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)

To determine the effect of thyroid-stimulating hormone (TSH) on secretion of calcitonin by the thyroid, 50 male Sprague-Dawley rats were randomly separated into seven groups. The groups received different diets, medications, or operations [propylthiouracil (PTU), iodine-deficient diet, (LID), acute or chronic thyroxine treatment, sham operation (SO), hemithyroidectomy (Htx), and total thyroidectomy (Ttx)]. two weeks to six months later, serum TSH concentrations were increased in the Htx, Ttx, and LID groups when compared with SO animals. Serum calcitonin concentrations were increased in the LID- and PTU-treated groups and were decreased in animals that chronically received thyroxine. Serum calcium concentrations were increased in the LID animals, decreased in the Ttx animals, and were similar in the other groups. These findings suggest that TSH stimulates both follicular and parafollicular cells in the rat thyroid and that iodine deficiency causes hypercalcemia and hypercalcitonemia.
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PMID:Iodine deficiency produces hypercalcemia and hypercalcitonemia in rats. 64 56

Review of medical records in 600 consecutive cases of primary hyperparathyroidism revealed 10 patients with a documented history of iodine 131 (131I) treatment. In seven cases 131I had been given because of Graves' disease and in three cases for ablation of thyroid remnants after tumor operations. All but one of the patients were women. Their age at the time of 131I treatment ranged from 21 to 72 years, and the interval to detection of hypercalcemia was between 3 and 27 years. It is noteworthy that all patients treated for Graves' disease had absorbed radiation doses large enough to cause permanent hypothyroidism, and half of them showed complete absence of the thyroid gland at subsequent operation for hyperparathyroidism. Furthermore, parathyroid adenomas had developed at the sites of thyroid remnants in cases with 131I ablation after tumor operations. Our findings support other observations indicating that not only external radiation but also radiation from 131I is a risk factor for development of hyperparathyroidism, and it is emphasized that age at the time of radiation treatment may be of decisive importance in this context.
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PMID:Hyperparathyroidism after treatment with radioactive iodine: not only a coincidence? 258 8

Bone metastasis from a thyroid papillary cancer of a 59-year-old woman had been successfully treated with radiotherapy (6,000 rad) and iodine-131 (120 mCi). One year later, the patient developed leukocytosis (maximum 143,000/mm3) and hypercalcemia (16.0 mg/dl). A colony stimulating factor (CSF) was detectable in her plasma, and nude mice that had been given metastatic tissues similarly developed leukocytosis and hypercalcemia. Leukocytosis and hypercalcemia seemed to have been caused by the CSF produced in the bone metastasized tissues of this thyroid cancer.
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PMID:[A case report of thyroid papillary cancer that manifested leukocytosis and hypercalcemia after radiotherapy in bone metastasis]. 264 65

The mammalian thyroid gland is composed of 2 distinct endocrine cell populations concerned with the synthesis of 2 different classes of hormones. Follicular cells secrete the metabolically active iodothyronines whereas the C-(parafollicular) cells are concerned with the production of calcitonin, a hormone that influences blood levels of calcium and phosphorus, and bone cell metabolism. The synthesis of metabolic thyroid hormones is different than in other endocrine glands because the final assembly of hormone occurs within the follicular lumen. This extracellular synthesis of thyroid hormones is made possible by thyroglobulin, a glycoprotein synthesized by follicular cells. The secretion of thyroid hormones under the influence of pituitary thyrotrophin (TSH) from stores in the luminal colloid is initiated by elongation of microvilli and formation of pseudopods. FD&C Red No. 3 is a tetraiodinated derivative of fluorescein which in lifetime studies increases the incidence of thyroid follicular cell adenomas in male Sprague-Dawley rats. The striking changes in circulating levels of thyroid hormones and morphologic evidence of follicular cell stimulation are the result of alterations in the peripheral metabolism of thyroxine. An inhibition by FD&C Red No. 3 of 5'-deiodinase in the liver and kidney would explain the lower serum triiodothyronine (T3) levels. The pituitary, sensing the lowered circulating levels of T3, increased the secretion of thyroid stimulating hormone which resulted in the morphologic evidence of follicular cell stimulation in the long-term studies. Other xenobiotics increase the incidence of thyroid tumors in rodents by a direct effect on the thyroid gland to disrupt 1 of 3 or more possible steps in the biosynthesis of thyroid hormones. Physiologic perturbations alone, such as iodine deficiency or partial thyroidectomy, can disrupt thyroid hormone economy in rodents and, if sustained, increase the development of thyroid tumors. The wide variety of drugs, chemicals, and physiologic perturbations which increase thyroid tumor development appear to act through a secondary (indirect) mechanism to promote tumor development by causing a long-standing hypersecretion of thyroid stimulating hormone. Nodular and/or diffuse hyperplasia of C-cells occurs with advancing age in many strains of laboratory rats and in response to long-term hypercalcemia in certain animal species and human beings. Focal or diffuse hyperplasia often precedes the development of C-cell neoplasms. Radiation and the feeding of diets high in vitamin D resulting in hypercalcemia have been reported to increase the incidence of C-cell tumors in rats.
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PMID:The effects of xenobiotics on the structure and function of thyroid follicular and C-cells. 267 79

