Search PubMed⌕ Search

Biomedical subjects

L E Mallette

Publications and source records attributed to L E Mallette.

At least 37 records · Page 2Linked to original sources
PubMed1990

Hereditary hyperparathyroidism and multiple ossifying jaw fibromas: a clinically and genetically distinct syndrome.

A large previously reported family with hyperparathyroidism has been reinvestigated recently because of the occurrence of multiple ossifying jaw fibromas in two affected members of the third generation similar to the jaw tumors of four of five affected members of the first generation. These maxillary and mandibular tumors can be differentiated from the "brown tumors" of hyperparathyroidism because they can appear and enlarge even though the hypercalcemia is surgically corrected. These tumors are histologically distinct fibroosseous lesions without the giant cells seen in "brown tumors." The parathyroid enlargement was mostly uniglandular, with multiple tumors found occasionally. Studies in DNA linkage were performed within this large family and a similar family in Houston to determine if the gene for this syndrome, termed HRPT2, is linked to DNA markers on chromosome 11, to which the gene for multiple endocrine neoplasia (MEN) type 1 has been linked. (This linkage is supported by our findings in one family with MEN 1 reported here.) Linkage studies were also performed with markers on chromosome 10, to which the genes for MEN 2A and MEN 2B have been linked. Evidence against close linkage with chromosome 10 and chromosome 11 markers suggests that this clinically distinct syndrome is also genetically distinct.

Female↗
PubMed1989

Cyclic therapy of osteoporosis with neutral phosphate and brief, high-dose pulses of etidronate.

We have designed a cyclic regimen for the treatment of osteoporosis based on the activate, depress, free, and repeat (ADFR) concept. Osteoclastic bone resorption is activated by 7 days of oral neutral phosphate and inhibited with a brief pulse (5 days) of etidronate disodium at a high dose (20 mg/kg body weight). Patients next take calcium supplements for 48 days before resuming phosphate to enter the next cycle. Osteoporotic women increased the bone mineral density of the lumbar spine at 6 months by 7.2 +/- 5.2% (mean +/- SD, N = 14) and at 12 months by 8.2 +/- 4.0% (N = 8). Control observations in regularly exercising postmenopausal women (N = 30) showed no significant change in spine mineral density after 20 months (0.5 +/- 3.2%), confirming the stability of the measurement technique. The two patients who responded poorly to the cyclic regimen each showed a blunted rise in serum PTH during oral phosphate administration, suggesting that the rise in PTH induced by oral phosphate may be an important component of this cyclic regimen. This preliminary study does not identify which component or components of the regimen are responsible for the increase in bone mass but provides positive encouragement for randomized studies designed to determine the optimum dosage, duration, and timing of each component of the regimen.

Adult↗
PubMed1989

The role of parathyroid ultrasonography in the management of primary hyperparathyroidism.

High-resolution, real-time sonography can be used to assess the size and location of the parathyroid glands. The authors review the types of information provided by sonography and outline the ways in which it contributes to the management of primary hyperparathyroidism. Sonography usually can differentiate parathyroid adenoma from hyperplasia. In milder cases, with less parathyroid enlargement, this differentiation is difficult but can be facilitated by determining three dimensions for each gland. Preoperative knowledge of the presumptive location of an adenoma is most useful when the strategy of unilateral neck exploration is to be used because it will allow the exploration always to begin on the correct side. Sonographic evidence of hyperplasia should trigger a preoperative search for multiple endocrine neoplasia and will alert the surgeon that a bilateral neck exploration and thymectomy will be needed. A more universal benefit is the ability to predict or exclude intrathyroidal and subcapsular parathyroid tumors, thus guiding the decision for thyroid versus thymic exploration in the event of a missing abnormal gland. Sonography often fails to visualize parathyroid tumors in an ectopic position away from the thyroid bed. Such tumors, however, may be anticipated when the sonogram shows only three enlarged glands in cases of hyperplasia, or only three glands of normal size in a patient with strong biochemical evidence of hyperparathyroidism. Because it is noninvasive and inexpensive and can provide a wealth of information, the authors have adopted sonography as a routine preoperative procedure for primary hyperparathyroidism.

Adenoma↗
PubMed1989

Lithium treatment increases intact and midregion parathyroid hormone and parathyroid volume.

