroid hormone value, an indication that the hypercalcemia was not mediated by parathyroid hormone and might be associated with 1,25-dihydroxyvitamin D.
The episode resolved readily with administration of corticosteroids, an outcome suggesting that this is an effective treatment of hypercalcemia of this origin. On follow-up, while receiving antifungal therapy for P. brasiliensis the patient's calcium values remained normal.
Congenital mesoblastic nephroma (CMN) is a rare renal tumor. It can be detected antenatally especially with judicious use of ultrasonography.
A premature female neonate 28 weeks’ gestation, complicated by polyhydramnios, was born to a 28-year-old woman. An abdominal mass was detected antenatally. At the end of the first week of life, the newborn had hypertension that was controlled by hydralazine. Ultrasonography and CT scan showed a right-sided renal heterogeneous solid mass. Right nephrectomy was performed and the histology showed CMN.
Congenital mesoblastic nephroma; Polyhydramnios; Neonatal hypertension
Hypercalcemia in children is a medical emergency and often manifests as nonspecific symptoms such as nausea, vomiting, weight loss, and anorexia. Severe hypercalcemia is a rare complication of malignancy in children, while it can be seen in various types of malignant tumors. It is usually associated with significant morbidity and may be severe enough to threaten life. Incidence of hypercalcemia in hematopoietic malignancies including acute lymphoblastic leukemia (ALL) is very rare and unusual, especially as the initial manifestation of the disease. In this paper a 6-year-old boy who had severe hypercalcemia and gastrointestinal symptoms before the onset of common and usual manifestations of ALL is introduced.
Acute lymphoblastic leukemia; Hypercalcemia; Children
To determine the cause of refractory hypercalcemia in a patient with metastatic renal cell carcinoma.
We describe the clinical, pathologic, and immunostain findings in a patient with metastatic renal cell carcinoma and hypercalcemia of malignancy refractory to intravenous bisphosphonates.
A 57-year-old man with a remote history of clear cell renal cell carcinoma was referred to our clinic for evaluation of resistant hypercalcemia 12 years after nephrectomy. The patient had simultaneous elevation of serum 1,25-dihydroxyvitamin D and parathyroid hormone–related peptide. Computed tomographic scan of the chest and abdomen demonstrated numerous ring-enhancing lesions in the liver, and histologic examination of a biopsy specimen revealed liver tissue infiltrated by a malignant neoplasm composed of cells with clear and eosinophilic cytoplasm, arranged in tubules and nests. Findings were morphologically consistent with renal cell carcinoma of clear cell type, and positive immunostaining with the epithelial markers EMA and CAM 5.2 were supportive of the morphologic impression of renal cell carcinoma. The tumor showed expression of 25-hydroxyvitamin D 1α-hydroxylase by immunostaining. After failing to respond to intravenous bisphosphonates, the hypercalcemia improved with prednisone treatment.
In some patients with renal cell carcinoma, hypercalcemia of malignancy is associated with simultaneous elevation in serum 1,25-dihydroxyvitamin D and parathyroid hormone–related peptide. As our case exemplifies, it is imperative to identify such patients because hypercalcemia due to elevated 1,25-dihydroxyvitamin D levels may respond better to glucocorticoid treatment than to the conventional management with bisphosphonates.
hypercalcemia; calcium; 25-hydroxyvitamin D2; 25-hydroxyvitamin D3 1-alpha-hydroxylase; parathyroid hormone; parathyroid hormone-related protein; neoplasms; renal cell carcinoma
Association of dysregulated calcium homeostasis and granulomatous disease is well established. There exist reports in the literature of granulomatous reactions produced by silicones associated with hypercalcemia. In this case series we report four young women that underwent methacrylate injections in gluteus, thighs and calves that developed granulomas with posterior appearance of hypercalcemia. This complication presented as subacute around 6 months after the procedure. The four patients have as common elements the presence of moderate to severe renal insufficiency, suppressed PTH and elevated calcitriol levels for the degree of renal function. In the image studies, two patients presented in the nuclear magnetic resonance of the gluteus hypodense nodular images compatible with granulomas. Two patients had a positron emission tomography performed showing increased metabolic activity in the muscles of the gluteal region compatible with granulomas. Two patients had a partial surgical resection of the gluteal lesions with the finding of methacrylate associated to foreign body granulomas. In these patients hypercalcemia was treated with oral or local injections of corticoids, intravenous bisphosphonates or ketoconazole with good response. Although the prevalence of this complication with methacrylate injection is not common, hypercalcemia secondary to granulomas should be considered in the differential diagnosis of patients with hypercalcemia when there is a history of this procedure, and especially if they have a reduction in their renal function.
