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PubMed2004

Providing optimal preoperative localization for recurrent parathyroid carcinoma: a combined parathyroid scintigraphy and computed tomography approach.

PURPOSE: The incidence of parathyroid carcinoma is approximately 0.5% to 5% in patients with primary hyperparathyroidism. Recurrent parathyroid carcinoma is treated with surgical resection of all sites of disease to ameliorate systemic manifestations of hyperparathyroidism, primarily hypercalcemia. This study investigates the role of parathyroid scintigraphy and computed tomography (CT) imaging in recurrent parathyroid carcinoma. MATERIALS AND METHODS: A retrospective chart review was performed on 8 patients diagnosed with recurrent parathyroid carcinoma at our tertiary care institution between 1975 and 2001. Surgical reports, histopathology, parathyroid scintigraphy, and CT findings were recorded. Surgical reports and radiologic studies were compared for concordance of recurrence sites. RESULTS: There were 32 imaging studies before reoperation: 15 parathyroid scintigraphy and 17 CTs. Of 15 sites of recurrence potentially seen on scintigraphy, 10 were true-positive (67%). Of 17 sites of recurrence potentially seen on CT, 9 were true-positive (53%). Of the 8 false-negatives on CT, 7 of these recurrences were in the surgical bed (88%). There were 9 instances in which CT and scintigraphy were performed preoperatively for comparison and correlation. CT and scintigraphic findings were incongruent in 7 of 9 of these cases (78%). CONCLUSION: Successful surgical intervention for recurrent parathyroid carcinoma requires accurate preoperative localization studies and complete excision of metastases. Our data supports combined analysis of parathyroid scintigraphy and CT for patients with recurrent disease before reoperation. Additionally, our review suggests that sensitivity may be optimized with SPECT parathyroid scintigraphy and close correlation with CT.

Aged↗
PubMed1996

Receptors for parathyroid hormone and parathyroid hormone-related peptide: from molecular cloning to definition of diseases.

The parathyroid hormone/parathyroid hormone-related peptide receptor belongs to a distinct family of G protein-coupled receptors, the members of which usually signal through at least two second messenger systems, adenylate cyclase and phospholipase C. The parathyroid hormone/ parathyroid hormone-related peptide receptor is most abundantly expressed in bone, kidney and growth-plate chondrocytes, and, at lower levels, in a variety of fetal and adult tissues. To search for human diseases that are caused by parathyroid hormone/parathyroid hormone-related peptide receptor defects, genomic DNA of patients with pseudohypoparathyroidism type Ib and of patients with Jansen's metaphyseal chondrodysplasia was screened for mutations in all coding exons of the receptor gene. Inactivating parathyroid hormone/parathyroid hormone-related peptide receptor mutations were excluded in patients with pseudohypoparathyroidism type Ib. However, a receptor mutation that causes agonist-independent, constitutive cAMP accumulation was identified in a patient with Jansen's metaphyseal chondrodysplasia, a rare form of short-limbed dwarfism associated with hypercalcemia despite normal or low concentrations of parathyroid hormone and parathyroid hormone-related peptide. These findings allow the conclusion to be drawn that parathyroid hormone/parathyroid hormone-related peptide receptors mediate the endocrine actions of parathyroid hormone, which are required for the control of calcium homeostasis and the autocrine-paracrine actions of parathyroid hormone-related peptide, which are required for normal growth-plate development.

Adult↗
PubMed2004

Menin inactivation leads to loss of transforming growth factor beta inhibition of parathyroid cell proliferation and parathyroid hormone secretion.

Primary hyperparathyroidism is a common endocrine disorder caused by parathyroid gland enlargement and excessive parathyroid hormone (PTH) secretion. However, the precise mechanisms of tumorigenesis of the parathyroids are unknown. Here we have investigated the roles of transforming growth factor (TGF)-beta and menin, the product of the multiple endocrine neoplasia type 1 (Men1) gene, in the proliferation and PTH production of parathyroid cells from either patients with secondary hyperparathyroidism or Men1. TGF-beta was expressed in the parathyroid endocrine cells. Addition of TGF-beta to parathyroid cells from patients with secondary hyperparathyroidism inhibited their proliferation and PTH secretion. These responses to TGF-beta were lost when menin was specifically inactivated by antisense oligonucleotides. Moreover, TGF-beta did not affect the proliferation and PTH production of parathyroid cells from a Men1 patient. These results indicate that menin is required for TGF-beta action in the parathyroid. We conclude that TGF-beta is an important autocrine/paracrine negative regulator of parathyroid cell proliferation and PTH secretion and that loss of TGF-beta signaling due to menin inactivation contributes to parathyroid tumorigenesis.

