Familial medullary carcinoma of the thyroid, adrenal pheochromocytoma and parathyroid hyperplasia. A syndrome of multiple endocrine neoplasia.
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Adenoma↗
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Results for “parathyroid carcinoma”
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Prognostic value of immunocytochemical determination of parathyroid hormone-related peptide expression in cells of mammary ductal carcinoma. Analysis of 7 years of the disease course.
Parathyroid hormone-related peptide (PTHrP) participates in the development of humoral hypercalcaemia of malignancy. The peptide is thought to affect growth and differentiation of normal and neoplastic cells. The present study aimed at evaluation of the relationship between survival time and development of distant metastases in patients with ductal mammary carcinoma on the one hand and PTHrP expression on the other. Immunocytochemical reactions using mouse monoclonal (clone 212-10.7) anti-PTHrP (38-64) antibodies were performed in paraffin sections originating from 47 patients with ductal mammary carcinoma. Expression of the protein was quantified employing a scale, considering the number of positive cells and intensity of the reaction (immunoreactive score, IRS). Survival time of the patients, determined during the course of a 7-year observation was also analysed. The obtained results demonstrated a relationship between intensity of PTHrP expression and the survival time. Patients with high expression of PTHrP (IRS>6) manifested longer survival than patients with lower PTHrP expression (IRS< or =6; Cox'es F test, P<0.05). Moreover, in the group with the lower PTHrP expression, a negative relationship was detected between expression of the protein and the survival time (Cox'es model, P<0.05). No relationship was detected between PTHrP expression and the development of distant metastases.
Adult↗
Comparison of preoperative imaging techniques (thallium technetium scan and ultrasonography) and intraoperative staining (with methylene blue) in localizing the parathyroid glands.
We carried out a prospective study to compare the predictive value of preoperative thallium technetium scan, ultrasound (US) and intraoperative staining of the parathyroid glands (with methylene blue) in patients with parathyroid adenoma, parathyroid hyperplasia, thyroid carcinoma and thyrotoxicosis, in the Istanbul School of Medicine, Department of General Surgery. Methylene blue was given at a dose of 5 mg/kg/body weight in a 500 ml 5% Dextrose +0.9% saline solution 1 hour before surgery. All adenomas (10 patients), hyperplastic parathyroid glands (12 patients) and 45 of 52 suppressed glands (82%) were stained. In patients with thyroid carcinoma (7) and thyrotoxicosis (5), 42 of 48 normal parathyroid glands (87%) were stained. There were no maneuver-related complications. Thallium technetium scan (TT) accurately identified 10 of 10 (100%) parathyroid adenomas and 13 of 26 (50%) hyperplastic parathyroid glands. US successfully localized 10 of 10 (100%) adenomas and 18 of 26 (66%) hyperplastic glands. Neither technique was successful in identifying normal glands. The intraoperative identification of the parathyroid glands with methylene blue was found to be an effective, safe and cost-effective technique which helps the surgeon in the dissection and shows abnormal parathyroid glands more accurately than preoperative imaging techniques.
Adult↗
Immunohistochemical detection of parathyroid hormone-related protein in a squamous cell carcinoma arising from mature cystic teratoma causing humoral hypercalcemia of malignancy.
BACKGROUND: Humoral hypercalcemia of malignancy is a cancer-related hypercalcemia caused by the production of humoral factors by malignant cells in patients without bone metastases. Squamous cell carcinomas are the tumors most frequently associated with humoral hypercalcemia of malignancy, and parathyroid hormone-related protein (PTH-rP) is the main humoral factor implicated. Squamous cell carcinoma arising from mature cystic teratoma is a rare diagnosis itself, much less the description of associated hypercalcemia, despite the fact that the normal keratinocytes produce parathyroid hormone-related protein. CASE: We present a well-documented case of squamous cell carcinoma arising from mature cystic teratoma of the ovary, complicated by hypercalcemia in a patient with high levels of plasma parathyroid hormone-related protein and immunohistochemical evidence of parathyroid hormone-related protein expression by the tumor cells. CONCLUSION: In this case, the carcinoma cells had already produced PTH-rP in the primary tumor although the serum calcium levels had not been significantly high at surgery. It is therefore suggested that hypercalcemia may have occurred after PTH-rP production had overcome the homeostatic level during the terminal stage.
Aged↗
Increased parathyroid hormone-related peptide in patients with hypercalcemia associated with islet cell carcinoma.