Lithium carbonate is known to alter calcium metabolism by lowering urinary calcium excretion and increasing serum calcium concentrations. Several investigators have reported increases in serum immunoreactive PTH (iPTH) values after a few weeks or months of lithium treatment, and several cases of primary hyperparathyroidism developing during lithium treatment have been reported. To determine whether the increases in serum iPTH might be the result of increased renal retention of inactive PTH fragments rather than stimulation of parathyroid function, we measured plasma intact PTH by immunoradiometric assay and estimated parathyroid size by ultrasonography in men who had received short term (less than 6 months) or long term (greater than 3 yr) lithium treatment and in normal subjects. Serum ionized calcium was higher by 0.03-0.04 mmol/L in subjects treated short term (mean, 1.7 months) with lithium than in normal subjects, but plasma intact PTH and serum midregion iPTH values were not different. The absence of a reciprocal decrease in PTH values is compatible with a lithium-induced shift in the set-point for the inhibition of PTH secretion by calcium toward a higher calcium value. Both plasma intact PTH and serum midregion PTH values were higher in subjects during longer term (mean, 103 months) lithium treatment, and estimated parathyroid volume was 3-fold higher. Serum phosphate was lower, and serum chloride and plasma 1,25-dihydroxy-vitamin D values were higher in those treated with lithium long term, probably from the biological action of the increased PTH. We conclude that long term lithium treatment increases circulating biologically active PTH and causes parathyroid enlargement. Whether this chronic stimulus to parathyroid growth might lead to adenoma formation in certain susceptible individuals and whether a PTH-induced increase in skeletal remodelling occurs that might hasten the appearance of osteopenia remain to be determined.

Adult↗
PubMed1989

Successful treatment of resistant Paget's disease of bone with pamidronate.

Several agents are available for treatment of Paget's disease of bone, but their long-term use may be limited by resistance or adverse effects. I have treated two patients with exceptionally severe polyostotic Paget's disease (serum alkaline phosphatase values 25- to 30-fold above normal), in whom salmon calcitonin, sodium etidronate, and plicamycin each had become ineffective or could not be used. Pamidronate (3-amino-1-hydroxypropylidene-1,1-bisphosphonate) decreased serum alkaline phosphatase to normal or near-normal values and almost completely relieved symptoms, without recognizable adverse effects, except for transient mild hypocalcemia. The symptomatic and biochemical responses were maintained through 2 years of treatment and for more than 6 months after the treatment was discontinued. Thus, pamidronate can be very effective in severe, resistant cases of Paget's disease. Further study of this potent agent is needed to define the optimum regimen for maximum effectiveness and minimal long-term toxicity.

Adult↗
PubMed1989

Regulation of blood calcium in humans.

Serum calcium in humans is closely regulated, with a maximum excursion of values throughout the day of less than 6%. A number of hormonal controls serve to maintain the stability of the serum calcium value. The three most important hormones--PTH, 1,25-dihydroxyvitamin D, and calcitonin--act chiefly on three organs--intestine, bone, and kidney. A set of simple diagrams that summarize these control mechanisms is presented. Organ diagrams are used to indicate the normal fluxes of calcium (or other ions) and the sites of hormone action, while a feedback loop diagram summarizes the interactions among the various factors. The feedback loop diagram predicts the direction of changes observed in each parameter in various disorders of calcium metabolism and may be useful for constructing experimental models or for teaching purposes.

Bone and Bones↗
PubMed1988

Synthetic human parathyroid hormone 1-34 fragment for diagnostic testing.

Since bovine parathyroid extract became unavailable for stimulatory testing, the differentiation between hypoparathyroidism and pseudohypoparathyroidism has been made from the measurement of serum parathyroid hormone (PTH) values alone. Responsiveness to PTH can once again be tested with teriparatide acetate, the newly available, biologically active 1-34 fragment of human PTH. The PTH infusion test can be used to confirm a preliminary diagnosis based on serum immunoreactive PTH values, to differentiate between type 1 and type 2 pseudohypoparathyroidism, or to detect a subtle abnormality of calcium metabolism in normocalcemic patients with features suggesting pseudohypoparathyroidism. Of several variables used to express changes in renal metabolism of cyclic adenosine 3',5'-monophosphate (cAMP) or phosphate, the 30-minute change in cAMP excretion per unit of glomerular filtration and the 60-minute percentage fall in the tubular maximum for phosphate reabsorption provide the best discrimination. Teriparatide has a low incidence of adverse reactions and provides an effective diagnostic tool.

