Relation of biochemical, cytologic, and morphologic parameters to the result of gammagraphy with technetium 99m sestamibi in primary hyperparathyroidism

The aim of this study was to analyze the possible relation of biochemical, cytologic, and morphologic parameters to the results of parathyroid gammagraphy with Tc 99m sestamibi in primary hyperparathyroidism. We studied 46 consecutive patients with primary hyperparathyroidism who were undergoing surgery. All the patients were given a preoperative parathyroid gammagraphy with Tc 99m sestamibi and a complete preoperative biochemical study. During the surgical intervention we recorded the weight and size of the pathologic glands to calculate the volume of each. We also determined the percentage of the chief and oxyphil cells in the pathologic glands. Tc 99m sestamibi sensitivity is higher in adenomas (91%) than in hyperplasia (67%) or double adenomas (50%). No relation was found between biochemical or cytologic parameters and gammagraphic results. Weight and gland volume were significantly greater for adenomas than for hyperplasia (P < 0.0014 and P < 0.0004, respectively), and statistically significant differences in both of them were observed between the glands with positive and negative sestamibi.     

The false negative technetium-99m-sestamibi scan in patients with primary hyperparathyroidism: correlation with clinical factors and operative findings

False negative (FN) results limit the efficacy of technetium-99m-sestamibi scanning for parathyroid localization. We determined the incidence of FN results and attempted to correlate it with clinical and operative findings. One hundred forty-six patients underwent parathyroidectomy; 89 had primary hyperparathyroidism (76 single adenoma and 13 multiglandular disease) and underwent sestamibi scanning. The false negative rate was 22 per cent with an overall sensitivity of 77 per cent and a positive predictive value of 99 per cent. Patients with single adenomas were more likely to have a true positive scan than those with multiglandular disease [83% vs 38%; odds ratio (OR) = 7.754, 95% confidence interval (CI) = 2.184-27.524; P < or = 0.0001]. Inferior adenomas (90% vs 59%; OR = 6.261, 95% CI = 2.037-19.243; P < or = 0.0001) and larger adenomas (1422.3 +/- 1576.2 vs 474.6 +/- 193.2 g; P < or = 0.0001) were more likely to be detected by sestamibi imaging. Patients with normal preoperative calcium levels were more likely to have an FN sestamibi scan. Sestamibi parathyroid imaging is limited by a 22 per cent FN rate and is less accurate for detecting abnormal parathyroid tissue in patients with small adenomas, multiglandular disease, superior adenomas, or preoperative normocalcemia.     

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.     

The positive effect of adenoma weight and oxyphil cell content on preoperative localization with 99mTc-sestamibi scanning for primary hyperparathyroidism

BACKGROUND: Although the sensitivity of sestamibi scanning (MIBI) is high in patients with solitary parathyroid adenomas, negative sestamibi scan results are inevitable. The exact mechanism of visualization of abnormal and hyperfunctioning parathyroid tissue is not yet clear. The aims of this clinical study were (1) to evaluate positive and negative sestamibi scan results with regard to adenoma weight and oxyphil cell content and (2) to compare the effects of adenoma weight and oxyphil cell content on the results of sestamibi scanning. PATIENTS: The patients were divided in 2 groups according to their sestamibi scan results. Group 1 consisted of 27 patients with positive sestamibi scan results, and group 2 consisted of 20 patients with negative sestamibi scan results. Parathyroid adenoma weight and oxyphil cell content were determined in all patients. RESULTS: The weight and oxyphil cell content of the parathyroid adenomas in the patients of group 1 were significantly higher than those in the patients of group 2 (P = .001). An adenoma weight >600 mg and an oxyphil cell content >20% increased the rate of obtaining a positive sestamibi scan result 10- and 4-fold, respectively. CONCLUSIONS: Both adenoma weight and oxyphil cell content were found to significantly correlate with positive sestamibi scan results. In patients with high-weight adenomas, adenoma weight was the most significant factor in obtaining positive MIBI scan results, whereas in patients with low adenoma weights, high oxyphil cell content was the most significant factor in obtaining positive MIBI scan results.     

Tc99m-sestamibi scintigraphy and cell proliferation in primary hyperparathyroidism: a causal or casual relationship?