OBJECTIVE: To report the high prevalence of increased parathyroid hormone-related peptide (PTHrP) in patients with islet cell carcinoma and associated hypercalcemia. DESIGN: We conducted a retrospective study of PTHrP levels in patients with hypercalcemia and eucalcemia associated with islet cell carcinoma and compared these findings with those in healthy subjects. MATERIAL AND METHODS: Using a sensitive PTHrP immunochemiluminometric assay, we measured PTHrP levels in 17 patients with islet cell carcinoma and 110 healthy subjects. The differences between PTHrP levels in patients with normal and those with high serum calcium concentrations were analyzed statistically. RESULTS: PTHrP levels were significantly higher (P < 0.01) in 10 patients with hypercalcemia and islet cell carcinoma (median, 14.0 pmol/L; range, undetectable to 40.1) than in 7 patients with eucalcemia and islet cell carcinoma (median, undetectable; range, undetectable to 1.3 pmol/L) or in the 110 healthy subjects (median, undetectable; range, undetectable to 4.2 pmol/L). The range of increased PTHrP levels in hypercalcemic islet cell carcinoma was 2 to 20 times the upper normal limit (2.0 pmol/L). Decreased PTHrP and serum calcium and increased parathyroid hormone levels were demonstrated in two patients after effective therapy. For all seven eucalcemic patients with islet cell carcinoma, PTHrP levels did not differ significantly from those in healthy subjects. CONCLUSION: PTHrP levels are increased in a substantial proportion of patients with hypercalcemia and islet cell carcinoma and seem to decrease after treatment of the underlying tumor. Measurement of PTHrP levels may be useful for confirming the diagnosis of hypercalcemia associated with malignant disease and for monitoring of therapy.
Adult↗
Hypercalcemia associated with parathyroid hormone-related protein at the terminal stage of uncomplicated squamous cell carcinoma in the head and neck region.
BACKGROUND: Parathyroid hormone-related protein (PTHrP) is mainly responsible for hypercalcemia in squamous cell carcinomas (SCCs). METHODS: We retrospectively checked the appearance of hypercalcemia among 33 patients who died with head and neck SCC. Serum concentrations of C-terminal region of PTHrP (C-PTHrP) were measured in 15 of them. The intracellular PTHrP expression was immunohistochemically stained in 42 SCC sections obtained from the 33 before the appearance of hypercalcemia. RESULTS: Hypercalcemia appeared in 24 of the 33, and increased serum C-PTHrP levels were confirmed in 11 of 12 hypercalcemic patients. PTHrP was identified in all SCC sections, and a stronger intensity than in normal squamous epithelia was observed in 50% of those obtained within 1 year before the onset of hypercalcemia. CONCLUSION: A high incidence of PTHrP-induced hypercalcemia was shown among patients dying with head and neck SCCs. The intracellular increase in PTHrP might be observed preceding hypercalcemia.
Adult↗
Syndrome resembling hyperparathyroidism associated with squamous cell carcinoma.
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Carcinoma↗
Parathyroid hormone-related protein in an esophageal squamous cell carcinoma with tumor-induced hypercalcemia.
Cancers from patients with tumor-induced hypercalcemia usually produce a circulating factor that mimics the parathyroid hormone activity, termed parathyroid hormone-related protein. Incidence of tumor-induced hypercalcemia appears to be high in patients with squamous cell carcinoma of the esophagus, and the presence of parathyroid hormone-related protein have been shown in some primary esophageal cancers. In the present study, we have investigated the presence of parathyroid hormone-related protein in a patient with metastasized squamous cell carcinoma of the esophagus complicated with tumor-induced hypercalcemia. Protein was searched by immunohistochemistry, and messenger RNA was investigated by reverse transcriptase-polymerase chain reaction and S1 nuclease assay. Both messenger RNA and protein were detected in hepatic metastases, whereas normal esophageal mucosa and primary cancer did not express detectable protein or messenger RNA using the S1 nuclease assay. Reverse transcriptase-polymerase chain reaction was positive in all these tissues, including normal esophageal mucosa. In conclusion, the present case suggests that tumor-induced hypercalcemia due to esophageal squamous cell carcinoma may be caused by parathyroid hormone-related protein mostly released by liver metastases.
Carcinoma, Squamous Cell↗
Humoral hypercalcemia of hepatocellular carcinoma associated with elevated levels of parathyroid-hormone-related-peptide.
Parathyroid-hormone-related-peptide (PTHrP) has been shown to be important in the pathogenesis of hypercalcemia of malignancy. The malignancies most commonly associated with hypersecretion of PTHrP include squamous cell carcinoma and breast cancer. The pathogenesis of hypercalcemia associated with hepatocellular carcinoma was evaluated in this study. Two male patients with hepatocellular carcinoma were found to have severe hypercalcemia at initial presentation. PTHrP was measured with radioimmunoassay in these two patients before treatment as well as in nine other patients with hepatocellular carcinoma but without hypercalcemia. The levels were markedly elevated in the two patients with hypercalcemia (29.3 and 32.1 pM), but were less than 5 pM in the nine patients without hypercalcemia. These results suggest that PTHrP was important in the pathogenesis of hypercalcemia associated with hepatocellular carcinoma in these men.
