The role of thyroid resection during reoperation for persistent or recurrent hyperparathyroidism

BACKGROUND: The role of "blind" thyroid lobectomy in the surgical management of patients with persistent or recurrent primary hyperparathyroidism is not known. We reviewed our experience with reoperation for hyperparathyroidism to determine the utility of blind thyroid resection in this setting. METHODS: From 1982 to 1995, 269 patients underwent reoperation for hyperparathyroidism at our institution. All patients had biochemical confirmation of hyperparathyroidism and underwent noninvasive and if necessary invasive localization studies. Patients who underwent thyroid lobectomy in an attempt to extirpate the hyperfunctioning parathyroid gland form the basis of this report. RESULTS: Thirty-two of 269 patients (12%) underwent thyroid lobectomy to remove a parathyroid gland. Intrathyroidal parathyroids were confirmed in 19 of 32 patients (59%). In 18 of 19 patients (94%), preoperative or intraoperative ultrasonography correctly identified an intrathyroidal lesion suspicious or a parathyroid. Only 1 of 6 patients (17%) undergoing a blind thyroidectomy had an intrathyroidal gland identified. Ultrasonography had a sensitivity of 95% and a negative predictive value of 99.5% in detecting an intrathyroidal parathyroid gland. CONCLUSIONS: The prevalence of an intrathyroidal parathyroid gland in our series is low (19 of 269, 7%). Ultrasonography can be used reliably to select patients for thyroid resection, reducing the need to perform a blind thyroid lobectomy and avoiding the potential morbidity of thyroid resection in this clinical setting.     

MIBI-scintigraphy. A simple and reliable method for localization of pathological parathyroid glands

99Tcm-sestamibi scintigraphy was used to localise enlarged parathyroid glands in 25 patients with primary hyperparathyroidism previously operated in the neck, 20 of whom had recurrent disease and five had previously undergone surgery for thyroid disorders. Of the 18 patients for whom positive scans were obtained, nine were operated on the scan findings being confirmed. Crucial information was provided in two cases of intrathyroidal and one case of intramediastinal localisation of the pathological gland were not operated on as the hypercalcaemia was only marginal or the symptoms were vague. Though preoperative localisation of pathological parathyroid glands is a prerequisite for neck exploration in patients with persistent or recurrent hypercalcaemia due to primary (or secondary) hyperparathyroidism, the procedure is not cost-effective before the initial operation.     

Primary hyperthyroidism 1996

55 prospectively documented patients aged 20-84 (median 67) years (47 women, 8 males) underwent surgery for primary hyperparathyroidism (pHPT). The most frequent symptoms and associated conditions were nephrolithiasis (42%) and neuropsychiatric symptoms (39%). Only one case of asymptomatic and one case of "normocalcemic" pHPT were found in this series. 47 patients (89%) were cured following initial neck exploration, and 3 further patients (6%) were cured by a second operation. Reoperation also led to cure in 2 patients operated on elsewhere in the first instance. 6 patients (11%) had double adenoma (bilaterally) and 36% of the adenomas had an ectopic location, with an intrathyroidal adenoma in 2 cases. In 2 patients sternotomy was carried out. Persistent pHPT was observed in 3 patients (following initial exploration in 2 cases and reoperation in one). These patients had a supernumerary adenomatous gland with ectopic location in 2 cases and a double adenoma with ectopic position of one adenoma in a further case. One 80-year-old patient died post-operatively from intestinal ischemia. 2 patients had permanent postoperative hypoparathyroidism; in no case was a permanent recurrent laryngeal nerve palsy observed. Bilateral parathyroid exploration with thyroid mobilization by capsular dissection is the procedure of choice for pHPT. In 2 patients with the MEN 2A-syndrome and with medullary thyroid carcinoma thyroidectomy, lymphadenectomy and autotransplantation of normal parathyroids to the arm was performed, with normal parathyroid function in both cases.     

