Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a case of pituitary adenoma in association with parathyroid carcinoma as an unusual combination of multiple endocrine neoplasia (MEN). A 48-year-old man had a trans-sphenoidal hypophysectomy and transcranial partial removal of a recurrent pituitary chromophobe adenoma followed by a course of radiotherapy in 1980. Four years later, he developed hypercalcemic crisis from a parathyroid carcinoma with invasion to the adjacent thyroid gland and skeletal muscle. A hemithyroidectomy and resection of the left lower parathyroid gland was performed. Three years later, he had local recurrence and anterior chest wall metastasis accompanied by hypercalcemia. After resection of the remnant and metastatic lesion, eucalcemia was achieved. There was no family history of endocrine tumors. This case illustrates the rare association of a malignant parathyroid tumor and a chromophobe adenoma of the pituitary as a variant of MEN syndrome.
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PMID:Parathyroid carcinoma in a patient with non-secretory pituitary tumor: a variant of multiple endocrine neoplasia type-I? 135 78

We describe the rare case of a 19 year-old patient with multiple endocrine neoplasia (Wermer syndrome), presenting with insulinomas as well as primary hyperparathyroidism. Echocardiography revealed evidence of calcific deposits in the interventricular septum. The latter may be explained by long-standing hypercalcemia.
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PMID:[Myocardial calcinosis in a juvenile patient with Wermer syndrome (multiple endocrine neoplasia type I)]. 136 28

Nineteen patients were surgically treated for hyperparathyroidism associated with multiple endocrine neoplasia type 1 syndrome. Fourteen patients (74%) had removal of three or more parathyroid glands at the first operation, and five (26%) by removal of 2 1/2 or fewer glands. Two patients had recurrent hypercalcemia during the mean follow-up period of 65 months. One had a recurrence 10 years after subtotal parathyroidectomy. Reexploration in this patient revealed enlargement of the remaining tissue in the neck and an enlarged supernumerary gland in the aorticopulmonary window. The other patient had persistent hypercalcemia after removal of two hyperplastic parathyroid glands until after another 1 1/2 more glands were removed. After reoperation the patient was normocalcemic for 10 years before hypercalcemia was again noticed. The patient subsequently died from renal carcinoma metastases, which might have been the cause of the hypercalcemia before death.
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PMID:Primary hyperparathyroidism in patients with multiple endocrine neoplasia type 1: experience by a single surgical team in Japan. 136 3

Hypercalcemia was corrected in 62 (90%) of 69 patients after re-operation for primary hyperparathyroidism during a mean follow-up of 6.3 years. Failed primary exploration was mainly due to inadequate visualization of the pathological parathyroid glands, often in association with misleading or absent peroperative histology. Other causes included seeding of parathyroid adenoma tissue, truly recurrent adenomas, and recurrent hyperplasia, especially in patients with multiple endocrine neoplasia type 1. A considerable number of parathyroid glands missed at the primary operations were subsequently found in essentially normal positions. Ectopic superior glands were most frequently positioned para-esophageally or retro-esophageally, while abnormally placed inferior glands were generally situated within or close to the thymus. Glands in 3 patients were dissected from around the large vessels in the mediastinum. Concomitant thyroid procedures during the primary operation yielded few abnormal parathyroids and made the re-exploration considerably more difficult. We suggest a semilateral approach and caudal identification of the recurrent laryngeal nerve to reduce the hazards of difficult parathyroid re-operations. Mediastinal exploration may require total removal of the thymus and careful dissection of the middle mediastinum.
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PMID:Causes of failed primary exploration and technical aspects of re-operation in primary hyperparathyroidism. 141 26