Costs and Cost Analysis↗
PubMed1988

Synthetic human parathyroid hormone-(1-34) for the study of pseudohypoparathyroidism.

The synthetic amino-terminal fragment of PTH, PTH-(1-34), was recently released for clinical testing of PTH responsiveness. We measured the urinary cAMP and phosphaturic responses to infusion of PTH-(1-34) [3U/kg BW (200 U maximum), iv in 10 min] in patients with pseudohypoparathyroidism and idiopathic hypoparathyroidism, as well as normal subjects. The protocol used data from 5 30-min urine collections and 4 blood samples. Based on the results in 7 patients with pseudohypoparathyroidism (hypocalcemia with increased serum immunoreactive PTH concentrations), 2 patients with suspected pseudohypoparathyroidism, 9 patients with surgical hypoparathyroidism, and 10 normal subjects, this testing protocol differentiated well among these conditions. The patients with pseudohypoparathyroidism had blunted cAMP and phosphaturic responses to PTH-(1-34) administration compared to those of either normal or hypoparathyroid subjects. Induced hypercalcemia failed to restore a normal cAMP response to PTH-(1-34) infusion in 2 patients with pseudohypoparathyroidism. Calculation of the cAMP response to PTH-(1-34) as nanomoles per dL glomerular filtrate during the first 30 min after infusion provided better differentiation among groups than other parameters of cAMP metabolism. Calculating the phosphaturic response as the percent fall in tubular maximum for phosphate reabsorption during the first hour after infusion gave the best degree of statistical separation among groups. We conclude that this new diagnostic agent is effective for the study of renal responsiveness to PTH, and that the protocol described here reliably differentiates patients with pseudohypoparathyroidism from those with hypocalcemia due to other causes.

Adult↗
PubMed1988

Treatment of Paget's disease of bone with salmon calcitonin nasal spray.

Subcutaneous daily or bidaily administration of synthetic salmon calcitonin is an effective form of therapy for Paget's disease, but the requirement for parenteral injection deters geriatric patients from using the drug. This study compares a new intranasal preparation of salmon calcitonin to subcutaneous drug in 18 patients with Paget's disease using two different protocols. In the first protocol, 15 patients not previously treated with salmon calcitonin were given the agent for 3 months by either the intranasal or subcutaneous route. Seven patients treated with intranasal calcitonin had a mean fall in the serum alkaline phosphatase of 33% over a 3-month period compared to a fall of 40% in the subcutaneously treated group; the difference between the two treatment groups was not statistically significant. In the second protocol, three patients previously stabilized on subcutaneous calcitonin were switched to the nasal spray with no subsequent change in alkaline phosphatase values during 6 months of treatment. These results demonstrate that intranasal salmon calcitonin is effective in lowering the serum alkaline phosphatase in Paget's disease. Ease of administration and patient acceptance make intranasal calcitonin a reasonable alternative for geriatric patients.

Administration, Intranasal↗
PubMed1987

The spectrum of metabolic bone disease in lymphoblastic leukemia.

Eight patients with childhood acute lymphoblastic leukemia (ALL) and hypercalcemia, osteopenia, or vertebral compression fractures seen at our institution during the last 12 years were evaluated for biochemical evidence of bone disease. Five patients were hypercalcemic, three had abnormal phosphorous levels, and four had elevated alkaline phosphatase values. Parathyroid hormone (PTH) was measured by a polyvalent radioimmunoassay in five patients and these levels were abnormally high in three patients. Four of these five patients also had PTH measured by a midregion-specific radioimmunoassay. One patient had a high PTH value. Two patients had low levels and one patient had a normal PTH level. Although these studies suggest diverse biochemical mechanisms may be contributing to the bone changes and hypercalcemia seen in childhood ALL, ectopic PTH production as well as ectopically produced fragments of PTH may have a role in mediating bone resorption and hypercalcemia.

