Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Background: Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTH-rP) are two potent hypercalcemic hormones that act on the same targets. Autonomous secretion of the former is involved in primary hyperparathyroidism (PHPT), whereas the latter is responsible for humoral hypercalcemia of malignancy (HHM). Methods: From 250 consecutive, hypercalcemic serum samples sent to our laboratory for assessment of intact PTH, we were able to obtain clinical information, as well as an additional plasma sample for PTH-rP measurement, in 134 patients. At the time of sampling, patients could be classified into seven groups: cancer without known bone metastases (CaNoMeta, n=36), cancer with bone metastases (CaMeta, n=9), no evidence of cancer (noEvCa, n=71), sarcoidosis (Sarc, n=3), end-stage renal disease (ESRD, n=12), vitamin D overdose (VIT-D, n=2), and hyperthyroidism (Thyr, n=1). Results: In the CaNoMeta group, 29/36 patients had elevated PTH-rP levels, 9/36 patients had inappropriately elevated PTH levels, and 5/36 had elevated levels of both hormones. In the CaMeta group, three of the nine patients had inappropriately elevated PTH levels, two of them with concomitantly elevated PTH-rP levels. In the NoEvCa group, 63/71 patients had an inappropriate elevation of PTH levels and were diagnosed as having PHPT. Four of the 71 patients had elevated levels of both PTH and PTH-rP; three of them were in poor health and died within a short period of time. All of the ESRD patients had very high PTH and normal PTH-rP levels, except for one woman with high PTH-rP and undetectable PTH levels; she died from what later turned out to be a recurrent bladder carcinoma. In the Sarc, Vit-D, and Thyr groups, both PTH and PTH-rP levels were normal. Conclusions: (1) Elevated PTH-rP levels are a common finding in cancer patients without bone metastases. Intact PTH, however, should always be measured in hypercalcemic patients with malignancy because concurrent primary hyperparathyroidism is not rare. (2) Primary hyperparathyroidism accounts for hypercalcemia in 90% of patients without evidence of cancer whose PTH-rP levels may also be found to be elevated in a few cases, even some with surgically demonstrated parathyroid adenoma.
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PMID:Diagnostic approach to hypercalcemia: relevance of parathyroid hormone and parathyroid hormone-related protein measurements. 1139 97

The etiology, pathophysiology, and diagnosis of hypercalcemia associated with malignant diseases are discussed. In humans, calcium is controlled by three mechanisms: parathyroid hormone, which regulates bone resorption and renal reabsorption of calcium; calcitonin, an antagonist of parathyroid hormone; and cholecalciferol, which regulates calcium absorption from the gastrointestinal tract. Hypercalcemia of malignancy (HCM) results primarily from increased bone resorption by osteoclasts and, to a lesser extent, from increased renal tubular reabsorption. In most tumors, parathyroid hormone-related protein (PTHrP) is the primary mediator of calcium. PTHrP stimulates increased bone resorption by osteoclasts. This stimulation also activates transforming growth factor-beta (TGF-beta), which stimulates tumor cells, thus perpetuating the cycle. Hypercalcemia is usually defined as a serum calcium concentration greater than 12 mg/dL, corrected for the serum albumin concentration. In diagnosing HCM, it is important to rule out other causes of hypercalcemia, such as primary hyperparathyroidism.
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PMID:Overview of hypercalcemia of malignancy. 1175 5

To assess how two different serum markers of bone resorption may reflect changes in bone turnover, we compared age- and sex-related changes in serum C-terminal telopeptide of type I collagen (betaCTx) and tartrate-resistant acid phosphatase activity (TRAP) in 136 healthy men and 184 normal women. Serum levels of the two markers were also assessed in several groups of patients of both sexes presenting with the most common metabolic and endocrine bone diseases: established osteoporosis (n = 77), primary hyperparathyroidism (n = 44), glucocorticoid excess (n = 17), chronic renal failure (n = 39), active Paget's disease of bone (n = 5), humoral hypercalcemia of malignancy (n = 3), osteomalacia (n = 3), hyperthyroidism (n = 10), post-surgical hypoparathyroidism (n = 10), acromegaly (active disease, n = 8) and Cushing's syndrome (n = 10). In men the regression of betaCTx with age showed an initial decrease in bone resorption followed by an increase thereafter, starting from the sixth decade of life. No age-related change in serum TRAP activity was observed. In women, by contrast, a slight but significant linear correlation of both serum betaCTx and TRAP with age (r = 0.223, p<0.003 and r = 0.333, p<0.0001, respectively) was found, the two markers being positively correlated (r = 0.238, p<0.002). In each class of patients the mean Z-scores of betaCTx were significantly higher than those of TRAP activity. Moreover, compared with normal subjects, serum betaCTx seems to be characterized by a superior sensitivity relative to TRAP measurement, at least in the disorders studied.
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PMID:Gender differences in serum markers of bone resorption in healthy subjects and patients with disorders affecting bone. 1190 26

