The localization of parathyroid tissue by ultrasound scanning prior to surgery in patients with hyperparathyroidism

Ultrasonic localization of parathyroid tissue has been attempted in 24 patients with hyperparathyroidism prior to surgical exploration of the neck. All 24 patients had biochemically proven hyperparathyroidism. Standard contact diagnostic ultrasound equipment fitted with a 5 MHz transducer was used, and transverse and longitudinal scans of the region of the thyroid gland were performed at 5 mm intervals. The normal anatomical structures identified were the lobes of the thyroid gland, trachea, common carotid arteries, and jugular veins. The longus colli muscle on each side was used as a major landmark. These structures define the site where most parathyroid glands are found in the neck. In 18 of the 24 patients the suspected parathyroid tumor was visualized preoperatively and confirmed at operation. The abnormal glands ranged in size from 5 to 12 mm in transverse diameter. In 3 patients false-positive diagnoses were made by ultrasound; at operation the abnormalities proved to be thyroid nodules protruding from the posterior surface of the thyroid gland. Ultrasonography is of little value in the presence of multinodular goiter. Three adenomas and 3 hyperplastic parathyroid glands greater than 5 mm in diameter were not identified. Localization of enlarged parathyroid glands by echography may be difficult when normal anatomical landmarks are altered by the presence of multinodular goiter or because of previous surgery. The sensitivity of this technique for identifying in the neck parathyroid glands larger than 5 mm in diameter was found to be 79.3% with 11.5% false-positive and 8.6% falsenegative results.     

Fifty-three reoperations for hyperparathyroidism

Fifty-three patients, 35 with persistent and 7 with recurrent hyperparathyroidism, had parathyroid surgery. There were 11 patients who had prior thyroid surgery before being identified as having hyperparathyroidism. Forty patients had parathyroid adenomas and 13 (8 dialysis patients) had parathyroid hyperplasia. Thallium-210-iodine 123 subtraction scanning proved to be the most accurate in localizing parathyroid adenomas (60 percent) but not parathyroid hyperplasia. Resection of 3 3/4 parathyroid glands in primary parathyroid hyperplasia and total parathyroidectomy with parathyroid autotransplantation in tertiary parathyroid hyperplasia are the treatments of choice and would have prevented reoperation in this group. Careful neck exploration, resection of the thymus, and even thyroidectomy would probably have led to the correct location of the missed parathyroid adenomas. Mediastinotomy should not be performed at initial surgery. A careful history and preoperative calcium and phosphorus determinations in all thyroid surgery patients will reveal occult hyperparathyroidism. Twenty-one such patients were identified in our overall parathyroid series.     

A new method with high sensitivity and specificity for localization of abnormal parathyroid glands.

A novel method for localization of abnormal parathyroid glands involving color-processing of nuclear scintigrams of the neck after injection of Thallium-201 and Technetium pertechnetate is presented with surgical correlation. Preoperative localization of single parathyroid adenomas was successful in 88% of previously unoperated patients and in 85.7% of those with adenomas not located at previous surgery. Eighty-three per cent of glands with secondary hyperplasia, 66% of glands with primary hyperplasia, and one carcinoma were localized. No abnormal studies were seen in non-hyperparathyroid hypercalcemia, and no false positive studies were seen. Localization appeared related to larger adenomas (300-5000 mg), although one of 60 mg was localized. Color-comparison dual-isotype scintigraphy was useful for localization of parathyroid adenomas and hyperplastic glands and exceeded the reported sensitivity of either ultrasonography or computerized tomography. It deserves wider evaluation in preoperative management of at least hyperparathyroidism of the primary or persistent types.     

