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Preoperative localization of suspicious parathyroid adenomas by assay of parathyroid hormone in needle aspirates.

OBJECTIVE: To determine the usefulness of parathyroid hormone (PTH) measurement in needle aspirates of a suspicious neck mass to confirm its parathyroid nature in patients with primary hyperparathyroidism. METHODS: Thirty-three patients with surgically proved primary hyperparathyroidism were submitted to neck ultrasound (US), parathyroid scintigraphy, and assay of PTH in the aspirate (PTHa) of the suspicious cervical mass. RESULTS: Based on the results of neck US and parathyroid scintigraphy, patients were divided into two groups. Group 1: 16 patients (seven with nodular goiter) with concordant positive US and scintigraphic results. In all but one patient, PTHa was detectable and often markedly elevated (> 1000 pg in 12 patients, between 292 pg and 803 pg in three patients and 53 pg in one patient). The patient with undetectable PTHa had a small lower left parathyroid adenoma (8x8x10 mm). Group 2: 17 patients (12 with nodular goiter) with discordant US and scintigraphic results. PTHa established the parathyroid nature of the mass in 13 cases (> 1000 pg in 8 patients, between 501 pg and 953 pg in three patients and 90 and 79 pg in two patients): 11 of these had a suspected lesion by US examination but the scintigraphy results were negative; two had a mass that gave positive scintigraphy results but was of uncertain origin according to US: in both cases an intrathyroidal parathyroid adenoma was found. PTHa was undetectable in four cases (three with nodular goiter): all of these had equivocal US results, and three had positive scans and one a negative scan. CONCLUSIONS: Assay of PTHa is a simple method and should be useful for confirming the parathyroid nature of a cervical mass in patients with discordant or non-diagnostic US and scintigraphic results.

Adenoma↗

Expression of transcripts encoding a parathyroid hormone-related peptide in abnormal human parathyroid tissues.

A PTH-related peptide (PTHRP) has been identified and its cDNA cloned from human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The human PTHRP gene has been recently isolated and found to be a complex transcriptional unit using multiple promoters and containing alternatively spliced 3' exons which result in three mRNA classes, each class encoding a PTHRP with a unique carboxy-terminus. The PTHRP gene appears to be expressed in a number of normal tissues, and PTHRP transcripts have been previously reported to be overexpressed in a small sample of human parathyroid adenomas. In the present study we surveyed RNA prepared from a total of 60 abnormal human parathyroid glands for PTHRP gene expression using a combination of Northern blotting and RNase protection techniques. Apparent overexpression of PTHRP mRNA was observed in two thirds of parathyroid adenomas, whereas no overexpression was found in 7 examples of sporadic primary hyperplasia, 5 examples of secondary hyperplasia, and 3 examples of parathyroid carcinoma. Apparent overexpression was also observed in 1 of 4 cases of multiple endocrine neoplasia type 1, 1 of 2 examples of multiple endocrine neoplasia type 2, and 1 gland considered to represent tertiary hyperparathyroidism. Northern analysis of poly(A)+ RNA prepared from three representative adenomas using region-specific probes indicated that two putative promoters are used and revealed a pattern of preferential splicing of transcripts to include the most distal 3' exon. These findings suggest that the PTHRP gene is commonly overexpressed in adenomatous parathyroid glands, but not in sporadic primary hyperplasia, that this overexpression does not seem to be dependent on the use of a single specific promoter, and that adenomatous parathyroid cells appear to preferentially use one of several alternative splicing pathways. It is presently not known whether PTHRP is secreted by abnormal parathyroid tissues and, if so, in what form.

Adenoma↗

Applicability of tissue aspirate for quick parathyroid hormone assay to confirm parathyroid tissue identity during parathyroidectomy for primary hyperparathyroidism.

