Carcinoma of the parathyroid.
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60 patients suffering from primary hyperparathyroidism were operated during the period from 1980 till september 1988. The operation was successful in 55 cases. Most patients had single adenomas of the parathyroid glands. There was only one case with a four-gland-hyperplasia and one case with a parathyroid carcinoma. Rare observations were: one woman with a truly recurrent primary hyperparathyroidism, two patients with a papillary carcinoma of the thyroid gland in addition to the hyperparathyroidism and one patient with a large cystic parathyroid adenoma. Most of the patients had severe clinical symptoms of the primary hyperparathyroidism, mainly renal stones, in some cases bone changes. Only three patients were asymptomatic.
Currently, >300,000 patients with end-stage renal disease require dialysis. Secondary hyperparathyroidism is a serious complication of end-stage renal disease and can lead to renal osteodystrophy and other organ failure. Vitamin D sterols and phosphate binders are used to treat hyperparathyroidism, but they can cause hypercalcemia, which contributes to vascular and soft-tissue calcification. Cinacalcet (Sensipar) is the first agent in its class that treats secondary hyperparathyroidism by increasing the sensitivity of calcium sensing receptors. It is also indicated for the treatment of hypercalcemia in patients with parathyroid carcinoma. All clinical trials concluded that cinacalcet is effective for the reduction of parathyroid hormone, serum calcium, phosphorus, and calcium-phosphate product levels. Cinacalcet is available as a once-daily oral therapy. Adverse effects are generally mild.
Better understanding of pathogenesis and natural history of various endocrine diseases along with development of new and sensitive assays for accurate measurement of hormones and of modern image diagnostic procedures for clear demonstration of pathological tissues has enabled us to detect many kinds of endocrine diseases much more frequently than before and to perform a more refined and rational surgical intervention. Endocrine surgery is now a challenging and fascinating field of general surgery. This fact is best exemplified as follows: (1) different therapeutic approaches for intrathyroidal and extrathyroidal papillary carcinomas of the thyroid, (2) early detection and 131I treatment of clinically occult hematogenous metastasis of follicular carcinoma of the thyroid, (3) clinical usefulness of the serum calcitonin and CEA concentrations as sensitive tumor markers in the treatment of medullary thyroid carcinoma, (4) rational use of preoperative localization test and unilateral neck exploration for parathyroid adenoma, and specific surgical intervention for metastatic parathyroid carcinoma, (5) how to treat adrenal incidentalomas and a trial of subclassification of pheochromocytomas into epinephrine- and norepinephrine-secreting tumors, and (6) intraoperative localization of insulinoma by ultrasound and newly developed surgical approaches for gestrinoma.
In primary hyperparathyroidism (pHPT), parathyroidectomy is the treatment of choice, but anatomic variations of ectopic glands may cause surgical failure. Reliable preoperative noninvasive localization procedures would have a positive impact on the operative time and increase recovery rate. We retrospectively evaluated 186 patients with pHPT who were studied before successful parathyroidectomy by double tracer scintigraphy (99mTc-pertechnetate+201TI chloride or 99mTc-pertechnetate +99mTc-sestamibi, 160 patients), ultrasonography (148 patients) and computerized tomography (CT) scan (92 patients). During bilateral neck exploration, 159 (85.5%) single adenomas, 6 (3.2%) parathyroid carcinomas, and 3 (1.6%) double adenomas were found. Moreover, 18 (9.7%) patients had diffuse chief cells parathyroid hyperplasia. Removed parathyroid glands were in ectopic sites in 41 (22.0%) cases, mainly localized in the upper mediastinum or behind the esophagus. The overall sensitivity was 83.5 and 85.2% for 99mTc-pertechnetate+201TI chloride and 99mTc-pertechnetate+99mTc-sestamibi scintigraphy respectively, 80.4% for CT scan and 81.1% for ultrasonography. In patients with ectopic glands, sensitivity was 81.2, 79.5, 73.3 and 81.6% respectively. In 36 out of 41 patients with ectopic glands in whom the removed parathyroids were correctly localized, mean operative time was 95 min, and in 5 patients without preoperative localization it was 260 min. In conclusion, in pHPT, preoperative localization of an enlarged parathyroid is helpful, especially in ectopic adenomas and in anatomic variations in location, and it has been proved to reduce operative time and morbidity rate.