Despite extensive study since the first report of familial benign hypercalcemia (FBH, or hypocalciuric hypercalcemia) in 1972, there is no evidence of the specific abnormal gene product. FBH is highly suitable for either a candidate gene or a reverse genetics approach to localizing the genetic abnormality, because it is inherited in an autosomal dominant pattern, is highly penetrant, does not affect survival, and can be diagnosed in families with readily available measurements. Importantly, several candidate genes have been cloned and mapped. Therefore, we collected blood samples and extracted leukocyte DNA from 94 members of 4 families with well documented FBH (44 affected, 45 unaffected, and 5 unclassifiable). We digested the DNA samples with various restriction endonucleases, conducted standard Southern blotting, and searched for restriction fragment length polymorphisms for the following candidate genes (probe names in parentheses): multiple endocrine neoplasia (MEN) type 1 (pMCMP.1, pHBI59, p3C7, and pTHH26), MEN 2a (MCK2 and cTB14.34), basic fibroblast growth factor (pHFL1-7), (Ca2+,Mg2+)ATPase isoform 4 (hPMCA4), membrane Na/Ca exchanger (cNC28 M-A), PTH (pPTH-LF), and calbindin-D28K (pSKCalb). In addition, we used the anonymous variable number tandem repeat marker pYNH24 to verify pedigree structures by excluding misinheritances. Data were analyzed using the Linkage program. For none of the genes was there significant linkage with the FBH trait; logarithm of odds scores ranged from -1.3 to -26.0 at a recombination fraction of 0.001, and from 0.6 to -5.6 at a recombination fraction of 0.10. We conclude that FBH is unrelated to the MEN syndromes and is not caused by mutations in any of the calcium-regulating or -binding proteins or growth factors studied thus far.
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PMID:Genetic linkage analysis in familial benign hypercalcemia using a candidate gene strategy. I. Studies in four families. 151 76

The recent advances in molecular biology and cytogenetics have made it possible to localize, clone and characterize some of the genetic abnormalities which result in disorders of phosphate and calcium homeostasis. Thus, the genes causing X-linked hypophosphataemic rickets, Lowe syndrome, X-linked recessive hypoparathyroidism, Di George syndrome, multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 2 and vitamin D-dependent rickets type I have been mapped. In addition the genes involved in the pathogenesis of the humoral hypercalcaemia of malignancy, vitamin D-dependent rickets type II, pseudohypoparathyroidism, and some of the autosomal forms of hypoparathyroidism have been cloned and the mutations characterized. The molecular and genetic studies which have mapped and identified these disease genes are described and the implications of these developments in clinical practice and in further elucidation of the mineral metabolic defects are discussed.
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PMID:Molecular genetics of mineral metabolic disorders. 152 19

Among 2000 descendants of an English immigrant to Tasmania, Australia, the diagnosis of multiple endocrine neoplasia type 1 was found to be very highly probable or highly probable in 130 and moderately probable in 22. Another 242 children and siblings were 50% likely to have inherited this dominant gene. In all age groups, especially the elderly, the majority of affected members had symptoms of only one endocrine disorder or were asymptomatic. In teenagers, the most common presentation was pituitary lesions and the second most common presentation was insulinomas. Frequently, pituitary lesions or insulinomas developed before any parathyroid lesions could be detected. Elevation of gastrin levels, usually associated with hypercalcemia, was rarely seen in patients younger than 25 years. The classic presentation with symptoms of multiple endocrinopathy may represent only a small fraction of these patients in the community.
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PMID:The natural history of multiple endocrine neoplasia type 1. Highly uncommon or highly unrecognized? 167 2

A review of 106 patients with multiple endocrine neoplasia (MEN) type 1 reported between 1966-1989 in Japan was conducted in order to clarify the natural history of this disease. Sporadic MEN 1 was found in 61 patients, and familial MEN 1 was found in 45 patients from 15 families. The mean ages at diagnosis of the two groups were 46.2 and 41.3 years, respectively, and the male to female ratio was 3:4. With regards to the involvement of the pituitary, parathyroid and endocrine pancreas, the combination of three endocrine glands was 31%, and that of two was 48%, in which the pituitary, parathyroid and endocrine pancreas had tumorous lesions in 60%, 88% and 63%, respectively. The first clinical manifestations of MEN 1 were the symptoms of hyperparathyroidism (32%), pituitary tumors (26%), peptic ulcer (28%) and hypoglycemia (13%). These symptoms appeared between 6 and 57 years of age (mean 34 years). The main clinical symptoms of the pituitary tumors were acromegaly and gigantism (37%), galactorrhea-amenorrhea syndrome (20%), Cushing's disease (10%) and visual disturbance due to compression of the tumor (20%). The clinical manifestations of hyperparathyroidism were mainly asymptomatic hypercalcemia (41%), nephrolithiasis (42%) and osteitis fibrosa (5%). In the patients with pancreatic tumor, Zollinger-Ellison syndrome (52%) and hypoglycemic symptoms (42%) were found. Tumors in the adrenal cortex, thyroid, carcinoid and lipoma were detected in association with MEN 1 in the frequencies of 28%, 21%, 9% and 5%, respectively. Death was reported in 37 patients between 9 and 86 years of age (mean 50.0 years). The cause of death was gastrointestinal bleeding and perforation (45%), surgery (24%) and disseminated carcinomatosis (18%). Recently, the gene predisposing to this syndrome has been assigned to chromosome 11 (11q13) in non-Japanese cases but not yet in Japanese MEN 1 patients.
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PMID:[Clinical characteristics in multiple endocrine neoplasia type 1 in Japan: a review of 106 patients]. 167 21

