Primary hyperparathyroidism associated with two enlarged parathyroid glands

An increasingly recognized although small percentage of patients with primary hyperparathyroidism have enlargement of two parathyroid glands. We have treated nine patients with primary hyperparathyroidism associated with such double parathyroid gland enlargement. In four of these patients, marked asymmetry of the two enlarged glands was noted and the failure to recognize and excise a second enlarged parathyroid gland resulted in persistent or recurrent hyperparathyroidism. In one of these patients, the second enlargement was present in a super-numerary mediastinal gland. The subsequent excision of the second enlarged parathyroid gland resulted in normocalcemia in each instance. This contrasts with five patients in whom initial excision of two enlarged glands resulted in normocalcemia with no recurrence of hypercalcemia. Only three patients fulfilled the histologic criteria of true double adenomas. The remainder showed multiglandular hypercellularity. This experience supports identifying all parathyroid glands and recognizing that even minimal enlargement of a gland may be important pathophysiologically, regardless of its histopathologic classification. Excision of both enlarged glands, even if asymmetric, is appropriate.     

Multiple parathyroid adenomas: report of thirty-three cases

An increasing number of patients with primary hyperparathyroidism are found to have two or three enlarged parathyroid glands. Of 865 patients successfully operated on by one surgeon (J.N.A.), multiple enlarged parathyroid glands (adenomas) were found and resected in 33 cases (3.8%), with resulting normocalcemia lasting from 1 to 22 years (mean 5.8). Twenty-nine patients had two adenomas and four had three adenomas. In 28 patients the multiple adenomas were synchronous. Twenty-five patients underwent removal of all of the enlarged parathyroid glands in one operation; in three patients one adenoma was removed, reoperation for persistent hypercalcemia was performed, and a second adenoma was resected with cure. In five patients one adenoma was removed, normocalcemia ensued for 3 to 18 years, and a second (metachronous) adenoma occurred and was resected successfully. Although 10 of 70 enlarged parathyroid glands removed were labeled hyperplasia, cure in all but one of our patients by selective resection of only enlarged parathyroid glands emphasizes the unreliability of histologic criteria in differentiating between parathyroid adenoma and hyperplasia. Based on this study, we support the existence of multiple adenomas and advocate removal of only macroscopically enlarged parathyroid glands in patients with primary hyperparathyroidism.     

Anatomical heterogeneity of parathyroid glands in posttransplant hyperparathyroidism

Successful renal transplantation may be complicated by persistent hyperparathyroidism due to diffuse parathyroid hyperplasia remaining from a prolonged period of pretransplant chronic renal failure treatment. Posttransplant hyperparathyroidism is distinct from primary hyperparathyroidism, being characterized by multiple gland involvement and diffuse hyperplasia rather than a single adenoma. The gross pathologic anatomy of the parathyroid glands was assessed in 17 successful renal transplant recipients. Individual and total gland volumes were measured at the time of total parathyroidectomy and forearm reimplantation. Parathyroid hyperplasia was heterogenous in both location and gland size. Right-sided glands were enlarged more than left-sided ones. Subjects with primary tubulointerstitial disease exhibited greater hyperplasia than patients with glomerular disorders. Clinicians should be aware of the heterogeneity of the gland enlargement in patients with diffuse parathyroid hyperplasia, so that these patients are not misdiagnosed as suffering from adenomatous parathyroid disease.     

Initial failure of surgical exploration in patients with primary hyperparathyroidism

To determine the causes of failures of cervical exploration for primary hyperparathyroidism, we reviewed 892 patients operated on by one surgeon from 1953 to 1990. Twenty-seven patients (3%) remained hypercalcemic or developed hypercalcemia within 6 months of surgery. Of these, five patients had one adenoma removed initially; at reoperation, three patients had a second adenoma that was successfully removed, whereas the other two patients had hyperplasia and required subtotal parathyroidectomies. No enlarged parathyroid glands were identified in 22 patients. Eventually, six patients became normocalcemic spontaneously, seven patients underwent re-exploration with a successful outcome in all but one case, two patients had ectopic hyperparathyroidism associated with carcinoma elsewhere, and seven patients refused reoperation and remain hypercalcemic. The failure rate of surgical exploration for primary hyperparathyroidism can be reduced by systematically exploring all four parathyroid glands. All abnormal parathyroids should be removed with histologic verification. When no abnormal glands are found, localization studies should be performed before re-exploration.     