Parafibromin is the 531-amino-acid protein product encoded by HRPT2, a putative tumor suppressor gene recently implicated in the autosomal dominant hyperparathyroidism-jaw tumor familial cancer syndrome, sporadic parathyroid cancer, and a minority of families with isolated hyperparathyroidism. Parafibromin contains no identified functional domains but bears sequence homology to Cdc73p, a budding yeast protein component of the RNA polymerase II-associated Paf1 complex. This study addressed the expression and functional properties of human parafibromin. A survey of human and mouse tissues analysed with polyclonal antibodies to parafibromin showed specific immunoreactivity in adrenal and parathyroid glands, kidney, heart, and skeletal muscle. Subcellular fractionation and laser confocal microscopy of normal human parathyroid gland demonstrated expression of parafibromin in both the cytoplasmic and nuclear compartments. Parafibromin was expressed in four parathyroid adenomas but was absent from two parathyroid carcinomas. Transient overexpression of wild-type parafibromin, but not its Leu64Pro missense mutant implicated in parathyroid cancer and familial isolated hyperparathyroidism, inhibited cell proliferation, and blocked expression of cyclin D1, a key cell cycle regulator previously implicated in parathyroid neoplasia. These results demonstrate that human parafibromin is a nucleocytoplasmic protein with functions consistent with its postulated role as a tumor suppressor protein.
A case of multiple endocrine neoplasia syndrome type-2A (MEN-2A) with primary hyperparathyroidism and medullary carcinoma of thyroid initially treated by surgery is reported. The presence of pulmonary nodules six years after the initial treatment was thought to be related to metastasis of medullary carcinoma, and the increase in serum calcium concentrations was assumed to be caused by persistence of parathyroid adenomatous or hyperplastic tissue. The patient underwent surgery again and the pulmonary nodules were confirmed to be metastases of a parathyroid carcinoma, a very rare entity in MEN-2A syndrome.
Among 18 surgical patients with primary hyperparathyroidism at this institution, 3 patients (16.7%) were found to have associated nonmedullary thyroid neoplasms. Histological examination of the parathyroid tumors revealed two to be parathyroid adenomas and the other to be parathyroid carcinoma. Histology of the thyroid neoplasms were papillary carcinoma, follicular carcinoma and follicular adenoma, respectively. Therefore, in the diagnosis of primary hyperparathyroidism, it is necessary to take into consideration association with not only medullary thyroid carcinoma, but nonmedullary thyroid neoplasms as well.
The true incidence of carcinoma of the parathyroid gland is probably about 1 percent of cases of primary hyperparathyroidism. Overreporting may occur if the diagnosis is based on histologic appearances alone because the histologic criteria are less than definitive. Carcinoma of the parathyroid gland, if diagnosed early and treated with adequate surgical excision, is associated with a satisfactory long-term prognosis. However, the possibility of distant metastases or locally recurrent disease is not necessarily excluded by a prolonged interval of disease-free status, and the physician should continue to follow the patient on a regular basis by physical examination and routine serum calcium analysis.
The aims of this study were: (a) to define the accuracy of a preoperative parathyroid imaging protocol based on the combination of technetium-99m pertechnetate/technetium-99m methoxyisobutylisonitrile (99mTcO4/ 99mTc-MIBI) scan and neck ultrasound (US) in selecting patients with primary hyperparathyroidism (pHPT) eligible for a limited neck exploration, and (b) to investigate the potential role of the intraoperative gamma probe (IGP) in radio-guided minimally invasive surgery. 99mTcO4/99mTc-MIBI subtraction scan was performed by means of potassium perchlorate administration with the aim of effecting rapid 99mTcO4 wash-out from the thyroid. Minimally invasive surgery using an IGP was commenced some minutes following the injection of a low, 70 MBq, 99mTc-MIBI dose. Intraoperative PTH (i-PTH) was measured. On the basis of preoperative imaging, 21 pHPT consecutive patients were selected for a limited neck dissection. In 18 of them, a single parathyroid adenoma was found at surgery and IGP allowed performance of parathyroidectomy through a small, 2-2.5 cm, skin incision with a relatively short surgical duration (mean 38 min). i-PTH rapidly normalised in all cases. In two patients, a parathyroid carcinoma was diagnosed at surgery; consequently, a wide neck exploration associated with a near-total thyroidectomy was performed. No loco-regional metastatic lesions were found and i-PTH rapidly normalised after carcinoma excision. In one patient, i-PTH remained elevated after removal of the enlarged parathyroid gland which was localised by 99mTcO4/99mTc-MIBI scan and US. A bilateral exploration was needed to remove a contralateral enlarged parathyroid gland. Combined, 99mTcO4/99mTc-MIBI scan and US imaging correctly localised a single parathyroid gland in 20/21 patients (95.2%); thus, this protocol appears to be accurate enough for the preoperative selection of pHPT patients eligible for limited neck surgery. Moreover, in these selected patients the IGP seems to be helpful in performing radio-guided minimally invasive surgery.