Cell Division↗
PubMed1988

Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas.

Previous work based on the relative tissue content of glucose-6-phosphate dehydrogenase isoenzymes suggested that parathyroid adenomas, like primary hyperplasia, may be multicellular (not clonal) in origin. We have reexamined this issue by using two independent molecular genetic methods. We report tumor-cell-specific restriction-fragment-length alterations involving the parathyroid hormone gene from two human parathyroid adenomas. These abnormal restriction fragments indicate that in each case a clonal proliferation of cells was present and also suggest that DNA alterations involving the parathyroid hormone locus may be important in the tumorigenesis or clonal evolution of some parathyroid adenomas. In addition, we used a restriction-fragment-length polymorphism in an X-linked gene (hypoxanthine phosphoribosyltransferase) to examine the clonality of eight parathyroid adenomas in women. Of these eight adenomas, six had the DNA hybridization pattern of monoclonality, and two had an equivocal pattern. None of five hyperplastic parathyroid glands had a monoclonal pattern. We conclude that some (and perhaps many) single parathyroid adenomas are monoclonal neoplasms. Our observations suggest that there is a fundamental biologic difference between parathyroid adenomas and primary hyperplasia--a difference that could prove useful in distinguishing these entities clinically.

Adenoma↗
PubMed2000

[Diagnosis of parathyroid cysts: value of parathyroid hormone level in puncture fluid].

OBJECTIVE: Determine a means of establishing the diagnosis of parathyroid cysts preoperatively. PATIENTS AND METHODS: Classically, crystal-clear watery fluid removed by fine-needle aspiration of a suspected thyroid mass raises the suspicion of a parathyroid cyst. Immunoradiometric assay of parathyroid hormone level in the fluid may give the diagnosis sparing unnecessary surgery. RESULTS: Over the last 5 years, among the 12 patients presenting a suspected thyroid cyst containing a crystal-clear fluid, we were able to diagnose 3 cases of parathyroid cysts due to the considerable elevation of parathyroid hormone in the puncture fluid. None of these patients had hyperparathyroidism. In patients with a thyroid cyst, parathyroid hormone level in the puncture fluid was nil. CONCLUSION: The parathyroid nature of cervical cysts containing crystal-clear fluid can be established by assaying parathyroid hormone in the puncture fluid. Non-functional parathyroid cysts may be treated by repeated aspiration. Serum calcium level must be checked regularly to detect potential hyperparathryoidism.

Adult↗
PubMedDate not supplied

Value of parathyroid hormone assay for preoperative sonographically guided parathyroid aspirates for minimally invasive parathyroidectomy.

PURPOSE: The key to successful parathyroid surgery is accurate preoperative tumor localization. This study investigates the use of ultrasound (US)-guided parathyroid fine needle aspiration (FNA) as a confirmatory diagnostic method in patients with hyperparathyroidism undergoing minimally invasive parathyroidectomy. METHODS: Patients were selected for minimally invasive parathyroidectomy based on the finding of a single parathyroid adenoma identified with US and/or sestamibi scans and confirmation of the suspected parathyroid lesion via FNA and parathyroid hormone (PTH) assay. The value of aspirate obtained from the thyroid gland intraoperatively served as the negative control. RESULTS: A total of 56 tissue FNAs were performed in 27 patients. US detected masses suggestive of parathyroid lesion in all 27 patients, and 31 US-guided FNAs were performed. No complications related to the procedure were noted. Intraoperatively, FNA was performed in the thyroids of 25 patients undergoing minimally invasive parathyroidectomy. Aspirates from lesions subsequently confirmed as having developed from the parathyroid gland had a mean PTH level of 4,677 +/- 123 pg/ml (range, 3,600-5,000 pg/ml), which was significantly higher than thyroid aspirates, which yielded a mean PTH level of 48 +/- 7 pg/ml (range, 5-57 pg/ml). The sensitivity of US and sestamibi scans in the detection of abnormal parathyroid glands was 88% and 77%, respectively. The sensitivity of US-guided FNA in confirming the parathyroid origin of a lesion was 100%. CONCLUSION: US-guided FNA for PTH assay can be performed safely for the confirmation of lesions identified with preoperative US for the selection of patients eligible for minimally invasive parathyroidectomy.

