Double Parathyroid Adenomas Research Articles

Existence and Anatomic Distribution of Double Parathyroid Adenoma

Existence and Anatomic Distribution of Double Parathyroid Adenoma

Clinical and surgical aspects of double adenoma in patients with primary hyperparathyroidism.

The incidence of double parathyroid adenoma in 277 prospectively documented patients suffering from primary hyperparathyroidism was 5.4 per cent (15 patients). Patients with double adenoma were all symptomatic and had a significantly higher parathyroid hormone (PTH) level and tumour weight than those with a solitary adenoma or four-gland hyperplasia. In 11 patients the adenomas were located bilaterally. Bilateral neck exploration must be performed routinely to deal successfully with this condition at initial operation. In six patients one enlarged gland was found in the thymus or posterior mediastinum. These locations should be explored, especially in patients with high PTH levels, in those in whom all four parathyroid glands cannot be detected or if only one small adenoma is found. In all such patients, selective resection of the enlarged parathyroid glands resulted in normocalcaemia (median follow-up 3.5 years). Selective resection of the pathological glands is the treatment of choice.

Existence and Anatomic Distribution of Double Parathyroid Adenoma

Double parathyroid adenomas occur in 2% to 15% of primary hyperparathyroidism cases, but the very existence of double adenomas has been controversial. This study was conducted to evaluate the clinical significance and anatomic distribution of parathyroid double adenomas. Mono-institutional retrospective study of the medical records of 183 unselected consecutive patients who underwent intervention for primary hyperparathyroidism between 1996 and 2003. A total of 14 (7.65%) patients were found to have double parathyroid adenomas. Intraoperative parathyroid hormone (PTH) levels were measured in every case. Two enlarged parathyroid glands were identified in four possible configurations: two both superior, one both inferior, two both right, three both left, two right superior and left inferior, and three left superior and right inferior. There was a preferential crossed bilateral distribution of double adenomas. In all patients, intraoperative PTH levels dropped by at least 50% from baseline after removal of both abnormal parathyroid glands. In this series, no patient developed persistent hypoparathyroidism or had recurrent laryngeal nerve injuries or neck hematoma. All patients remained normocalcemic 9 to 96 months postoperatively. One patient had persistently elevated PTH values with normal serum calcium levels. The drop in intraoperative PTH levels and maintenance of normocalcemia postoperatively confirm previous reports that double adenomas do exist and are not simply missed cases of four-gland hyperplasia. There was a preferential crossed bilateral distribution of double adenomas in this series.

The clinical significance and anatomic distribution of parathyroid double adenomas.

Parathyroid double adenomas are reported to occur in 3% to 12% of cases of primary hyperparathyroidism, but the very existence of double adenomas has been controversial. This study was undertaken to evaluate the clinical significance and anatomic distribution of parathyroid double adenomas. The medical records of 384 consecutive patients who underwent operation for primary hyperparathyroidism were reviewed. A total of 27 patients (7%) were found to have double parathyroid adenomas. Intraoperative parathyroid hormone (PTH) levels were measured in each case. Two enlarged hypercellular parathyroid glands were identified in 6 possible configurations: 10 both superior, 3 both inferior, 5 both right, 3 both left, 5 right superior and left inferior, and 1 left superior and right inferior. There was preferential distribution to the bilateral superior position (p = 0.008). In all patients intraoperative PTH levels dropped by at least 50% from baseline and into the normal range after removal of both abnormal parathyroid glands. All patients remain normocalcemic 1 to 26 months postoperatively. Two patients have persistently elevated PTH values with normal serum calcium levels. The drop in intraoperative PTH levels and maintenance of normocalcemia postoperatively confirm previous reports that double adenomas do exist and are not simply missed cases of four-gland hyperplasia. Their incidence is more than would be expected by chance alone. The preferential occurrence of bilateral superior double adenomas suggests the possibility that these may represent hyperplasia of parathyroids arising from the fourth branchial pouch rather than isolated neoplastic events.

Section 1. Parathyroid: Intraoperative quick parathyroid hormone assay in the surgical management of hyperparathyroidism

Intraoperative quick parathyroid hormone (QPTH) assay is claimed to prevent failure during parathyroidectomy for hyperparathyroidism. The causes of operative failure have included multiglandular disease, ectopic parathyroid glands, supernumerary parathyroid glands, errors in frozen section evaluations, and missed diagnosis. A QPTH assay has been recognized as a useful method of determining whether hyperfunctioning tissues have been completely excised. However, an intraoperative QPTH assay may fail to detect the presence of double parathyroid adenomas. Use of this assay in conjunction with preoperative and intraoperative localization studies has led to the advocacy of more directed cervical procedures, such as limited, video-assisted, and endoscopic parathyroidectomy.