Parathyroid carcinoma is a rare clinical entity with a reported incidence of between 0.5% and 4% of all patients with primary hyperparathyroidism. Equally as unusual is the presence of an intrathyroidal parathyroid gland, which is usually found at the time of exploration by exclusion after extensive dissection has been performed in the usual anatomic locations for the parathyroid glands. This is the description of a case of intrathyroidal parathyroid cancer that presented as primary hyperparathyroidism with a left neck mass. On exploration, an enlarged left lobe of the thyroid was present and no left superior pole parathyroid gland was found with exploration. A left thyroid lobectomy was performed that confirmed a parathyroid cancer that was entirely intrathyroidal. This is the first known reported case in the literature of a carcinoma arising within the thyroid gland.
PURPOSE: Previous studies have shown high sensitivity of positron emission tomography (PET) with 11C-methionine in the pre-operative localisation of parathyroid adenoma and hyperplasia. Nonetheless, in secondary and tertiary hyperparathyroidism (HPT) and in patients with recurrent disease, pre-operative localisation of adenomatous (PTA) or hyperplastic tissue is still a problem with all available methods. The aim of this study was to define the optimal imaging protocol and to compare the diagnostic value of 11C-methionine PET and 99mTc-methoxyisobutylisonitrile (MIBI) single-photon emission computed tomography (SPECT): in particular, we wished to define the benefit of 11C-methionine in those patients with inconclusive or negative conventional imaging. METHODS: Thirty highly pre-selected patients with HPT were enrolled. Sixteen patients had primary HPT, 12 patients had secondary HPT, and two patients had recurrences of parathyroid carcinomas. All patients had ultrasound of the neck, dual-phase scintigraphy with 99mTc-MIBI and PET with 11C-methionine. SUV(parathyroid)/SUV(cervical soft tissue) (target-to-background) and SUV(parathyroid tissue)/SUV(thyroid tissue) (target-to-non-target) ratios were calculated. After surgery, histology of specimens was obtained in all patients but one. RESULTS: In 12 patients with secondary or tertiary HPT, 36 hyperplastic parathyroid glands were histologically verified. Twenty-five of 36 lesions (69%) were detected with 11C-methionine PET and 17 (47%) with 99mTc-MIBI scintigraphy. PET studies were positive in 17/18 (94%) cases in which HPT was related to adenomas or carcinomas. 99mTc-MIBI scintigraphy/SPECT yielded pathological lesions in 9/18 cases (50%). All eight atypical localisations of parathyroid glands were detected with PET but only six of the eight were detected with 99mTc-MIBI scintigraphy/SPECT. In 10/11 patients with recurrent HPT and non-diagnostic scintigraphy/SPECT, hyperfunctional parathyroid tissue was identified with 11C-methionine PET. The highest SUV(parathyroid)/SUV(cervical soft tissue) ratio was found 10 min, and the highest SUV(parathyroid tissue)/SUV(thyroid tissue) ratio 40 min post injection. In three patients clear delineation of hyperfunctional tissue was only achieved after 40 min post injection. CONCLUSION: 11C-methionine PET is a clinically useful method in highly pre-selected patients with recurrent primary HPT as well as in secondary and tertiary HPT if ultrasound and 99mTc-MIBI SPECT are inconclusive or negative. PET imaging of atypical PTA localisations is more accurate than conventional scintigraphy. In order to achieve optimal contrast of parathyroid glands versus thyroid tissue and adjacent soft tissue, imaging at both 10 min and 40 min is recommended.