hypercalcemia; methacrylate; granulomatous disease
Familial Hypocalciuric Hypercalcemia (FHH) is a generally benign disorder caused by heterozygous inactivating mutations in the Calcium-Sensing Receptor (CaSR) gene resulting in altered calcium metabolism.
We report a case of unusually severe neonatal FHH due to a novel CaSR gene mutation that presented with perinatal fractures and moderate hypercalcemia.
A female infant was admitted at 2 weeks of age for suspected non-accidental trauma (NAT). Laboratory testing revealed hypercalcemia (3.08 mmol/L), elevated iPTH (20.4 pmol/L) and low urinary calcium clearance (0.0004). Radiographs demonstrated multiple healing metaphyseal and rib fractures and bilateral femoral bowing. The femoral deformity and stage of healing were consistent with prenatal injuries rather than non-accidental trauma (NAT). Treatment was initiated with cholecalciferol, 400 IU/day, and by 6 weeks of age, iPTH levels had decreased into the high-normal range. Follow up radiographs demonstrated marked improvement of bone lesions by 3 months. A CaSR gene mutation study showed heterozygosity for a T>C nucleotide substitution at c.1664 in exon 6, resulting in amino acid change I555T in the extracellular domain consistent with a missense mutation. Her mother does not carry the mutation and the father is unknown. At 18 months of age, the child continues to have relative hyperparathyroidism and moderate hypercalcemia but is otherwise normal.
This neonate with intrauterine fractures and demineralization, moderate hypercalcemia and hyperparathyroidism was found to have a novel inactivating missense mutation of the CaSR not detected in her mother. Resolution of bone lesions and reduction of hyperparathyroidism was likely attributable to the natural evolution of the disorder in infancy as well as the mitigating effect of cholecalciferol treatment.
FHH; Neonatal hyperparathyroidism; Hypercalcemia; NHPT; CaSR; Vit D
Primary hyperparathyroidism (PHPT) is a common endocrine disorder in adults in whom the typical presentation is incidentally discovered as asymptomatic hypercalcemia. PHPT is much less common in children and adolescents, but has greater morbidity in this age group, as most young patients with PHPT will have symptomatic hypercalcemia or complications such as kidney stones, abdominal pain, and skeletal fragility. An important feature of PHPT in younger patients is the relatively high prevalence of germline inactivating mutations of the CASR gene, which encodes the calcium-sensing receptor. Biallelic CASR mutations cause neonatal severe hyperparathyroidism, a life-threatening condition that presents within days of life with marked hypercalcemia, respiratory distress, failure to thrive, and skeletal demineralization. By contrast, more common heterozygous CASR mutations are generally associated with a benign variant of PHPT termed familial hypocalciuric hypercalcemia. Appropriate management of PHPT in children and adolescents requires distinction between familial hypocalciuric hypercalcemia, which generally requires no specific treatment, and other forms of PHPT that are best treated by parathyroidectomy.
calcium sensing receptor; hypercalcemia; MEN1; osteoporosis; parathyroid; primary hyperparathyroidism; PTH
Context. Severe hypercalcemia is a life-threatening condition. Atypical parathyroid adenoma and parathyroid carcinomas are uncommon causes which can be difficult to differentiate. Objective. We report a case of a 36-year-old male with very high serum calcium due to a possible atypical parathyroid adenoma versus parathyroid carcinoma. Case Illustration. A serum calcium level of 23.2 mg/dl was noted on admission. He was initially treated with IV hydration, pamidronate, and salmon calcitonin to lower his calcium levels. He also underwent a surgical en bloc resection of parathyroid mass. Pathology showed a mixed picture consistent with possible atypical adenoma versus parathyroid carcinoma. However, due to the possible involvement of the recurrent laryngeal nerve, parathyroid carcinoma was more likely. Also after operation the patient developed hungry bones syndrome and his calcium was replaced vigorously. He continues to be on calcium, vitamin D, and calcitriol supplementation. Results. A review of the literature was conducted to identify previous studies pertaining to parathyroid adenomas and parathyroid cancer. Conclusion. We thereby conclude that hypercalcemia requires very careful monitoring especially after operation. Also it can be very difficult to distinguish between atypical parathyroid adenomas and parathyroid carcinomas as in our case and no clear cut guidelines yet exist to differentiate the two based on histology.