Parathyroid hormone-related protein (PTHrP) and PTH share the common PTH/PTHrP receptor. Although an elevated level of circulating PTHrP in patients with malignancies causes hypercalcemia as does PTH, chronic and systemic effects of PTHrP on bone metabolism in humans are not well understood because tumor-burden patients showing hypercalcemia usually have a poor prognosis. We investigated bone and calcium metabolism in a patient with malignant islet cell tumors showing hypercalcemia due to the elevated plasma PTHrP level for 7 years. Hypercalcemia and hypercalciuria continued throughout the clinical course in spite of frequent infusions of bisphosphonates. Bone resorption markers and a bone formation marker were consistently elevated as seen in primary hyperparathyroidism, a disease caused by an autonomous hypersecretion of PTH. Based on biochemical measurements including bone markers and serum 1,25-dihydroxyvitamin D, the clinical features of this case essentially are the same as those of primary hyperparathyroidism except for the elevated level of plasma PTHrP with suppressed intact PTH level. Therefore, it is suggested that chronic and systemic effects of PTHrP on bone as well as calcium metabolism are indistinguishable from those of PTH in human.
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PMID:Parathyroid hormone-related protein induced coupled increases in bone formation and resorption markers for 7 years in a patient with malignant islet cell tumors. 1200 5

Bisphosphonates (BP) are pyrophosphate analogs that include very potent inhibitors of bone resorption. BPs act directly on the osteoclast, suppressing isoprenylation by inhibiting farnesyl diphosphate synthase in the cholesterol pathway, which causes osteoclast inactivation. BPs should therefore reduce the bone loss produced by any cause, including hyperparathyroidism and hypercalcemia of malignancy (MIH), caused by parathyroid hormone (PTH) and PTH-related protein (PTHrP), respectively. BPs at higher doses than used in osteoporosis are indeed the treatment of choice for malignancy-induced hypercalcemia. Limited, but convincing, data show that BPs at doses effective in osteoporosis also reverse bone loss associated with mild primary hyperparathyroidism (PHPT).
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PMID:Bisphosphonates and primary hyperparathyroidism. 1241 93

In lung cancer patients, hypercalcemia is a fairly common metabolic problem associated with malignancy. However, the occurrence of hypercalcemia in lung cancer patients means an ominous prognostic sign. As hypercalcemia often causes early death, quick diagnosis and treatment for hypercalcemia are required. A 69-year-old woman was admitted to our hospital with anorexia caused by hypercalcemia. On admission, serum level of PTH was elevated and PTHrP was normal. From the results of CT findings and transbronchial lung biopsy, the cause of the hypercalcemia was determined as lung cancer incidentally complicated with primary hyperparathyroidism. First, serum calcium level was returned to normal through hydration with saline and bisphosphonates. Next, left hemithyroidectomy for primary hyperparathyroidism was performed. Histologically, the tumor was diagnosed as parathyroid adenoma. Fifteen days later, left lower lobectomy for primary lung cancer was performed under a video-assisted thoracoscopic approach. Histologically, the tumor was diagnosed as a moderately differentiated adenocarcinoma. Four years and three months after the operation, the patient is alive and well with no sign of recurrence. When a lung cancer patient is complicated with hypercalcemia, we need to consider that primary hyperparathyroidism is a possible cause of the hypercalcemia.
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PMID:A case of lung cancer with hypercalcemia which was incidentally complicated with primary hyperparathyroidism due to parathyroid adenoma. 1247 97

During an annual physical examination, a middle-aged adult female olive baboon (Papio anubis) in the time-mated breeding colony at the Biologic Resources Laboratory at the University of Illinois at Chicago was found to have a high serum calcium value (> 12 mg/dl). To determine the cause of the hypercalcemia, additional diagnostic tests, including thoracic and abdominal radiographs and a parathyroid panel (parathyroid hormone (PTH), ionized calcium, and parathyroid hormone-related protein (PTH-rp) assays), were performed. The radiographs did not reveal lesions suggestive of neoplasia. A parathyroid panel was obtained twice. Both times the PTH (23.4 and 46.4 pmol/L, normal = 2.91 to 4.57 pmol/L) and ionized calcium (1.68 and 2.10 mmol/L, normal = 1.31 to 1.37 mmol/L) were increased above values for adult females with normal calcium concentration. A tentative diagnosis of primary hyperparathyroidism was made. After a gamma-radiation scan and magnetic resonance imaging of the neck were done, exploratory surgery was performed to identify and remove the affected gland. After gland removal, the baboon's serum calcium, PTH (1.6 pmol/L), and ionized calcium (1.59 mmol/L) values decreased. Results of histologic examination confirmed the diagnosis of benign solitary parathyroid adenoma.
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PMID:Primary hyperparathyroidism in an adult female olive baboon (Papio anubis). 1254 Jan 72