AIM: (99m)Tc-MIBI radio-guided surgery results, obtained in a group of 141 patients with primary hyperparathyroidism (HPT), are reported. METHODS: All patients were preoperatively evaluated by a single day protocol based on double-tracer parathyroid scintigraphy and neck ultrasound, and then operated by the same surgical team. In 102 patients (72.3%) with a high scan/ultrasound probability of solitary parathyroid adenoma and normal thyroid gland, a minimally invasive radio-guided surgery was planned. In the other 39 patients (27.7%) with scan/ultrasound evidence of multi-glandular disease (n=8) or concomitant nodular goiter (n=31), the intraoperative gamma probe was used during a standard bilateral neck exploration. Intraoperative quick parathyroid hormone (PTH) levels were routinely measured. The minimally invasive radio-guided surgery technique we developed, consisted of: a) injection of a low 37 MBq (99m)Tc-MIBI dose in the operative theatre during anaesthesia induction, b) patient's neck scan with a hand-held gamma probe just before the surgical cut to localize the cutaneous projection of the parathyroid adenoma, c) intraoperative probe detection of the parathyroid adenoma and its removal through a small 2-2.5 cm skin incision. RESULTS: Minimally invasive radio-guided surgery was successfully performed in 99/102 patients (97.0%). The gamma probe was particularly useful in patients with an ectopic parathyroid adenoma in the upper mediastinum (n=11) or to the carotid bifurcation (n=1) or located deep in the neck (n=8). Minimally invasive radio-guided surgery was also obtained in 18/23 patients who had previously undergone thyroid/parathyroid surgery. The mean operative time for minimally invasive radio-guided surgery was 38 min. No major surgical complication was recorded. Conversion to bilateral neck exploration was required in only 3 cases because of intra-operative diagnosis of parathyroid carcinoma (n=2), and persistence of elevated quick PTH levels after removal of the preoperatively visualized parathyroid adenoma (n=1). Among patients treated by standard bilateral neck exploration, the gamma probe was useful in localizing a thymical enlarged parathyroid gland in 1 patient with multi-glandular disease, a parathyroid adenoma located deep in the neck in 4 patients with concomitant nodular goiter and an ectopic parathyroid adenoma to the carotid bifurcation in another. However, in some other patients with a parathyroid adenoma located near to the thyroid, it was difficult to intraoperatively distinguish the parathyroid adenoma from a MIBI avid thyroid nodule. CONCLUSION: It can be concluded that: (a) in primary HPT patients with high scan/ultrasound probability of solitary parathyroid adenoma and normal thyroid gland, the gamma probe appears to be an effective, rapid and safe technique to perform minimally invasive radio-guided surgery; b) a (99m)Tc-MIBI dose as low as 37 MBq appears to be adequate to successfully perform radio-guided surgery; c) the measurement of quick PTH is recommended during minimally invasive radio-guided surgery; d) minimally invasive radio-guided surgery can be performed also in HPT patients with previous parathyroid/thyroid surgery thus limiting surgical trauma; e) with the possible exception of parathyroid adenoma located in ectopic sites or deep in the neck, the gamma probe technique does not seem recommendable in HPT patients with concomitant nodular goiter.
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Problems regarding diagnosis and treatment of hormonally active and hormonally inactive parathyroid carcinomas arise from opposite sides, as is shown in two resp. cases. In functionally active tumors parathyroid origin is clear--but how to prove malignancy in early tumor stages? In inactive tumors malignancy is sound--but how to prove their parathyroid origin? Meticulous histologic examination (semithin-Layer) and cytophotometric DNA-measurement may be helpful diagnostic tools for active tumors, immunohistochemistry and analysis of parathormone fragments in plasma and tumor-cell-culture for inactive tumors. Nevertheless the surgeon's decision for radical surgery sometimes will have to be put on the intraoperative macroscopic situs--in order to provide curative treatment.
The anatomy and catheterization techniques of the internal mammary artery (i.m.a.) are described. The diagnostic criteria and importance of i.m.a. angiography in thymoma, lymphoma, carcinoma, parathyroid adenoma, diseases of the breast, and trauma are discussed. The role of i.m.a. catheterization for i.a. infusion therapy in lung carcinoma, mesothelioma and chest wall metastases of breast carcinoma and embolization of i.m.a. in bleeding following trauma or tumour ulceration are described. Transcatheter treatment of mediastinal parathyroid adenoma is also described.