Stapedial reflex: a biological index found to be abnormal in clinical and subclinical hypothyroidism

INTRODUCTION: Parathyroidectomy via cervical exploration is an effective primary-modality treatment for hyperparathyroidism, with cure rates of greater than 95%. We retrospectively reviewed 866 consecutive parathyroidectomies performed by a single surgeon between 1960 and 1997. We attempted to describe the polymorphic variation in multiglandular disease, the anatomic locations of pathologic glands, and the operative strategy and techniques which we believed were important to minimizing morbidity and maximizing curative success. METHODS: The cases of 329 males and 537 females (age, 1-88 years) were reviewed. There were 766 operations performed: primary hyperparathyroidism (713), tertiary hyperparathyroidism (100), reoperations (53). The strategy for primary exploration includes a bilateral neck exploration, early recurrent laryngeal nerve skeletonization, and identification of at least four glands. RESULTS: Normocalcemia was achieved in 98.2% of cases after initial cervical exploration. Persistent hypercalcemia occurred in 7 patients (<1%). Nine patients (1%) suffered persistent postoperative hypocalcemia. Unilateral recurrent laryngeal nerve injury occurred in two patients (<1%). Other perioperative complications included: reoperation for hematoma, repaired carotid artery injury, unexplained dysphagia, pneumothorax, deep venous thrombosis, and aspiration pneumonia. There were two mortalities (<1%) attributable to severe, comorbid disease. Ectopic glands were found in 120 cases. The frequency of glands at these sites were as follows: mediastinal (4.9%), intrathymic (8.4%), intrathyroid (6.7%), and retroesophageal/retrotracheal (3.5%). Thyroid resections provided diagnosis of concomitant thyroid carcinoma in 8.0% of resected patients. The pathology of patients with primary hyperparathyroidism (PHPT) consisted of single adenomas (77.2%), hyperplasia (21.0%), normal glands (1%), double adenomas (<1%), and parathyroid carcinoma (<1%). The distribution of adenomas was as follows: left upper, 25.3%; left lower, 27.3%; right upper, 26.8%; right lower, 20.6%. Hyperplastic glands were found in ectopic positions as follows: intrathymic (7.5%), intrathyroid (11.3%), mediastinal (2.5%), and retroesophageal/retrotracheal (0%). The average volume difference between the largest and smallest hyperplastic gland of each case was 1.80 + 4.40 cm3. Reoperations were performed upon 53 referred patients and 7 patients after failed exploration. Normocalcemia was attained in 98.3% of cases. Glandular pathology was identified in the previous operative field in 52 patients (86.7%). Adenomas were identified in 56.0% (n = 23) and hyperplasia in 39.0% (n = 16). CONCLUSIONS: In our series, we were able to attain normocalcemia in 98.2% of cases after initial cervical exploration. We believe that identification of four glands, an exhaustive search of ectopic sites, bilateral exploration, and liberal use of biopsy and intraoperative frozen section were essential to curative success. The pathologist should identify parathyroid tissue in the specimen and differentiate the "abnormal" from "normal" gland. Morphologic criteria alone cannot be used because of polymorphic variation in hyperplasia in which pathologic glands may appear normal. Early identification of the recurrent laryngeal nerve allows for a safer neck exploration by alerting the surgeon to the location and course of the nerve. A bilateral approach does not contribute increased morbidity from recurrent laryngeal nerve injury.     

Hypercalcemia caused by ectopic production of parathyroid hormone in a patient with papillary adenocarcinoma of the thyroid gland

Hypercalcemia and elevation of a serum PTH level (9800 pg/mL (normal: 160-520) were found in a 72-yr-old woman who had a lung cancer. She underwent pulmonary lobectomy for a suspected PTH-producing lung cancer. However, hypercalcemia and elevation of the serum PTH level were persistent postoperatively. Subsequent examination, using parathyroid scintiscanning, revealed a hot spot in the right lower part of the thyroid gland, suggesting hypercalcemia caused by a parathyroid tumor. She underwent bilateral exploration of the neck; however, four apparently normal parathyroid glands were seen. Therefore, hemithyroidectomy was performed for the possibility of an intrathyroidal parathyroid adenoma. Serum calcium and PTH levels declined after this operation. A nodular lesion was found in the cut sections of the resected specimen, which was consistent with the result of the scintiscanning. Histological examinations revealed a papillary adenocarcinoma of the thyroid gland, and the PTH-immunoreactivity in the tumor cells was confirmed. These findings strongly suggest that PTH could be produced ectopically by the papillary adenocarcinoma of the thyroid gland.     