Adenoma↗
PubMed1980

Pituitary stimulation of parathyroid hormone secretion: evidence in cattle for a parathyroid stimulating hormone.

A number of previous investigations have indicated that the pituitary may directly stimulate secretion of parathyroid hormone. Others have disagreed. With the recent development of an in vitro bovine parathyroid perfusion system, the direct effect of suspected secretagogues can be assessed on a dynamic, ongoing basis. A partially purified pituitary extract (preparation A) was injected into calves. The plasma calcium increased an average of 1.1 mg/100 ml plasma. No increase of immunoreactive parathyroid hormone (iPTH) was detected, however, in the peripheral plasma prior to the increase in plasma calcium concentration. Since the peripheral plasma iPTH concentration has been shown to be relatively insensitive to changes in the secretion rate, the inability to detect a change in the iPTH concentration does not preclude a direct stimulating effect of the pituitary on the parathyroid. When preparation A was tested on in vitro perfused bovine parathyroid glands, a 30% average increase in secretion of c-iPTH (carboxy terminus) and a 56% average increase in secretion of n-iPTH (amino terminus) was observed under normocalcemic conditions. Under conditions of hypercalcemia, there was an average increase in the c-iPTH secretion rate of 60% and an average n-iPTH secretion rate increase of 88%. A failure of TSH, LH, GH, ADH, oxytocin, and prolactin to stimulate iPTH was observed. Previous reports have eliminated ACTH, MSH, and lipotropin as possible parathyroid secretagogues. The concept of a parathyroid stimulating hormone (PTSH) located in the pituitary that can directly stimulate the parathyroid gland to secrete parathyroid hormone is consistent with the results of this investigation.

Animals↗
PubMed1992

Estimated weight of the residual parathyroid gland after parathyroidectomy using plasma levels of the parathyroid hormone.

The possibility of estimating the total weight of the parathyroid glands based on the plasma concentration of the parathyroid hormone (PTH) would be of great help when searching for the parathyroid glands during surgery on patients with secondary hyperparathyroidism. Thus, we studied the relationship between the levels of carboxyl-terminal PTH (C-PTH), midportion PTH (M-PTH) and intact PTH, and the weight of the parathyroid glands resected for secondary hyperparathyroidism. The subjects studied were 11 patients with secondary hyperparathyroidism caused by chronic renal failure. The pre- and post-operative differences in the plasma C-PTH levels and plasma M-PTH levels were significantly correlated with the weight of the resected parathyroid glands (p less than 0.001 for both), but there was no correlation between the differences in the levels of intact PTH and the weight of the resected parathyroid glands. From these relationships we estimated the weight of the residual parathyroid gland after parathyroidectomy using the levels of each PTH. All patients in whom the residual parathyroid gland was estimated to be heavy based on the levels of M-PTH showed recurrence of hyperparathyroidism after the parathyroidectomy. We therefore found that estimation of the weight of the parathyroid glands from the levels of M-PTH is both possible and useful.

Adult↗
PubMed2003

Coexistence of a parathyroid adenoma and parathyroid cyst causing primary hyperparathyroidism.

The association of a functional parathyroid cyst with a parathyroid adenoma is an uncommon finding. In this report we describe the clinical history of a 60-yr-old man, presenting with the following findings: hypercalcemia (18.9 mg/dl), elevated serum parathormone levels (1320 pg/dl), hypercalciuria (228 mg/dl), and hyperphosphaturia (155 mg/dl). Neck ultrasound, magnetic resonance imaging (MRI) and 99Tc Sestamibi scintigraphy led to the identification of a left parathyroid adenoma, located at the lower pole of the left thyroid gland lobe, associated with a parathyroid cyst, located at the upper extremity of the same thyroid lobe. Parathyroidectomy was performed and the histological examination confirmed the diagnosis of a parathyroid adenoma with aspects of cystic degeneration and an upper parathyroid cyst. Analysis of the crystal clear intracystic fluid showed elevated parathyroid hormone (PTH) levels (137.000 pg/ml). The patient is normocalcemic at 2 yr after surgery without signs of recurrent parathyroid enlargements. Aetiology, diagnosis and management of parathyroid cyst will be discussed.