HYPOTHESIS: Intraoperative quick parathyroid hormone (PTH) assay for tissue aspirate facilitates the confirmation of parathyroid tissue identity and allows a more selective use of frozen section examination during parathyroidectomy for primary hyperparathyroidism. DESIGN: A retrospective review of a prospective protocol of the applicability and accuracy of quick PTH assay for tissue aspirate as a biochemical frozen section tool. SETTING: A university hospital department of surgery. PATIENTS: Quick PTH assay for aspirate obtained from suspected parathyroid gland excised during parathyroidectomy for primary hyperparathyroidism. MAIN OUTCOME MEASURES: The accuracy of this biochemical identification of parathyroid tissue identity was correlated with histological examination and outcome. RESULTS: Quick PTH assay was performed for aspirate from at least 1 excised parathyroid gland in 122 (98%) of 125 patients while 13 patients (10%) had PTH aspirate for nonparathyroid tissues including thyroid (n = 10), thymic (n = 2) and lymphatic (n = 1) tissues. Frozen section examination was performed for 15 patients (12%), including the 3 patients who did not undergo tissue aspirate for quick PTH assay. All except 3 patients had an aspirate assay value of greater than 1500 pg/mL (range, 625 to >1500 pg/mL) for parathyroid tissue while the value of PTH aspirate for nonparathyroid tissue ranged from 27 to 229 pg/mL (median, 72 pg/mL) in 13 patients. The median size of abnormal parathyroid gland was 70 to 15,000 mg (median, 775 mg). CONCLUSIONS: With the availability of quick PTH assay, tissue aspirate for PTH assay can be adopted as an alternative to traditional frozen section examination to confirm parathyroid gland identity. Frozen section examination can be employed more selectively.

Adenoma↗

Resetting of parathyroid hormone secretion after vitamin D3 treatment in hypoparathyroidism and after parathyroid adenectomy in primary hyperparathyroidism.

The relationship between parathyroid hormone (PTH) secretion and extracellular calcium (Ca) level is reciprocal causality. The equilibrium operating point determines basal PTH secretion rate and basal extracellular Ca level. We studied how this equilibrium was achieved in the subjects with decreased PTH secretion or decreased parathyroid glands number. Basal/maximum ratio of serum PTH, which reflects the basal secretory state of parathyroid glands, was increased in 9 hypoparathyroid patients treated with vitamin D3 (VD3) [7 patients with idiopathic hypoparathyroidism] and in seven of nine parathyroid adenectomized patients. There was a negative correlation between the ratio and basal serum Ca level in the patients with IHP after VD3 treatment (r = 0.7167, P < 0.05) and in the patients after parathyroid adenectomy (r = 0.7760, P < 0.05). The regression curves in these two groups coincided regardless of the difference in maximum PTH secretion rate, which suggested that the basal secretory state of parathyroid glands was determined by extracellular Ca level in a similar manner in these subjects. There was a sigmoidal relationship between basal/maximum ratio of serum PTH and basal serum Ca level, when the data were collected from 15 hypoparathyroid patients before or after VD3 treatment, 9 parathyroid adenectomized patients, and 10 normal subjects (r = 0.9057, P < 0.001). This sigmoidal curve is thought to represent the fundamental relationship between the basal secretory state of parathyroid glands and extracellular Ca level.

Adenoma↗

Parathyroid localization by catheterization of large cervical and mediastinal veins to determine serum concentrations of intact parathyroid hormone.

A success rate of about 90% has been achieved after primary operations for hyperparathyroidism, compared with 60% to 80% in most series of secondary operations. The present reoperative series involved 29 patients who underwent venous catheterization with blood sampling for the determination of intact parathyroid hormone before undergoing repeat parathyroid surgery. Blood samples were taken from the internal jugular veins, innominate veins, and superior caval vein. No attempt was made to perform superselective catheterization of the small neck and mediastinal veins. The reoperations were done by four surgeons who did 1, 2, 13, and 13 of the reoperations, respectively. In all patients, distinct step-ups in parathyroid hormone concentrations were found. On average, the gradient between the highest and lowest value was about 5. Close to the location of the step-ups, diseased parathyroid tissue was found in 27 of the patients. In two cases no parathyroid tissue was found, and these patients remained hyperparathyroid postoperatively. They had been treated by the surgeon who did only two of the operations. When the step-up was observed in the left innominate vein, we could not differentiate mediastinal from low cervical adenomas. No patient developed hypoparathyroidism. To avoid this complication, autotransplantation of diseased parathyroid tissue into the abdominal subcutaneous fat was done in nine patients. No case of recurrent laryngeal nerve paralysis occurred. The introduction of reliable assays for the analysis of parathyroid hormone can make selective catheterization unnecessary when localizing remaining parathyroid glands in patients with persistent hyperparathyroidism.

Adolescent↗

Differences in PTH (1-84) release in response to ambient calcium concentrations of parathyroid adenoma fragments and dispersed parathyroid adenoma cells in culture.