Nonadenomatous thymic unencapsulated parathyroid tissue as a cause of persistent primary hyperparathyroidism

Primary hyperparathyroidism may be caused by ectopic intrathymic parathyroid adenomas or hyperplastic parathyroid glands. The association of the ectopic inferior parathyroid glands and the thymus is due to their common embryologic origin from the third pharyngeal pouch. We report a case of primary hyperparathyroidism due to an unusual pathologic parathyroid gland formation: nonadenomatous thymic unencapsulated parathyroid tissue. Two unsuccessful neck exploration revealed only two normal parathyroid glands within the cervical area. Radiologic imaging studies failed to localize an ectopic parathyroid adenoma. Mediastinal exploration and thymectomy showed one small focus of unencapsulated hypercellular parathyroid tissue expanding peripherally along the septa of thymic adipose tissue. The hyperparathyroidism resolved with the surgical procedure.     

Prenatal strategies for reducing severe thalassemia in pregnancy

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism with a prevalence ranging between 0.5 and 4%. Because of their aggressiveness, prompt diagnosis and treatment are mandatory. A parathyroid carcinoma was found in four patients (4.5%) of 88 patients who underwent surgical cervical exploration for primary hyperparathyroidism at the Institute Nacional de la Nutrición in a period of seven years. Our paper gives the clinical characteristics, diagnosis, treatment and outcome of the four patients.     

Thyroid paraganglioma: report of a case

A case of thyroid gland paraganglioma is reported in a 48-year-old woman with cold thyroid nodule. Review of the literature reveals only 4 cases of intrathyroidal paraganglioma but none of them have complete immunohistochemical study. The main differential diagnosis in this localization, namely medullary carcinoma and trabecular hyalinizing adenoma, are discussed.     

Expression and function of a scavenger lipoprotein pathway in porcine luteal cells

PURPOSE: To evaluate the usefulness and cost-effectiveness of routine preoperative technetium-99m sestamibi-iodine-123 subtraction scanning in patients with parathyroid gland disease. MATERIALS AND METHODS: Tc-99m sestamibi-I-123 subtraction scanning was performed in 65 patients with primary hyperparathyroidism who were referred for evaluation before first surgery. RESULTS: Focal tracer uptake was detected in the mediastinum in two patients who then underwent primary sternotomy; a parathyroid adenoma, anterior to the ascending aorta, was resected in each case. In a third patient, imaging showed tracer uptake above the thyroid gland; this patient underwent resection of an undescended parathyroid adenoma located in the sheath of the right carotid artery. Initial surgery was curative in all patients. Preoperative subtraction scans depicted 56 of 59 (95%) solitary adenomas. Four patients had hyperplasia; two had double adenoma. Imaging findings indicated multiple parathyroid involvement in five of these patients and facilitated location of 12 of 15 (80%) enlarged glands. Four adenomas and two hyperplastic glands that weighed less than 100 mg were detected. The positive predictive value for any suspected location was 96%. Average surgery time was reduced from 120 to 90 minutes. CONCLUSION: Preoperative subtraction scanning is useful in planning parathyroid surgery and appears to be cost-effective.     

Parathyroid hyperplasia in primary hyperparathyroidism: a review of 85 cases

Parathyroid hyperplasia of all four glands was found to be the cause of primary hyperparathyroidism in 85 of 557 cases seen at the Massachusetts General Hospital between 1930 and 1973. There were 66 cases of chief cell hyperplasia and 19 cases of clear cell hyperplasia that were grossly, microscopically, and ultrastructurally distinct. Although the clinical findings overlap, there are several differences in the signs and symptoms between these two forms of hyperplasia. Both types are treated by subtotal removal of all the parathyroid tissue. Removal of insufficient tissue has left residual hyperparathyroidism in 45% of those with chief cell hyperplasia and 11% of those with clear cell hyperplasia after what was thought to be definitive surgery. Postoperative hypoparathyroidism was found in 15% of the patients with chief cell hyperplasia and in none with clear cell hyperplasia. These findings further suggest that removal of three and one-half glands in the more than 86% of patients with one gland involvement (adenoma or carcinoma) as the cause of primary hyperparathyroidism is unwarranted.     