Adenoma↗
PubMed2003

CYP2D6, GST-M1 and GST-T1 enzymes: expression in parathyroid gland and association with the parathyroid hormone concentration during early renal replacement therapy.

AIMS: The purpose of this research was to characterize CYP2D6, GST-M1 and GST-T1 enzyme expression in human parathyroid tissue, and to determine whether or not there is any association between deficiencies in these enzymes and serum parathyroid hormone concentrations in patients with end-stage renal disease. METHODS: Surgical human parathyroid tissue was obtained and evaluated by immunohistochemistry for cellular localization of CYP2D6, GST-M1 and GST-T1 and colocalization of CYP2D6 with parathyroid hormone. Blood samples were collected from 328 Caucasian patients with end-stage renal disease for genetic testing of CYP2D6*3, *4, *5, *6, *7 and GST-M1*0 and GST-T1*0 alleles. Clinical chemistry data and serum intact parathyroid hormone (iPTH) concentrations were obtained from patient medical records. In 277 of the patients, the same laboratory performed all clinical tests. RESULTS: CYP2D6, GST-M1 and GST-T1 were present in human parathyroid tissue. CYP2D6 was colocalized with parathyroid hormone in parathyroid chief cells. Within the end-stage renal disease population, a nonfunctional CYP2D6 genotype was present in 18.2%[95% confidence interval (CI) 8.0, 28.4] of patients in the 1st iPTH concentration quintile (iPTH < 64 pg x mL(-1)), in 0% (95% CI 0, 7.5) of those in the 2nd quintile, in 1.8% (95% CI 0, 9.3) of those in the 3rd quintile, in 9.1% (95% CI 1.5, 16.7) of those in the 4th quintile, and in 16.7% (95% CI 6.8, 26.5) of those in the 5th quintile (iPTH > 347 pg x mL(-1)) (P = 0.001). Out of 12 CYP2D6-deficient females, seven were in the 1st iPTH concentration quintile and the remaining five were in the 5th quintile. Patients deficient in the GST-M1 and GST-T1 enzymes displayed a far more uniform frequency distribution relative to serum iPTH concentrations. CONCLUSIONS: The presence of CYP2D6, GST-M1 and GST-T1 in parathyroid cells was observed. An association is reported between a lack of CYP2D6 and iPTH concentrations in newly diagnosed end-stage renal disease patients. Gender and concomitant deficiency in GST-M1 and/or GST-T1 appear to define this association further. It remains to be established whether these associations reflect a cause-effect relationship between deficient expression of metabolizing enzymes and severity of secondary manifestation of renal failure.

Adolescent↗
PubMed2006

Loss of nuclear expression of parafibromin distinguishes parathyroid carcinomas and hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from sporadic parathyroid adenomas and hyperplasias.

Parathyroid carcinoma is notoriously difficult to diagnose with confidence in borderline cases. Commonly there is a long lag time between diagnosis and clinical evidence of malignant behavior even in histopathologically straightforward lesions. There is therefore a need for a novel adjunctive marker to assist in the diagnosis of carcinoma. Parafibromin is the protein encoded by the putative tumor suppressor gene HRPT2. Mutations predicted to inactivate parafibromin were first detected in the germline of patients with hyperparathyroidism-jaw tumor (HPT-JT) syndrome. Subsequently, somatic mutations have been identified in the majority of sporadic carcinomas. We performed immunohistochemistry for parafibromin on 115 parathyroid tissues comprising 4 HPT-JT-related tumors (3 adenomas and 1 carcinoma), 11 sporadic parathyroid carcinomas, 79 sporadic adenomas, 3 multiple endocrine neoplasia 2A-related adenomas, 2 sporadic primary hyperplasias, 2 multiple endocrine neoplasia (MEN)-1-related hyperplasias, 6 secondary hyperplasias, 4 tertiary hyperplasias, and 4 normal parathyroid glands. There was complete absence of nuclear staining in 3 of 4 (75%) HPT-JT-related tumors and 8 of 11 (73%) sporadic parathyroid carcinomas and focal weak staining in 1 of 4 HPT-JT tumors and 2 of 11 sporadic parathyroid carcinomas. Only 1 parathyroid carcinoma exhibited diffuse strong nuclear expression of parafibromin. In contrast, 98 of 100 non-HPT-JT-related benign parathyroids showed diffuse strong nuclear positivity and 2 of 100 showed weak positive staining. We conclude that, in the correct clinical and pathologic context, complete absence of nuclear staining for parafibromin is diagnostic of parathyroid carcinoma or an HPT-JT-related tumor.

