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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lithium has proved to be a highly effective preventive measure in mood disorders and an increasing number of patients are receiving long-term lithium carbonate therapy. Among other biologically and clinically important effects of lithium, the possible induction of hyperparathyroidism was first suggested in 1973 by Garfinkel et al. About thirty other case reports have since been described, but they could simply have represented the coincidental occurrence of primary hyperparathyroidism and lithium carbonate treatment in the same patients. Eleven cross-sectional studies of calcium metabolism in patients treated with lithium carbonate have been reported. Evidence of a causal relationship of lithium to hyperparathyroidism can lead to a loss of effectiveness of lithium in controlling the affective symptoms. Interestingly, coexistence with hypothyroidism is not uncommon. Low serum phosphate, high serum chloride are also observed. Bone mineral content may decrease. In addition, several studies have shown that lithium treatment increases serum magnesium level. Unusual metabolic features are associated with hyperparathyroidism and long-term lithium treatment: low urinary calcium excretion, absence of nephrolithiasis, and normal urinary cyclic AMP excretion. Lithium inhibition of PTH sensitive adenylcyclase in the kidney would explain these features. In vitro studies suggested that lithium is a potent inhibitor of several hormone responsive adenylcyclase systems. It is possible that the tissue susceptibility to adenylcyclase inhibition in an individual may decide the nature of endocrine dysfunction seen during lithium treatment. Information about the time course with which abnormalities may develop is derived from longitudinal studies. Several months to several years are needed for lithium inducing primary hyperparathyroidism. In vitro studies provide strong evidence that lithium can induce a shift in the set-point for inhibition of PTH secretion by calcium and a direct stimulation of PTH secretion. The extent to which we can extrapolate these data to the clinical situation is discussed. In vivo data from Shen an Seely are compatible with these two mechanisms. These alterations should cause parathyroid hyperplasia. The possibility that a generalized parathyroid stimulus might lead to formation of a single adenima is not proved. Several recommendations regarding parathyroid function in patients receiving lithium have been suggested. Measurement of total calcium and serum proteins or of serum calcium ion values when available should be performed before therapy is begun. If elevated values are obtained, lithium treatment should be deferred and evaluation for hyperparathyroidism performed. Serum calcium should be monitored periodically during lithium treatment. Sustained hypercalcemia or true hyperparathyroidism require parathyroidectomy. If hypercalcemia is mild without complication and psychiatric symptoms well controlled, perhaps surgery should not be employed.
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PMID:[Hyperparathyroidism with lithium]. 808 38

Primary hyperparathyroidism (PHPT) is found not uncommonly in patients with cancer. In this report, however, we describe a patient where both humoral hypercalcaemia of malignancy and PHPT were present coincidentally. A 47-year-old man was found to have PHPT due to parathyroid hyperplasia. Serum parathyroid hormone (PTH) levels, which were elevated before parathyroidectomy, were undetectable post-operatively; however, hypercalcaemia persisted. Nephrogenous cyclic adenosine monophosphate was elevated along with this undetectable PTH, indicative of the presence of a PTH-like factor in the serum. This was confirmed by the finding of an elevated level of PTH-related protein (PTHrP) in plasma (9.1 pmol/l, normal < 2.6 pmol/l). Secondary carcinoma was identified in a lesion in the region of the manubrium sternii. This stained positively for PTHrP by immunocytochemistry and PTHrP messenger RNA was detected by in-situ hybridization. This case illustrates the value of sensitive PTH assays in distinguishing PHPT from other causes of hypercalcaemia and also shows the importance of considering primary hyperparathyroidism in the differential diagnosis of the patient with cancer and hypercalcaemia.
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PMID:Coincidental occurrence of primary hyperparathyroidism and cancer-associated hypercalcaemia in a middle-aged man. 831 76

Primary hyperparathyroidism is a rare disease of childhood. The condition is even rarer in the neonatal and infant stages. The disease, with its main manifestation-hypercalcemia-often is fatal. The authors successfully treated a 2.5-month-old boy who had primary parathyroid hyperplasia. The patient had recurrent pneumonia and failure to thrive. Blood test results showed an abnormally high level of calcium, which was resistant to medical therapy. Further investigations showed high levels of parathyroid hormone. The patient underwent neck exploration, which showed hyperplasia of the all four parathyroid glands. Total parathyroidectomy was performed, with one gland being autotransplanted to the deltoid muscle. The patient had an immediate hypocalcemic period, followed by normocalcemia. In light of the present case and others in the Literature, the authors recommended total parathyroidectomy followed by autotransplantation of a gland to an accessible muscle.
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PMID:Primary hyperparathyroidism in infancy: a case report. 870 21