In a previous study we observed that during perfusion of normal human parathyroid tissue, the release of PTH (1-84) was modulated by ambient extracellular calcium (Ca++) and lithium (Li+) concentrations in the media and preliminary studies indicated that this stimulus-response coupling was absent in human parathyroid adenoma fragments. The present study compares the responsiveness of parathyroid adenoma fragments and isolated parathyroid adenoma cells from the same adenoma and their response to Ca++ changes and Li+ presence in culture media. The data indicate that parathyroid adenoma tissue fragments fail to respond to ambient changes in Ca++ and Li+. In contrast, dispersed parathyroid cells preparations responded with a significant increase of PTH (1-84) release (50%) under the influence of low ambient calcium concentrations. Six of the dispersed cell preparations also responded with a 45% decrease in PTH release under the influence of a high Ca concentration in the medium. Isolated parathyroid cells obtained from the same adenoma's did not respond to the presence of Li++ in the medium. These data suggest tat human parathyroid adenoma tissue functions autonomously and is not sensitive to calcium regulation in the tissue configuration as opposed to the isolated cell suspensions. The nature of this difference remains elusive.

Adenoma↗

Parathyroid autotransplantation in patients with parathyroid disease and total thyroidectomy. Indications in 117 cases.

Parathyroid autotransplantation is a known and increasingly utilized procedure. It is indicated in patients with primary parathyroid hyperplasia, in patients with primary hypercalcemia who have normal parathyroid tissue devascularized during surgery, in patients with secondary and tertiary parathyroid hyperplasia, and in patients with total thyroidectomy when normal parathyroid tissue is accidentally or unavoidably removed or completely devascularized. No normal viable parathyroid tissue should be autotransplanted. This procedure was performed in 13 dialysis patients, 27 primary hypercalcemic patients and 77 patients with thyroidectomy. The hypercalcemic patients had autotransplantations into muscle pockets in the volar surface of the forearm, while the thyroidectomy patients had autotransplantation into the sternocleidomastoid muscles. The application of parathyroid autotransplantation is a major technical and physiologic breakthrough in the field of thyroid and parathyroid surgery. It should greatly reduce the morbidity associated with permanent hypocalcemia in this type of extensive surgery.

Adult↗

Intraoperative parathyroid hormone levels in thyroid and parathyroid surgery.

OBJECTIVE: To determine the utility of intraoperative parathyroid hormone measurement in predicting postoperative hypocalcemia after thyroid and parathyroid surgeries that places total parathyroid function at risk. STUDY DESIGN: Retrospective case review. METHODS: The case records of 23 patients undergoing total or completion thyroidectomy and 30 patients undergoing parathyroid exploration were reviewed. All patients had intraoperative parathyroid hormone levels measured. Samples were taken before dissection and 10 minutes after the resection was completed. Serial ionized calcium levels were measured in the postoperative period. Percentages of reduction in PTH levels from preoperative to postresection levels were calculated. Percentages of reduction in PTH level and the absolute value of the intraoperative PTH values were compared with postoperative ionized calcium levels. RESULTS: In the 23 patients who underwent thyroid surgery, the average preoperative and postoperative PTH values were 50 pg/mL (range, 17-87 pg/mL) and 34 pg/mL (range, 4-93 pg/mL), respectively. The average decrease in PTH was 39% (range, 39%-90%). The incidence of hypocalcemia was significantly higher in patients with intraoperative PTH levels less than 15 pg/mL relative to patients with PTH levels greater than 15 pg/mL in this setting ( P=.006). In the 30 patients who underwent parathyroid exploration, average preoperative and postoperative PTH levels were 291 pg/mL (range, 65-1675 pg/mL) and 113.8 pg/mL (range, 6.5-1263 pg/mL) respectively. The intraoperative PTH level did not correlate with postoperative calcium levels in the parathyroid group. Percentages of decrease in PTH levels greater than 60% was statistically associated with surgical cure in this population. CONCLUSIONS: The study demonstrates that intraoperative PTH levels greater than 15 pg/mL after total or completion thyroidectomy indicate a low risk of postoperative hypocalcemia and that these patients may be candidates for outpatient surgery. In the parathyroid group, intraoperative PTH levels do not correlate well with postoperative calcium levels.

Calcium↗

Dopamine-stimulated parathyroid hormone release in vitro: further evidence for a two-pool model of parathyroid hormone secretion.