BACKGROUND: Sestamibi scintigraphy has become the fundamental technique for preoperative location of hyperfunctioning glands responsible for hyperparathyroidism, especially in the case of adenomas. However, little is known about the mechanisms of tracer uptake and retention by these glands, mechanisms that have been related to an increased gland metabolism. Our goal was to determine whether there is a relationship between the positive result of gammagraphy with sestamibi, for diagnosing the location of parathyroid adenomas, and the cell proliferation index. PATIENTS AND METHODS: Six glands corresponding to sestamibi false negatives and 12 true positives were studied in patients with single-adenoma primary hyperparathyroidism. The following data were recorded in all the patients: age, gender, clinical and analytical data, gland weight, and parathyroid hormone (PTH)/gland weight ratio. An immunohistochemical study of the glands was also done with the use of Ki67, with determination of the mean proliferation index of each group for comparison purposes. RESULTS: On comparing the 2 groups, we found no differences between the clinical or analytical parameters. Differences were found only for proliferation index-(5.7% in true positive glands versus 0.3% in false negative glands (P <.004). CONCLUSION: Tracer (sestamibi) uptake by hyperfunctioning parathyroid adenomas in primary hyperparathyroidism might be linked to a higher gland metabolism activity, probably related to cell proliferation.     

Clinicopathologic and radiopharmacokinetic factors affecting gamma probe-guided parathyroidectomy

HYPOTHESIS: The kinetics of technetium Tc 99m sestamibi (MIBI) in primary hyperparathyroidism are variable and affected by the cellular size of the abnormal glands, the parathyroid hormone levels, and the functional expression of P-glycoprotein (Pgp). The success of gamma probe-guided parathyroidectomy is closely related to the parathyroid-to-thyroid activity ratio at the time of surgery. Preoperative determination of maximum uptake ratio may improve the surgical outcome. DESIGN: Thirty-one patients with primary hyperparathyroidism attributed to a solitary parathyroid adenoma (27 patients) or multiglandular hyperplasia (4 patients) underwent dynamic MIBI imaging preoperatively. Maximum MIBI activity and activity elimination half-life in the abnormal parathyroid glands and thyroid glands were measured, and the maximum uptake ratio was calculated. After a second MIBI injection on the day of surgery, all patients underwent gamma probe-guided parathyroidectomy and cervical exploration. Timing of surgery after MIBI injection was individualized according to the optimal time to surgery (time to maximum uptake ratio), which was determined by preoperative scintigraphy. During surgery, the gamma probe was used to measure ex vivo counts of excised lesions and adjacent postexcision normal tissue (background). Image characteristics, MIBI kinetics, and gamma probe findings were correlated with gland volume, oxyphil cell content, Pgp expression, and serum parathyroid hormone levels. RESULTS: Probe localization of abnormal glands at maximum uptake ratio was successful in all patients. The volume of the parathyroid lesion ranged from 0.03 to 9.8 mL (median, 0.7 mL). Parathyroid maximum MIBI activity correlated with the volume of the gland (r = 0.54, P = .002) and serum parathyroid hormone level (r = 0.58, P = .001). No correlation between maximum MIBI activity and oxyphil cell content or Pgp expression could be demonstrated. Elimination half-life of MIBI from parathyroid inversely correlated with Pgp (r = -0.36, P = .05). The ex vivo lesion-background count ratio positively correlated with volume of the gland (r = 0.66, P = .001) and parathyroid hormone level (r = 0.48, P = .006). Ex vivo lesion counts and Pgp expression were negatively correlated (r = -0.37, P = .04). CONCLUSIONS: A strong relationship between volume of the parathyroid gland, serum parathyroid hormone levels, and MIBI uptake exists in primary hyperparathyroidism. Gamma probe-guided localization of abnormal gland(s) can be more successful if surgery is undertaken at maximum uptake ratio. High Pgp expression increases MIBI parathyroid clearance rate, decreases gamma probe counts, and may significantly alter the optimal time to surgery.     