Radioguided parathyroidectomy is equally effective for both adenomatous and hyperplastic glands

OBJECTIVE: To determine the utility of radioguided parathyroidectomy for patients with hyperparathyroidism, we studied the properties of 180 resected, hyperfunctioning parathyroid glands. SUMMARY AND BACKGROUND DATA: Radioguided resection of hyperfunctioning parathyroid glands has been shown to be technically feasible in patients with parathyroid adenomas. Radioguided excision may obviate the need for intraoperative frozen section because excised parathyroid adenomas uniformly have radionuclide ex vivo counts >20% of background. The feasibility and applicability of radioguided techniques for patients with parathyroid hyperplasia are unclear. METHODS: Between March 2001 and September 2002, 102 patients underwent neck exploration for primary (n = 77) and secondary/tertiary (n = 25) hyperparathyroidism. All patients received an injection of 10 mCi of Tc-99m sestamibi the day of surgery. Using a gamma probe, intraoperative scanning was performed, looking for in vivo radionuclide counts > background to localize abnormal parathyroid glands. After excision, radionuclide counts of each ex vivo parathyroid gland were determined and expressed as a percentage of background counts.RESULTS Although patients with single adenomas had higher mean background radionuclide counts, the average in vivo counts of all enlarged glands were higher than background. Notably, in vivo counts did not differ between adenomatous and hyperplastic glands, suggesting equal sensitivity for intraoperative gamma detection. Ectopically located glands were identified in 22 cases and all were accurately localized using the gamma probe. Postresection, mean ex vivo radionuclide counts were highest in the single parathyroid adenomas and lowest in hyperplastic glands. Importantly, in all hyperplastic glands, the ex vivo counts were >20%. CONCLUSIONS: In patients with hyperparathyroidism, radioguided surgery is a sensitive adjunct for the intraoperative localization of both adenomatous and hyperplastic glands. In this series, all 180 enlarged parathyroids were located with the gamma probe. We have also shown that the ">20% rule" for ex vivo counts not only applies to parathyroid adenomas but also to hyperplastic glands. Therefore, radioguided resection is equally effective and informative for both adenomatous and hyperplastic glands.     

Parathyroidectomy: Review of 338 consecutive cases for histology,location, and reoperation

Three hundred thirty-eight consecutive parathyroidectomies for hyperparathyroidism were performed over a 22 year period. There were 53 dialysis patients (31 male and 22 female), 285 patients (165 female and 120 male) with primary hyperparathyroidism, 55 patients (19 percent) with parathyroid hyperplasia, and 230 patients with 236 parathyroid adenomas. The location of the adenomas were right upper in 57, right lower in 59, left upper in 60, and left lower in 60. Forty-three patients of the last 194 operated on had histories of childhood head and neck irradiation (21.6 percent), 34 patients (79.6 percent) had associated thyroid disease, and there were 10 with thyroid carcinomas. In the 285 patients, 54 percent had thyroid disease, and 18 had thyroid carcinomas. Twenty-three patients required reoperation for persistent or recurrent hypercalcemia, and 19 neck reexplorations and 6 mediastinotomies were performed. The identification and biopsy as indicated of all four parathyroid glands at initial neck exploration would have prevented over 70 percent of reoperations.     

Blood Supply and Parathyroid Hormone Secretion in Pathological Parathyroid Glands

The blood supply of pathologic parathyroid glands and the relation between parathyroid hormone secretion and parathyroid blood perfusion was studied during surgery for hyperparathyroidism. Blood flow in 39 single adenomas and 20 glands classified as primary or secondary hyperplasia were studied intraoperatively with laser Doppler flowmetry. The ipsilateral inferior thyroid artery was occluded during continuous flowmetry recording, which resulted in a 40% reduction of parathyroid blood flow in both groups. In 12 patients with single adenomas, intact parathormone (iPTH) was measured intraoperatively before and during occlusion of the ipsilateral inferior thyroid artery and after extirpation of the adenoma. During occlusion the iPTH levels were mainly unchanged despite blood flow reduction of up to 80%. After removal of the adenoma the iPTH normalized within 15 minutes. In a control group of eight single adenomas, iPTH was measured similarly without vascular occlusion, demonstrating comparable iPTH levels. This study demonstrates similar routes of vascularization for single adenomas and hyperplastic glands, as was earlier seen for normal parathyroid glands. The increased parathyroid hormone secretion from single adenomas appears to remain mainly unchanged during significant blood flow reduction.     

Parathyroid pathology in an intrathyroidal position.