The role of hyperplasia in multiple parathyroid adenomas

BACKGROUND: Parathyroid adenoma is the most common cause of primary hyperparathyroidism (pHPT). Adenomas usually involve only a single gland, and the remaining glands are normal or suppressed. Multiple parathyroid adenomas have been reported to occur in as high as 11% of patients with pHPT. The significant incidence of multiple adenomas with histologic similarities to hyperplasia has raised the possibility that adenoma is a continuation of the hyperplasia state. To test this theory, we used molecular genetics to compare clonality and proliferative activity of parathyroid adenoma with its corresponding normal glandular tissue. Furthermore, we devised a scheme to definitively distinguish between the different parathyroid states on a molecular level, because histologic distinction is unreliable. METHODS: The study included three patients with a diagnosis of singular parathyroid adenoma and three with double parathyroid adenomas. Paraffin-embedded surgical specimens of both adenomas and normal glands were retrieved from each patient. Clonal analysis of the phosphoglycerolkinase (PGK) gene has suggested that parathyroid adenomas are monoclonal. Clonality of parathyroid adenomas and normal parathyroid glands was studied by polymerase chain reaction-based restriction fragment length polymorphic analysis for the PGK gene. Proliferative activity of the specimens was also analyzed using the immunohistochemical markers PCNA and Ki-67. RESULTS: All adenomas were monoclonal and all normal parathyroid glands were polyclonal for the PGK gene in both the single and double adenoma specimens. All adenomas stained positive for proliferative activity. In the three patients with singular adenoma, proliferative activity was not detected in the normal parathyroid tissue. However, in the double adenoma group, two of the three patients showed hyperproliferative activity in the normal glands. CONCLUSION: Proliferative activity consistent with hyperplasia was present in some normal glands of multiple adenoma patients. Our observation supports the theory that multiple adenomas may be a continuation of the hyperplasia state.     

Results of operative treatment of 615 patients with primary hyperparathyroidism

This is a report of 615 patients who were operated on for primary hyperparathyroidism during the 20 years from 1950 to 1979. There were twice as many females in the series as males, mainly because of a sharp rise in the incidence in females over the age of 45 years. Identification of all parathyroid glands and confirmation by frozen section was always attempted. Only macroscopically enlarged glands were removed, regardless of histologic findings. Enlargement of 1 gland was found in 433 patients, of 2 glands in 106, and of 3 glands in 43. In 33 patients all glands were enlarged. Bilateral exploration of the neck is mandatory in order to prevent persistent hyperparathyroidism. An abnormal location of parathyroid glands was found in 263 patients; location within the thymus was the most frequent. Most ectopically located parathyroids can be removed through the neck. Sternotomy gave disappointing results; in only 3 of 9 patients was an enlarged parathyroid found. Persistent hyperparathyroidism necessitating reoperation occurred in 25 patients. The results of reoperation were not as favorable as those of primary operations and gave rise to more complications, especially inadvertent removal of all parathyroid tissue. The mean follow-up time was 5.6 years. During this period no patient developed true recurrent hyperparathyroidism arising in a previously identified normal appearing gland. Therefore, we advise removal of only those glands that are macroscopically enlarged.     

Parathyroidectomy by elective route with perioperative measurement of parathyroid hormone. Report of 80 cases

STUDY AIM: The aim of this study was to report a series of 80 patients treated by unilateral neck exploration for a sporadic primary hyperparathyroidism. PATIENTS AND METHOD: Between April 1992 and November 1998, 80 patients (65 women and 15 men, mean age: 63.5 years) with a single gland enlargement localized by ultrasonography, were operated on through a short unilateral neck incision, under general anesthesia in 72 cases and local in eight cases. The enlarged gland was removed with intraoperative pathological examination and intraoperative monitoring of parathyroid hormone. RESULTS: Mean duration of surgery was 25 minutes. There was no postoperative mortality or morbidity. Mean duration of hospital stay was two days. The enlarged gland was an adenoma in 75 cases and an hyperplasia in five. Adequate intraoperative parathyroid hormone decrease was observed. Postoperative calcemia was normal in 78 patients (97.5%). Among 76 surviving patients, with a 31-month follow-up, there was only a suspicion of persistent hyperparathyroidism in two patients. CONCLUSIONS: Minimal invasive approach by unilateral neck exploration may be performed with safety and efficiency in patients with a single gland enlargement under intraoperative monitoring of parathyroid hormone.     

