Multiple Gland Hyperplasia Research Articles

Comparison of [18F]fluorocholine PET/CT with [99mTc]sestamibi and ultrasonography to detect parathyroid lesions in primary hyperparathyroidism: a prospective study

Primary hyperparathyroidism is a common endocrine disorder produced by the increase of parathyroid hormone (PTH) due to a benign adenoma of a single parathyroid gland, or as multiple gland hyperplasia, or as a rare malignant tumor. Preoperative imaging scans are frequently necessary for the minimally invasive parathyroidectomies to identify the location of enlarged parathyroid glands and to design the procedure. The diagnostic reliability of [18F]fluorocholine positron emission tomography/computed tomography (FCH PET/CT), [99mTc]sestamibi [multiplexed ion beam imaging (MIBI)] and cervical ultrasonography was analyzed in 37 patients diagnosed with primary hyperparathyroidism undergoing minimally invasive parathyroidectomy. The three preoperative imaging techniques were correlated with intraoperative and histopathological findings as well as changes in biochemical parameters (serum PTH and calcium levels). Statistical analysis was carried out with SPSS version 24.0. In 30 of 37 patients (81.1%), FCH PET/CT correctly localized the pathological gland. In 3 cases of ectopic adenomas, the accuracy of the techniques was 100% (3/3) for FCH PET/CT, 66.7% (2/3) for MIBI, and 33.3% (1/3) for neck ultrasonography. Neither neck ultrasonography nor MIBI were able to locate pathological parathyroid glands in those patients with multiglandular disease, while FCH PET/CT correctly located one patient (1/3, 33.3%) with two adenomas and 3 patients (3/6, 50.0%) with hyperplasia. The three imaging techniques, FCH PET/CT, MIBI and neck ultrasound yielded a sensitivity of 92.1%, 57.9% and 32.4%, a positive predictive value of 94.6%, 84.6% and 78.6%, and a diagnostic accuracy of 96.4%, 85.7% and 79.0%, respectively. In this group of patients diagnosed with primary hyperparathyroidism, FCH PET/CT was superior to MIBI and neck ultrasound in detecting adenomas, particularly in the presence of ectopic glands or multiglandular disease.

Preoperative Localization Studies in Primary Hyperparathyroidism.

Primary hyperparathyroidism (pHPT) is the third most frequently seen endocrine disease and it is the most common cause of hypercalcemia seen in ambulatory patients. PHPT is most often (80%-85%) caused by a single parathyroid adenoma, followed by double adenoma (4%-5%), multiple gland hyperplasia (10%-15%), and parathyroid carcinoma (<1%). The diagnosis of pHPT is biochemically established and the only curative treatment is surgery. Since the cause of pHPT is typically single-gland disease, it is possible to determine the majority of pathological glands with preoperative localization methods and use the minimally invasive parathyroidectomy (MIP) approach. MIP has become the standard treatment for pHPT in selected patients. There are both noninvasive and invasive preoperative localization methods. Noninvasive methods currently used include ultrasonography (US), parathyroid scintigraphy, 4-dimensional computed tomography (CT), magnetic resonance imaging, and positron emission tomography-CT with 18F-fluoroquinolone and 11C-methionine. Preoperative invasive localization methods include parathyroid hormone (PTH) measurement with fine-needle aspiration biopsy, lateralization with PTH measurement via bilateral jugular vein sampling, selective venous sampling, and parathyroid arteriography. The aim of this study was to evaluate preoperative localization studies used in cases of pHPT.

Diagnosis, management, histology and genetics of sporadic primary hyperparathyroidism: old knowledge with new tricks.

Primary hyperparathyroidism (pHPT) is a common endocrinopathy resulting from inappropriately high PTH secretion. It usually results from the presence of a single gland adenoma, multiple gland hyperplasia or rarely parathyroid carcinoma. All these conditions require different management, and it is important to be able to differentiate the underlined pathology, in order for the clinicians to provide the best therapeutic approach. Elucidation of the genetic background of each of these clinical entities would be of great interest. However, the molecular factors that control parathyroid tumorigenesis are poorly understood. There are data implicating the existence of specific genetic pathways involved in the emergence of parathyroid tumorigenesis. The main focus of the present study is to present the current optimal diagnostic and management protocols for pHPT as well as to review the literature regarding all molecular and genetic pathways that are to be involved in the pathophysiology of sporadic pHPT.

Feasibility of unilateral parathyroidectomy in patients with primary hyperparathyroidism and negative or discordant localization studies.