A systematic approach based on the embryology of the parathyroid glands should allow for the appropriate identification of both normal and abnormal glands at the time of parathyroidectomy. The exact role of subtotal thyroidectomy as part of this approach remains in question because of the low incidence of intrathyroidal adenomas reported in the past. From 1978 to 1992, 97 cervical explorations were performed in 96 patients (mean age: 56 years) with hyperparathyroidism. Four patients (4%) were found to have intrathyroidal parathyroid adenomas and were cured by ipsilateral partial or subtotal thyroid lobectomy on the side of a missing gland. One parathyroid adenoma completely replaced the right lobe of the thyroid, whereas two inferior and one superior intrathyroidal adenomas were found in the remaining three patients. The 4% incidence of intrathyroidal adenomas is higher than that reported in most series and suggests that this entity may be a more common cause of failed parathyroid explorations than is currently thought. Ipsilateral thyrotomy or subtotal thyroid lobectomy continues to be a potentially curative procedure for hyperparathyroidism when there is a missing and presumably diseased superior or inferior gland.     

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.     

Surgeon Performed Ultrasound Facilitates Minimally Invasive Parathyroidectomy by the Focused Lateral Mini-incision Approach

Background Minimally invasive parathyroidectomy (MIP) is now widely accepted where a single adenoma can be localized preoperatively. In our unit, MIP is offered once a parathyroid adenoma is localized with a sestamibi (MIBI) scan, with or without a concordant neck ultrasound. The aim of this study was to compare the accuracy of surgeon performed ultrasound (SUS) with radiologist performed ultrasound (RUS) in the localization of a parathyroid adenoma in MIBI-positive primary hyperparathyroidism (PHPT). Patients and Methods This is a prospective study of patients undergoing parathyroidectomy for sporadic primary hyperparathyroidism (PHPT) from April 2005 to October 2006 at the University of Sydney Endocrine Surgical Unit. Patients were then divided into those who underwent preoperative RUS or SUS. Results Two-hundred eighteen patients formed the study group. One hundred forty-eight (66%) patients had RUS and 87 (39%) had SUS. Overall, RUS correctly localized the parathyroid adenomas in 121 of 148 (82%) patients. Surgeon performed ultrasound correctly localized the abnormal parathyroid adenoma in 72 of 87 (83%) of cases. There was no significant difference in the proportion of patients with single gland disease, double adenomas, or hyperplasia correctly localized by SUS or RUS. Incorrect interpretation of ultrasound imaging was due to cystic degeneration in thyroid nodules, lymph nodes, retro-esophageal location of adenomas and ectopic and small parathyroid glands. Conclusions Surgeon performed ultrasound is a useful adjunctive tool to MIBI localization for facilitating MIP and when performed by experienced parathyroid surgeons, it can achieve accuracy rates equivalent to that of a dedicated parathyroid radiologist.     

Intraoperative parathyroid hormone estimation: a valuable adjunct to parathyroid surgery.

Serial measurements of serum intact parathyroid hormone (PTH) and adjusted total calcium levels were performed on 10 patients during unilateral neck exploration for a solitary parathyroid adenoma localised preoperatively by ultrasound scan. Frozen section was performed peroperatively to establish the presence of parathyroid tissue. Levels of PTH were shown to be within the normal range within 15 min of adenoma removal (a mean of 13.4% of their preoperative values), allowing clear early distinction from unsuccessful surgery where no change occurred. Frozen section wrongly identified thyroid tissue as parathyroid in one case leading to a failure of the initial neck exploration. Our findings show that intraoperative PTH measurements can accurately predict whether all hyperfunctioning parathyroid tissue has been removed. This is not always possible using frozen section techniques. The wider use of intraoperative PTH measurement, particularly in difficult cases, may avoid the need for prolonged explorations to identify all four glands and, perhaps, biopsy of normal glands, replacing the current standard use of frozen section as a more reliable indicator of the success of parathyroid surgery.     

Incidental preclinical hyperparathyroidism identified during thyroid operations.