Influence of 1,25-dihydroxycholecalciferol on parathyroid activity in patients with primary hyperparathyroidism.

Parathyroid morphology and blood chemistry were studied in five patients with primary hyperparathyroidism treated with 1,25-dihydroxycholecalciferol (1,25-DHCC) for 2 to 11 days before planned operation. Before the institution of treatment all patients were hypercalcemic, whereas the serum immunoreactive parathyroid hormone (iPTH) concentration either was elevated or normal. During the treatment the urinary phosphate excretion was significantly increased, whereas the calcium excretion and the serum concentrations of calcium and phosphate were unaffected or only slightly changed. Serum iPTH decreased during the first days of treatment, but returned then to increased levels close to the pretreatment ones. The treatment was tolerated well by the patients. Light and electron microscopy of the removed parathyroid glands disclosed one adenoma in each of the five patients, the other glands exhibiting either a slight hyperplasia or a normal appearance. Both the adenomatous and the non-adenomatous parathyroid tissue showed a predominance of dark chief cells and three of the adenomas exhibited a varying number of atrophic and oxyphil cells. The non-adenomatous glands were composed of atrophic and dark chief cells. Signs of low functional activity were ultrastructurally observed in the parathyroid parenchymal cells. It is suggested that 1,25-DHCC treatment of patients with primary hyperparathyroidism inhibits parathyroid hormone secretion.     

Long-term follow-up of patients with tertiary hyperparathyroidism treated by resection of a single or double adenoma

OBJECTIVE: To determine whether patients with tertiary hyperparathyroidism due to single- or two-gland disease undergoing limited resection have similar long-term outcomes compared with patients with hyperplasia undergoing subtotal or total parathyroidectomy. SUMMARY BACKGROUND DATA: Tertiary hyperparathyroidism occurs in less than 2% of patients after renal transplantation. Approximately 30% of these cases are caused by one or two hyperfunctioning glands. Nevertheless, the standard operation for this disease has been subtotal or total parathyroidectomy with autotransplantation. METHODS: Seventy-one patients underwent surgery for tertiary hyperparathyroidism. At the time of surgery, 19 patients who had a single or double adenoma underwent limited resection of the enlarged glands only (adenoma group). The remaining 52 patients with three- or four-gland hyperplasia had subtotal or total parathyroidectomy with implantation (hyper group). Long-term cure rates between the two groups were compared. RESULTS: In the adenoma group, 7 patients had a single adenoma and 12 underwent resection of a double adenoma. In the hyper group, 49 patients had subtotal and 3 had total parathyroidectomies. After surgery, 70 of 71 patients (99%) were cured of their hypercalcemia. The incidence of postoperative transient hypocalcemia was significantly higher in the hyper group (27% vs. 5%). No patients in either group had permanent hypocalcemia requiring long-term supplementation. With up to 16 years of follow-up, there have been no recurrences in the adenoma group, whereas three patients (6%) in the hyper group have had recurrent or persistent hyperparathyroidism. CONCLUSIONS: Patients with tertiary hyperparathyroidism who underwent limited resection of a single or double adenoma only had equivalent long-term cure rates compared with patients undergoing more extensive resections. Therefore, the authors recommend in patients with tertiary hyperparathyroidism and enlargement of only one or two parathyroid glands that the resection be limited to these abnormal glands only.     