A 51-year-old man was hospitalized with a gait disturbance and hypoesthesia below the level of his chest. These symptoms were due to a spinal tumor which was surgically resected and identified as an ependymoma. Additionally, the patient had hypercalcemia and a family history of insulinoma. An endocrine evaluation revealed parathyroid hyperplasia and a pancreatic islet cell tumor. Magnetic resonance imaging disclosed a pituitary microadenoma. He was diagnosed with spinal ependymoma and multiple endocrine neoplasia type 1 (MEN 1). A review of the literature revealed that chromosome 11q13 abnormalities have been reported in both ependymoma and MEN 1. We discuss the pathogenesis of these diseases.
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PMID:Multiple endocrine neoplasia type 1 associated with spinal ependymoma. 873 83

Information on genetic abnormalities in primary hyperparathyroidism has accumulated gradually. Genetic alterations responsible for tumorigenesis have been identified in multiple endocrine neoplasia types 1 and 2. Point mutations in a calcium-sensing receptor gene were recently found to be responsible for familial hypocalciuric hypercalcaemia and neonatal severe hyperparathyroidism. Evidence has been provided that abnormalities of cell cycle regulation participate at tumorigenesis in parathyroid adenoma and carcinoma. Clonal analysis has shown that in renal hyperparathyroidism the parathyroid glands initially grow diffusely and polyclonally, after which foci of nodular hyperplasia are transformed to monoclonal neoplasia. Somatic changes of specific genes have been suspected of being responsible for parathyroid tumorigenesis in renal hyperparathyroidism. However, the genetic loci responsible for the frequent monoclonality largely remain to be identified, and heterogeneous genetic abnormalities may contribute to the progression of secondary parathyroid hyperplasia.
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PMID:Molecular genetics of hyperparathyroid disease. 882 31

In vivo dynamic tests of parathyroid gland function have provided useful information about the secretory behavior of parathyroids in various clinical disorders, but the limitations of this approach must be recognized when applied to studies of parathyroid gland physiology. Set point abnormalities have been documented in vivo both in primary hyperparathyroidism and in familial hypocalciuric hypercalcemia. Such findings are consistent with in vitro results obtained in studies of dispersed parathyroid cells from patients with primary hyperparathyroidism and with recently described alteration in calcium receptor expression in patients with FHH. The assessment of parathyroid gland function in patients with end-stage renal disease presents distinct methodological problems, however, because of marked variation in the degree of parathyroid gland enlargement. Neither the four parameter model originally used to describe set point abnormalities both in vitro and in vivo or alternative approaches to the assessment of PTH secretion in vivo adequately address this important issue. Results from recent in vivo studies of patients with chronic renal failure do not support the view that the set point for calcium-regulated PTH release is abnormal in secondary hyperparathyroidism or that treatment with calcitriol lowers the set point for calcium-regulated PTH release in patients with uremic secondary hyperparathyroidism. The concept of set point disturbances has strongly influenced discussions about the pathogenesis of secondary hyperparathyroidism, and it has served as a focal point for examining the therapeutic response to calcitriol in patients with this disorder. This matter requires careful reconsideration, however, in light of recent clinical findings and the development of techniques to directly assess the molecular mechanisms responsible for regulating calcium-mediated PTH release in renal failure and other disorders of mineral metabolism. Although knowledge in this area remains limited, the extent of parathyroid hyperplasia and the role of factors that influence the development of parathyroid gland enlargement may ultimately prove to be particularly important modifiers of parathyroid gland function in chronic renal failure.
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PMID:In vivo assessments of calcium-regulated parathyroid hormone release in secondary hyperparathyroidism. 894 64

Activating germline mutations in the cysteine-rich domain of the RET proto-oncogene are found in >92% of the cases of multiple endocrine neoplasia type 2A (MEN2A) and 85% of familial medullary thyroid carcinoma (FMTC). In virtually 100% of patients with identified mutations one of five cysteines is altered by a missense mutation. In a MEN2A family with 14 affected and 11 unaffected living members, hypercalcemia was diagnosed in eight patients and histological evaluation revealed parathyroid hyperplasia in all cases examined (10/10). No member of this family showed any evidence for the existence of pheochromocytoma. This is the first documentation of a family without pheochromocytoma but with a high incidence of parathyroid disease. Genetic analysis revealed the presence of an unusual heterozygous mutation in exon 11 of the RET proto-oncogene representing a duplication of 12 bp resulting in the insertion of four amino acids between codon 634 (Cys) and 635 (Arg), thus creating an additional cysteine residue.
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PMID:A duplication of 12 bp in the critical cysteine rich domain of the RET proto-oncogene results in a distinct phenotype of multiple endocrine neoplasia type 2A. 909 63