PTH and PTH-related protein (PTHrP) cause primary hyperparathyroidism and humoral hypercalcemia of malignancy (HHM), respectively. These syndromes are similar in several important ways, but differ in several characteristic, yet unexplained, ways. Two of the unresolved questions in HHM and hyperparathyroidism involve renal physiology. 1) Why does renal proximal tubular production of 1,25-dihydroxyvitamin D [1,25-(OH)(2)D] differ between the two syndromes? 2) Do distal tubular calcium responses to PTH and PTHrP differ in the two syndromes? To address these questions, we compared the two peptides, human PTH-(1-34) and PTHrP-(1-36), in a direct, head to head study using a continuous, steady state infusion of each peptide at the same dose in normal human volunteers for 46 h. We had previously described such methods as applied to PTHrP, but a direct multiday comparison of PTHrP to PTH has not previously been reported. In two groups (seven subjects each) of healthy young (25- to 35-yr-old) normal volunteers, PTH and PTHrP infused at 8 pmol/kg.h displayed similar calcemic effects, although PTH was slightly more potent in this regard. Both peptides also displayed similar phosphaturic effects. In addition, both peptides had similar effects on renal tubular calcium handling, yielding fractional calcium excretion values of approximately 3.5%, some 50% below the values (6.5%) observed in subjects rendered similarly hypercalcemic by the infusion of calcium. In contrast to these several quantitatively similar effects of PTH and PTHrP, PTH tended to be selectively more effective than PTHrP in stimulating renal production of 1,25-(OH)(2)D. These studies indicate that renal tubular calcium reabsorption is likely to contribute to hypercalcemia in patients with HHM. In addition, PTH may be selectively more effective than PTHrP in stimulating 1,25-(OH)(2)D production, in contrast to its phosphaturic, calcemic effects and its effects to stimulate nephrogenous cAMP excretion and renal tubular calcium reabsorption.
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PMID:Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1-36) [hPTHrP-(1-36)] versus hPTH-(1-34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers. 1267 45

Parathyroid hormone (PTH) and PTH-related protein/peptide (PTHrP) bind to the same PTH/PTHrP receptor and stimulate osteoblasts to secrete pro-inflammatory cytokines like interleukin (IL)-6. In patients with primary hyperparathyroidism, elevation of plasma levels of tumor necrosis factor (TNF)-alpha and IL-6 was also described. We, therefore, postulated that PTHrP secreted from cancer cells stimulates the secretion of cytokines and causes increases in their blood levels. Blood concentrations of several cytokines (TNF-alpha, IL-1beta, IL-5, IL-6, IL-8, IL-11 and IL-12) in cancer-bearing patients with or without elevation of blood PTHrP were measured by ELISA. The patients with high plasma PTHrP levels (n=29, intact PTHrP: 8.5 +/- 1.4 pmol/l, normal: <1.1) had higher serum type 1 collagen C-telopeptide (ICTP). Twenty of the patients were hypercalcemic. Plasma concentrations of TNF-alpha, IL-6 and IL-8 were significantly increased in patients with high PTHrP, in either the presence or absence of hypercalcemia. The concentrations of TNF-alpha and IL-6 were also significantly correlated with those of PTHrP. Our observations indicate that high plasma levels of PTHrP in cancer-bearing patients contribute not only to the development of hypercalcemia, but also to the development of the syndrome caused by an excess of pro-inflammatory cytokines.
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PMID:Elevation of circulating plasma cytokines in cancer patients with high plasma parathyroid hormone-related protein levels. 1450 17

A differential diagnosis for hyperparathyroidism includes all causes of hypercalcemia; the primary causes of which are primary hyperparathyroidism and humoral hypercalcemia of malignancy. Benign familial hypocalciuric hypercalcemia is a rare condition of primary importance because failure to recognize this entity leads to unnecessary surgery. There are a plethora of other rare causes of hypercalcemia that can be distinguished from primary hyperparathyroidism by history and laboratory profiles. This article discusses the main and less common causes of hypercalcemia and provides guidance for distinguishing among them.
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PMID:Hypercalcemic hypocalciuria: a critical differential diagnosis for hyperparathyroidism. 1526 23


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