Sensitivity and Utility of Parathyroid Scintigraphy in Patients with Primary Versus Secondary and Tertiary Hyperparathyroidism

Introduction Parathyroid scintigraphy (PS) may be used to localize hyperactive parathyroid glands preoperatively. Performance of PS in the setting of secondary and tertiary hyperparathyroidism (HPT) is not well quantified. The performance of PS in secondary/tertiary HPT versus primary HPT may reflect physiologic as well as radiopharmaceutical kinetic differences between multigland hyperplasia versus adenoma. The aim of this study was to review the performance of PS in secondary/tertiary HPT with a comparison to that for primary HPT. Moreover, we evaluated (1) the sensitivity of PS in detecting enlarged glands, and (2) PS detectability as a function of gland weight. Methods We performed a retrospective review of the Mayo Clinic database from 2000 to 2004. We identified 40 patients with secondary or tertiary HPT as well as a matched control group of 40 patients with primary HPT who had had preoperative PS and underwent parathyroid surgery. Results Parathyroid scintigraphy correctly localized all enlarged glands in 88% of patients in the primary HPT group. PS correctly identified both the number and locations of all hyperplastic glands in only 28% of the secondary/tertiary HPT patients. PS failed to identify one enlarged gland in 23% of the patients and two or more enlarged glands in 40% of the patients. PS correctly detects the largest gland in 88% of the patients with secondary and tertiary HPT. The mean gland weight detectable by PS was 612 ± 120 mg for primary HPT. In secondary/tertiary HPT, glands detected by PS had a mean weight of 950 ± 109 mg, whereas the mean weight was 276 ± 34 mg for undetected glands (P < 0.002). Conclusions Parathyroid scintigraphy is a sensitive study for localizing parathyroid glands preoperatively in primary HPT patients. Its sensitivity is low in secondary and tertiary HPT patients. Thus PS has limited value as a preoperative localization study in secondary/tertiary HPT patients.     

Prospective evaluation of the efficacy of technetium 99m sestamibi and iodine 123 radionuclide imaging of abnormal parathyroid glands.

BACKGROUND. Technetium 99m sestamibi is an isonitrile radionuclide imaging agent that, when used with subtraction iodine 123 thyroid scans, has the potential for imaging abnormal parathyroid glands. METHODS. We prospectively evaluated 20 patients with hyperparathyroidism to study the efficacy of Tc 99m sestamibi and 123I subtraction radionuclide scanning for the imaging of abnormal parathyroid glands. All patients underwent neck exploration and histologic confirmation of all parathyroid glands identified. RESULTS. The solitary adenomas in 11 of 16 patients with primary hyperparathyroidism were localized with sestamibi scans. The scans in four of five patients with diffuse parathyroid hyperplasia showed bilateral localization consistent with enlarged glands. The fifth patient previously underwent a subtotal parathyroidectomy, and a fifth supernumerary gland was localized with the sestamibi scan. Four patients had hyperparathyroidism related to kidney disease. Three of these had bilateral localization of enlarged glands. The fourth patient had undergone two previous operations, and a fifth supernumerary gland was localized with the sestamibi scan. CONCLUSIONS. The preliminary data indicate that Tc 99m sestamibi in combination with 123I radionuclide scanning may be useful in the preoperative localization of abnormal parathyroid glands. This technique localized all of the solitary adenomas that were subsequently resected, and in two reoperative cases it identified the remaining solitary gland causing persistent hypercalcemia.     

Heterogeneous gland size in sporadic multiple gland parathyroid hyperplasia

BACKGROUND: The success rate for bilateral exploration in patients with primary hyperparathyroidism approaches 95%. Multiglandular parathyroid hyperplasia accounts for approximately 10% to 30% of primary hyperparathyroidism. The incidence of recurrent or persistent hyperparathyroidism is highest in familial forms of the disease, in which multiglandular disease is more common; this may be due to asymmetric enlargement of parathyroid glands. Because of improvements in tumor-imaging capability, some surgeons are now advocating unilateral exploration for primary hyperparathyroidism, but there is limited experience concerning how often these imaging methods fail. STUDY DESIGN: The outcomes of 7 patients who had sporadic primary hyperparathyroidism with multigland hyperplasia were reviewed. We gathered demographic data and laboratory values and reviewed radiologic tests, surgical findings, pathologic findings, and postoperative followup. RESULTS: All patients underwent preoperative localization with ultrasonography and technetium/sestamibi scans. The sensitivity of these two tests for the dominantly enlarged gland was 100% for both, but dropped to 0% and 5%, respectively, for all other enlarged glands. The sensitivity of CT and MRI for the dominant tumor was 67% (2 of 3) and 50% (1 of 2), respectively. Six of 7 patients underwent subtotal (3(1/2) gland) parathyroidectomy. The mean volume of all glands was 1.51+/-5.89 cm3 compared with a mean of 5.66+/-11.4 cm3 for all dominant glands and 0.123+/-0.1 cm3 for all nondominant hyperplastic glands. There was a large amount of variability between the volumes of dominant and other glands as demonstrated by large SDs from the mean. CONCLUSIONS: There is a marked heterogeneity in gland size in patients with sporadic multigland hyperplasia, which is similar to that found in multiple endocrine neoplasia type I. This heterogeneity may result in failure to recognize multigland disease if a unilateral neck exploration is performed. Intraoperative parathyroid hormone assay may prove to be an important adjunct in this population of patients who have unsuspected multigland disease.     