Adolescent↗
PubMed1987

Heritable syndrome of pseudoxanthoma elasticum with abnormal phosphorus and vitamin D metabolism.

A patient with pseudoxanthoma elasticum was documented to be hyperphosphatemic and mildly hypercalcemic for six years. Complications included metastatic calcification, absorptive hypercalciuria, and renal insufficiency. The 1,25-dihydroxyvitamin D value was elevated, despite normal serum parathyroid hormone values, high serum phosphate levels, and renal insufficiency. Either increased dietary calcium or prednisone seemed to suppress the 1,25-dihydroxyvitamin D value. Nephrolithiasis or abnormalities suggestive of pseudoxanthoma elasticum occurred in the patient's father, daughter, and several siblings, suggesting a distinct familial syndrome in which connective tissue changes are accompanied by abnormalities of phosphorus and vitamin D metabolism that may resemble those in the syndrome of familial tumoral calcinosis. Nine similar cases were described before 1970.

Calcitriol↗
PubMed1987

Familial cystic parathyroid adenomatosis.

Although the commonest familial form of primary hyperparathyroidism is parathyroid hyperplasia, a few families have manifested parathyroid adenomas. We describe a family in which four members developed cystic parathyroid adenomas. Although calcium levels returned to normal after resection of the adenoma, a second adenoma would often develop several years later (we have termed this temporal sequence adenomatosis). Each adenoma had a cystic histologic appearance, and three of four normal-sized parathyroid glands also contained many cysts. No other endocrine tumors have appeared, but in three patients the hyperparathyroidism was complicated by fibrous maxillary or mandibular tumors that resembled ossifying fibromas rather than the brown tumors generally found in patients with hyperparathyroidism. Each patient with an adenoma was hypercalciuric, but two were obligate carriers of hypocalciuric hypercalcemia. This familial occurrence of the rare cystic parathyroid adenoma suggests the presence of a distinct hereditary syndrome. The genetic basis may be the simultaneous inheritance of familial hypocalciuric hypercalcemia and another trait that may increase the urinary excretion of calcium.

Adenoma↗
PubMed1987

Autogenous parathyroid grafts for generalized primary parathyroid hyperplasia: contrasting outcome in sporadic hyperplasia versus multiple endocrine neoplasia type I.

Sixteen patients with generalized primary parathyroid hyperplasia were treated with attempted total parathyroidectomy and placement of an autogenous parathyroid graft in the forearm musculature; these patients have been followed for up to 79 months. We assessed completeness of parathyroidectomy on the basis of the background immunoreactive parathyroid hormone (iPTH) value 3 to 7 days after surgery, which predicted the chance of a graft-independent recurrence or persistence of hyperparathyroidism (0/8 if undetectable versus 4/5 if normal or high). Total parathyroidectomy was sometimes difficult to achieve because of the presence of supernumerary or ectopic parathyroid glands; to enhance the success rate of total parathyroidectomy, we suggest both the use of preoperative ultrasonography to locate intrathyroidal parathyroids and a routine search for supernumerary parathyroids that includes transcervical thymectomy. Graft function was monitored by measuring the secretory gradient for iPTH (the difference between the two antecubital fossae). Gradients on postoperative days 3 to 7 were barely detectable, but by 3 weeks, larger iPTH gradients were noted in every case. By 4 months, the graft could maintain normal serum calcium levels in all but one case. Autonomous graft function has evolved in four of six evaluable patients with type I multiple endocrine neoplasia (MEN I), but in none of the nine patients with sporadic hyperplasia (p = 0.043). A prospective study is needed to determine whether the use of a smaller number of parathyroid fragments for the autogenous graft in known MEN I patients might delay recurrence.

Adult↗
PubMed1986

Parathyroid cell surface autoantibodies that inhibit parathyroid hormone secretion from dispersed human parathyroid cells.

Serum autoantibodies directed toward antigenic determinants on the surface of human parathyroid cells (PTAb-CS) have been demonstrated in a subset (8 of 23) of adult patients with idiopathic hypoparathyroidism (IHP). In sera from 3 of 8 patients with PTAb-CS, binding of these autoantibodies to their respective parathyroid cell surface antigen(s) resulted in marked inhibition of parathyroid hormone (PTH) secretion in an in vitro dispersed human parathyroid cell (dPTC) system. In 1 subject evaluated longitudinally, circulating levels of PTAb-CS, and the magnitude of the inhibitory effect on PTH secretion, temporally correlated with the clinical course of the hypoparathyroidism. These findings suggest a causative role for antibodies directed against cell surface antigens in parathyroid dysfunction in some cases of "autoimmune" hypoparathyroidism.