原発性上皮小体腺腫(double adenoma)の2例

Most cases of primary hyperparathyroidism are a single adenoma and double parathyroid adenomas are rare. If two swollen glands are detcted at the back of the thyroid lobes, we consider that the cause of the primary hyperparathyroidism is double parathyroid adenomas or hyperplasia. Recently, we treated two cases of double parathyroid adenomas. Two swollen glands were removed, and the values of serum calcium and parathyroid hormone were normalized after surgical treatment. These cases are discussed with reference to the procedures of preoperative diagnosis and surgery.

Intraoperative parathyroid hormone monitoring fails to detect double parathyroid adenomas: A 2-institution experience

Background. We hypothesized that intraoperative parathyroid hormone monitoring (IOPTH) reliably would detect double parathyroid adenomas. Methods. This was a retrospective study of 20 patients undergoing conventional parathyroidectomy with resection of exactly 2 abnormal glands. Full exploration was performed regardless of IOPTH values, which were measured after anesthetic induction and 5 and 10 minutes following removal of the first abnormal parathyroid gland. Failure to fall below 50% of baseline value by 10 minutes following resection of the first gland indicated the presence of multiglandular disease. Results. All patients were cured. All excised glands were hypercellular on histology. Mean IOPTH values in 9 of the 20 patients with true negative results (noncurative decrease, another gland present) were 66% ± 7% at 5 minutes and 83% ± 15% at 10 minutes. The IOPTH values in 11 of the 20 patients with false positive results (curative decrease, another gland present) were 28% ± 4% at 5 minutes and 18% ± 2% at 10 minutes. The false positive rate of IOPTH was 55%. Conclusions. We found that IOPTH failed to reliably detect the presence of double parathyroid adenomas. These data suggest that caution should be exercised when terminating limited parathyroid exploration based on a curative fall in IOPTH values. (Surgery 2001;130:1005-10.)

Synchronous water-clear cell double parathyroid adenomas a hitherto uncharacterized entity?

Water-clear cell hyperplasia is a rare but well-documented cause of primary hyperparathyroidism. Parathyroid adenomas of the water-clear cell type are exceptionally rare, and only 2 cases have been reported. We describe a patient with synchronous water-clear cell double parathyroid adenomas, an entity that has not previously been reported. In our case, the enlarged superior parathyroid glands were completely replaced by water-clear cells, with only a minute rim of extracapsular, histologically unremarkable parathyroid tissue. The inferior parathyroid glands were grossly unremarkable, and incisional biopsy specimens were histologically normal (no foci of water-clear cells were identified). The findings in this case are most consistent with the diagnosis of double adenomas of the water-clear cell type. We acknowledge that despite molecular proof of monoclonality of the 2 lesions, it is not possible to entirely exclude the possibility that this unusual case could be due to asymmetric hyperplasia.

The role of hyperplasia in multiple parathyroid adenomas.

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. 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. 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. 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.

Double parathyroid adenoma, a clinically nondistinct entity of primary hyperparathyroidism.

Double parathyroid adenoma (DA) has been suggested to be a clinically distinct entity of primary hyperparathyroidism (HPT). Altogether 659 patients with sporadic primary HPT were analyzed retrospectively by evaluating consecutive primary operations for more than three decades. Patients with postoperatively persistent HPT and those with incomplete medical, operative, or histologic records were disregarded. The mean age (+/- SD) at surgery was 60.9 +/- 12.7 years; 78% of the patients were female; and the duration of postoperative follow-up averaged 7.8 +/- 7.2 years. DA, defined as two enlarged parathyroid glands, was found in 77 patients (12%). Enlargement of a single gland (SA) or three or more glands (MA) occurred in 80% and 8%, respectively. DAs were bilateral in 72% of patients, and the weight of the two glands differed by 317 +/- 407 mg. The three histologic subgroups of patients exhibited no significant discrepancy with respect to age, classic symptoms of HPT, proportion of overtly asymptomatic individuals, or parathyroid tissue weight. A lower female predominance and extent of hypercalcemia and higher preoperative serum creatinine level occurred with DA and MA compared to SA. SA and DA differed from MA with respect to variably strong trends to lower postoperative incidences of recurrent HPT and hypoparathyroidism. DA seems to comprise an underrated histologic cause of HPT, which is eligible for a conservative operative approach. Clinical characteristics consistent with a distinct entity of sporadic primary HPT were not seen.