The rationale against routine subtotal parathyroidectomy for primary hyperparathyroidism

Our therapeutic approach to the treatment of primary hyperparathyroidism has been the resection of only the abnormally enlarged parathyroid gland, the normal-appearing parathyroids being left intact. During the past twenty-five years we have operated on 292 patients with primary hyperparathyroidism. In all cases the serum calcium levels returned to within normal limits during the immediate postoperative period, and there were no instances of permanent hypoparathyroidism. To determine the long-term efficacy of this therapeutic approach, a retrospective study of 101 patients operated on for primary hyperparathyroidism during a nine year period from July 15, 1965 through June 30, 1974 was made. Of the 101 patients, eight were dead and nine could not be located. Of the remaining eighty-four patients, only two required reoperation because of recurrent hypercalcemia; one had MEA-I and eventually three and a half glands were removed, and the other had recurrent hypercalcemia after a three year normocalcemic interval, and after a second operation with resection of an enlarged parathyroid gland, he has remained normocalcemic. The other eighty-two patients (97 per cent of those reevaluated and 82 per cent of the total operated on) have remained symptom-free and normocalcemic for periods ranging from three to twelve years. Only one patient (if we exclude the patient with MEA-I) has elevated serum parathormone levels with borderline levels of serum calcium. Our results suggest that the optimal surgical treatment of primary hyperparathyroidism, except for cases of MEA, is resection of only the abnormally enlarged parathyroid glands after exploration and identification of all four glands in every case. If all four glands are enlarged, three and a half should be resected.     

Clinical characteristics and surgical treatment of sporadic primary hyperparathyroidism with emphasis on chief cell hyperplasia

In 570 patients with sporadic primary hyperparathyroidism, the age, sex, symptoms, and preoperative serum calcium values were related to the histopathologic diagnoses, operative findings, and the extent and outcome of parathyroid surgery. Renal stone formation was especially prevalent in younger patients with slight hypercalcemia and parathyroid chief cell hyperplasia, whereas neuromuscular and psychiatric disturbances were overrepresented among older women with higher serum calcium values. Serum calcium concentration was inversely correlated to the proportional incidence of chief cell hyperplasia and positively correlated to the glandular weight of both adenomas and hyperplasias. Glandular size was markedly irregular in chief cell hyperplasia, with increased gland weights of no more than two glands in 78% of patients. During follow-up, for as long as 27 years, normocalcemia was obtained in 91% of patients with adenomas, with failures mainly depending on difficulties in identifying the parathyroid glands. The rate of normocalcemia was lower (80%) among patients with hyperplasia, but an inability to visualize the glands was not a major cause of failure. In patients with hyperplasia with asymmetric and more markedly enlarged glands, it appeared sufficient to remove only the enlarged glands, whereas the findings advocated a subtotal 3- to 3.5-gland resection in patients with more symmetrically or less enlarged hyperplastic glands.     