The purpose of this study was to examine the feasibility of unilateral parathyroidectomy in patients with primary hyperparathyroidism and negative or discordant localization studies. We included in our study 72 patients with preoperative diagnosis of primary hyperparathyroidism who had negative or discordant preoperative studies. In 66 patients, studies were discordant while in six were both negative. In 40 (55.6%) patients initial approach was a bilateral exploration. In 32 cases (44.4%) initial surgery was a unilateral exploration: in 26 conservative approach was successful, in six mini-invasive surgery failed and a bilateral exploration was necessary due to IOPTH negative test (five cases) or to the impossibility to find a pathological gland during exploration (one case). Intra-operative PTH test showed a sensitivity of 93.2%, a specificity of 92.3%, and an accuracy of 93.1%. Multiple gland disease was found in 8 (11.1%) patients (two double adenoma and six multiple gland hyperplasia). Mean operative time was lower in unilateral exploration group (87.9±43.8min). Comparing unilateral surgery in negative or discordant studies with 77 consecutive patients who underwent focused surgery with positive and concordant studies, conversion to bilateral exploration rate was statistically significantly higher in the first group (15.6%). We believe that unilateral parathyroidectomy can be safely performed also in patients with discordant localization studies with a high cure rate; in these cases, however, the use of intra-operative PTH is absolutely necessary. We suggest the need for referral of these patients to high-volume medical centers for thyroid and parathyroid surgery.

Surgery for multiple endocrine neoplasia type 1-associated primary hyperparathyroidism

Surgery in patients with multiple endocrine neoplasia type 1 (MEN1)-associated primary hyperparathyroidism (pHPT) is difficult as the condition it is caused by asymmetrical multiple gland hyperplasia. It is uncertain which operative procedure provides the best outcome with regard to long-term normocalcaemia. All patients who had surgery for genetically confirmed MEN1-associated pHPT between 1987 and 2009 were identified from a prospective database. Clinical data, operative procedures and outcome were analysed retrospectively. A total of 47 patients were identified. Twenty-three patients underwent total parathyroidectomy with thymectomy and autotransplantation (TPTX + AT), 11 patients subtotal parathyroidectomy (3-3.5 glands, SPTX) with thymectomy, and 13 patients selective gland excision (fewer than 3 glands, SGE). Rates of persistent disease, recurrent disease and permanent hypoparathyroidism after TPTX + AT were 4 per cent (1 patient), 4 per cent (1 patient) and 22 per cent (5 patients) respectively. Respective rates after SPTX were 0 per cent, 18 per cent (2 patients) and 45 per cent (5 patients), which were not statistically different from those following TPTX + AT. SGE resulted in persistent disease in 23 per cent (3 patients) and a significantly higher rate of recurrent disease (46 per cent, 6 patients; P = 0.004 versus TPTX, P = 0.210 versus SPTX), but permanent hypoparathyroidism did not occur. TPTX + AT and SPTX both seem adequate surgical procedures for the treatment of MEN1-associated pHPT and are associated with fewer recurrences than SGE.

From mild to severe primary hyperparathyroidism: the Brazilian experience

Primary hyperparathyroidism often presents as an asymptomatic disorder. In our institution, routine serum calcium measurements have now been used as part of medical examination for 23 years. Out of 124 patients consecutively seen at our institution, 47% presented with no symptoms related to the disease, while 25% presented with severe skeletal involvement and osteitis fibrosa cystica, 25% with renal stone disease without overt bone involvement, and 2% with the typical neuropsychiatric syndrome. This same pattern is seen in the city of São Paulo. In severe disease pathological fractures are frequently seen, especially in long bones of the lower extremities, and also loss of lamina dura of the teeth and salt-and-pepper appearance of the skull. Bone mineral density is extremely low in these patients but usually show remarkable recovery following surgical cure. Serum PTH and bone markers are considerable higher in severely affected patients, who also have a high rate of vitamin D deficiency, and the parathyroid lesion is easier located compared with asymptomatic patients. From pathological specimens 87% had histological confirmation of a single adenoma, 6.4% multiple gland hyperplasia and 3.8% carcinoma.

A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003

To systematically review the current preoperative diagnostic modalities, surgical treatments, and glandular pathologies associated with primary hyperparathyroidism. A systematic literature review. Of the 20,225 cases of primary hyperparathyroidism reported, solitary adenomas (SA), multiple gland hyperplasia disease (MGHD), double adenomas (DA), and parathyroid carcinomas (CAR) occurred in 88.90%, 5.74%, 4.14%, and 0.74% of cases respectively. Tc 99m -sestamibi and ultrasound were 88.44% and 78.55% sensitive, respectively, for SA, 44.46% and 34.86% for MGHD, and 29.95% and 16.20% for DA, respectively. Postoperative normocalcemia was achieved in 96.66%, 95.25%, and 97.69% of patients offered minimally invasive radio-guided parathyroidectomy (MIRP), unilateral, and bilateral neck exploration (BNE). Intraoperative PTH assays (IOPTH) were helpful in approximately 60% of bilateral neck exploration conversion (BNEC) surgeries. The overall prevalence of multiple gland disease (MGD and DA) was lower than often suggested by conventional wisdom. Furthermore, preoperative imaging was less accurate than it is often perceived for accurately imaging MGD. MIRP and UNE were more successful in achieving normocalcemia than is typically quoted. IOPTH was a helpful but not "fool-proof" adjunct in parathyroid exploration surgery. These results support a greater role for the treatment of primary hyperparathyroidism using less invasive approaches. EMB rating: B-3.

