Double Adenomas Research Articles

Double Adenomas of the Pituitary

Double Adenomas of the Pituitary

Localization of hyperfunctioning parathyroid glands by means of thallium-201 and iodine-131 subtraction scintigraphy in patients with primary and secondary hyperparathyroidism

The accuracy of the preoperative localization of hyperfunctioning parathyroid glands by subtraction scintigraphy with 201Tl and 131I was evaluated by comparison with the operative findings. The subjects were 67 consecutive patients with hyperparathyroidism (HPT), including 24 with primary and 43 with secondary HPT. In primary HPT, surgery revealed 26 adenomas weighing 0.26-15.80 g (mean +/- SD; 3.01 +/- 3.04 g). Two patients had double adenomas. Scintigraphy correctly localized 25/26 adenomas (96.2%) in primary HPT for a sensitivity, specificity, and accuracy of 96.2%, 98.5%, and 97.9%, respectively. In secondary HPT, 163 hyperplastic glands weighing 0.03-5.08 g (0.85 +/- 0.93 g) were found. Scintigraphy correctly localized 79 glands (48.5%) weighing 0.03-5.08 g (1.19 +/- 1.10 g), but 84 glands (51.5%) weighing 0.04-2.70 g (0.51 +/- 0.50 g) were not detected. Thus, the sensitivity, specificity, and accuracy of scintigraphy were respectively 48.5%, 100%, and 51.2%, in secondary HPT. These results show that scintigraphy with 201Tl and 131I can be used to locate abnormal parathyroid glands with an efficacy equal to or better than that of the conventional methods with 201Tl and 99mTc or 201Tl and 123I.

Unilateral neck exploration for primary hyperparathyroidism: analysis of a controversy using a mathematical model.

Most endocrine surgeons explore both sides of the neck and identify all parathyroid glands when operating on patients with primary hyperparathyroidism. Others, however, advocate the unilateral approach, i.e., if an adenoma and a normal gland are identified, the contralateral side is not explored. We analyzed the strategy of the unilateral approach using a mathematical model to determine the variables that influence the probability of missing a tumor on the unexplored side of the neck. Assuming the frequency of single adenoma is 80%, hyperplasia 14%, double adenomas 4%, triple adenomas 1%, and carcinoma 1%, and the probability of missing a tumor on the explored side is 5%, we found that: 1. Only 41% of the patients treated by the unilateral approach undergo unilateral exploration. This is increased to 62% when a localization study with a sensitivity of 80% is used pre-operatively. 2. The probability of missing a tumor on the unexplored side of the neck parallels the prevalence of multiple adenomas. Half of the patients with triple adenomas and two-thirds of the patients with double adenomas will have a missed tumor when treated by the unilateral approach. 3. Patients who undergo unilateral exploration have an additional 7% to 8% probability of missing a tumor that would have been found if bilateral exploration is performed. This risk is lowered to 2% by a pre-operative localization study that is 80% sensitive. 4. A prospective study will require 684 patients, randomized to the unilateral or bilateral approach, to have an 80% statistical power (alpha = 0.05, beta = 0.20) of detecting a difference between a 5% and a 10% risk of missing a tumor.

Primary hyperparathyroidism in younger and older patients: symptoms and outcome of surgery.

Two-hundred and fifty patients undergoing initial exploration for primary hyperparathyroidism were analyzed for differences in clinical presentation, biochemical status, pathology, and outcome of surgery. In patients less than 60 years of age (younger patients, n = 119) the most common preoperative symptoms and signs were fatigue (40.3%), bone pain (33.6%), renal stones (31.0%), hypertension (27.7%), and psychiatric illness (27.7%). In patients greater than or equal to 60 years of age (older patients, n = 131) the most frequent symptoms and signs were hypertension (46.6%), fatigue (35.1%), bone pain (30.5%), muscle weakness (28.2%), and joint pain (22.9%). Renal stones were 2.6 times more common (p less than 0.001, chi 2) in younger patients and hypertension 1.7 times more common (p less than 0.05, chi 2) in older patients. There was no significant difference in the preoperative and postoperative laboratory values typically associated with primary hyperparathyroidism. Double adenomas were more common in older (9.2%) than in younger patients (2.5%, p less than 0.05, chi 2). Surgical cure was obtained in 98.8% of patients, and after parathyroidectomy 83% of the younger and 82% of the older patients experienced substantial relief of pre-operative symptoms. Specific questioning revealed most patients to be symptomatic and older patients appear to receive the same clinical and metabolic benefits from parathyroidectomy as younger patients.