Persistent or recurrent hyperparathyroidism in patients with double adenomas.

Are double parathyroid adenomas a discrete clinical entity or are all hyperplastic parathyroid glands of varying size? This investigation was done to determine whether patients with persistent or recurrent hyperparathyroidism and double adenomas (DA) differ in clinical profile or in response to treatment from patients with hyperplasia. From 1982 to 1993, 37 unselected patients with persistent (11) or recurrent hyperparathyroidism (26) were treated. Twenty-one had DA and 16 had hyperplasia. DAs were defined as two abnormal and two normal parathyroid glands. Patients with persistent or recurrent hyperparathyroidism caused by DA were older and had more muscle weakness, neuropsychiatric disorders, constipation, and weight loss (p < 0.001) than patients with persistent or recurrent hyperparathyroidism caused by hyperplasia. Nephrolithiasis was more common in patients with recurrent hyperparathyroidism caused by hyperplasia than in patients with recurrent hyperparathyroidism caused by DA (p < 0.001). Serum Ca2+ levels before operation were similar in these groups with variable parathyroid hormone levels. No recurrences occurred in either group (DA [mean, 6 yr]; hyperplasia [mean, 5 yr]). Postoperative levels of serum Ca2+ and parathyroid hormone were normal in both groups. Patients with persistent or recurrent hyperparathyroidism caused by DA are older, have different clinical manifestations, and are cured by resection of the second adenoma. These findings support the concept that DA and hyperplasia are distinct entities.

GIANT DOUBLE PARATHYROID ADENOMA PRESENTING AS A HYPERCALCAEMIC CRISIS

The largest documented case of a double parathyroid adenoma is reported. The patient presented in hypercalcaemic crisis with a large intrathoracic mass. After removal of a massive cystic parathyroid adenoma from the right superior mediastinum, a second very large parathyroid adenoma was found on the contralateral side adjacent to the left thyroid lobe. This case illustrates the importance of the cervical approach, as well as routine bilateral neck exploration, for all cases of primary hyperparathyroidism.

Double parathyroid adenomas. Clinical and biochemical characteristics before and after parathyroidectomy.

There is considerable debate about whether double parathyroid adenomas are a discrete entity or represent hyperplasia with parathyroid glands of varying sizes. This distinction is important because it impacts on the extent of parathyroid resection and the success of the parathyroid operation. Double parathyroid adenomas have been reported to occur in 1.7% to 9% of patients with primary hyperparathyroidism (HPT). It is important for surgeons to differentiate between double adenoma and hyperplasia with glands of varying sizes using gross examination during the initial procedure because microscopic findings of a small biopsy specimen at frozen-section examination may not be diagnostic. From 1982 to 1992, 416 unselected patients (309 women and 107 men) with primary HPT without familial HPT or multiple endocrine neoplasia (MEN) were treated by one surgeon at the University of California at San Francisco. Double adenoma occurred in 49 patients, solitary adenoma in 309 patients, and hyperplasia in 58 patients. The authors analyzed the clinical manifestations, the preoperative and postoperative serum levels of calcium, phosphate, and parathyroid hormone (PTH), and the success rate and outcome after parathyroidectomy and compared their results in 49 patients with double adenomas to the results for patients with solitary adenomas or hyperplasia. Ten of the patients with double adenomas (20.4%) were referred for persistent HPT after removal of one abnormal parathyroid gland. The ages of the patients with double adenoma, single adenoma, and hyperplasia were 61 +/- 14, 56 +/- 15, and 58 +/- 7 years, respectively. Fatigue, muscle weakness, and bone pain were common in patients with double adenomas, whereas nephrolithiasis occurred more frequently in patients with solitary adenoma (p = 0.0001). Serum calcium and PTH levels (per cent of upper limit of normal) fell from 11.5 +/- 1.2 mg/dL and 487% to 9.5 +/- 0.8 mg/dL and 61% for patients with double adenomas; from 11.9 +/- 0.9 mg/dL and 378% to 9.3 +/- 1.4 mg/dL and 101% for patients with single adenoma; and from 10.9 +/- 0.5 mg/dL and 418% to 9.1 +/- 0.7 mg/dL and 94% for patients with hyperplasia, respectively. There was no recurrence in the patients with double adenomas with a mean follow-up time of 5.8 years. Double adenomas are a discrete entity and occur more often in older patients. Patients with double adenomas can be successfully treated by removal of the two abnormal glands.