The entity of preclinical hyperparathyroidism has never been clearly investigated. The authors believe that the incidence of pathologic abnormalities of the parathyroid glands before the development of any symptoms or hypercalcemia (serum calcium > 12.0 mg/dl) is more frequent than has been reported. Over a 14-year period, parathyroid glands were examined during thyroid operations in over 800 patients. Serum calcium and phosphorous levels were measured in all patients preoperatively. Thirty-six patients had additional parathyroid operations for a preclinical form of hyperparathyroidism, defined by abnormal appearing parathyroid glands at the time of thyroid surgery. None of the 36 patients had symptoms of hyperparathyroidism preoperatively. Nine patients had borderline hypercalcemia (serum calcium 10.6 to 12.0 mg/dl), and the remainder were considered normocalcemic. The average age was 53 (range 21 to 75) with a male to female ratio of 1:3. Nine of the 36 patients had thyroid cancer. There were eight patients with parathyroid adenoma and 28 patients with parathyroid hyperplasia. Of 13 patients who had a history of neck irradiation, five had parathyroid adenoma and eight had parathyroid hyperplasia. Only two patients with parathyroid hyperplasia remain on calcium medication. Since preoperative normocalcemia does not preclude the presence of parathyroid pathology, the authors urge careful identification and examination of the parathyroid glands during thyroid operations. It adds little time to the procedure. Excision of parathyroid disease along with the thyroid gland can be performed safely and prevents the need for further operation with its associated morbidity.     

Intraoperative sestamibi scanning in reoperative parathyroidectomy

BACKGROUND: Reoperative neck exploration for hyperparathyroidism is often difficult even for experienced surgeons. Recent advances in preoperative and intraoperative localization techniques have improved successful resection rates. This prospective study evaluates the accuracy and clinical utility of intraoperative technetium 99m sestamibi scanning for localizing hyperfunctioning parathyroid tissue in reoperative neck explorations. PATIENTS AND METHODS: Eleven patients underwent reoperative neck exploration for hyperparathyroidism. Two patients had 3 prior neck explorations, 1 had 2 prior neck explorations, and 8 patients had 1 prior neck operation. Preoperative studies included sestamibi scintigraphy and ultrasound in all patients, magnetic resonance imaging in 4, computed tomography scan in 3, parathyroid arteriogram in 1, and selective venous sampling in 1. All patients underwent intraoperative technetium 99m sestamibi scanning and parathyroid hormone assay. RESULTS: Preoperative technetium 99m sestamibi scanning and ultrasound each successfully localized 7 of 11 hyperfunctioning glands (64%). Intraoperative technetium 99m sestamibi scanning correctly localized 10 of 11 hyperfunctioning glands (91%). Intraoperative parathyroid hormone assay confirmed successful excision of hyperfunctioning tissue in all 11 patients. Postoperatively, all 11 patients had low-normal or normal calcium levels. CONCLUSIONS: Intraoperative technetium 99m sestamibi correctly localized 91% of hyperfunctioning glands compared with 64% localization for preoperative technetium 99m sestamibi and preoperative ultrasound. Intraoperative technetium 99m sestamibi scanning and parathyroid hormone monitoring are useful in reoperative neck explorations for hyperparathyroidism.     

彩色多普勒超声对慢性肾脏病甲状旁腺腺体形态学的诊断价值

目的以彩色多普勒超声观察药物治疗无效的继发性甲状旁腺功能亢进（SHPT）患者腺体超声信号特征,及局部无水酒精注射前后超声影像学改变。方法选择SHPT患者16例,甲状旁腺采用彩色多普勒超声观察甲状旁腺大小、回声及血流信号,并观察无水酒精注射前后上述指标改变及药物注射的安全性。结果16例患者探测到35枚增生的腺体,左侧16枚,右侧19枚;上极10枚,下极25枚。增生的腺体多位于下极,左右两侧无明显差异。增生腺体体积与甲状旁腺素（PTH）之间无直线相关。35枚腺体均可见血流信号,增生腺体多为低回声信号。无水酒精注射后甲状旁腺血流信号较注射前明显减少,效果确切,术后无不良反应。结论彩色多普勒超声对于SHPT中增生腺体的筛查、无水酒精注射治疗及术后疗效的观察有重要意义。     

Impact on surgery of preoperative localization of parathyroid lesions with dual radionuclide subtraction scanning

In an effort to localize parathyroid lesions preoperatively, scanning with radioactive thallium and technetium was performed in 20 patients considered clinically to have hyperparathyroidism. In the 11 found at surgery to have single parathyroid adenomas, scanning correctly localized the lesion in 10; in the other patient the lesion was in the unscanned mediastinum. Preoperative scanning was not as rewarding in the seven patients with parathyroid hyperplasia. A thyroid lesion was the source of an abnormality seen on the parathyroid scan in one patient, while neck scanning and surgical exploration were negative in another. Comparison of the patients who had parathyroid adenomas localized in the neck with a control group of similar patients who did not undergo preoperative scanning showed that the average surgical time was reduced by 50% with preoperative localization and there was a decrease in the number of nonparathyroid tissue biopsies.     