Clinical outcomes and fiscal consequences of bilateral neck exploration for primary idiopathic hyperparathyroidism without preoperative radionuclide imaging or minimally invasive techniques

Background. Radionuclide imaging-directed, minimally invasive parathyroid operation is promoted in the surgical literature and public domain as the fastest, most successful, and cheapest means of treating primary idiopathic hyperparathyroidism. The validity of these claims is unproven. This study reviews the treatment outcome results of a large series of patients treated with standard parathyroid operation without preoperative localization studies. Cost comparisons are made between this series and previous reports of selected patients in whom preoperative radionuclide imaging preceded minimally invasive parathyroid operation. Methods. Diagnosis, treatment, and outcome data for 688 consecutive patients undergoing first neck exploration for primary idiopathic hyperparathyroidism were prospectively collected. All patients in our series underwent standard bilateral neck exploration without preoperative localization studies. Intraoperative methylene blue was used to aid identification of all parathyroid glands. Surgical findings, pathological diagnosis, operative time, length-of-stay, and treatment success data were collected. Cost data were calculated for our series using the identical calculations used in previous reports. Our outcome and calculated cost data were compared with previous reports by centers advocating scan-directed, minimally invasive parathyroid operation. Results. Of 2752 predicted total glands, 2520 (91.6%) were identified using standard neck exploration without radionuclide localization studies. Single adenoma, with at least 1 normal gland, was found in 542 patients (78.8%), with 8 in a fifth gland. Multiple-gland hyperplasia was identified in 98 patients (14.2%) and of these 22 (3.2%) were double adenomas. Ten patients had parathyroid carcinoma (1.5%), and all received definitive surgical treatment during the primary operation. Cure rates were assessed by measurement of normal serum calcium and parathyroid hormone levels at 3 and 12 months after operation, and were 97.7% in our series. Mean operating time for the entire series was 65 minutes, decreased to 35 minutes in patients with single adenomas, and mean recovery room time was 30 minutes. Mean total costs for patients undergoing standard exploration for single adenoma was $1107, and increased to $1243 when patients with multigland disease, hyperplasia, or malignancy were included. Conclusions. Our series demonstrates operative times and treatment outcomes with costs that are approximately one-third less than those for scan-directed, minimally invasive operation for primary idiopathic hyperparathyroidism. Thus, claims that scan-directed parathyroid operation is the cheapest, fastest, and most successful means of treatment are not supported by these data. (Surgery 2003;133:32-9.)

Use of a rapid intraoperative parathyroid hormone assay in the surgical management of parathyroid disease.

To evaluate the utility of a rapid intraoperative parathyroid hormone (PTH) immunoradiometric assay in the surgical management of parathyroid disease, particularly with reference to limiting extent of cervical exploration. Nonrandomized prospective study. Academic tertiary care center. Forty-three consecutive patients undergoing parathyroid exploration for adenoma or hyperplasia had rapid PTH assays performed from blood drawn at induction and 7 minutes after resection of all hyperfunctioning parathyroid tissue. Excision of all hyperfunctioning parathyroid tissue as assessed by bilateral neck exploration, postoperative normalization of serum calcium and PTH levels, and resolution of clinical symptoms. The intraoperative rapid PTH assay accurately reflected whether all hyperfunctioning parathyroid tissue was excised in every patient. In 41 patients, all hyperfunctioning parathyroid tissue was resected at the time of surgery and confirmed by a corresponding decrease in the intraoperative postexcision rapid PTH determination as well as by subsequent normalization of postoperative serum calcium and PTH levels and resolution of clinical symptoms. In 2 patients, the postexcision rapid PTH assay determination was not consistent with removal of all hyperfunctioning parathyroid disease and both patients demonstrated persistent hyperparathyroidism postoperatively. The intraoperative rapid PTH assay may be of significant benefit in permitting directed unilateral parathyroid explorations for adenoma when combined with preoperative localization with a technetium-99m sestamibi scan. Additionally, the rapid PTH assay has proved to be of benefit in confirming excision of all hyperfunctioning parathyroid tissue in patients with multiple gland hyperplasia, particularly those who may harbor ectopic parathyroid tissue.