Primary hyperparathyroidism in the 1990s. Choice of surgical procedures for this disease.

Many advances have occurred in recent years in the diagnosis, localization, and treatment of primary hyperparathyroidism. Several different operative choices for primary hyperparathyroidism also have been proposed--a unilateral approach versus the standard bilateral parathyroid exploration. The unilateral approach is based on the concept that if an enlarged parathyroid gland and a normal gland are found on the first side of the neck that is explored, then this is an adenoma and the second side should not be explored. Only if both glands on the initial side are recognized to be abnormal is the second side explored. The theoretical advantages of this unilateral approach are a decrease in operative morbidity rates--hypoparathyroidism and nerve injuries--and a decrease in operative time. Furthermore, proponents argue that if persistent hyperparathyroidism occurs, the second side can be easily explored because it was previously untouched. In the hands of several expert parathyroid surgeons, excellent results have been achieved. However, the unilateral approach has a number of disadvantages. It places considerable pressure on the surgeon and pathologist, for they have only one parathyroid gland other than the large one to examine. There is a significant potential risk of missing double adenomas or asymmetric hyperplasia because the second, ipsilateral parathyroid gland may appear normal or near normal in these conditions. This could lead to an increased incidence of persistent or recurrent hyperparathyroidism. Furthermore, a significant reduction of operative time may be questioned, especially when the time for performing special fat stains, which often are performed with unilateral explorations, is added. Finally, even if the intent is to perform a unilateral exploration, a bilateral exploration will be necessary about half of the time. The authors strongly recommend a bilateral parathyroid exploration for all patients undergoing an initial parathyroid operation. In cases of adenoma, bilateral visualization of normal parathyroid glands and careful biopsy of only one of them will minimize hypoparathyroidism. This operative approach will lead to better results, especially for the less experienced parathyroid surgeon.

Diagnosis and treatment of primary hyperparathyroidism

Primary hyperparathyroidism is nowadays not uncommon in Japan. The incidence is considered to be one in every 2,500 to 5,000 persons. Many advances have occurred in diagnosis, localization study, and treatment of the disease. Surgery remains the treatment of choice for patients with primary hyperparathyroidism. Notwithstanding, there are still controversies concerning the management of primary hyperparathyroidism. One of the current disputable points is whether the use of localization study in patients who are undergoing and initial operation is justified or not. Another is whether unilateral exploration is justified or not. The basic reasons for these persistent controversies is the lack of consensus about incidence of multiglandular hyperplasia or double adenomas. Our observation implies that the incidence of hyperplasia or double adenomas among all the patients with primary hyperparathyroidism in Japan is lower than that in western countries. Since diagnostic accuracy of noninvasive localization studies has recently improved, it seems reasonable to adopt unilateral neck exploration in our country. It is also characteristic in Japan that the incidence of parathyroid carcinoma is relatively high (6%) compared with that reported in many other countries.

Parathyroid Exploration: A Review of 125 Cases

Cervical exploration was performed in 106 patients with primary hyperparathyroidism and in 19 patients with chronic renal failure. Initial exploration for primary hyperparathyroidism was successful in 97% of the cases. Single adenomas were found in 84, double adenomas in six, and multiple-gland hyperplasia in 12 patients. Two of the four patients in whom cervical exploration failed were ultimately given the diagnosis of benign familial hypocalciuric hypercalcemia. Thirteen adenomas were ectopic. Preoperative thallium-technetium scans and ultrasound correctly localized only 63% of the adenomas. Only 45% of the ectopic adenomas were correctly localized. All four glands should be examined at initial exploration. Because of the occurrence of double adenomas, contralateral exploration is always indicated regardless of whether an enlarged gland and a normal one are found on the first side. All enlarged parathyroids should be removed when dealing with single or multiple adenomas; subtotal parathyroidectomy (3 1/2 glands) should be performed in multiple-gland hyperplasia. Frozen section confirmation of excised parathyroid tissue is essential. If exploration is unsuccessful, ectopic locations such as the retroesophageal areas, thymus, anterior and posterior mediastinum, carotid sheath, and thyroid lobe must be searched carefully. Preoperative localization studies are not as reliable as an experience parathyroid surgeon.