Intraoperative Jugular Venous Sampling Aids Detection of an Undescended Parathyroid Adenoma

Introduction A missed parathyroid adenoma is an important cause of persistent or recurrent primary hyperparathyroidism. Despite the widespread use of preoperative localizing tests and the advent of the rapid intact blood parathyroid hormone assay (iPTH), difficult operative cases are encountered when abnormal parathyroid glands cannot be identified. Methods Over a 5-year period, 466 neck explorations were performed for primary hyperparathyroidism. This retrospective report describes the use of intraoperative jugular venous sampling to locate and remove successfully undescended parathyroid adenomas in three patients. Results Intraoperative jugular venous sampling for iPTH analysis was performed when a thorough neck exploration in combination with peripheral iPTH failed to reveal a source of hyperparathyroidism in patients with biochemically confirmed hyperparathyroidism. In all patients, a two- to fourfold iPTH gradient was observed between the affected and unaffected sides, and an undescended adenoma was located near the carotid bifurcation. Conclusions Intraoperative jugular venous sampling with iPTH analysis may be a useful technique for successfully detecting an undescended adenoma when other, more routine measures have failed.     

Preoperative imaging of abnormal parathyroid glands in patients with hyperparathyroid disease using combination Tc-99m-pertechnetate and Tc-99m-sestamibi radionuclide scans.

OBJECTIVE: To evaluate the efficacy of combined Tc-99m-pertechnetate and Tc-99m-sestamibi radionuclide scanning for imaging abnormal parathyroid glands in hyperparathyroid disease in a prospective study. SUMMARY BACKGROUND DATA: Established methods to localize abnormal parathyroid glands lack accuracy for routine use. Tc-99m-sestamibi used in conjunction with iodine-123 has excellent potential for preoperative imaging in patients with hyperparathyroid disease. An alternative method for parathyroid imaging was studied using Tc-99m-pertechnetate and Tc-99m-sestamibi. METHODS: Thirty patients with hyperparathyroid disease had Tc-99m-pertechnetate and Tc-99m-sestamibi subtraction radionuclide scanning to visualize abnormal parathyroid glands before surgery. The patients had surgery and pathologic confirmation of all parathyroid glands. RESULTS: In 23 patients with primary hyperparathyroidism, 12 of 13 solitary adenomas were visualized. Six of nine patients with diffuse hyperplasia had bilateral uptake consistent with diffuse hyperplasia. Three of nine patients had negative scans. One patient previously operated on for diffuse hyperplasia had only one gland scanned. Seven patients with renal failure-associated hyperparathyroid disease were scanned: five had bilateral uptake of Tc-99m-sestamibi consistent with hyperplasia, and two who had been previously operated on had localization of remaining abnormal parathyroid glands. CONCLUSIONS: Tc-99m-pertechnetate combined with Tc-99m-sestamibi subtraction radionuclide scanning is less cumbersome to implement than iodine-123 combined with Tc-99m-sestamibi scanning. It has a high sensitivity for imaging solitary parathyroid adenomas or persistent solitary hyperplastic glands. However it does not have the resolution necessary to delineate all parathyroid glands in diffuse hyperplasia.     

Ultrasonic localization and cytologic identification of parathyroid tumors

Ultrasonic examination of the parathyroid glands was performed in 55 consecutive patients with subsequent surgically verified hyperparathyroidism. Ultrasound located 26 of 37 parathyroid adenomas in the neck. Eleven of 48 hyperplastic glands in the neck were visualized by ultrasound in 16 patients with primary or uremic hyperplasia. A parathyroid adenoma was revealed in all 3 patients with hypercalcemic crisis and in all 5 patients with an adenoma and a previously unsuccessful exploration of the neck. Two of 3 glands were visualized by ultrasound prior to secondary explorations in 3 patients with primary hyperplasia associated with the multiple endocrine neoplasia syndrome type I. Undetected parathyroid glands were generally small and located in regions of the neck difficult to detect by ultrasound. It was often difficult to unequivocally establish that identified lesions represented a parathyroid gland. Nodules and cysts of the thyroid and lymph nodes were misinterpreted for parathyroid lesions. Ultrasonically guided fine-needle biopsies were obtained from 8 parathyroid lesions, 7 thyroid tumors, and 2 lymph nodes. By cytologic examination these tissues could be discriminated after a differential staining of the aspirates.

