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Biomedical subjects

G W Edelson

Publications and source records attributed to G W Edelson.

9 recordsLinked to original sources

Hypercalcemic crisis.

Hypercalcemic crisis or severe hypercalcemia represents a life-threatening emergency. The most common cause is hypercalcemia of malignancy, although granulomatous diseases, previously undetected primary hyperparathyroidism, medication-induced hypercalcemia, and a few rarer causes may result in this endocrine emergency as well. The clinical presentation and prognosis depend on the acuity of the development of hypercalcemia, the degree of hypercalcemia, and the underlying cause. Certainly, patients with malignancy who develop hypercalcemia superimposed on their already debilitated state are more likely to have a poor outcome than a previously relatively healthy patient with thiazide-induced hypercalcemia, for example. The clinical presentation of patients with hypercalcemic crisis varies depending once again on the underlying cause and degree and rapidity of the hypercalcemia. Most patients experience some constitutional symptoms, neurologic symptoms, gastrointestinal symptoms, and renal manifestations of hypercalcemia. Immediate and effective therapy directed toward the pathophysiology of hypercalcemia is essential. General measures must be implemented to reverse the dehydration, to promote urinary calcium excretion, to avoid prolonged immobilization, and to identify the underlying cause of hypercalcemia. Specific measures directed at inhibiting bone resorption, increasing renal sodium and calcium excretion, and occasionally at decreasing intestinal absorption of calcium (or more specifically blocking vitamin D metabolism) should also be implemented. Obviously the more reversible the underlying cause of hypercalcemia, the more aggressive one should be with the therapy. The literature was reviewed to compile comparative data that practitioners may use in choosing among the various pharmacologic therapies available for the treatment of acute hypercalcemia. Despite all the advances in the field, hypercalcemic crisis still carries a significant mortality risk, although with appropriate therapy with the aforementioned general and specific measures, the calcium level can effectively be lowered in most patients.

Calcium

Presentations of diabetic feet.

Those afflicted with diabetes mellitus have high rates of morbidity and mortality owing to the many complications of the disease. The complications can manifest themselves as ophthalmic, renal, vascular, neurologic, and pedal diseases. Unfortunately, the most often overlooked or neglected complications involve the feet. It is estimated that in the United States foot disease is five times more prevalent in diabetic patients than in those without diabetes. In fact, 20% of all diabetic patients admitted to hospitals in the United States are admitted for foot disease, with foot and ankle ulcers being the most common presentation.

Diabetes Complications

Insulin resistance in hypertension: a focused review.

The associations between insulin resistance, hyperinsulinemia, and hypertension are well recognized. The insulin resistance and hyperinsulinemia associated with hypertension is the result of increased renal tubular sodium reabsorption, increased sympathetic nervous system activity, and increased arterial wall smooth muscle reactivity. In insulin resistant states, intracellular calcium and sodium accumulation is thought to be the fundamental underlying abnormality. These is evidence that hyperinsulinemia is an independent risk factor for coronary artery disease. Therefore, therapeutic considerations in patients with insulin resistance should include nonpharmacologic methods for increasing insulin sensitivity as well as avoiding the deleterious effects on insulin action and lipid metabolism of various antihypertensive medications. Of the currently available antihypertensives therapies, the angiotensin-converting enzyme inhibitors, the alpha antagonists, and the calcium channel blockers are the most rational choices for treating patients with hypertension with evidence of coexisting insulin resistance.

Animals

Hypercalcemia associated with Wegener's granulomatosis and hyperparathyroidism: etiology and management.

We report a case of hypercalcemia in a patient with coexisting hyperparathyroidism and Wegener's granulomatosis. Parathyroidectomy with removal of an adenoma resulted in a low parathyroid hormone level but high calcitriol levels and hypercalcemia persisted. In various granulomatous diseases, hypercalcemia has been shown to be the result of overproduction of 1,25-dihydroxy-vitamin D by disease-activated macrophages. Chloroquine has been demonstrated to effectively reduce the extrarenal synthesis of 1,25-dihydroxyvitamin D and serum calcium concentration in hypercalcemic patients with sarcoidosis. Hypothesizing that a similar mechanism would explain hypercalcemia in Wegener's granulomatosis as well, a therapeutic trial of chloroquine was initiated. The patient responded to chloroquine 500 mg twice daily with significant decreases in serum 1,25-dihydroxyvitamin D and calcium levels. This report extends previous observations of hypercalcemia associated with other granulomatous diseases to Wegener's granulomatosis and demonstrates an effective reduction of serum calcitriol and calcium levels in response to chloroquine therapy.

Calcitriol

Mucin-producing parathyroid carcinoma.

A 67-year-old white male presented with symptomatic hypercalcemia (15.6 mg/dl) in December 1989. He had undergone thyroidectomy for removal of a mucin-producing adenocarcinoma of the thyroid in 1967, and after eight years of follow-up during which time no other neoplasms were detected, he was reported as a unique case of this syndrome. Mild hypercalcemia (less than 11.0 mg/dl) was first noted in 1987, and this had remained stable until shortly before the acute presentation. Multiple lung nodules were observed radiographically and presumed to be granulomatous until increased size was observed shortly before presentation. Serum intact PTH was 190 pg/ml (n 10-55), but at neck exploration no parathyroid tissue was found and surgery did not resolve the hypercalcemia. Serum PTHrP was undetectable. Biopsies from all three lobes of the right lung revealed numerous nodules of metastatic adenocarcinoma with cords of tumor cells surrounded by mucin. The histology was similar to that obtained 23 years earlier. Following left upper lobe resection with removal of a 3-cm nodule, hypercalcemia resolved. The tumor stained strongly positive with a peroxidase stain for PTH using a polyclonal antibody. Northern blot hybridization of total RNA from the tumor confirmed the presence of message for PTH but not PTHrP. The original diagnosis has been revised to that of a unique case of mucin-producing parathyroid cancer with an extraordinarily long latency period before recurrence.

Adenocarcinoma

A unique case of adult hypophosphatemic osteomalacia.

A 36-year-old Russian man presented with neck and low back pain in September 1990. He was of normal stature, and there were no stigmata of rickets. The family history was negative for bone disease. He was found to have hypophosphatemia (2.3 mg/dl), impaired phosphate reabsorption (TmP/GFR 2.08), hyperphosphatasemia (254 IU/l), normocalcemia, normal vitamin D metabolite levels, and secondary hyperparathyroidism. Clinically, his spinal movements were quite impaired and there was moderate proximal muscle weakness. On skeletal radiographs, there was generalized osteosclerosis and multiple ligamentous calcifications. Transiliac biopsy was diagnostic for severe osteomalacia. He was treated with oral phosphate (240 mEq daily) and calcitriol (4 micrograms daily) with resultant very slow clinical, biochemical, and histomorphologic improvement. The patient had hypophosphatemic osteomalacia with some features of X-linked hypophosphatemia, but sporadic and of relatively late onset. The osteopenia, height loss, incapacitating weakness, and glycinuria that are characteristics of sporadic adult onset nonfamilial hypophosphatemia, with or without an associated tumor, and the low serum calcitriol levels that may be an additional characteristic of tumor-induced osteomalacia were absent. Other known causes of acquired renal tubular dysfunction were ruled out. The etiology, pathogenesis, and nosology of the disorder remain obscure, but treatment based on experience with other forms of hypophosphatemic osteomalacia was ultimately effective.

Adult