In an attempt to better define hyperplasia from adenoma and for more accurate discernment of grossly normal but histologically abnormal presumed hyperfunctioning gland, parathyroid tissue obtained at operation was subjected to flow cytometric analysis producing DNA histogram. Seventeen abnormal specimens and seven normal specimens obtained from parathyroidectomy cases were placed in RPMI 1640 culture medium, treated to produce a monodispersed cell suspension, and stained with propidium iodide fluorescent dye to provide a measure of DNA content that could be graphically demonstrated. All cell cycles for affected cell populations could be demonstrated on DNA histogram in the G0G1, S, and G2M phases. Proliferative index was arbitrarily derived by combining percentages of G2M plus S phases. It was apparent that the value so derived showed a tendency for higher value for the abnormal parathyroid tissue but the overlap was sufficient so that no specific discriminating value could be placed on DNA histogram. While flow cytometry may not be of significant use in intraoperative identification of abnormal parathyroid tissue, the values obtained may indicate that a spectrum of activity occurs in hyperparathyroidism that cannot be fully appreciated at the present time and that may in the light of incomplete knowledge manifest itself in the clinical state of hyperparathyroidism and hypercalcemia. The findings of our flow cytometry study may indeed lend credence to the view that all hyperparathyroidism represents a four-gland hyperfunction although this does not support as a consequence routine subtotal parathyroidectomy but should stimulate further inquiry into the pathogenesis of primary hyperparathyroidism.
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PMID:DNA histogram of parathyroid tissue in determining extent of parathyroidectomy. 407 81

There is an increasing use and variety of beta-adrenoceptor blocking agents (beta-blockers) available for the treatment of hyperthyroidism. Recent comparative studies suggest that atenolol (200mg daily), metoprolol (200mg daily); acebutolol (400mg daily), oxprenolol ( 160mg daily), nadolol ( 80mg daily) and timolol (20mg daily) produce a beneficial clinical response equal to that seen with propranolol ( 160mg daily). Most beta-blockers reduce resting heart rate by approximately 25 to 30 beats/min, although a lesser reduction is seen with those possessing intrinsic sympathomimetic activity such as oxprenolol and pindolol. While earlier studies employing large doses of intravenous propranolol concluded that beta-blockade reduced myocardial contractility, more recent non-invasive studies suggest that the predominant cardiac effect is on heart rate. In patients with cardiac failure, beta-blockers may, however, produce a profound fall in cardiac output. Nevertheless, in combination with digoxin they may be useful in controlling the atrial fibrillation of thyrocardiac disease. beta-Blockers improve nervousness and tremor (although to a lesser extent with cardioselective agents) and severe myopathy, and they also reduce the frequency of paralysis in patients with thyrotoxic periodic paralysis. There is often subjective improvement in sweating but usually no major effect on eye signs. Recent studies show a 10% reduction in oxygen consumption/basal metabolic rate with long term oral use of selective or nonselective beta-blockers. In addition, many agents (propranolol, metoprolol, nadolol and sotalol but not acebutolol, atenolol or oxprenolol) reduce circulating tri-iodothyronine (T3) concentration by between 10 and 40%, although the clinical significance of this effect (if any) is not established. beta-Blockers may also have endocrinological effects on gastrin, cyclic AMP, catecholamines and other hormone levels. Given in adequate dosage, propranolol has been shown to control thyrotoxic hypercalcaemia. Minor side effects (nausea, headaches, tiredness, etc.) are quite common but overall beta-blockers are well tolerated by the thyrotoxic patient. The major use of these drugs is in symptomatic control while awaiting definitive diagnosis or treatment. As an adjunct to antithyroid drugs or radioactive iodine, beta-blockers will produce a satisfactory clinical response in the weeks to months before these forms of therapy produce a euthyroid state. beta-Blockers are more convenient than antithyroid drugs in the control of patients receiving therapeutic radioiodine, in that continuous therapy and assessment of biochemical response is possible.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Use of beta-adrenoceptor blocking drugs in hyperthyroidism. 614 1