Preoperative parathyroid gland localization with technetium-99m sestamibi in secondary hyperparathyroidism

Technetium-99m sestamibi scintigraphy has become a valuable tool in locating parathyroid glands in patients with primary hyperparathyroidism. The aim of this study was to evaluate its usefulness in secondary hyperparathyroidism. Twenty patients were injected intravenously with 740 MBq of 99mTc-sestamibi and images were obtained at 15 min and 2 h post injection. All patients underwent parathyroid ultrasonography (US) as well as bilateral surgical neck exploration and 64 parathyroid glands were removed. US revealed at least one enlarged gland in 15/20 patients (75%), while 99mTc-sestamibi scintigraphy showed focal areas of increased uptake in at least one gland in 17/20 patients (85%). When imaging results for all glands were evaluated according to surgical results, sensitivity was 54% for parathyroid scintigraphy and 41% for US, and specificity was 89% for both imaging techniques. There was a discrepancy between the two imaging modalities in 28 glands (35%). The mean surgical weight of US-positive glands (1492+/-1436 mg) was significantly higher than that of US-negative glands (775+/-703 mg) (P<0.05). However, there were no significant differences in weight between sestamibi-positive and sestamibi-negative glands. When only sestamibi-positive glands were considered, a positive correlation between uptake and weight was found (r=0.4, P<0.05). In conclusion, parathyroid US and 99mTc-sestamibi scintigraphy are complementary imaging techniques in the preoperative localization of abnormal parathyroid glands in patients with secondary hyperparathyroidism. The limited sensitivity of the techniques means that patients will still require bilateral neck exploration; therefore routine preoperative parathyroid scanning in renal patients is not justified.     

Intra-operative parathyroid hormone assay for simplified localization of parathyroid adenomas

Lack of success in parathyroid surgery is usually due to failure to identify the abnormal parathyroid gland correctly at operation. The surgeon may be helped by rapid parathyroid hormone (PTH) assay in peripheral blood after removal of a suspected adenoma, and by frozen section histology, but these are not true localization techniques. We have adapted a non-isotopic immunoassay for rapid measurement of PTH in samples from the upper, middle and lower thyroid veins taken at operation, before exploration begins. Fifteen patients with primary hyperparathyroidism were operated on. In 10 the parathyroid adenoma was located easily, and was associated with high local venous PTH levels. In four patients the abnormal parathyroid was not immediately apparent but the assay indicated its location, which was confirmed after further exploration. In one patient there was no difference in PTH levels in the six venous samples. An ectopic adenomatous gland was successfully identified behind the thymus. The operation was successful in all patients as shown by a fall in the plasma calcium to the normal range. We conclude that intra-operative selective venous sampling and rapid PTH assay facilitates operative localization of parathyroid adenomas.     

Intrathyroidal parathyroid glands can be a cause of failed cervical exploration for hyperparathyroidism

BACKGROUND: The incidence of intrathyroidal parathyroid glands remains controversial. The purpose of this study was to determine the incidence in a series of patients with hyperparathyroidism. METHODS: Three hundred nine patients underwent parathyroidectomy. Patients were divided into two groups: uniglandular disease versus hyperplasia. RESULTS: Eighteen of 309 patients (6%) had abnormal intrathyroidal parathyroid glands. The incidence was 3% (7 of 222) in patients with uniglandular disease versus 15% (11 of 73) in those with hyperplasia. With a mean follow-up of 54 months, 12 patients are eucalcemic, 5 have persistent hypocalcemia, and 1 has recurrent hypercalcemia. There were no recurrent laryngeal nerve injuries. CONCLUSIONS: These data suggest that an intrathyroidal adenoma is an uncommon cause of failure, whereas abnormal intrathyroidal parathyroid tissue may be a more common cause of failure in patients with hyperplasia.     