Journal Article↗
Hypercalcemia induced by parathyroid hormone-related peptide after treatment of squamous cell carcinoma of oral cavity.
Squamous cell carcinoma of the head and neck is a rare cause of humoral hypercalcemia of malignancy. This paraneoplastic syndrome is usually one of the presenting symptoms of the disease. We report a case of squamous cell carcinoma of the oral cavity that presumably elaborated parathyroid hormone-related peptide (PTH-rP) and caused hypercalcemia only after radiotherapy and chemotherapy.
Carcinoma, Squamous Cell↗
Parathyroid hormone immunohistochemistry in dogs with primary and secondary hyperparathyroidism: the question of adenoma and primary hyperplasia.
In primary hyperparathyroidism, calcium homeostasis is disrupted by excessive synthesis and secretion of parathyroid hormone (PTH), which is usually caused by a solitary adenoma, or less often by nodular hyperplasia or carcinoma of the parathyroid glands. So far, the distinction between these forms of primary hyperparathyroidism has been made by histological examination. In this report clinical and histological findings, including PTH immunohistochemistry, are described in five dogs with primary hyperparathyroidism, three dogs with secondary hyperparathyroidism due to chronic renal failure, and eight control dogs. In the dogs with primary hyperparathyroidism, nodular adenomatous hyperplasia was found in two animals and parathyroid adenoma in three. The dogs with chronic renal failure had diffuse parathyroid gland hyperplasia. The parathyroid glands of the control dogs and the inactive cells surrounding the hyperplastic nodules showed slight to moderate, localized, paranuclear PTH immunolabelling. In the primary nodular and secondary diffuse hyperplasia, all parathyroid cells had a diffuse cytoplasmic PTH labelling pattern, sometimes in combination with localized paranuclear labelling. In parathyroid adenoma, areas with either paranuclear labelling or diffuse cytoplasmic labelling were observed. As both parathyroid adenoma and primary nodular parathyroid gland hyperplasia have characteristics of intrinsic autonomy (i.e., suppression of the remaining endocrine tissue), there would seem to be no functional difference between the two abnormalities. It is argued that primary (multi)nodular hyperplasia is a multiple form of parathyroid adenoma.
Adenoma↗
A nationwide clinical survey of patients with multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma in Japan.
MEN (multiple endocrine neoplasia) type 2 syndrome is an inherited disease characterized by medullary thyroid carcinoma, pheochromocytoma, hyperparathyroidism and/or developmental anomalies. Germ-line mutations of the RET proto-oncogene have recently been identified as the underlying cause of the syndrome. Accordingly, several investigators have advocated prophylactic total thyroidectomy for medullary thyroid carcinoma at an early age in MEN 2 gene carriers identified by DNA analysis. Before applying this strategy in Japan, the biological behavior of each category of tumor in MEN 2 syndrome, and medullary thyroid carcinoma in particular, should be well understood. We conducted a nationwide questionnaire survey to clarify the clinicopathological features of MEN 2 in Japan, obtaining data for 230 patients diagnosed as having MEN 2. They included 84 males and 146 females, with a median age of 37.5 years (range 5-83). Patients were categorized as 179 with MEN 2A, 17 with MEN 2B, 12 with familial medullary thyroid carcinoma and 22 'other'. Medullary thyroid carcinoma, pheochromocytoma and parathyroid lesions occurred in 224 (97%), 132 (57%) and 25 (11%) patients respectively. Twelve patients (5.2%) died of medullary thyroid carcinoma and 11 patients died of other or unknown causes. Of 163 patients for whom follow-up data were obtained, 82 (50%) experienced recurrences of medullary thyroid carcinoma, including symptomatic recurrent tumors in 24 patients and elevated calcitonin levels alone in 54. In the era of RET mutational analysis for screening relatives of patients with MEN 2, these data provide useful information about surgical management for patients with MEN 2 in Japan.
Adolescent↗
Hypercalcaemia and elevated levels of parathyroid hormone-related protein in cutaneous squamous/basal cell carcinoma.
A patient with mixed squamous/basal cell carcinoma of the skin presented with hypercalcaemia and elevated serum levels of parathyroid hormone-related protein (PTH-rP). The tumour was resected, PTH-rP levels declined and the patient became normocalcaemic. This is the first case to associate squamous cell carcinoma of the skin with hypercalcaemia and significant levels of PTH-rP.
Aged↗
Undefined complications of parathyroid adenoma, parathyroid hyperplasia (primary hyperparathyroidism), thyroid follicular adenoma, thyroid papillary carcinoma, temporal astrocytoma, cerebellar meningioma, and hemangioma of external auditory meatus and oral papilloma.