Most cases of primary hyperparathyroidism are due to either a parathyroid adenoma or to parathyroid hyperplasia. Parathyroid carcinoma is a very rare cause of hyperparathyroidism. Although the diagnosis of parathyroid carcinoma is usually established based on pathological criteria of vascular and capsular invasion, some clinical and biochemical features differentiate it from benign forms of hyperparathyroidism. We report the case of a middle-aged woman with a long standing history of nephrolithiasis, who presented with a palpable neck mass, weight loss, severe hypercalcemia and hypophosphatemia, as well as very high serum levels of intact parathyroid hormone. Surgical neck exploration revealed a large tumor that invaded trachea, esophagus, reccurrent laryngeal nerve, right apical pleura and right carotid artery. Pathological examination confirmed the invasive nature of the tumor. Along with the case report, we review the literature and discuss the diagnostic and therapeutic options of this rare condition.
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PMID:Primary hyperparathyroidism due to parathyroid carcinoma. 920 27

Chronic uremia is associated with secondary hyperparathyroidism (HPT). The purpose of the present investigation was to study the reversibility of secondary HPT after reversal of uremia by an isogenic kidney transplantation in the rat. Secondary HPT was induced in two models: Model A comprised 5/6 nephrectomized rats kept on a standard diet (N = 12; PTH 210 +/- 43 pg/ml; plasma urea 24 +/- 2 mmol/liter; and normal control rats, N = 12; PTH 45 +/- 5 pg/ml; plasma urea 6 +/- 0.2 mmol/liter); and Model B comprised 5/6 nephrectomized rats kept on a high phosphorus diet (N = 12; PTH 769 +/- 157 pg/ml; plasma urea 18 +/- 2 mmol/liter). The parathyroid function was examined by measuring the secretory response of PTH to an acute induction of hypo- and hypercalcemia. Acute hypocalcemia in the hyperphosphatemic uremic rats did not significantly increase serum PTH levels (N = 6, delta Ca2+ -0.56 mmol/liter; maximal PTH 1045 +/- 164 pg/ml; basal PTH 690 +/- 134 pg/ml; NS). During hypercalcemia the PTH levels were significantly higher than in the normal controls (N = 6; minimal PTH 24 +/- 5 pg/ml vs. normal controls 5 +/- 0.2 pg/ml, P < 0.05). After 20 weeks of uremia, the uremia was reversed by the isogenic kidney transplantation. One week after reversal of the uremia the PTH levels became normal in both models A and B (28 +/- 6 and 63 +/- 16 pg/ml, respectively) and the kidney transplanted rats from model B had a normal secretory response of PTH to both hypo- and hypercalcemia. To study whether both parathyroid cell hypertrophy and hyperplasia could be down-regulated, 8 uremic glands (N = 9) or 20 normal glands (N = 6) were implanted into one normal rat. Within two weeks the rats regained normocalcemia and PTH levels remained normal from the third day after the increase of glandular mass. The 20 gland rats all had normal PTH suppressibility in response to calcium (minimal PTH 5 +/- 0.3 pg/ml). In conclusion, experimental severe secondary hyperparathyroidism is reversible very quickly after the reversal of uremia. Hyperphosphatemia in uremia is important for the non-suppressibility of the parathyroid glands to calcium. In non-uremic rats even severe parathyroid hyperplasia can be controlled, resulting in normal plasma PTH and Ca2+ levels and in a normal response to hypercalcemia. Thus, the minimal PTH secretion obtained during the induction of hypercalcemia is not an expression of the parathyroid mass.
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PMID:Reversibility of experimental secondary hyperparathyroidism. 935 Jun 46

The purpose of this study was to assess the diagnostic utility of parathyroid ultrasonography to differentiate causes of hypercalcemia in dogs. We analyzed qualitative and quantitative ultrasound imaging findings and clinical pathology data from 33 dogs that underwent parathyroid ultrasound examination as part of the diagnostic evaluation for hypercalcemia. Diagnoses of the diseases causing hypercalcemia included parathyroid carcinoma (n = 5), parathyroid adenoma (n = 15), parathyroid adenomatous hyperplasia (n = 6), chronic renal insufficiency (n = 3), and hypercalcemia of malignancy (n = 4). All parathyroid lesions were round or oval and hypoechoic compared with surrounding thyroid parenchyma. Adenomatous and adenocarcinomatous glands were 4 mm or larger in longest linear measurement on US examination and were statistically significantly larger than hyperplastic glands. (p < 0.001) Linear measurements of parathyroid glands acquired at the time of ultrasound examination correlated well with direct size determination after surgical excision. (r2 = 0.9, p < 0.0001) Parathyroid lesions > or = 4 mm are highly suspicious for parathyroid adenoma or carcinoma, while US lesions < 4 mm most likely represent primary adenomatous hyperplasia or secondary parathyroid hyperplasia. Parathyroid size estimation from ultrasound examination is an accurate predictor of true size.
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PMID:High-resolution parathyroid sonography. 940 14


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