Bovine parathyroid tissue was placed in an in vitro perifusion system for the study of parathyroid hormone secretion stimulated by low calcium and dopamine. Dopamine caused a transient increase in parathyroid hormone release, while low calcium caused a sustained increase in parathyroid hormone secretion. The dopamine response was similar to that caused by isoproterenol. After parathyroid hormone release had been stimulated by dopamine there was no response to isoproterenol, suggesting they cause the release of the same cellular pool of hormone. Inhibition of protein synthesis with cycloheximide eliminated the response to low calcium, with no effect on dopamine-stimulated parathyroid hormone release. These studies suggest dopamine stimulates the release of a limited quantity storage pool of parathyroid hormone, while low calcium causes a sustained release of hormone by stimulating secretion of newly synthesized hormone. Low calcium has little or no effect on release of the storage granule pool of parathyroid hormone.

Animals↗

Regulation of parathyroid hormone release and cytosolic calcium by extracellular calcium in dispersed and cultured bovine and pathological human parathyroid cells.

Alterations in parathyroid glandular sensitivity to calcium may contribute to the hypersecretion of PTH in hyperparathyroidism. Since the cytosolic calcium concentration may mediate the effects of extracellular calcium on PTH release, we have employed the calcium-sensitive intracellular dye QUIN-2 to examine the relationship between extracellular calcium, cytosolic calcium, and PTH secretion in adult, neonatal, and cultured bovine as well as pathological human parathyroid cells. PTH release was measured using C- and N-terminal radioimmunoassays. Neonatal bovine parathyroid cells showed a greater set-point for secretion (the Ca++ concentration causing half of the maximal inhibition of PTH release) than adult cells (1.27 +/- 0.11 vs. 1.06 +/- 0.11 mM extracellular calcium, P less than 0.01), and a slightly higher extracellular calcium was necessary to raise the cytosolic calcium concentration to a given level in neonatal than in adult bovine parathyroid cells. In individual neonatal and adult cell preparations, there was a close correlation between the set-point for secretion and the "set-point" for cytosolic calcium (r = 0.832, P less than 0.001). In cells from five human parathyroid adenomas, which had an increase in set-point for secretion, the extracellular calcium concentration necessary to raise the cytosolic calcium concentration to a given level was slightly greater than in the neonatal cells. In four preparations of human parathyroid cells there was a significant correlation between the set-points for secretion and cytosolic calcium (r = 0.856, P less than 0.01). Because neonatal bovine and pathological human parathyroid glands show cellular hyperplasia, we studied the temporal relationship between cellular proliferation and the regulation of PTH release and cytosolic calcium concentration in cultured bovine parathyroid cells. Cellular proliferation, estimated by 3H-thymidine incorporation, increased significantly in culture from 104 +/- 10.1 counts/well on day 1 (first 24 h in culture) to 588 +/- 188 and 6,156 +/- 649 counts/well on days 2 and 4, respectively. In cultured cells on day 1, highly Ca++ (2-3 mM) inhibited maximal PTH release by 58.8 +/- 3.2%, which decreased significantly (P less than 0.001) to 38.2 +/- 1.9 and 17.1 +/- 3.7% on days 2 and 4, respectively. The cytosolic calcium observed at 3 mM calcium on day 1 was 701 +/- 43 nM, which declined to 466 +/- 60 and 314 +/- 14 nM on days 2 and 4 (P less than 0.05). There was a close correlation between this progressive decrease in maximal inhibition of PTH release and the cytosolic calcium at high extracellular calcium in cultured cells (r = 0.99, P < 0.001). Thus, during active proliferation of cultured cells, there is an alteration in the regulation of cytosolic calcium at a given extracellular calcium concentration, and changes in the regulation of PTH release and cytosolic calcium by extracellular calcium may be related to enhanced cellular proliferation.

Animals↗

Monoclonality of parathyroid tumors in chronic renal failure and in primary parathyroid hyperplasia.

The pathogeneses of parathyroid disease in patients with uremia and nonfamilial primary parathyroid hyperplasia are poorly understood. Because of multigland involvement, it has been assumed that these common diseases predominantly involve polyclonal (non-neoplastic) cellular proliferations, but an overall assessment of their clonality has not been done. We examined the clonality of these hyperplastic parathyroid tumors using X-chromosome inactivation analysis with the M27 beta (DXS255) DNA polymorphism and by searching for monoclonal allelic losses at M27 beta and at loci on chromosome band 11q13. Fully 7 of 11 informative hemodialysis patients (64%) with uremic refractory hyperparathyroidism harbored at least one monoclonal parathyroid tumor (with a minimum of 12 of their 19 available glands being monoclonal). Tumor monoclonality was demonstrable in 6 of 16 informative patients (38%) with primary parathyroid hyperplasia. Histopathologic categories of nodular versus generalized hyperplasia were not useful predictors of clonal status. These observations indicate that monoclonal parathyroid neoplasms are common in patients with uremic refractory hyperparathyroidism and also develop in a substantial group of patients with sporadic primary parathyroid hyperplasia, thereby changing our concept of the pathogenesis of these diseases. Neoplastic transformation of preexisting polyclonal hyperplasia, apparently due in large part to genes not yet implicated in parathyroid tumorigenesis and possibly including a novel X-chromosome tumor suppressor gene, is likely to play a central role in these disorders.