Bisphosphonates are commonly used for the treatment of osteoporosis, Paget's disease, multiple myeloma and hypercalcemia. Collapsing focal segmental glomerulosclerosis (FSGS) is known to occur uncommonly with exposure to bisphosphonates, specifically pamidronate and alendronate; it has rarely and equivocally been reported with zoledronate therapy. We describe the case of a 36-year-old African American female with metastatic breast cancer who presented with nephrotic-range proteinuria and acute kidney injury within 2 weeks of exposure to a single dose of zoledronate. The patient had a partial recovery of her renal function and showed improved proteinuria to a subnephrotic level after discontinuing zoledronate. In contrast to 2 prior reports of zoledronate-induced collapsing FSGS, the causative role of the exposure described here is certain. Our case necessitates the addition of zoledronate to the list of known causes of collapsing FSGS. Furthermore, it highlights the importance of periodically monitoring renal function and urine protein excretion with the use of zoledronate, which allows prompt diagnosis and withdrawal of the drug to increase the probability of renal recovery.
Focal segmental glomerulosclerosis; Bisphosphonates; Zoledronate
Hypercalcemia is a common problem in clinical practice and can be related to endocrine disorders or malignant disease, especially in elderly patients. Although rare, other causes can also be responsible.
Granulomatous inflammation of the skin and lymph nodes induced by intravenous or injectable silicone is a rare condition of hypercalcemia that is usually not within the scope of differential diagnosis. Here, we report a 72-year-old woman with symptomatic hypercalcemia related to cosmetic treatment of the neck. Topical applied liquid silicone by means of a focal ultrasound device induced extensive granulomatous inflammation of the skin and local lymph nodes, being the underlying cause for hypercalcemia in this case.
In rare cases, symptomatic hypercalcemia can be caused by silicone due to a severe granulomatous tissue reaction. This is the first time that a transdermal silicone treatment has been reported to cause severe granulomatous tissue inflammation.
hypercalcemia; granulomatous inflammation; silicone; ultrasound treatment
Hypophosphatasia (HPP) is an inborn error of metabolism characterized by defective bone mineralization caused by a deficiency in alkaline phosphatase (ALP) activity due to mutations in the tissue-nonspecific ALP (TNALP) gene. The clinical expression of the disease is variable. Six forms of HPP are identified according to age at presentation and clinical features. Patients with the infantile form are normal at birth. First symptoms appear within the first 6 months of life. Along with skeletal findings, HPP patients may present with hypercalcemia, seizures, pseudotumor cerebri, and pulmonary insufficiency. Seizures in HPP are refractory to conventional antiepileptic drugs, but are responsive to pyridoxine. Herein, we report a case of HPP who presented with pyridoxine-responsive seizures in the early neonatal period and was found to have hypercalcemia, skeletal demineralization and increased intracranial pressure. Key words: Hypophosphatasia, pyridoxine-responsive seizures, bisphosphonates, alkaline phosphatase, bone resorption, hypercalcemia
Conflict of interest:None declared.
