Albumin-Corrected Calcium and the Prevalence and Categories of Hypercalcemia in Hospitalized Patients With 1-Year Follow-Up of Undiagnosed Cases

ObjectiveTo assess the impact of using corrected calcium versus total calcium on hypercalcemia case detection in hospitalized patients.MethodsPatients hospitalized from June 2012 to June 2017 with a corrected calcium level of ≥10.5 mg/dL were identified by medical record review. One-year follow-up data through June 2018 were acquired. Albumin-corrected calcium level was calculated: (4 − albumin concentration in g/dL) × 0.8 + total serum calcium in mg/dL.ResultsA group of 1067 patients had a corrected calcium level of ≥10.5 mg/dL. The prevalence of hypercalcemia was 0.73% with total calcium and 1.09% with corrected calcium, respectively, with a 49% relative increase. Most patients (62%) had mild hypercalcemia (10.5-11.9 mg/dL); 3.7% had severe hypercalcemia (>14 mg/dL). With corrected calcium, the most common categories of hypercalcemia were malignancy (35.4%), hypercalcemia that was not further evaluated (31.1%), and hyperparathyroidism (22.4%). All patients in the unidentified category had albumin levels <2.8 g/dL. At the 1-year follow–up, 63% of the unidentified cases had normal calcium levels, and 26.8% had mild persistent hypercalcemia. Of those with persisting hypercalcemia at 1 year, 16.8% were diagnosed with hyperparathyroidism.ConclusionUsing albumin-corrected calcium resulted in an ∼50% increase in the detection of hypercalcemia cases. Although hypercalcemia resolved in majority of the undiagnosed cases at 1 year, a number of these remained abnormal. Detecting hypercalcemic disorders by correcting for low albumin level can help identify conditions such as hyperparathyroidism. Adding auto-calculated albumin-corrected calcium to routine laboratory tests could be a cost-effective intervention to improve the detection of hypercalcemic disorders.     

Gigantic mammary hyperplasia in pregnancy associated with pseudohyperparathyroidism

This is the first report of hypercalcemia due to benign gigantic mammary hyperplasia in a pregnant women. Endocrinologic examinations did not disclose any known cause for the symptomatic hypercalcemia. Bilateral total mastectomy decreased the serum calcium level to normal. The case is presented with discussion and a literature review.     

Hypercalcemia and Local Production of Parathyroid Hormone-Related Protein by a Perisellar Rhabdomyosarcoma After Remote Pituitary Irradiation

ObjectiveTo describe a case of metastatic rhabdomyosarcoma originating from the sphenoid sinus in a patient previously treated with conventional irradiation for a prolactinoma, presenting as hypercalcemia in the setting of a normal level of serum parathyroid hormone-related protein (PTHrP).MethodsWe report the case of a patient who underwent remote pituitary irradiation for a prolactinoma and then presented decades later with hypercalcemia of unknown cause. His clinical course, the initial biochemical and radiologic investigations, and the results of examination of pathology specimens are reviewed.ResultsThe patient was found to have a mass in the sphenoid sinus. The pathologic features were consistent with alveolar rhabdomyosarcoma. Although he had a normal serum PTHrP level, staining of his tumor with an antibody against PTHrP revealed local production of PTHrP at the tumor margins. His bone marrow biopsy specimen showed 100% involvement with rhabdomyosarcoma.ConclusionPTHrP staining of pathology specimens might explain hypercalcemia of undetermined cause in patients with a known malignant lesion, in whom elevated serum PTHrP levels cannot be demonstrated. (Endocr Pract. 2005;11:184-189)     

Emergencies in Oncology: Current Management

Malignant neoplasms may cause life-threatening complications requiring prompt diagnosis and emergency therapy. Whether or not the underlying neoplasm is potentially curable, the physician can often provide worthwhile prolongation of life and dramatic symptomatic relief. Among the serious complications of neoplasia are superior vena cava obstruction, airway obstruction, pericardial tamponade, spinal cord compression, brain metastasis, meningeal involvement by cancer, hyperuricemia, hypercalcemia and hyperkalemia.     