Adult↗

Parathyroid autotransplantation. An investigation of parathyroid autograft function.

During a four-year period, 27 patients underwent total parathyroidectomy with autotransplantation of parathyroid tissue to the forearm. In order to minimize the risk of persistent or recurrent hyperparathyroidism (HPT), a routine thymic resection and a wide excision of fat tissue around the parathyroids was performed to ensure excision of possible supernumerary glands or rudimentary parathyroid tissue. The indications for operation were HPT secondary to chronic renal failure in 24 patients (22 of whom had hypercalcaemia) and persistent or recurrent primary HPT in 2 cases. One further patient, who had a multiple endocrine neoplasia syndrome type I, underwent this procedure at the primary parathyroid operation. Preoperative hypercalcaemia was reversed in all patients but three during the first postoperative days, concomitantly with a fall in the parathyroid hormone (PTH) level. Fourteen patients showed marked hypocalcaemia postoperatively, necessitating calcium or vitamin D supplementation. This medication could later be discontinued in all of them. Thirteen patients, including two of those with primary HPT, never required any supplemental therapy. Survival of the grafts was documented by several observations. In all patients normal serum calcium values were being maintained without supplemental therapy at follow-up. During induced hypocalcaemia a PTH secretory response was demonstrated in all eight studied patients with a gradient between the grafted and non-grafted arm. In two patients in whom the grafts were examined histologically 19 and 28 months after the transplantation, viable parathyroid tissue was observed. In the initial part of the study excised tissue was cryopreserved. Since persistent hypocalcaemia did not occur in our patients, we have now abandoned this safety precaution. Thus, total parathyroidectomy with autotransplantation of parathyroid tissue is a valuable method for restoring long-term parathyroid function in patients with secondary HPT and uraemia. It also appears of value in selected cases of primary HPT.

Adolescent↗

Disruption of the Golgi zone and inhibition of the conversion of proparathyroid hormone to parathyroid hormone in human parathyroid tissue by tris(hydroxymethyl)aminomethane.

Tris(hydroxymethyl)aminomethane (Tris, Tromethamine, THAM) and other non-amphoteric amines were previously reported to inhibit the conversion of proparathyroid hormone to parathyroid hormone in bovine parathyroid glands incubated in vitro. This inhibition correlated with a striking dilation of the Golgi complex. This work has now been extended to normal, hyperplastic, and adenomatous parathyroid glands from human subjects. The tissues were incubated for up to 3 hours with 3H-leucine in physiologic solutions (control) or in the same solutions containing 50 mM Tris. In one case, diethylamine also was tested. Electron microscopy revealed that the amines produced a dilation of the Golgi complex and swelling of vesicles, predominantly in the region of the Golgi zone. Other organelles were normal in appearance. During the same period, Tris reduced by sixfold the ratio of the parathyroid hormone to proparathyroid hormone, from a control value of 2:1 to 1:3. It was apparent that Tris exerted the same biochemical and morphologic actions in human parathyroid tissues as it was previously shown to do in bovine glands. These studies support the concept that the Golgi zone is that region in the parathyroid gland in which proparathyroid hormone to parathyroid hormone conversion is initiated and that Tris inhibits this conversion through disruption of the converting site.

Adenoma↗

Autotransplantation of avian parathyroid glands: an animal model for studying parathyroid function.