A 59-year-old woman who had parathyroid adenoma, parathyroid hyperplasia, thyroid follicular adenoma, thyroid papillary carcinoma, astrocytoma of the right temporal lobe, cerebellar meningioma, capillary hemangioma of the left external auditory meatus and papilloma of the left upper gingiva is reported. Dynamic magnetic resonance imaging, computed tomography with contrast-enhancement and gastrofiberscopy revealed no remarkable findings in the pituitary, pancreas, adrenals, stomach or duodenum. Similar lesions were not found in any family members. Defect of the causative genes of multiple endocrine neoplasia types I and IIa, MENIN and RET was not detected. Further follow-up of this patient and family members is needed.
Adenoma↗
PTH mRNA transcription analysis in infantile tumors associated with hypercalcemia.
The ability of infantile hypercalcemic tumors (three rhabdoid renal tumors, one cellular mesoblastic nephroma, and one hepatoblastoma) to produce parathyroid hormone (PTH) was tested using RNA-DNA hybridization. Results were compared with those obtained in one lung epidermoid carcinoma and one parathyroid adenoma from adult patients. Elevated plasma immunoreactive PTH (iPTH) concentrations were observed in three of five children. The only tumor in which PTH-RNA hybridization could be detected was the parathyroid adenoma. The integrity of the RNA preparations was further confirmed by positive hybridization obtained with a glucagon DNA probe in both normal pancreas and the rhabdoid tumors. Quantitative bone histomorphometry of tumor-bearing nude mice showed a reduction in bone formation and increased bone resorption, the opposite of what occurs in hyperparathyroidism. The PTH-like protein, which was detected by radioimmunoassays (RIA) in the sera of three patients, could not be correlated with tumor PTH mRNA transcription within the limits of our assays. In order to explain this discrepancy, we suggest that the tumors produce a factor (not PTH) which, in turn, elicits the excess iPTH which we detected by RIA.
Aged↗
Papillary carcinoma of thyroid with exuberant nodular fasciitis-like stroma.
We describe two cases of papillary carcinoma of the thyroid containing prominent nodular, fasciitis-like stroma. In one of the cases infiltration into the adjacent parathyroid gland and metastases to two cervical lymph nodes occurred. In the lymph nodes and the parathyroid gland the carcinoma grew without any fasciitis-like stroma. This unusual change in tumour stroma seems to be reactive in nature and confined only to the thyroid and adjacent soft tissues.
Adult↗
Parathyroid hormone-related protein, an autocrine regulatory factor in alveolar epithelial cells.
Alveolar epithelial cells in vivo, primary cultures of adult rat type II cells, and human A549 alveolar carcinoma cells express parathyroid hormone-related protein (PTHrP). Here we demonstrated that type II cells and A549 cells also express the PTHrP receptor and that they exhibit differentiation-related responses to the amino-terminal PTHrP fragment, PTHrP-(1-34). PTHrP receptor expression in A549 cells was shown by detection of a 0.3-kb reverse transcriptase polymerase chain reaction product formed by primers specific for PTHrP receptor. In situ hybridization studies localized the site of production of PTHrP and PTHrP receptor mRNA in rat lung cells with morphology and location typical of type II cells. Primary cultures of such type II cells also expressed PTHrP receptor mRNA. Incubation with PTHrP-(1-34) stimulated disaturated phosphatidylcholine (DSPC) synthesis in A549 cells and increased the release of newly synthesized DSPC by cultured type II cells and A549 cells. In addition, PTHrP-(1-34) increased the number of lamellar bodies per type II cell and increased their expression of alkaline phosphatase in a dose-dependent manner. Thus PTHrP-(1-34) promoted a differentiated type II cell phenotype. Since cultured type II cells, alveolar epithelial cells in vivo, and A549 cells express PTHrP and the PTHrP receptor, PTHrP-(1-34) may be an autocrine regulatory factor in type II cells and lung cancer cells.
Animals↗
Contrast MRI in multiple endocrine neoplasia type 1 (MEN) associated with renal cell carcinoma.
The radiologic work-up of a patient with multiple endocrine neoplasia type 1 (MEN 1) syndrome and multiple endocrine nodules, with coincidental renal cell carcinoma, is described. Parathyroid adenoma was differentiated from multiple thyroid nodules by gadolinium-enhanced MRI. Adrenal enlargement due to a nonfunctioning adenoma and a renal cell carcinoma next to a simple renal cortical cyst were identified by typical signal intensities on T1- (pre- and post-Gd-DPTA) and T2-weighted images. Insulinoma was visualized only retrospectively.
Adenoma↗