The differential diagnosis of hypercalcemia has expanded to over 25 separate disease states, with primary hyperparathyroidism and malignancy accounting for 80-90% of all hypercalcemic patients. Primary hyperparathyroidism comprises the majority of hypercalcemic patients among the ambulatory population, but malignancy accounts for up to 65% of such patients in the hospital. Factors favoring primary hyperparathyroidism include a family history of hyperparathyroidism or multiple endocrine neoplasia, a history of childhood radiation to the head and neck, the postmenopausal state, a history of renal calculi or peptic ulcer, hypertension, the induction of hypercalcemia by thiazides, or an asymptomatic patient with a prolonged, stable mild hypercalcemia. The usefulness of the serum calcium, parathyroid hormone, chloride, phosphorus, serum 25-OHD, and 1,25-(OH)2D, and urinary calcium in the differential diagnosis of hypercalcemia is discussed. The pitfalls of an excessive reliance on the serum PTH in diagnosing hyperparathyroidism are stressed. The discriminant values of the serum calcium, chloride, phosphorus, and parathyroid hormone are explored, with the serum parathyroid hormone, chloride, and calcium proving most useful in separating primary hyperparathyroidism from other forms of hypercalcemia. Multivariate discriminant analysis using the serum calcium, phosphorus, and chloride and the hematocrit achieves an accuracy of 95-98% and is the most economical method of identifying hyperparathyroidism. The addition of the amino-terminal or intact PTH assay increases the accuracy to 99% and is essential in the presence of renal insufficiency.
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PMID:Differential diagnosis of hypercalcemia. 176 70

The nuclear DNA content of paraffin-embedded parathyroid tumors from 49 patients with proven primary hyperparathyroidism was determined by flow cytometric analysis. The lesions included 14 primary and 11 locally recurrent or metastatic lesions from 16 carcinoma patients, 28 single adenomas from 28 patients, and 15 hyperplastic glands from five patients with familial multiple endocrine neoplasia type 1. No abnormal DNA stemline was found in any of the hyperplastic glands. One (3.6%) of the adenomas was aneuploid. There was no difference in ploidy patterns between the primary and recurrent lesions of the carcinomas and five (31%) of the carcinomas expressed aneuploidy. Four of the five patients with aneuploid carcinoma had recurrences including pulmonary metastases. One of them died of this disease 12 years after the initial operation, and all except one of the others are hypercalcemic even after removal of the successive recurrent or metastatic tumors. Of the 11 patients with diploid carcinoma, four had either local recurrence or pulmonary metastasis. Two of them are living with normocalcemia 3 and 6 years, respectively, after removal of the recurrent tumors and the others are alive with mild hypercalcemia. The remaining seven patients with diploid carcinoma, however, have no recurrence 2 to 5 years after the initial operation. Thus aneuploid parathyroid carcinomas are likely to show more malignant behavior than those with a diploid DNA pattern. All of the patients with adenoma and hyperplasia have been normocalcemic after a mean follow-up interval of 37 months. This study indicates that flow cytometric analysis of nuclear DNA content is a valuable adjunct to histologic examination in the diagnosis of parathyroid carcinoma and the prediction of the clinical outcome.
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PMID:Flow cytometric DNA analysis of parathyroid tumors with special reference to its diagnostic and prognostic value in parathyroid carcinoma. 196 27


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