Aged↗
PubMed1986

Pregnancy as state of physiologic absorptive hypercalciuria.

An increase in circulating, 1,25-dihydroxyvitamin D level and net intestinal calcium absorption have been previously demonstrated in pregnant women and have been widely regarded as compensatory mechanisms whereby fetal mineral demands are satisfied. The alternate possibility, that these adjustments might anticipate such demands, has not previously been considered. To examine the effects of pregnancy on the intestinal absorption and renal excretion of calcium, oral calcium tolerance tests were performed and urinary calcium excretion was measured in 16 healthy women receiving a moderate calcium intake during and after pregnancy. Circulating 1,25-dihydroxyvitamin D levels and indexes of parathyroid function were also measured. As expected, 1,25-dihydroxyvitamin D levels were significantly (p less than 0.05) elevated throughout pregnancy (94 +/- 11, 118 +/- 9, and 117 +/- 11 pg/ml in the first, second, and third trimesters, respectively, versus 51 +/- 5 pg/ml after delivery). Twenty-four-hour calcium excretion also increased sharply (247 +/- 54, 316 +/- 42, 300 +/- 61 mg versus 91 +/- 18 mg), often to the point of hypercalciuria. Calcium tolerance test results included significant increases in the calciuric and calcemic responses during each trimester, whereas fasting calcium excretion and parathyroid function remained normal. These findings portray normal pregnancy as a state of physiologic absorptive hypercalciuria and call into question the widespread practice of supplementing calcium intake in otherwise well-nourished women during pregnancy.

Adult↗
PubMed1986

Concomitant Graves' disease and primary hyperparathyroidism. Influence of hyperthyroidism on serum calcium and parathyroid hormone.

Two patients with coexistent Graves' disease and primary hyperparathyroidism were studied during medical treatment of their hyperthyroidism. Serum free calcium level was initially quite elevated (1.61 and 1.71 mM, normal 1.12 to 1.28 mM), but immunoreactive parathyroid hormone values were only slightly increased. The immunoreactive parathyroid hormone values of 153 and 173 nleq/ml (normal less than 150 nleq/ml) were far lower than expected in hyperparathyroid patients with a similar degree of hypercalcemia. As the patients became euthyroid during thionamide treatment, calcium values decreased to 1.39 and 1.61 mM, respectively, and parathyroid hormone increased to values clearly suggestive of hyperparathyroidism (454 and 229 nleq/ml, respectively). Parathyroidectomy and subtotal thyroidectomy cured both the hyperparathyroidism and the thyrotoxicosis in each case. These observations suggest that thyroid hormone had potentiated the osteoclastic effects of parathyroid hormone and that the resulting exacerbation of hypercalcemia had produced a relative suppression of hormone secretion by the abnormal parathyroid tissue.

Aged↗
PubMed1986

Serum gastrin level is increased by chronic hypercalcemia of parathyroid or nonparathyroid origin.

In patients with hypercalcemia with abdominal symptoms, gastrin concentration is often measured to exclude the Zollinger-Ellison syndrome. We found that interpretation of such measurements is clouded by a contradictory literature. We therefore measured serum gastrin concentrations in 78 patients with primary hyperparathyroidism, 36 with nonparathyroid hypercalcemia, 13 with hypocalcemia, and 33 normocalcemic controls. Gastrin values above normal occurred in 22% of those with primary hyperparathyroidism and 28% of those with nonparathyroid hypercalcemia. Values above 250 pg/mL occurred only in those with hypochlorhydria or multiple endocrine neoplasia, type 1 (MEN 1). After parathyroidectomy, gastrin levels fell significantly, but elevated values tended to recur in those with MEN 1 if hypercalcemia recurred. Thus, chronic hypercalcemia of either parathyroid or nonparathyroid origin may elevate serum gastrin concentrations, but marked elevations suggest either achlorhydria or MEN 1.

Adult↗