Splenic Sarcoidosis without Focal Nodularity: A Case of 1,25-Dihydroxyvitamin D-Mediated Hypercalcemia Localized with FDG PET/CT

ObjectiveTo report an uncommon cause of 1,25-dihydroxyvitamin D (1,25[OH]₂D)-mediated hypercalcemia associated with splenic sarcoidosis and illustrate the evaluation and potential role of fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in such patients.MethodsWe present detailed clinical features, laboratory results, imaging results, and pathology results for this rare entity, discuss evaluation and management options, and review previous literature.ResultsA 65-year-old male presented with symptomatic hypercalcemia, with a serum calcium level of 14.1 mg/dL 3 months after being initiated on ergocalciferol for vitamin D deficiency. He was found to have a suppressed parathyroid hormone level, normal 25-hydroxyvitamin D (25[OH]D) level, and elevated 1,25(OH)₂D level. Extensive evaluation did not yield a definitive diagnosis. Hiscalcium levels normalized and symptoms resolved on prednisone then recurred when prednisone was discontinued. FDG PET/CT showed intense uptake in the spleen. Splenectomy was performed, which resulted in resolution of hypercalcemia and yielded a diagnosis of splenic sarcoidosis.Conclusion:Splenic sarcoidosis causing hypercalcemia has been rarely reported. Our case is unique in that the spleen lacked typical focal nodularity on cross-sectional CT imaging, which is expected in sarcoid involvement of the spleen. Our case adds to an emerging literature documenting the potential value of FDG PET/CT in localizing otherwise occult 1,25(OH)₂D-mediated hypercalcemia. (Endocr Pract. 2014;20:e28-e33)     

Hypercalcemia in glucocorticoid withdrawal

We found severe hypercalcemia in the course of hydrocortisone withdrawal in a patient who had undergone unilateral adrenalectomy to resect a cortisol-hypersecreting adenoma. Serum calcium gradually but progressively increased after unilateral adrenalectomy. Severe hypercalcemia developed on the 77th postoperative day (the 15th day after discontinuing hydrocortisone replacement). The serum concentration of calcium, PTH, 25(OH)D, and 1,25(OH)2D were 8.0 mEq/l, less than 100 pg/ml, 10.1 ng/ml and 29.6 pg/ml, respectively. This hypercalcemia was accompanied by marked urinary hydroxyproline excretion and less calcium excretion in the urine than the prevailing level of serum calcium. Serum concentrations of 25(OH)D, 1,25(OH)2D and PTH were not elevated during the severe hypercalcemia. We concluded that the hypercalcemia in this patient was due in part to enhanced bone resorption and increased renal tubular reabsorption of calcium as a result of glucocorticoid withdrawal, but not to the elevation of serum PTH or serum 25(OH)D and serum 1,25(OH)2D.     

PULMONARY HYALINE MEMBRANE DISEASE—A Panel Discussion: Pediatrician's Point of View

Elevated serum amylase is a frequent concomitant of perforated gastroduodenal ulcer. To determine if there might be significant correlation between an increase in amylase and some of the other factors associated with ulcer perforation, a study was made of the clinical records of 1,000 patients with perforation of gastroduodenal ulcers. Sixteen per cent of the patients had amylase levels of 200 Somogyi units or more. This rise in serum amylase comes about in cases of perforated peptic ulcer as a result of peritoneal lymphatic absorption of fluid containing pancreatic enzyme which is spilled through the perforation. Among patients with perforated ulcers and elevated serum amylase levels, the higher the amylase level, the higher the mortality rate.The factors of amount of abdominal fluid spill, the duration of the perforation before surgical closure, the size of the perforation, shock and recent ingestion of food were also studied for possible relationship with elevated serum amylase. All appeared to be statistical if not etiological associates of abnormal serum amylase levels.Because high amylase values so often occur in perforated ulcer, there is no amylase level that can be considered diagnostic of acute pancreatitis.     