Hypophosphatasia; pyridoxine-responsive seizures; bisphosphonates; Alkaline phosphatase; bone resorption; hypercalcemia
Vitamin D deficiency is widely prevalent across the globe. This has lead to widespread use of vitamin D supplements in populations. We present our experience of vitamin D toxicity in a subject resulting in hypercalcemia and CHB (Complete Heart Block). A 70-year-old female, known hypertensive for thirty five years and diabetic for seven years underwent total knee replacement (TKR) for osteoarthritis left knee in December 2010. For perioperative glycemic control, multiple subcutaneous injections of insulin were advised. Patient later presented with poor glycemic control, decreased appetite and constipation for last 1 month with history of episodes of transient loss of consciousness for 15 days and recurrent vomiting. Biochemical work-up showed hypercalcemia (Serum calcium 12.4 mg/dL). Sr. albumin, ALP, Sr. phosphorus and PTH levels were normal, thus suggesting PTH independent hypercalcemia. Strong suspicion led us to check vitamin D levels in dilution which were 2016 ng/mL, thus confirming vitamin D toxicity. Retrospective analysis of treatment history revealed patient receiving 4 injections of Architol (6 Lac units im) prior to presentation. Work-up for malignancy was negative, brain imaging and EEG were normal. Holter was suggestive of intermittent CHB. Patient was given hydration, injection calcitonin 100 I.U. subcutaneously, injection pamidronate 60 mg infusion, with serum calcium levels normalizing, with relief in constipation, vomiting and behavioral improvement. However, persistence of rhythm disturbances led to permanent pacemaker placement. The present case highlights the dangers of indiscriminate vitamin D usage, exposing patients to potentially life threatening complications.
Vitamin D toxicity; hypercalcemia; complete heart block
Milk-alkali syndrome is a rare cause of hypercalcemia characterized by the triad of hypercalcemia, renal insufficiency, and metabolic alkalosis that results from the overconsumption of calcium containing products. In the setting of pregnancy where there is a physiologic increase in calcium absorption, milk-alkali syndrome can be potentially life threatening. We report a case of a 26-year-old woman in her second trimester of pregnancy who presented with 2 weeks of flank pain, nausea, vomiting, anorexia, headache, and lightheadedness. The history revealed consumption of a large quantity of milk, calcium carbonate antacid, and calcium-containing prenatal vitamins. Her symptoms and hypercalcemia resolved with intravenous fluids and a loop diuretic. With the increased use of calcium carbonate for peptic ulcer disease, gastroesophageal reflux disease, and osteoporosis, milk-alkali syndrome has experienced a resurgence and must be considered in the differential diagnosis of hypercalcemia. In this clinical vignette we review the literature on milk-alkali syndrome in pregnancy and discuss important diagnostic and therapeutic considerations when managing the pregnant patient with hypercalcemia.
hypercalcemia; milk-alkali syndrome; pregnancy
While paraneoplastic syndromes in patients with malignant and metastasizing tumors are common, they are rarely associated with skin tumors showing predominantly local growth patterns. This case report relates to a patient with giant condyloma acuminatum, also called Buschke-Löwenstein tumor, with paraneoplastic hypercalcemia, who was successfully treated with conservative treatment.
The patient in question is a 48-year-old German man with a giant periscrotal tumor. Before and during the therapy, two episodes of symptomatic hypercalcemia occurred, which were successfully treated by bisphosphonates, intravenous fluids and diuretics. No evidence of lytic bone affection was found.
Paraneoplastic hypercalcemia may occur in patients who have a Buschke-Löwenstein tumor. For patients, where surgery is not an option, established medical therapies like bisphosphonates may be useful in addition to diuretics and infusions.
Paraneoplastic hypercalcemia; Buschke-Löwenstein tumor; Giant condyloma acuminatum
Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It usually presents with nonspecific symptoms, such as fever, rather than with overt lymphadenopathy. Reports of hypercalcemia, as the initial presentation of IVLBCL, are limited in the literature, despite it being a well-known complication of various solid cancers. We present a 68-year-old male with severe hypercalcemia and increased levels of serum parathyroid hormone-related protein. He was diagnosed with IVLBCL, involving the bone marrow and spleen, and was successfully treated with rituximab-containing chemotherapy. A few previous case reports have shown hypercalcemia in patients with IVLBCL. Much like our case, previous cases with hypercalcemia had advanced diseases, including bone marrow invasion. Although it was an extremely rare manifestation of IVLBCL, we suggest that IVLBCL should be a part of the differential diagnosis in patients with unexplained hypercalcemia. Therefore, an active work-up might be recommended, including positron emission tomography/ computed tomography scan and bone marrow examination, which may be useful for early diagnosis.
Intravascular lymphoma; Hypercalcemia; Parathyroid hormone-related protein