Biomarkers, Tumor↗
PubMed1977

Vitamin A stimulation of parathyroid hormone: interactions with calcium, hydrocortisone, and vitamin E in bovine parathyroid tissues and effects of vitamin A in man.

The effect of vitamin A, a membrane surface-active agent, on parathyroid hormone secretion was studied in vitro, using bovine parathyroid tissue, and in vivo in man. Parathyroid tissues were incubated with vitamin A (retinol), retinoic acid, and calcium, and with hydrocortisone and vitamin E, agents that antagonize the membrane effects of vitamin A. The stimulation of parathyroid hormone release by vitamin A, 10(-6) to 10(-9) mol/1 in vitro, was dose and time dependent. Retinoic acid did not stimulate secretion. High calcium concentration, hydrocortisone, 10(-5) mol/1 and 10(-6) mol/1, and vitamin E, 10(-5) mol/1, antagonized vitamin A-induced parathyroid hormone secretion. Vitamin A increased the lysosomal cathepsin D activity of parathyroid tissues. In human studies, eleven healthy men received two intramuscular injections of vitamin A palmitate, 25 000 units each, within 24 h. In every subject, serum parathyroid hormone increased after vitamin A administration. Our studies indicate that: (1) vitamin A stimulates parathyroid hormone secretion in vitro, possibly through modification of the cell or secretion granule membrane, or through stimulation of lysosomal proteolytic activity, and (2) vitamin A increases serum parathyroid hormone in vivo, and this effect may be important in clinical states of vitamin A excess.

Adult↗
PubMed1999

Parathyroid autotransplantation with total thyroidectomy for thyroid carcinoma: long-term follow-up of grafted parathyroid function.

BACKGROUND: Permanent hypoparathyroidism is a major complication of thyroidectomy. Autotransplantation of parathyroid glands has been attempted to prevent this complication. However, no direct data have been available to assess grafted parathyroid function after long-term follow-up in terms of the serum intact parathyroid hormone (PTH) concentration. METHODS: Eighty-four consecutive patients with differentiated thyroid carcinoma who underwent total thyroidectomy and bilateral modified neck dissection from 1992 to 1996 were enrolled. They concomitantly underwent total parathyroidectomy and autotransplantation of all parathyroid glands to the pectoralis major muscle. The serum intact PTH concentration was periodically measured as an index of grafted parathyroid function. RESULTS: The mean follow-up was 34 months. In all autotransplanted patients serum intact PTH concentrations fell below detectable limits immediately after surgery. They were restored to the normal range within 1 month postoperatively and were maintained during observation in 80 (95%) of 84 patients. Seventy-eight of 80 patients with normal intact PTH values were normocalcemic without any treatment and the remainder were normocalcemic with 1 microgram of 1 alpha-vitamin D3. Four hypoparathyroid patients were normocalcemic with 2 micrograms of 1 alpha-vitamin D3. The postoperative average serum intact PTH concentration of patients having more than 2 autotransplanted parathyroid glands was almost equal to that of patients with preservation of the parathyroid glands in situ. The incidence of permanent hypoparathyroidism was inversely correlated with the number of autotransplanted parathyroid glands. CONCLUSIONS: The recovery patterns of the intact PTH concentration indicate that the glands were grafted successfully and functioned for a long period. This feasible method of parathyroid autotransplantation bears comparison with the previous reports in terms of the incidence of permanent postoperative hypoparathyroidism, and it can be performed simply and is reproducible.