Gastric asthma: a clinical update for the general practitioner

Asthma is an inflammatory disease of the airways characterized by increased airway reactivity with airflow obstruction. It is exacerbated by multiple triggers, and one common, often overlooked trigger is gastroesophageal reflux (GER). The prevalence of GER in asthmatics is estimated at between 34% and 80%. Up to 24% of asthmatics may have silent GER without the classic reflux symptoms (heartburn, acid regurgitation, and dysphagia). Since most patients are initially seen at the primary care level, it is essential for the primary physicians to recognize the underlying cause of the disease. This review briefly discusses the pathogenesis and clinical features of gastric (reflux-triggered) asthma and provides clues for its diagnosis in primary care practice. The current diagnostic approach to such patients and its management relevant to general practitioners is also discussed.     

Hypercalcemia in infants presenting with apnea.

To our knowledge apnea in infants has not been associated with hypercalcemia. We describe seven hypercalcemic infants aged 2 days to 3 months who had presented with apnea; six of the seven were otherwise healthy. The apneic attacks were brief, and normal breathing was restored spontaneously or after tactile stimulation. The attacks stopped and the apnea monitoring was discontinued when the children were 1 month to 2 years of age. The only abnormal finding common to all of the patients was hypercalcemia. Idiopathic infantile hypercalcemia was diagnosed in six of the patients and familial benign hypercalcemia in one. Our findings suggest that determination of the plasma calcium level be included in the investigation of apnea in infancy.     

Congenital Craniopharyngioma and Hypercalcemia Induced by Parathyroid Hormone-Related Protein

ObjectiveTo report a case of congenital craniopharyngioma and parathyroid hormone-related protein (PTHrP)-associated humoral hypercalcemia.MethodsDetails of this unusual case are reviewed, from detection of fetal hydrocephalus and a brain tumor, through cesarean delivery at 36 weeks of gestation, to subsequent laboratory studies, management, and confirmation of the diagnosis.ResultsAlthough PTHrP has been well documented as a cause of humoral hypercalcemia of malignancy (HHM) in adult patients with cancer, HHM is uncommon in children. In addition, HHM has rarely been ascribed to nonmalignant tumors. To the best of our knowledge, we report the first case of a neonate with congenital craniopharyngioma and refractory hypercalcemia (peak ionized calcium level of 1.92 mmol/L; normal, 1.05 to 1.3) attributed to an elevated PTHrP value of 8.6 pmol/L (normal, less than 4.7). Intact parathyroid hormone was appropriately undetectable (less than 10 pg/mL; normal, 15 to 65). Despite calcitonin treatment, the hypercalcemia persisted. Although pamidronate infusion stabilized the serum calcium level, the baby did not survive.ConclusionThe diagnosis of craniopharyngioma was confirmed at autopsy, and immunohistochemical studies substantiated that the craniopharyngioma produced PTHrP. (Endocr Pract. 2007;13:67-71)     

Panic attacks and supraventricular tachycardias: the chicken or the egg?

Panic attacks occur in about 2 % of the population. Symptoms include a racing or pounding heart beat, chest pain, dizziness, light-headedness, nausea, difficulty in breathing, tingling or numbness in the hands, flushes or chills, dreamlike sensations or perceptual distortions. The symptoms of paroxysmal supraventricular tachycardia (PSVT) may be similar. A PSVT is often difficult to document on the ECG since it has often ceased before the patient comes to medical attention. Besides, a tachycardia may still be present and even be documented but interpreted as a phenomenon secondary to the panic attack. In addition, ECG abnormalities between episodes can often not be identified. The evidence that in some patients paroxysmal SVT is the cause, but not the consequence of a panic attack, is based on observations that catheter ablation was able to cure patients presenting with panic disorders. To better establish the prevalence of SVT as the underlying mechanism of a panic attack, there is a need for prospective studies and/or registries. Whereas gastric ulcer has in some patients changed from a psychosomatic disorder to an infectious disease, we may hypothesise that a certain proportion of panic disorders may mutate into an underlying arrhythmia rather than a primary psychiatric disorder.     