Parathyromatosis in hyperparathyroidism

Recurrent hyperparathyroidism after parathyroidectomy may present a difficult diagnostic problem. A rare ethology is parathyromatosis (multiple nodules of hyperfunctioning parathyroid tissue scattered through the neck and mediastinum) due to spillage of otherwise benign parathyroid tissue during surgery. We present a case of recurrent hyperparathyroidism and parathyromatosis due to tissue spillage during surgical removal of probable double adenomas, a rare cause of primary hyperparathyroidism. Thus, parathyromatosis must be included in the differential diagnosis of recurrent or persistent hyperparathyroidism, distinguished from parathyroid carcinoma by histologic criteria. The surgeon must be careful of parathyroid spillage during surgery, even of benign tumors of the parathyroids.

Strategy in reoperative surgery for hyperparathyroidism.

Eighty-three patients undergoing reoperations for hyperparathyroidism were studied. Preoperative diagnosis was reviewed, and localization was employed in selected patients. Cervical reexploration was carried out in a systematic manner, and mediastinotomy was required in 11 patients. Sixty patients had had previous parathyroid exploration. Missed adenomas were found in 34, of which 28 were single and 6 were double adenomas. Fourteen single adenomas were in normal locations and 14 were in ectopic locations. Seventeen patients had hyperplasia; 6 were wrongly diagnosed as adenoma, 3 had inadequate excision, 2 had supernumerary glands, and 6 had remnant hypertrophy. Three patients had recurrent carcinoma. Two had wrong diagnoses and 4 had uncertain diagnoses. Reoperation eliminated hypercalcemia in 71 patients (85.5%). Eight patients developed permanent hypoparathyroidism, and 1 had a permanent recurrent nerve palsy. Reoperative parathyroid surgery can be minimized with thorough initial cervical exploration, correct pathologic interpretation, and adequate parathyroid resection.

Preoperative localization of parathyroid adenomas

During a 12-month period, 64 patients were operated on for primary hyperparathyroidism. Sixty-one had single adenomas and 3 had double adenomas. Preoperative imaging was used to localize the adenomas. Half of the patients (32 of 64) had magnetic resonance, thallium-201/technetium-99m subtraction scintigraphy, and high-resolution ultrasonography; the other 32 patients had 1 or 2 of the imaging modalities. Sensitivity and specificity of magnetic resonance imaging was 82 percent and 97 percent, respectively; the sensitivity and specificity of the other two modalities was 59 and 98 percent for subtraction scintigraphy and 73 and 98 percent for ultrasonography. The use of preoperative imaging facilitated surgical exploration, reduced operating time, and resulted in an increased number of successful operations. There were no negative explorations in this series as compared with 19 negative explorations (2.6 percent) in our prior experience with 720 operations.

THE USE OF PRE‐OPERATIVE SCAN PRIOR TO NECK EXPLORATION FOR PRIMARY HYPERPARATHYROIDISM

A group of patients with diagnosed primary hyperparathyroidism (PHP) in Auckland between 1982 and 1986 is reviewed. Of the 119 patients, 55 had pre-operative scanning, 36 had no scanning prior to surgery and 29 were managed conservatively. Of the 52 patients who had pre-operative localization with ultrasound scanning, only 27 (52%) had their adenoma correctly predicted upon neck exploration. Of the 14 patients investigated with thallium-201 and technetium-99m (T1/Tc) subtraction scanning, 10 (71%) had their adenoma positively identified in the predicted locations, whereas the cause of the parathyroid pathology was correctly identified in 33 of the 36 patients (92%) who had surgery alone with no pre-operative scanning. In 11 patients both ultrasound and T1/Tc subtraction scanning were employed. In eight patients the results of the two scanning modalities agreed, and in seven of these eight patients the adenoma was correctly predicted (six single adenomas and one with double adenoma). In the three patients in whom the results of the two modalities differed, the T1/Tc subtraction scanning correctly predicted the site of the adenoma in two patients and in the third patient (with a small 223 mg adenoma) both modalities were incorrect. Of the six patients with histologically proven parathyroid hyperplasia, only three had pre-operative localization with ultrasound alone, and all three had incorrect predictions (one false positive for adenoma, and two false negative scans). Overall the results cast doubt over the usefulness of pre-operative scanning as a routine investigation prior to initial neck exploration for primary hyperparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