Inhibition of lymphoproliferative response and its restoration with a glucan immunomodulator in mice with experimental larval toxocarosis

Primary hyperparathyroidism is unusual in children. It is most commonly due to a solitary sporadic parathyroid adenoma, though parathyroid hyperplasia and related familial syndromes should be considered. In the case presented here, an 11-year-old boy with primary hyperparathyroidism had preoperative imaging studies that localized to the inferior aspect of the left side of the neck anteriorly, and a parathyroid adenoma was successfully resected. Screening for familial syndromes involving hyperparathyroidism should be individually considered in children with primary hyperparathyroidism. Preoperative localizing studies and the role of unilateral surgery are controversial issues in adults with primary hyperparathyroidism. Although such issues have not been addressed in children, localization and unilateral surgery proved successful in this case.     

Collagen deposition and mechanical strength of colon anastomoses and skin incisional wounds of rats

BACKGROUND: The purpose of this study was to prospectively evaluate parathyroid localization using technetium-99m-sestamibi (MIBI). STUDY DESIGN: Technetium-99m-sestamibi scintigraphy was performed in 124 patients with hyperparathyroidism and the results were correlated with serum calcium and parathyroid hormone (PTH) levels, weight, location, and pathology of parathyroid tissue, and associated thyroid abnormalities. RESULTS: Hyperparathyroidism was primary in 118 patients, secondary in four patients, and tertiary in two patients. The parathyroid pathology was a solitary adenoma in 95 patients (77 percent), double adenoma in five (4 percent), hyperplasia in 14 (11 percent), carcinoma in one (1 percent), and unconfirmed in nine (7 percent) who underwent noncurative parathyroidectomy. Associated thyroid disease was present in 29 (23 percent) patients. Fourteen patients (11 percent) had undergone previous parathyroid exploration. The mean calcium level was 11.4 +/- 0.8 mg/dL (range, 8.3 to 13.7 mg/dL) and the mean adjusted PTH level was 395 +/- 702 (range, 70 to 4,331). The sensitivity and positive predictive value of MIBI scintigraphy were 81 and 89 percent, respectively, in patients with a solitary adenoma and 37 and 100 percent, respectively, in patients with multiglandular disease. The mean adjusted PTH level was higher in patients with true-positive scans compared with false-negative scans (440 +/- 628 compared with 243 +/- 499, p > 0.05). The mean adenoma weight was 1,877 +/- 3,212 mg in patients with a true-positive scan compared with 485 +/- 296 mg with a false-negative scan (p > 0.05). CONCLUSIONS: The sensitivity and positive predictive value of MIBI scintigraphy is comparable to or better than the results reported for other localization procedures. Its lack of sensitivity for detection of multiglandular disease precludes its use in lieu of routine bilateral neck exploration in the management of patients with hyperparathyroidism.     

Unusual presentations of sellar arachnoid cyst

Parathyroid carcinoma is a rare endocrine malignancy characterized by the exaggerated metabolic effects of the parathyroid glands. The preoperative differential diagnosis between parathyroid carcinoma and primary hyperparathyroidism is often difficult because many of the signs and symptoms are very similar. Intraoperative differentiation is obscured by the strict anatomic and histologic criteria required for diagnosis of parathyroid carcinoma. We have encountered three patients with parathyroid carcinoma during the last 10 years and managed them successfully. Two of them presented with recurrence of hypercalcemia, one 11 years after and the other 3 years after the primary operation for hyperparathyroidism; both patients were eventually diagnosed with parathyroid carcinoma. The third case was suspected as primary hyperparathyroidism preoperatively but confirmed as carcinoma subsequent to histologic examination.     