Hypercalcemia and Acromegaly-Clarifying the Connections: A Case Report and Review of the Literature

ObjectiveHypercalcemia in patients with acromegaly is rare and usually due to co-existent primary hyperparathyroidism. The etiology of hypercalcemia directly related to acromegaly is debated.MethodsWe present a case report of 1,25(OH)2D3-mediated hypercalcemia in a patient with acromegaly and discuss potential pathophysiological mechanisms contributing to the development of hypercalcemia late in the course of the disease.ResultsA 67-year-old female presented with classical features of acromegaly. A review of her previous photographs suggested a disease duration of approximately 10 years, and her serum calcium (Ca) was normal during this period. A biochemical work up confirmed a combined growth hormone (GH-) and prolactin (PRL-) cosecreting tumor with a GH level of 92.03 ng/mL (normal 0-3.61), an insulin-like growth factor-1 (IGF-1) level of 1,498 ng/ mL (59-225), and a PRL level of 223.3 ng/mL (2-17.4). Magnetic resonance imaging (MRI) of the pituitary showed a 1.9-cm macroadenoma. Her preoperative work up revealed new onset hypercalcemia with a corrected serum Ca level of 10.7 mg/dL (8.5-10.5), an ionized Ca level of 1.37 mmol/L (1.08-1.30), a parathyroid hormone (PTH) level of 13.0 pg/mL (10-60), and a high 1,25(OH)2D3 level of 72.6 pg/mL (15-60). She underwent resection of the pituitary adenoma with normalization of GH and PRL levels, and her IGF-1 level decreased to 304 ng/mL. Her serum Ca (9.3 mg/dL), ionized Ca(1.22) and 1,25(OH)2D3 levels (38.6 pg/mL) normalized after surgery.ConclusionWhile overt hypercalcemia in acromegaly is rare, it tends to occur late in the disease course. The hypercalcemia is mediated by elevated 1,25(OH)2D3 levels rather than PTH. (Endocr Pract. 2014;20:e86-e90)     

Mechanisms of neuropathic pain

Neuropathic pain refers to pain that originates from pathology of the nervous system. Diabetes, infection (herpes zoster), nerve compression, nerve trauma, "channelopathies," and autoimmune disease are examples of diseases that may cause neuropathic pain. The development of both animal models and newer pharmacological strategies has led to an explosion of interest in the underlying mechanisms. Neuropathic pain reflects both peripheral and central sensitization mechanisms. Abnormal signals arise not only from injured axons but also from the intact nociceptors that share the innervation territory of the injured nerve. This review focuses on how both human studies and animal models are helping to elucidate the mechanisms underlying these surprisingly common disorders. The rapid gain in knowledge about abnormal signaling promises breakthroughs in the treatment of these often debilitating disorders.     

The hyperkinetic child: some misleading assumptions.

There is much controversy in the literature concerning prevalence, cause, diagnosis and treatment of hyperkinesis. The subject is complex; there is much ambiguity, and many research studies and reports of successful treatment appear to be overly simplistic in their approach to the problem. The use of the term "hyperkinesis" as synonymous with "hyperactivity" and often also with "minimal cerebral dysfunction" causes much confusion. There appear to be some common underlying beliefs about hyperkinetic children; these are critically examined. From integration of reports in the literature with clinical experience, it is contended that the term hyperkinesis should be restricted to the definition used in the British studies, and hyperactivity should be considered only a symptom. Hyperactivity has a large number of underlying causes, and management plans need to be individualized.     

Effect of parathyroidectomy on calcium and phospholipase A2 in the liver of carbon tetrachloride-treated rats.

The present study shows that carbon tetrachloride fails to cause hypercalcemia in the serum and liver of rats after parathyroidectomy. Secondly, a diminution in the activity of calcium-dependent proteolytic enzyme, phospholipase A2 occurs in parathyroidectomized rats, suggesting a plausible protective mechanism against carbon tetrachloride toxicity.     

Screening laboratory tests for Crohn's disease.

The prevalence of abnormal values of initial screening laboratory tests was assessed for 24 children who eventually proved to have Crohn''s disease. The screening tests included in this analysis were fecal alpha 1-antitrypsin (FA) concentration, erythrocyte sedimentation rate (ESR), total leukocyte count, serum albumin level, hemoglobin concentration, and qualitative testing of stool for the presence of blood. Of the 24 patients, 21 had abnormal FA values, 17 had anemia, 19 had an increased ESR, 14 had hypoalbuminemia, rectal bleeding was found in 8, and none had leukocytosis. All 24 patients had at least one abnormal screening test value; the most frequently abnormal result was the FA concentration. Pediatric patients without elevated FA values, anemia, a high ESR, bloody stools, or hypoalbuminemia are unlikely to have active Crohn''s disease.     