Adolescent↗
PubMed1996

A direct effect in vitro of phosphate on PTH release from bovine parathyroid tissue slices but not from dispersed parathyroid cells.

BACKGROUND: Phosphate retention has long been considered to be of importance for the pathogenesis of secondary hyperparathyroidism in chronic renal failure. Hyperphosphatemia in vivo is associated with alterations of calcium and vitamin D levels, both of which are known to alter the parathyroid hormone (PTH) release independently. MATERIALS AND METHODS: We have investigated the direct effect of phosphate on PTH release in vitro using two different preparations of bovine parathyroid tissue: Acutely dispersed bovine parathyroid cells and tissue slices of 0.5 x 0.5 mm were prepared from bovine parathyroid glands. Parathyroid dispersed cells and tissue slices were incubated for 4 h in media containing normal phosphate (1.0 mM) or high phosphate (3.5 mM). RESULTS: High phosphate induced a significant (P < 0.01) increase in PTH release in the preparation of tissue slices, but not in preparations of dispersed cells. The 4 h incubation in high phosphate medium did not change the set-point for calcium. Bovine parathyroid tissue slices incubated in increasing phosphate concentrations from 1.0 to 3.5 mM and with a fixed calcium concentration of either 0.8, 1.2 or 1.8 mM responded with a dose dependent stimulation of PTH release. The degree of stimulation of release by high phosphate (3.5 mM), was significantly (P < 0.05) higher at low calcium levels (0.8 mM), 172% above baseline value (1.0 mM phosphate) as compared to high calcium levels (1.8 mM), 139% above baseline values. CONCLUSIONS: This study shows that phosphate directly stimulates the PTH release in bovine parathyroid glands, and that this effect is only seen in preparations of parathyroid tissue slices and not in preparations of dispersed cells. This indicated that maintenance of near normal architecture of the parathyroid glands is essential in order to elicit the effect of high phosphate on the PTH release.

Animals↗
PubMed1991

Expression of parathyroid hormone-related protein in abnormal human parathyroids.

The expression of parathyroid hormone-related protein (PTHrP) in abnormal human parathyroids was investigated. Northern blot analysis of RNA extracted from human benign parathyroid adenomata (n = 4) revealed multiple PTHrP mRNA species ranging in size from 1.8 to 4 kb. The relative abundance of PTHrP mRNA expressed in two of the adenomata was similar to that of a tumour (DAF) associated with humoral hypercalcaemia of malignancy, whereas PTHrP mRNA was of low abundance in a third and was undetectable in the fourth. PTHrP-like immunoreactivity was detected in extracts of abnormal parathyroid tissue (benign adenoma (n = 7), hyperplasia (n = 5) and parathyroid carcinoma (n = 2] using a sensitive specific two-site immunoradiometric assay for human (h) PTHrP(1-86) and a radioimmunoassay for hPTHrP(1-34). Ratios of hPTHrP(1-86)- and hPTHrP(1-34)-like immunoreactivities relative to hPTH(1-84)-like immunoreactivity in the parathyroid tissue extracts were, on average, less than 1%. PTHrP bioactivity in the extracts could not be distinguished from that of PTH, by an osteosarcoma cell bioassay. We conclude that, despite reports of over-expression of PTHrP mRNA in parathyroid adenomata, the potential contribution of PTHrP to the total PTH-like activity of adenomata and other abnormal parathyroid tissue may be insignificant relative to PTH.

Adenoma↗
PubMed1998

Characterization of the phosphatidylinositol-specific phospholipase C isozymes present in the bovine parathyroid and in human kidney HEK293 cells stably transfected with the human parathyroid Ca2+-sensing receptor.