---

Resumen El examen ultrasónico de las glándulas paratiroides ha atraído considerable interés en los últimos años gracias a su capacidad para localizar glándulas aumentadas de tarnano antes de emprender el tratamiento quirúrgico, pero la identidad de tumores detectados por el ultrasonido puede ser difícil de establecer en forma inequívoca en el ecograma. Con el fín de lograr una forma de discriminación citológica, hemos utilizado un método de biopsia con aguja fine guiada por el ultrasonido.El examen ultrasónico de las glándulas paratiroides fue realizado en 55 pacientes consecutivos con hiperparatiroidismo verificado ulteriormente por cirugía. El ultrasonido pudo localizar 26 de 37 adenomas paratiroideos en el cuello. Once de 48 glándulas hiperplásicas fueron visualizadas por ultrasonido en 16 pacientes con hiperplasia urémica o de origen urémico. Se demostró la presencia de adenoma paratiroideo en todos los pacientes (3) con crisis hipercalcémicas y en todos los pacientes (5) con adenoma que habían sido sometidos a exploraciones previas y no exitosas del cuello. Dos de tres glándulas fueron visualizadas por ultrasonido antes de exploración secundaria en 3 pacientes con hiperplasia primaria asociada con el síndrome de neoplasia endocrina múltiple tipo I. Aquellas glándulas paratiroides que no pudieron ser detectadas generalmente fueron de tamaño pequeño y estuvieron ubicadas en regiones del cuello de difícil acceso ultrasónico. Con frecuencia fue difícil establecer en forma inequívoca si las lesiones visualizadas representaban una glándula paratiroides; nódulos y quistes tiroideos, así como ganglios linfáticos, fueron interpretados equivocadamente como lesiones paratiroideas. Biopsias con aguja fina guiadas por ultrasonido fueron obtenidas en 8 lesiones paratiroideas, 7 tumores tiroideos y 2 ganglios linfáticos. Estos tejidos pudieron ser discriminados mediante examen citológico y la coloración diferencial del material aspirado.

---

Résumé L'échographie parathyroïdienne a été pratiquée consécutivement chez 55 malades dont l'hyperparathyroïdisme a été vérifié par l'intervention chirurgicale. L'échographie a permis de localiser 26 des 37 adénomes parathyroïdiens cervicaux. Onze parmi 48 glandes hyperplasiques cervicales ont été mises en évidence chez 16 malades qui présentaient un hyperparathyroïdisme primitif ou secondaire à un état urémique. Un adénome parathyroïdien fut découvert chez chacun des trois malades atteints d'hypercalcémie aiguë et chacun des 5 malades porteurs d'un adénome resté méconnu au cours d'une opération antérieure. Deux sur trois adénomes furent décelés avant une réintervention chez 3 malades qui étaient porteurs d'une hyperplasie primitive associée avec un syndrome MEN type I. Les parathyroïdes qui n'avaient pas été localisées étaient généralement de volume réduit et situées dans des régions difficilement accessibles à l'échographie cervicale. Souvent il fut délicat d'affirmer sans réticence que les lésions identifiées représentaient une glande thyroïde. Des nodules et des kystes thyroïdiens ainsi que des adénopathies furent confondus avec des adénomes parathyroïdiens. La biopsie à l'aiguille fine sous échographie fut pratiquée en présence de 8 lésions parathyroïdiennes, de 7 tumeurs thyroïdiennes et de 2 adénopathies. L'examen histologique après coloration des échantillons prélevés permit de définir leur nature avec exactitude.

---

---

Presented at the International Association of Endocrine Surgeons at Hamburg, September 1983.

---

Supported by the Swedish Medical Resarch Council (project no. 06264).     