The significance of low back pain in older adults.

A retrospective study of the practice of an orthopedic surgeon at a university teaching hospital was done to evaluate the significance of low back pain in older adults. All 259 patients in a 3-year period 50 years of age and over whose presenting complaint was low back pain or sciatica or both were identified and classified by final diagnosis. A comparison was similarly identified and classified. Systemic disease, particularly cancer, was much more prevalent in the older group. It was demonstrated that a simple screening routine consisting of measuring the erythrocyte sedimentation rate and serum concentrations of alkaline phosphatase and calcium would identify all cases of unsuspected malignant disease--that is, at least one of the values would be abnormal in every case.     

Hypercalcemia of Malignancy with Simultaneous Elevation in Serum Parathyroid Hormone-Related Peptide and 1,25-Dihydroxyvitamin D in a Patient with Metastatic Renal Cell Carcinoma

ObjectiveTo determine the cause of refractory hypercalcemia in a patient with metastatic renal cell carcinoma.MethodsWe describe the clinical, pathologic, and immunostain findings in a patient with metastatic renal cell carcinoma and hypercalcemia of malignancy refractory to intravenous bisphosphonates.ResultsA 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 1a-hydroxylase by immunostaining. After failing to respond to intravenous bisphosphonates, the hypercalcemia improved with prednisone treatment.ConclusionsIn 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 bisphosphonate therapy. (Endocr Pract. 2009;15:234-239)     

Suppressibility of Parathyroid Hormone in Primary Hyperparathyroidism

ObjectiveTo describe an unusual case of pathologically confirmed primary hyperparathyroidism in a patient presenting with severe hypercalcemia and an undetectable parathyroid hormone (PTH) level.MethodsWe present a detailed case report and outline the serial laboratory findings. In addition, the possible causes of low serum PTH levels in the setting of primary hyperparathyroidism are discussed.ResultsA 16-year-old female patient presented with severe epigastric pain, found to be attributable to acute pancreatitis. At hospital admission, her serum calcium concentration was high (14.0 mg/dL); the patient also had a normal serum phosphorus level of 3.6 mg/dL and an undetectable PTH level (< 0.2 pmol/L). An evaluation for non-PTH-mediated causes of hypercalcemia revealed a partially suppressed thyroid-stimulating hormone concentration and a below normal 1,25-dihydroxyvitamin D level, consistent with her suppressed PTH. One week after the patient was dismissed from the hospital, repeated laboratory studies showed a serum calcium value of 11.1 mg/dL, a serum phosphorus level of 2.8 mg/dL, and an elevated PTH concentration of 11.0 pmol/L, consistent with primary hyperparathyroidism. A repeated 1,25-dihy-droxyvitamin D measurement was elevated. A parathyroid scan showed a parathyroid adenoma in the left lower neck area, and she subsequently underwent successful surgical resection of a pathologically confirmed parathyroid adenoma.ConclusionThis case demonstrates that the serum PTH level can be suppressed in patients with primary hyperparathyroidism. Moreover, it emphasizes the need for careful evaluation of the clinical context in which the PTH measurement is determined. Consideration should be given to repeating measurement of PTH and serum calcium levels when the initial laboratory evaluation of hypercalcemia is unclear because dynamic changes in calcium metabolism may occur in the presence of secondary contributing factors. (Endocr Pract. 2007;13:785-789)     

Serum calcium level of freshwater snake, Natrix piscator, in response to vitamin D3 administration

The effect of i.m. injection of vitamin D3 (25 IU/100 g b.wt) on serum calcium level was investigated in Natrix piscator. This treatment evokes hypercalcemia at day 3 which progresses up to day 5. Thereafter, a decline was observed in the serum calcium level at day 10 and day 15.