CLINICAL STUDY OF 23 CASES OF PRIMARY HYPERPARATHYROIDISM

From January 1979 to August 1986, 23 patients underwent surgical operations for primary hyperparathyroidism. These consisted of 15 cases of single adenoma, one of double adenoma, one of adenocarcinoma, five of hyperplasia and one in which no pathological gland was found in the cervical region. There were nine males and 14 females, aged from 16 to 72 years. In 14 of these patients, the disease was diagnosed on the basis of urinary caliculus. Equivalent diagnostic value was given to ultrasound examination and Taliun scintigraphy in the preoperative localization study, and the lower limit of detection for pathological glands was 300 to 500 mg. In five cases operations were performed on the basis of biochemical data without positive findings on diagnostic imaging, and the glands could be found intraoperatively. Therefore, biochemical data seem to have value in the diagnosis and treatment of primary hyperparathyroidism.

Primary hyperparathyroidism in patients with multiple endocrine neoplasia syndromes. Surgical experience.

Forty-five patients with biochemically documented primary hyperparathyroidism as part of multiple endocrine neoplasia syndrome types 1 or 2 were surgically treated from 1960 through 1980. Hyperplasia occurred in 69% of the patients, single adenoma in 27%, and double adenomas in 4%. All but two patients with hyperplasia underwent subtotal parathyroidectomy. In this group, the cure rate was 93% and the incidence of permanent postoperative hypoparathyroidism 23%. In the adenoma group, treatment included excision of the adenoma and biopsy of at least one other gland. The cure rate was 76%, with no postoperative hypoparathyroidism. Analysis of patients with persistent hyperparathyroidism suggested that failure to recognize multiple gland disease was the principal cause of postoperative hypercalcemia. In view of the high incidence of hypocalcemia after subtotal parathyroidectomy, approximately 500 mg of tissue should be cryopreserved to allow transplantation should hypocalcemia ensue postoperatively.

Evaluation of Parathyroid Gland Lesions-Reply

In Reply.— Dr Dufour's letter underscores the difficulties that endocrine pathologists and surgeons face when they attempt to establish a clear differentiation between hyperplasia and adenoma of the parathyroid glands. It is necessary to recognize that parathyroid adenomas, like their counterparts in the adrenal, pituitary, and thyroid glands, develop from a background of cellular hyperplasia that can then progress to nodular hyperplasia, to adenoma formation, and, on rare occasions, to frank carcinomatous dedifferentiation. 1,2 Given this sequence of events, it follows that there will be instances where combinations of hyperplasia, nodular hyperplasia, single adenoma, or double adenomas coexist in the same patient and, at times, within the same parathyroid gland. Unfortunately, controversy over the classification of parathyroid histopathology has not resolved the endocrine surgeon's dilemma at the time of surgery. Only then can the extent of the disease, including the number of glands involved, and whether a particular gland is

Primary Hyperparathyroidism: Pathology and Therapy

More than 50 years ago, despite the controversy over whether parathyroid tumors were harmful or not, Felix Mandl, a steadfast and determined Viennese surgeon, made his decision to operate on the now famous Albert, a tramcar conductor who had been bedridden with osteitis fibrosa cystica involving much of his skeleton. The good news was that Albert stopped excreting his skeleton into his urine and within a few months after his parathyroidectomy was able to ambulate and return to a relatively normal life. The bad news was not long in manifesting itself; a year or two later, Albert noticed recurrence of his symptoms and finally agreed to a second operation, six years after the first. Unfortunately, it was unsuccessful and Albert succumbed to the musculoskeletal and metabolic ravages of hyperparathyroidism. A reasonable assumption is that Albert had either double adenomas, diffuse adenomatous hyperplasia, or multiglandular parathyroid disease. At least two lessons

Hyperparathyroidism due to double adenoma in an adolescent : J. M. Babut, P. Collignon, and M. Vidhaillet. Ann. Chir. Inf. 12:177–184, 1971

Hyperparathyroidism due to double adenoma in an adolescent : J. M. Babut, P. Collignon, and M. Vidhaillet. Ann. Chir. Inf. 12:177–184, 1971