Solitary parathyroid microadenoma

In our experience with operations for primary hyperparathyroidism, a recurring problem centers on patients whose solitary adenomas are too small to be appreciated at the initial exploration. We have seen four patients with parathyroid microadenomas, which we define as lesions less than 6 mm in diameter in externally undeformed parathyroid glands. Two such patients were fortuitously cured at the initial exploration even though the operative findings were inconclusive. One, a 25-year-old man, underwent excision of an externally normal gland that contained a 3 by 2 by 2 mm microadenoma. He is eucalcemic since the operation. The other patient, a 70-year-old woman with hypercalcemia, responded to prednisone. She then underwent a neck exploration at which the diagnosis of sarcoidosis was confirmed by lymph node biopsy examination. A 4 by 2 by 2 mm parathyroid microadenoma was incidentally removed. The patient is normocalcemic receiving low-dose steroid treatment since the operation. In a third patient, a 34-year-old practical nurse, three explorations were needed to find a parathyroid gland, which was negative for adenoma on frozen-section microscopy. The solitary adenoma, 6 by 3 by 3 mm, was appreciated only on permanent sections. The majority of oxyphil microadenomas should be suspected to be nonfunctioning, as in a 59-year-old woman in whom the lesion coexisted with primary chief cell parathyroid hyperplasia. The hyperparathyroidism responded well to three and a half-gland resection. The 2 by 2 by 2 mm oxyphil adenoma was also removed. Solitary parathyroid adenomas can be subtle and small. Appraisal of parathyroid disease at the operating table is not always straightforward. As more patients with early hyperparathyroidism appear on routine calcium screening, we may expect to see increasing numbers of challenging solitary parathyroid microadenomas.     

Localization of abnormal parathyroid glands using thallium-201

Ectopically located parathyroid adenomas may be difficult to find during initial neck exploration. They account for over 70 percent of missed adenomas found at reexploration. Preoperative localization of parathyroid adenomas would reduce unnecessary dissection and possibly reduce the number of negative results of initial neck exploration. Before reoperative parathyroid surgery is performed, some means of localization is mandatory to detect ectopic adenomas in the neck and mediastinum. Computed tomography and ultrasonography cannot effectively evaluate the mediastinum. Angiography and venous parathyroid hormone sampling are invasive, costly, and tedious to perform. We have shown that thallium-201 will accurately localize ectopic parathyroid adenomas. All 10 adenomas found in positions not immediately adjacent to the thyroid gland were detected by thallium-201 scintigraphy. One was a mediastinal adenoma resected with a median sternotomy. Our results suggest that thallium-201 scintigraphy should be the initial localization procedure of choice before all reexplorations. Its use before initial explorations, as well, will enable the surgeon to immediately direct attention to the area of the localized adenoma. If mediastinal uptake is found to be present, then median sternotomy may be performed during initial surgery provided a thorough neck exploration is performed first.     

Study of parathyroid transcription factor Gcm2 expression in parathyroid lesions

Glial cells missing 2 (Gcm2) is a master regulatory gene of parathyroid gland development, and it is exclusively expressed in the parathyroid gland. Diagnostic application of anti-Gcm2 antibody has not been reported yet. In this study, a total of 58 cases of parathyroid lesions including 40 adenomas, 2 atypical adenomas, 2 carcinomas, 9 hyperplastic lesions, 4 parathyroid cysts, and 1 case of recurrent hyperplasia of an autograft gland were stained with anti-Gcm2 antibody. Anti-Gcm2 was also applied to a variety of endocrine tumors, including thyroid tumors and nonendocrine tumors, and normal tissues from a variety of organs, including the parathyroid and thyroid glands. Gcm2 nuclear expression was seen in all the normal parathyroid glands, and cystic, hyperplastic, and neoplastic parathyroid lesions in a diffuse manner, whereas no Gcm2 expression was seen in any other normal tissues and tumors, including those of the thymus and thyroid gland. Anti-Gcm2 antibody is a highly sensitive and specific marker for parathyroid lesions. Although the immunohistochemistry stain for parathyroid hormone is a useful marker, its reaction tends to be variable in extent and intensity in parathyroid neoplasia, and it is often negative in parathyroid cysts, and Gcm2 would serve as a useful adjunct marker.