The sestamibi scan as a preoperative screening tool

Sestamibi scan is generally recognized in the literature to play a role in the imaging of parathyroid adenoma. Most institutions quote sensitivities ranging from 80 to 100 per cent. There is still a question as to whether patients need preoperative localization studies. Preoperative localization can potentially result in less invasive surgery, shorter operative times, decreased hospital stays, and decreased need for re-exploration. Our hypothesis is that the sestamibi scan is a sensitive predictor of parathyroid adenomas. The objectives of this study are to determine the sensitivity of sestamibi scan in detecting parathyroid adenoma, and to determine whether either parathyroid hormone (PTH) level or calcium level is an independent predictor of a positive scan. One hundred patients were retrospectively reviewed at Louisiana State University Health Sciences Center-Shreveport and Louisiana State University Health Sciences Center-Monroe from March 1993 through December 2000. All patients had a preoperative sestamibi scan. This scan was performed using the dual-phase technique in which the parathyroid glands are visualized after washout of tracer from the thyroid. The scan was followed by either a unilateral or bilateral neck dissection. There were 82 female patients and 18 male patients who ranged in age from 23 to 78 years. The median weight of glands with a positive scan was 795 mg. The median weight of glands with a negative scan was 480 mg. This difference was statistically significant (P < 0.04). Overall there were 107 adenomas. Of these 93 had positive scans and 14 had negative scans. This results in a sensitivity of 87 per cent. There were 67 glands that weighed at least 500 mg. Of these 67 glands 61 had positive scans and six had negative scans. This resulted in a sensitivity of 91 per cent. There were 40 glands that weighed less than 500 mg. Of these 40 glands 32 had positive scans and eight had negative scans. This resulted in a sensitivity of 80 per cent. Using multiple linear regression analysis calcium level correlated with the weight of the gland (P < 0.01). Calcium level also correlated with the PTH level (P < 0.01). However, neither the PTH level nor the calcium level correlated with a positive sestamibi scan. Sestamibi scan is a sensitive predictor for parathyroid adenoma greater than 500 mg (91% sensitivity). Even in smaller glands (<500 mg) 80 per cent sensitivity was demonstrated. Although the calcium level correlates with the PTH level neither PTH level nor calcium level is predictive of a positive sestamibi scan.     

Prospective evaluation of delayed technetium-99m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism

BACKGROUND: Delayed technetium-99m sestamibi single photon emission computed tomography (SPECT) scans were prospectively analyzed in a large series of patients with primary hyperparathyroidism. METHODS: Three hundred thirty-eight patients underwent sestamibi-SPECT and were explored. Prospective data included preoperative demographics, clinical, sestamibi, and operative findings, laboratory values, and pathologic and follow-up laboratory results from all patients. RESULTS: Between 1994 and 2000, 287 unexplored patients (85%) and 51 re-explored patients (15%) participated. The abnormal parathyroid glands excised from 336 of 338 patients included 299 single adenomas (88%) and 23 double adenomas (7%), and 14 patients had multigland hyperplasia (4%). Sestamibi SPECT correctly lateralized 349 of 400 abnormal parathyroid glands, with an overall sensitivity of 87%, an accuracy of 94%, and a positive predictive value of 86%. Precise localization occurred in 82% of the abnormal parathyroid glands. Sestamibi sensitivity was similar in unexplored (87%) and reoperative (92%) cases; two hundred eighty-six of 299 (96%) solitary adenomas, 38 of 46 (83%) double adenomas, but only 25 of 55 (45%) hyperplastic glands were identified. The mean weight of the true-positive glands (1252 +/- 1980 mg) was greater than that of the false-negative glands (297 +/- 286 mg) (P <.005). Three patients had persistent primary hyperparathyroidism, in spite of the excision of sestamibi-identified lesions in 2 cases. Follow-up indicated curative resection in 99% of the unexplored cases and 94% of the remedial cases. CONCLUSIONS: Sestamibi SPECT is highly accurate for the localization of parathyroid adenomas in unexplored and re-explored cases, where it is often the only imaging required. Its sensitivity is limited in multiglandular disease.     

Surgeon-performed ultrasound improves localization of abnormal parathyroid glands

With a secure diagnosis of hyperparathyroidism, preoperative localization of abnormal glands is the initial step toward limited parathyroidectomy (LPX). We investigated whether ultrasonography in the hands of the surgeon (SUS) could improve the localization of abnormal parathyroids when sestamibi scans (MIBI) were negative or equivocal. One hundred eighty patients with sporadic primary hyperparathyroidism (SPHPT) underwent preoperative SUS and MIBI scans before LPX guided by intraoperative parathormone assay. When the sestamibi scans were negative, SUS was used to localize the parathyroid, distinguish parathyroid from thyroid tissue, and to guide the intraoperative jugular venous sampling for differential elevation of parathyroid hormone (PTH). Operative findings, intraoperative hormone dynamics, and postoperative calcium levels determined successful localization. MIBI was negative or equivocal in 36/180 (20%) patients: (1) showed no parathyroid gland in 22 patients, (2) suggested an incorrect location for the abnormal gland in 9, and (3) was insufficient in recognizing multiglandular disease in 5. In these 36 patients, the addition of SUS led to the successful identification of the abnormal tissue in 19/36 (53%). In the remaining 17 patients with negative/equivocal scans, the parathyroid could not be clearly visualized by SUS. In these patients, SUS facilitated LPX by aiding preoperative transcutaneous jugular venous sampling for differentially elevated PTH (n=3) and identifying questionable thyroid nodule versus parathyroid tissue (n=1). Overall, SUS was useful in 23/36 (67%) patients with nonlocalizing MIBI scans, thus improving the rate of localization from 80 per cent to 93 per cent (P < 0.01). Surgeon-performed cervical ultrasonography improved the localization of abnormal parathyroids by MIBI scan, adding to the success of limited parathyroidectomy.     