The parathyroid glands of chickens were autotransplanted and the return of parathyroid function following transplantation was determined. Parathyroidectomy (PTX) resulted in a marked hypocalcemia (5.2 +/- 0.2 mg/dl) 4 hr following PTX. Plasma calcium (PCa) had declined to 4.3 +/- 0.2 mg/dl 24 hr after PTX. Parathyroid glands were transplanted subcutaneously 24 hr after removal and 24 hr later, PCa had risen to 8.6 +/- 0.5 mg/dl. Seven days after PTX. PCa increased to 10.3 +/- 0.2 mg/dl and by 14 days was indistinguishable from control levels (10.8 +/- 0.2 mg/dl vs. 11.0 +/- 0.2 mg/dl, respectively). When chicks with transplanted glands were fed a low Ca (0.08%) diet for 2 weeks they were able to maintain plasma PCa at levels comparable to control birds. Removal of the transplanted glands resulted in marked decreases in PCa (from 9.7 +/- 0.3 to 5.6 +/- 0.8 mg/dl), in the fractional excretion of phosphate, in urine cAMP, and in renal 25OH-vitamin D3-1 alpha-hydroxylase activity. Stepwise reductions in PCa and 1 alpha-hydroxylase activity were produced in partially PTX and fully PTX chicks by removing part or all of the parathyroid tissue. These data suggest that the transplanted parathyroid tissue was the major source of circulating PTH and that it may be possible to produce different degrees of acute hypoparathyroidism by varying the amount of transplanted parathyroid tissue removed surgically. Chickens with transplanted parathyroid glands thus provide a convenient animal model in which to study parathyroid function in an avian species.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Use of surgeon-performed office ultrasound and parathyroid fine needle aspiration for complex parathyroid localization.

BACKGROUND: This study investigates the utility of ultrasound guided parathyroid fine needle aspiration (FNA) as a localizing technique in patients with hyperparathyroidism (HPT) undergoing re-operative neck surgery or with unusually appearing or ectopically located glands. METHODS: Selected patients with HPT underwent surgeon-performed FNA with ultrasound guidance. Aspirate contents were sent for cytology and parathyroid hormone (PTH) levels. All patients subsequently underwent parathyroid exploration. RESULTS: 54 patients underwent 57 ultrasound guided parathyroid biopsies. Indications for FNA included prior parathyroid (n = 29), thyroid (n = 11), or other neck surgery (n = 2), or unusual parathyroid appearance or location (n = 12). A true positive was defined as a site where the PTH aspirate was >40 pg/mL and a hypercellular gland was removed at surgery. Based on this, there were 44 true positives, 10 true negatives, and 3 false negatives; there were no false positives. The median PTH level in positive aspirates was 11,665 pg/mL. Cytology was primarily helpful in excluding other diagnoses. CONCLUSION: Ultrasound guided FNA is a highly specific localization test for parathyroid tumors. This procedure can be successfully performed by surgeons in the office setting and is extremely valuable for directing parathyroid exploration in challenging cases. We recommend incorporating ultrasound and FNA as a pre-operative localization strategy for selected patients with HPT.

Adult↗

Parathyroid carcinoma versus parathyroid adenoma in patients with profound hypercalcemia.

The metabolic manifestations and operative findings in 10 patients with a diagnosis of parathyroid carcinoma were analyzed to determine whether they differ from those in patients with parathyroid adenomas and similar degrees of hypercalcemia. Two groups of patients with parathyroid adenomas were used for comparison. Group A consisted of eight patients with "atypical" benign adenomas (mean preoperative level of serum calcium: 13.4 mg/dl); group B consisted of 13 patients with benign typical adenomas--all with preoperative serum calcium levels greater than or equal to 13.0 mg/dl (mean: 14.2 mg/dl). The patients with carcinoma (mean preoperative level of serum calcium: 15.3 mg/dl) had a frequency of osteoporosis and osteitis fibrosa cystica (50%) comparable with that of group A (33%) and group B (62%). Seventy percent of the patients with carcinoma had renal disease (nephrolithiasis, nephrocalcinosis, or impaired renal function), whereas only 38% of group A and 15% of group B had similar disorders. The patients with carcinomas had the highest frequency of combined bone and renal disease (50% versus 14% in group A and 15% in group B). Anemia, peptic ulcer disease, and hypertension occurred with similar frequencies in the three groups. Three patients with recurrent parathyroid carcinoma died of profound hypercalcemia, renal failure, or cardiac arrhythmia. In general, although patients with parathyroid carcinomas have more profound metabolic abnormalities than do patients with primary hyperparathyroidism, the metabolic manifestations in patients with parathyroid carcinoma are comparable with those in patients with parathyroid adenomas and profound hypercalcemia. Furthermore atypical adenomas share many anatomic and histopathologic features with parathyroid carcinomas, and distinguishing between the two is sometimes possible only in cases of tumor recurrence.

Adenoma↗