A Density Test for the Intraoperative Differentiation of Parathyroid Hyperplasia from Neoplasia

A simple, instant, and reliable test called the Density Test, based on the difference in density between the normal and the diseased parathyroid tissue, was performed intraoperatively in 73 patients with primary hyperparathyroidism. Whereas the normal parathyroid tissue floated, the diseased tissue invariably sank in a mannitol solution with a density range between 1.049 and 1.069. With the aid of this test, a diagnosis of adenoma was made in 66 patients and of primary hyperplasia in the remaining seven. In every case the diagnosis was subsequently confirmed. Forty-two of the 66 patients with an adenoma (64%) had a unilateral exploration of the neck. The Density Test saved these patients from an unnecessary contralateral exploration by the finding of an adenoma and a normal second gland in the same side of the neck. These data show that the Density Test is useful in the intraoperative diagnosis of a diseased from a normal parathyroid tissue. Tissue that sinks within the density range of 1.049 and 1.069 is without exception diseased and should therefore be either partially or completely excised even if the gland is of average size or only of slight enlargement. If it does not sink, it is virtually certain to be normal and should be spared. The Density Test provides a valuable clue in the differentiation of primary parathyroid hyperplasia from neoplasia.     

The role of transcervical thymectomy in patients with hyperparathyroidism

BackgroundThe most common location for supernumerary or ectopic parathyroid glands is the thymus.MethodsA review of patients who underwent parathyroidectomy for hyperparathyroidism from 1990 to 2010 was completed to determine indications for thymectomy, the yield of parathyroid tissue, and outcome of therapy.ResultsSeventy of 379 patients with hyperparathyroidism underwent parathyroidectomy and transcervical thymectomy. Intrathymic parathyroid tissue was present in 23 (33%) patients, including supernumerary glands in 8 patients (11%). Indications for thymectomy were renal hyperparathyroidism in 35 patients (50%) and primary hyperparathyroidism with a missing inferior gland in 20 patients (29%), an ectopic adenoma in 9 patients (13%), hyperplasia in 5 patients (7%), and carcinoma in 1 patient (1%). Cure rates were similar (96% and 98%; P = not significant) and only transient hypocalcemia was higher (51% vs 24%, P < .05) after parathyroidectomy with thymectomy versus parathyroidectomy alone.ConclusionsTranscervical thymectomy results in a high yield of parathyroid tissue and is essential for cure of selected patients with hyperparathyroidism.     

Intraoperative fall in plasma levels of intact parathyroid hormone after removal of one enlarged parathyroid gland in hyperparathyroid patients.

Plasma levels of intact parathyroid hormone (PTH) were measured intraoperatively before and after removal of one enlarged gland in 20 hyperparathyroid patients. In 13 patients with a single parathyroid adenoma, plasma levels of intact PTH-(1-84) had declined at 15 min after removal of the adenoma by 86.5 +/- 4.4% of baseline in the antecubital vein and by 85.6 +/- 4.2% in the ipsilateral internal jugular vein. In seven patients with parathyroid hyperplasia, the corresponding figures for decline at 15 min after removal of one enlarged parathyroid gland were only 26.6 +/- 6.4% and 7.8 +/- 29.4%. The fall in PTH levels was significantly less in hyperplasia than in adenoma (p less than 0.001). Thus 15 min after removal of one enlarged parathyroid gland, the decline in plasma level of intact PTH may distinguish between single adenoma and multiglandular disease as the cause of hyperparathyroidism.     

A hemodialysis patient with secondary hyperparathyroidism in whom primary parathyroid adenoma was resected 27 years previously

We report here a dialysis patient with secondary hyperparathyroidism who had a history of parathyroidectomy for primary hyperparathyroidism 27 years previously. The patient was a 48-year-old male. In 1974, he was diagnosed as having primary hyperparathyroidism and an adenoma was completely resected in the Department of Urology, Osaka University Hospital. In 1997, he started hemodialysis for chronic renal failure by diabetic nephropathy. Since his intact-PTH was high, we started intravenous vitamin-D pulse therapy, but intact-PTH did not decrease. We could not detect any parathyroid glands by ultrasonography and 201TlCl-99mTcO4-scintigraphy around the thyroid gland. Finally, chest-CT and 99mTc-MIBI scintigraphy revealed a ectopic parathyroid gland in the mediastine, and the ectopic parathyroid gland was successfully resected in July, 2001. In order to distinguish whether the resected ectopic parathyroid gland was due to primary adenoma or secondary hyperplasia, we used an immunohistochemical technique to examine the expression of PRAD1/cyclin D1, Ki67, and p27 and sequence analysis of the MEN1 gene. As a result, the labeling index (LI) of PRAD1/cyclin D1 was 4, LI of Ki67 was 36, and LI of p27 was 257. Moreover, germline-mutation and somatic-mutation of MEN1 gene was not detected. These findings suggested that the resected parathyroid gland was a nodular hyperplasia of secondary hyperparathyroidism. In conclusion, immunohistochemical findings of parathyroid tissue and sequence analysis of MEN1 gene could be useful for the differential diagnosis of primary adenoma and secondary hyperplasia.     