A sensitive assay for measuring alpha-Gal epitope expression on cells by a monoclonal anti-Gal antibody

BACKGROUND: The distinction between solitary parathyroid adenoma and hyperplasia can sometimes be difficult during surgery for primary hyperparathyroidism (pHPT), especially in patients who have undergone previous thyroid or parathyroid surgery. The use of intraoperative parathyroid hormone (PTH) monitoring as a possible diagnostic tool was therefore investigated. METHODS: Intraoperative levels of PTH were measured in 119 patients during 121 operations (including 14 reoperations) for pHPT. The mean(s.d.) preoperative serum calcium level was 2.79(0.21) mmol/l. Blood samples were drawn before, and at 5 and 15 min after, excision of the first enlarged parathyroid gland. PTH was analysed electively in 61 patients and on-line by a modified assay for intact PTH in 48 patients. Both procedures were used in ten patients. RESULTS: The mean(s.d.) decline in PTH concentration in 101 patients with primary exploration due to solitary adenoma was 63(17) per cent after 5 min (n=84) and 83(10) per cent after 15 min. The patients with primary exploration because of multiglandular disease (n=6) were correctly predicted not to have parathyroid adenoma. CONCLUSION: Measurement of PTH levels during surgery for pHPT is a highly sensitive method for differentiating between single and multiple gland disease. The on-line monitoring of PTH is clinically useful in patients who have undergone previous neck surgery. Its role in pHPT surgery at primary exploration should be evaluated in prospective trials.     

A case of functioning parathyroid cyst

A case of functioning parathyroid cyst is reported. A 63-year-old woman consulted our hospital with the chief complaint of neck and joint pain. At that time, laboratory data showed a serum calcium level of 12.8 mg/dl and a phosphorus level of 2.2 mg/dl. Plasma levels of intact PTH were elevated to 278 pg/ml. Computerized tomography, ultrasonography and magnetic resonance imaging suggested parathyroid cyst on the left side of the thyroid gland. We performed left superior parathyroidectomy. The cyst measured 30 x 40 x 30 mm and was chocolate colored. The histopathological diagnosis was a functioning parathyroid cyst. Her postoperative course was uneventful and she was discharged on the 10th postoperative day without symptoms. To our knowledge, only 38 cases of functioning parathyroid cyst have been reported in the Japanese literature.     

Primary hyperparathyroidism secondary to parathyroid carcinoma: report of a case

Distinguishing parathyroid carcinoma from benign hyperparathyroidism is often difficult. Clinical features most commonly associated with parathyroid carcinoma, such as palpable cervical mass, markedly higher serum calcium, high parathyroid hormone immunoassay, and evidence of bone disease may not be present. Therefore, intraoperative recognition is essential. We report a case in which the presenting symptoms, physical examination, and laboratory analysis were consistent with benign disease. During surgery, the finding of an enlarged firm gland with surrounding inflammatory reaction altered the approach to include the possibility of parathyroid carcinoma. The gland and surrounding tissue were removed, and pathologic examination led to the diagnosis of carcinoma. At 18-month follow-up, the patient was free from recurrence. Any parathyroid gland with a gray appearance, firm texture, and surrounding inflammatory reaction should be treated as carcinoma. Initial intraoperative recognition offers the best chance for cure, since local recurrences are rarely curable.     

Management of hyperparathyroidism in an endemic goiter area

In an endemic goiter area patients with hyperparathyroidism (HPTH) frequently also have thyroid abnormalities. In a retrospective study of 95 patients with HPTH we assessed the diagnostic accuracy of imaging techniques (ultrasonography or radionuclide scanning) for preoperative localization of parathyroid adenomas. Altogether 86% of our patients had goiter, requiring thyroid resections in 37%. For 19 patients the parathyroid exploration was the second or third cervical operation, most of them due to goiter. We found that the overall rate of transient and permanent recurrent nerve paralysis is considerably increased in patients with previous neck surgery (26% vs. 7%). The combination of ultrasonography and radionuclide scanning can lead surgeons to the site of parathyroid lesions responsible for HPTH in 85% of cases, although frequent nodular goiters can produce pitfalls for correct imaging in iodine-deficient countries. In endemic goiter areas preoperative localization studies can be recommended in patients with primary HPTH--for evaluation of thyroid pathology possibly leading to resection or its accuracy in localizing parathyroid adenomas. These studies also seem justified in patients with previously unsuccessful neck explorations for HPTH.