Parathyroid Update: A Review of 220 Cases

A total of 220 patients have undergone cervical exploration for hyperparathyroidism by the author. A review of 125 cases was published in 1991. An additional 95 patients have been explored in the subsequent four years. Subtotal parathyoidectomy was performed in 39 patients with chronic renal failure. Exploration was successful in over 97% of the 181 patients diagnosed with primary hyperparathyroidism. Single adenomas were found in 146, double adenomas in 11, and multiple gland hyperplasia in 19 patients. Two of the five patients in whom cervical exploration failed were ultimately diagnosed with benign familial hypocalciuric hypercalcemia. Twenty-four adenomas were ectopic. Preoperative thallium-technetium scans and ultrasound correctly localized only 61% of the adenomas. Technetium sestamibi scans were correct in two of four adenomas. Only 47% of ectopic adenomas were correctly localized by isotope scanning and 29% by ultrasound. 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 examined carefully. Preoperative localization studies are not as reliable as an experienced parathyroid surgeon.

Screening for multiple endocrine neoplasia type I

BackgroundMultiple endocrine neoplasia type I (MEN I) is a familial condition inherited in autosomal dominant manner, characterized by primary hyperparathyroidism (multiple gland hyperplasia 95%), pancreatic islet cell tumours (65%) and pituitary adenomata (prolactinoma 5%). Screening of family members permits the identification of affected relatives and allows early treatment of the condition before the onset of complications.MethodsWe have employed a new sensitive immunochemiluminometric assay (ICMA) specific for intact parathyroid hormone together with measurement of serum calcium and prolactin to screen 102 relatives of patients with proven MEN (11 families) and 25 relatives of patients with non-MEN I familial hyperparathyroidism or multiple parathyroid gland hyperplasia.Results7 MEN I relatives with abnormal biochemical results had significant clinical symptoms (renal calculi 3, duodenal ulcer 3, secondary amenorrhea 1). 15 MEN I relatives had clinical or biochemical evidence of MEN I syndrome.ConclusionWe conclude that biochemical screening of MEN I kindred is worthwhile and the intact parathormone assay (ICMA) may increase diagnostic sensitivity.

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.

A clinical audit of thallium – technetium subtraction parathyroid scans

Eighty six consecutive thallium-technetium subtraction parathyroid scans performed over a three year period for hypercalcaemia have been evaluated. Twelve had chronic renal failure, 11 had hypercalcaemia due to non-hyperparathyroid causes and in 10 the imaging study was technically inadequate. The remaining 53 technically adequate studies performed for hypercalcaemia clinically thought to be possibly due to hyperparathyroidism have been analysed. Of 20 (38%) positive scans, 13 came to surgery (10 correctly localized parathyroid adenomas, 2 with multiple gland hyperplasia, and 1 papillary carcinoma of the thyroid). Of 33 (62%) negative scans, 9 had surgical exploration on the basis of strong clinical grounds and all had parathyroid adenomas. Multiple biochemical parameters have been assessed in relation to a positive outcome on scan. The adjusted calcium-phosphate product and the ratio of the adjusted calcium-phosphate product to creatinine (Ca x P/Cr) were both significantly lower in the scan positive group (P less than 0.01). The scan positive group had a significantly higher mean level of PTH (P less than 0.001) and lower mean level of phosphate (P less than 0.001). The present experience shows that parathyroid imaging is useful in localizing parathyroid adenomas in 50% of cases (10 out of 19). This figure is at the lower end of the range of previously published results. It is less effective in demonstrating multiple gland hyperplasia. The decision as to whether to undertake surgical exploration when the scan is negative has been based successfully on clinical judgement. We feel that an analysis of this nature is important, as it gives insights into the practical relevance of parathyroid imaging in the context of routine clinical work.

Medullary sponge kidney and hyperparathyroidism--a puzzling association.

28 adult patients with radiological evidence of medullary sponge kidney (MSK) were studied. Hypercalcemia and increased serum parathyroid hormone (PTH) values were found in 10 patients (36%). In 7 of them, parathyroid surgery was performed: a single adenoma was found in 6 cases and multiple-gland hyperplasia in 1 case. After surgery, 3 patients had normalization of calcium metabolism; 4 patients had persistence of hypercalciuria with progressive increase in serum PTH values (and recurrence of the adenoma in 1 case). Of the remaining patients, 10 (36%) had definite or marginal hypercalciuria, resulting from renal calcium leak in 8 and from intestinal calcium hyperabsorption in 2 of them. In 8 patients (28%), no evidence of disordered calcium metabolism was found. The association of MSK and hyperparathyroidism is not a chance occurrence. MSK might be a renal anatomical complication of primary hyperparathyroidism, or it might be regarded as an anatomic substrate--or rather as a consequence--of prolonged hypercalciuria, regardless of its pathogenesis. The lack of disordered calcium metabolism in a considerable number of patients, however, shows that the enigma of MSK is still far from being solved.