Expression of TRAIL and Fas in Primary Hyperparathyroidism

Aim: Differentiating between parathyroid lesions is still difficult and ambiguous. In cases of primary hyperparathyroidism, appropriate and prompt diagnosis is of great importance for effective treatment and follow-up. A great amount of mechanisms contribute to the pathogenesis of primary hyperparathyroidism, such as disturbance in balance between pro- and anti-apoptotic factors. Therefore, we examined whether immunohistochemical expression of apoptotic factors, TNF-related apoptosis-inducing ligand (TRAIL) and Fas, could have clinical utility as a marker of proliferative lesions of parathyroid gland. Materials and methods: Parathyroid specimens of 58 consecutive patients who had undertaken surgery due to primary hyperparathyroidism were incubated with purified mouse monoclonal antihuman antibodies: anti-TRAIL and anti-Fas. Staining was considered positive when at least 5% of the cells showed immunoreactivity. Results: The percentage of cells which were positively stained for TRAIL in parathyroid hyperplasia was 9.65%, in parathyroid adenoma 8.31%, and in normal controls 2.24%. Immunoreactivity for TRAIL was detected in 91.89% of parathyroid hyperplasias, 85.71% of parathyroid adenomas, and none in healthy glands. The percentage of cells with a positive reaction to Fas in parathyroid hyperplasia was 8.92%, in parathyroid adenoma 8.09%, and in normal tissue 1.9%. The expression of Fas was found in 94.59% of parathyroid hyperplasias, 90.48% of parathyroid adenomas, and none in healthy glands. Conclusions: In our study, hyperplasias demonstrated the highest expression of TRAIL and Fas, whereas in adenomas it was increased compared to normal tissue, but lower than in hyperplasias. These factors could be an additive tool in the differential diagnosis of parathyroid lesions.     

Hyperparathyroidism in multiple endocrine neoplasia syndrome.

BACKGROUND. We analyzed clinical findings and results of parathyroidectomy in 42 patients treated from 1936 to 1988 at the University of California, San Francisco (UCSF) for primary hyperparathyroidism and multiple endocrine neoplasia (MEN) syndrome to document results of parathyroidectomy and reasons for failed parathyroid operations. METHODS. Of the 42 patients (38 had MEN 1 syndrome; 4 had MEN 2A syndrome), 40 patients were treated surgically: 29 had initial parathyroidectomy at UCSF; 11 were referred to UCSF because of MEN syndrome. Eight of these 11 patients required reoperation for persistent or recurrent hyperparathyroidism. Patients with hyperplasia were treated with subtotal parathyroidectomy; the glands of those patients with solitary or double adenomas were removed with or without biopsy of the normal appearing glands. RESULTS. Overall, in seven (50%) of 14 patients with hyperplasia, three (16%) of 19 patients with solitary adenoma, and one (14%) of seven patients with double adenomas, recurrent or persistent hyperparathyroidism developed. Failure in patients with hyperplasia was due to missed supernumerary glands (13%) and missed ectopic glands (33%). Failure occurred in patients with solitary (three patients) or double (one patient) parathyroid tumors because of unrecognized hyperplasia. None of the four patient with MEN 2A syndrome had persistent or recurrent disease, but hypoparathyroidism developed in one patient; hypoparathyroidism developed in three patients with MEN 1 syndrome. CONCLUSIONS. These data suggest that although many patients with primary hyperparathyroidism and MEN syndrome have multiple abnormal parathyroid glands, two populations of patients exist; one population has solitary or double adenomas and recurrence is uncommon, whereas the other population of patients has hyperplasia and persistent or recurrent disease is common.