Herein we report a 36-year-old man with hyperparathyroidism and a past history of internal irradiation to the thyroid. Twelve years previously at age 24 years he had received 8 mCi of radioactive iodine for Graves' disease. An additional dose of 4 mCi was required 3 years later. A right lower parathyroid adenoma (28 X 23 X 20 mm, 5.7 g) was found at neck exploration. Although the association of external ionizing radiation to the head and neck and the subsequent development of hyperfunctioning parathyroid glands has been described in recent years, there are only 4 cases in the literature of parathyroid surgery for hyperparathyroidism secondary to earlier treatment with radioactive iodine for Graves' disease. In a long-term follow-up of 180 patients treated with radioactive iodine for Graves' disease, neither hypercalcemia nor hypophosphatemia was found. Whether internal radiation therapy can be a causative factor in the development of hyperparathyroidism should be elucidated in future. However, it seems reasonable to suggest that patients whose hyperthyroidism has been treated with radioactive iodine should have their serum calcium levels examined at 5-year intervals.
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PMID:[Hyperparathyroidism after radioactive iodine therapy for Graves' disease: a case report]. 668 66

A 24-year-old man with anorexia, repeated bouts of vomiting, and wasting was found to have florid thyrotoxicosis and hypercalcaemia. Pamidronate promptly reduced the serum calcium concentration to normal, and simultaneously abated the abdominal symptoms, which did not recur in spite of continuing severe hyperthyroidism, which was eventually controlled by radioactive iodine ablation of thyroid activity.
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PMID:Abdominal symptoms, hypercalcaemia and apathetic hyperthyroidism: treatment with pamidronate. 774 97

The cholecalciferol analogues 1(S),3(R)-dihydroxy-20(R)-[3'(S)-cyclopropyl-3'-hydroxyprop-1'(E)- enyl]-9,10-secopregna-5(Z),7(E),10(19)-triene (calcipotriol, MC 903), 1(S),3(R)-dihydroxy-20(R)-[3'-ethyl-3'-hydroxy- pentoxy]-9,10-secopregna-5(Z),7(E),10(19)-triene (KH 1060) and 1(S),3(R)-dihydroxy-20(R)-[5'-ethyl-5'-hydroxy-hepta- 1',3'(E)-diene-1'-yl]-9,10-secopregna-5(Z),7(E),10(19)-triene (EB 1089) have been modified in the side chain to increase their effects on cell differentiation and proliferation and to reduce the risk of inducing hypercalcemia. The effects of these analogues were tested on FRTL-5 cells, a strain of continuously growing and well-differentiated rat thyroid cells. FRTL-5 cells express a normal vitamin D receptor (VDR), and 1,25-(OH)2D3 potently attenuates the thyrotropin (TSH) stimulated production of the intracellular signalling molecule 3',5'-cyclic adenosine monophosphate (cAMP), iodide uptake and cell growth of these cells. These effects were also induced by the cholecalciferol analogues after 4 days of incubation. KH 1060 was the biologically most potent of the analogues and, compared to KH 1060, the IC50 values were 1.2-, 2.7- and 14-fold higher when 1,25-(OH)2D3, EB 1089 and MC 903, respectively, were used for the displacement of receptor bound [3H]1,25-(OH)2D3. As indicated by their VDR binding, 1,25-(OH)2D3 and EB 1089 were equipotent inhibitors of the TSH stimulated adenylyl cyclase activity, iodide uptake and FRTL-5 cell growth. The analogue MC 903 was the second most potent inhibitor of cell growth in spite of expressing the lowest affinity for the VDR and the weakest inhibition of TSH-stimulated adenylyl cyclase activity and iodide uptake. In conclusion, the biological effects of these cholecalciferol analogues in rat thyroid FRTL-5 cells seem to be mainly determined by their binding affinity for the VDR, although non-genomic effects can not be excluded.
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PMID:Vitamin D receptor binding and biological effects of cholecalciferol analogues in rat thyroid cells. 804 43

Iodide transport defect (ITD) is a rare disorder causing congenital hypothyroidism. We previously reported that homozygous T354P mutation in the sodium/iodide symporter (NIS) gene caused ITD. To clarify the prevalence of this mutation, artificial substitution introducing PCR followed by restriction enzyme analysis was developed as a rapid screening method to detect the T354P mutation. Three apparently unrelated families with ITD, one patient with low thyroidal 99mTc pertechnetate (99mTcO4-) uptake and 52 healthy controls (104 alleles) were analyzed for this mutation. All families with ITD harbored the mutation, suggesting that T354P is a recurrent mutation and a major cause of ITD. This was not a widespread mutation, because it was not detected in the 52 unrelated normal controls. Because two cases with homozygous T354P mutation developed multinodular goiters within their second decade of life though they had been maintained in euthyroid state, homozygous T354P mutation alone and/or low intrathyroidal iodide and high serum TSH level in early life might account for tumorigenesis. The patient with low thyroidal 99mTcO4- uptake did not harbor the T354P mutation. Because familial hypocalciuric hypercalcemia was also present in this family, a possibility of the combined abnormality of TSH receptor and calcium functions, which includes an abnormality around the G protein, may be examined further.
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PMID:Recurrent T354P mutation of the Na+/I- symporter in patients with iodide transport defect. 970 73


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