Parathyroid carcinoma

Renal cell carcinoma marker (RCC, gp200) Renal cell carcinoma (papillary carcinoma dear cell carcinoma) Parathyroid adenoma, breast carcinoma, embryonal carcinoma Renal proximal tubular brush border, epididymal tubular epithelium, breast parenchyma, thyroid follides... 

No excess of cancer was reported in two follow-up smdies of affected individuals in Turkey about 20-30 years after consumption of contaminated grain had ceased. " In mice, liver tumors were observed after exposure to HCB at 12-24mg/kg/day in the diet, but not at 6mg/kg/day. Hepatomas, hepatocellular carcinomas, bile duct adenomas, and renal cell adenomas were observed in rats after dietary administration." Liver tumors were also observed in 100% of surviving females and 16% of males after dietary administration to rats for 90 weeks. In another study, increased incidence of parathyroid adenomas and adrenal pheochromocytomas were observed in male and female rats and liver neoplastic nodules in females of the Ei generation in a two-generation feeding study. 

Hypercalcemia in parathyroid carcinoma PO Initially, 30 mg twice a day. Titrate dosage sequentially (60 mg twice a day, 90 mg twice a day and 90 mg 3-4 times a day) every 2-4 wk as needed to normalize serum calcium levels. 

Cinacalcet is the first representative of a new class of drugs that activates the calcium sensing receptor (CaR). CaR is widely distributed but has its greatest concentration in the parathyroid gland. Cinacalcet blocks PTH secretion by this mechanism and is approved for the treatment of secondary hyperparathyroidism in chronic kidney disease and for the treatment of parathyroid carcinoma. 

Cinacalcet (Sensipar) [Hyperparathyroidism Agent/ Calcimimetic] Uses Secondary hyperparathyroidism in CRF T Ca2+ in parathyroid carcinoma Action 4- PTH by T Ca-sensing receptor sensitivity Dose ... 

Secondary> hyperparathyroidism 30 mg PO daily Parathyroid carcinoma 30 mg PO bid titrate q2—4wk based on Ca PTH levels swallow whole take w/ food Caution [C, /—] w/ Szs Disp Tabs SE N/V/D, myalgia, dizziness, 4- Ca2+ Interactions T Effects W/ CYP3A4 inhibitors such as ketoconazole, itraconazole, erythromycin T effects OF drugs metabolized at CYP2D6 such as TCA, thioridazine, flecainide, vinblastine EMS Monitor ECG for signs of hypocalcemia (T QT interval) OD May cause severe hypocalcemia calcium salts can be given... 

FIGURE 8.6. Immunostained cyclin D1 in parathyroid carcinoma showing a monotonous population of tumor cells. Courtesy of M. A. Vasef. For a color representation of this figure, see Plate 4A facing page 99. 

In the studies of long-term exposure of rats to both triphenyltin hydroxide and bis(tributyltin)oxide, most of the tumors were found in endocrine glands. In addition to the pituitary adenomas associated with bis(tributyltin)oxide and triphenyltin hydroxide, there was also an increased incidence of pheochromocytomas of the adrenal gland, parathyroid carcinomas and pancreatic adenocarcinomas in animals from at least one sex. Triphenyltin hydroxide was associated with an increased incidence of testicular Leydig cell tumors in male rats at the highest dose. Hepatic tumors were found in male and female mice following 80 weeks of triphenyltin hydroxide administration. 

One female and one male patient had hyperparathyroidism with elevated serum alkaline phosphatase activities and extensive bone changes characteristic of generalized osteitis fibrosa cystica. In both instances, the serum acid phosphatase activity of the serum fell to normal values after removal of the parathyroid adenoma despite transitorily increased serum alkaline phosphatase activity. The fifth patient was a female with osteopetrosis involving the major part of the skeleton. The serum acid phosphatase was 8.7 K.A. units, the highest in the control series— yet the serum alkaline phosphatase was within normal limits. It would appear, therefore, that some patients with skeletal disease may have a slight but definitely elevated serum acid phosphatase activity, at least as determined by the Gutman method (GIO, G14), which cannot be explained by concurrent prostatic carcinoma or by a spillover of alkaline phosphatase activity to a pH of 5.0. 

A 64-year-old woman who 3 months before had finished a course of cyclophosphamide, doxorubicin, and fluorouracil chemotherapy for breast carcinoma developed calciphylaxis (59). She had no renal disease and had normal renal function and parathyroid hormone concentrations. 

Primary hyperparathyroidism is characterized by excessive secretion of PTtI that results in hypercalcemia. It is most often due to a solitary adenoma (80% to 85% of cases), less frequently (about 15%) due to chief cell hyperplasia involving all glands, and rarely due to parathyroid carcinoma (<1%). 

Nussbaum SR, Gaz RD, Arnold A. Hypercalcemia and ectopic secretion of parathyroid hormone by an ovarian carcinoma with rearrangement of the gene for parathyroid hormone. N Engl J Med 1990 323 1324-8. 

Primary hyperparathyroidism results from hyperplasia, adenoma, or carcinoma of the parathyroid glands and from ectopic production of the hormone by squamous cell carcinoma of the lung or by adenocarcinoma of the kidney. In about 10% of hyperparathyroidism, hyperplasia or tumors of the parathyroid glands occur due to familial disorders known as multiple endocrine neoplasia (MEN). MEN syndromes consist of three subtypes (I, IIA, IIB) and are... 

A review of the use of cinacalcet HCl for secondary hyperparathyroidism is provided in Chap. 44. Cinacalcet HCl is administered at a starting dose of 30 mg given orally twice daily for the treatment of parathyroid carcinoma. The dosage is titrated every 2 to 4 weeks in 30-mg increments twice daily. The maximum approved dosage is 90 mg three to four times daily. 

Collins MT, Skarulis MC, Bilezikian JP, et al. Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel calcimimetic agent. J CUn Endocrinol Metab 1998 83 1083-1088. 

In view of the known effects of adrenaline and noradrenaline on serum alkaline phosphatase activities of the dog (H12), it is surprising that reviews of pheochromocytomas barely mention this enzyme. High values may occur in this disorder because of such associated conditions as parathyroid adenomas (P2) or metastatic medullary carcinoma of the thyroid (S46) or, rarely, because pheochromocytomas may themselves metastasize to bone or liver (Jl). 

P2. Paloyan, E., Scanu, A., Straus, F. H., Pickleman, ]. R., and Paloyan, D., Familial pheochromocytoma, medullary thyroid carcinoma, and parathyroid adenomas. JAMA 214, 1443-1447 (1970). 

The distribution of cyclin D1 has also been examined in normal and neoplastic parathyroid tissue.212 In normal glands, cyclin D1 was present in 6% of cases. In contrast, cyclin D1 was present in 10 of 11 (91%) parathyroid carcinomas, 11 of 38 (39%) parathyroid... 

Another approach to the distinction of parathyroid adenomas and carcinomas involves the use of antibodies to the retinoblastoma (RB) protein. Cryns and coworkers reported the absence of RB protein in a small series of carcinomas, whereas this protein was present in adenomas. However, Vargas and cowork-ers i demonstrated positive staining for RB in 100% of adenomas and 80% of carcinomas. Farnebo and coworkers also demonstrated the lack of utility of RB immunoreactivity for the distinction of adenomas and carcinomas. 

FIGURE 10.27 Parafibromin stain of parathyroid adenoma (A) and parathyroid carcinoma (B). A, There is intense nuclear staining in the adenoma. B, In this area of the carcinoma, there is no staining of tumor cell nuclei. Other areas of the carcinoma, however, exhibited foci of positive staining. 

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