The regulation of parathyroid hormone secretion by the chief cells of the parathyroid is mediated by a 7-transmembrane (7-TM) Ca2+-sensing receptor (CaR), which signals via activation of pertussis toxin-insensitive G proteins, causing stimulation of phosphatidylinositol-specific phospholipase C (PI-PLC). We have identified the PI-PLC isoforms expressed in two model systems utilized for studying CaR signal transduction, i.e. dispersed bovine parathyroid cells and a human embryonic kidney cell line (HEK 293) stably transfected with the human parathyroid CaR-cDNA. All of the eight PI-PLC isozymes examined in this study were found to be expressed to varying extents in the bovine parathyroid gland and in the CaR-transfected HEK cells as assessed by immunoblotting. We localized the expression of the more abundant isozymes (beta1, beta2, beta3, gamma1, gamma2, delta2) to the chief cells of the bovine parathyroid by immunocytochemistry, while the two less abundant isozymes (delta1, beta4) were not detectable in parathyroid sections. G proteins activated by 7-TM receptors are known to activate mainly PI-PLC of the beta class. Therefore, beta1, beta2, beta3 and beta4, all expressed in the bovine parathyroid, are candidate isozymes for coupling to the CaR. A comparison of the levels of expression of PI-PLC isozymes between CaR-transfected HEK cells and non-transfected HEK cells suggested that the expression of the CaR in this human cell line does not cause a significant up-regulation of any of the PLCbeta and PLCgamma isozymes. PLCdelta2, showing predominantly nuclear localization in the parathyroid, was the sole PI-PLC isozyme with higher levels of expression in CaR-transfected HEK cells.

Animals↗
PubMed2003

Parathyroid surgical failures with misleading falls of intraoperative parathyroid hormone levels.

According to earlier reports, a decrease below 50% of baseline of intraoperative PTH levels measured 5 min after resection of the parathyroid adenoma predicts a cure of hyperparathyroidism. To reveal previously unrecognized pitfalls of intraoperative PTH measurements, we reviewed surgical failures in our series of parathyroidectomies combined with intraoperative PTH sampling. PTH measurements were performed in 251 patients with primary hyperparathyroidism (PHPT) between November 1999 and December 2002. PHPT due to parathyroid hyperplasia were found in 8 cases, double parathyroid adenomas in 6 cases, parathyroid carcinoma in 1 case and single parathyroid adenomas in 236 cases, all confirmed by histological examination. Of the 236 cases of single adenomas, initial surgery failed to cure PHPT in 4 patients. In 3 patients a false-positive decrease of intraoperative PTH (from 269 to 40 pg/ml, from 211 to 27 pg/ml, and from 140 to 59 pg/ml) was observed, whereas in the fourth patient a true-negative decrease of intraoperative PTH (from 758 to 401 pg/ml) was mistakenly interpreted as indication for a cure of PHPT. In each of the 4 patients in whom initial surgery failed the intervention included thyroid surgery and reoperative parathyroid surgery resulted in a permanent cure of PHPT. These observations support the possibility that thyroid surgery may compromise the blood supply of parathyroid adenomas resulting in a misleading drop of intraoperative PTH levels. Therefore, a careful evaluation of intraoperative PTH levels and, perhaps, other intraoperative aids such as histological evaluation of frozen sections are recommended when parathyroid surgery is combined with simultaneous thyroid intervention.

Adenoma↗
PubMed2002

Expression of parathyroid hormone-related protein (PTHrP) in parathyroid tissue under normal and pathological conditions.

Parathyroid hormone-related protein (PTHrP), a factor responsible for malignancy associated hypercalcemia, plays a physiological roles such as bone development and placental calcium transport. The expression of PTHrP in adult human parathyroid tissues under normal and pathological conditions was analyzed. By immunohistochemistry, PTHrP expression was detected in 86% of normal parathyroid (12/14 cases), 74% of adenomas (14/19) and 89% of hyperplasia secondary to chronic renal failure (16/18). PTHrP protein was observed mainly in the cytoplasm of oxyphil cells, consistent with the localization of its mRNA demonstrated by in situ hybridization. The rate of PTHrP-positive cells was higher in areas consisting of oxyphil cells than in those of non-oxyphil cells, regardless of whether the parathyroid was normal or pathological. In the normal parathyroid, an age-related increase in PTHrP expression was observed with a relative increase in oxyphil cells, reflecting aging and deterioration of parathyroid tissue. In adenoma, cases with a predominance of oxyphil cells expressed PTHrP, whereas clear cell adenoma did not. In secondary hyperplasia, the rate of PTHrP-expressing cells was higher than in normal parathyroid or adenoma, with varying levels of expression among nodules. We speculate that PTHrP could act through the paracrine/autocrine mechanism to regulate proliferation and differentiation of normal and neoplastic parathyroid cells.

Adenoma↗