Negative Imaging Studies for Primary Hyperparathyroidism Are Unavoidable: Correlation of Sestamibi and High-Resolution Ultrasound Scanning with Histological Analysis in 150 Patients

Background Preoperative localization studies with Tc^99m-sestamibi have become an integral step in the preoperative assessment of patients with primary hyperparathyroidism (PHPT). This enables scan-directed minimally invasive parathyroidectomy (MIP) to be the preferred treatment for PHPT in many units. This study aimed to identify factors that lead to negative imaging studies in patients with PHPT. Methods Over a 3-year period consecutive unselected patients with PHPT underwent Tc^99m-sestamibi scanning and high-resolution ultrasound (US) scanning by the same radiologist. When localization studies were concordant, patients underwent MIP. Those patients with negative imaging studies underwent bilateral neck exploration. Histology slides were independently reviewed and the proportion of chief cells and oxyphil cells within each adenoma was estimated. Results One hundred and fifty-eight patients underwent localization studies (38 men and120 women, aged 61.8 ± 15.2 years). Sestamibi scans were negative in 52 (32%) and positive in 106 (68%) patients. There was a higher incidence of hyperplasia in the group of patients with negative sestamibi scans (4 out of 52 vs. 4 out of 103, P < 0.05, χ² test). In patients with negative sestamibi scans the majority of adenomas were formed predominantly from chief cells (26 out of 36) while the majority of patients with adenomas composed predominantly of oxyphil cells had positive scans (21 out of 23) (P < 0.05, χ² test). The weight of parathyroid adenomas was higher when sestamibi scans were positive (median: 1,180 vs. 517 mg, P < 0.05, Student’s t-test). Conclusion Successful preoperative localization of parathyroid adenomas using Tc^99m-sestamibi scanning is influenced by the cytological predominance of individual tumors. Negative scans might therefore be unavoidable in a subgroup of patients.     

Detection of parathyroid adenoma in patients with primary hyperparathyroidism: the use of office-based ultrasound in preoperative localization

BACKGROUND: The purpose of this investigation is to show that preoperative localization of the parathyroid gland using office-based ultrasound (US) and Tc-99m sestamibi scan is superior to all other approaches in detecting a parathyroid adenoma. METHODS: We performed a retrospective analysis of 43 patients who underwent parathyroidectomy for primary hyperparathyroidism. All patients underwent office-based US and sestamibi scintigraphy. Upon completion of the localization studies, a plan for focused or full operation was determined. RESULTS: In 42 of 43 patients, office-based US performed by a surgeon and sestamibi scintigraphy successfully detected the location of a parathyroid abnormality (42/43 cases, sensitivity = 98%, P < .05 =.0001). Office-based US localized the abnormal gland to the specific side (right/left) in 36 of 43 cases (84%). Sestamibi alone localized to the specific side in 29 of 43 cases (67%) for a statistically significant difference (P = .03). US localized the abnormal gland to the specific quadrant (34/43 cases [79%] sensitivity versus 23/43 cases [53%] sensitivity using sestamibi scan alone to localize to the specific quadrant, P = .03). CONCLUSION: It is clear that the combined modalities of office-based US and sestamibi scintigraphy in preoperative localization have a high success rate and should be considered in parathyroid surgery.     

What is the link between nonlocalizing sestamibi scans, multigland disease, and persistent hypercalcemia? A study of 401 consecutive patients undergoing parathyroidectomy

BACKGROUND: We hypothesized that nonlocalizing sestamibi scans would correlate with multigland disease and persistent primary hyperparathyroidism. METHODS: We reviewed records for 401 consecutive patients who underwent parathyroidectomy from 1999 to 2004. Gender, age, preoperative imaging, surgical findings, gland weight and volume, and 6-month calcium levels (Ca) were examined. RESULTS: We identified 289 women and 112 men, 297 of whom had a preoperative sestamibi scan localized to a single gland (localized group; LG). Ninety-six percent of the LG were found to have single-gland disease, and 4% had multigland disease (MGD). In the nonlocalized group (NLG), 76% had single-gland disease and 24% MGD. Mean gland weight was greater in the LG than in the NLG (1128 mg vs 699 mg; P < .05). Mean gland volume was larger in the LG (1.34 cc vs 0.89 cc; P < .05). A localizing sestamibi scan had a positive predictive value (PPV) of 96% and a likelihood ratio of 2.29 for predicting "curative" intraoperative parathyroid hormone drop after removal of a single abnormal gland. Patients were stratified into normocalcemic (NCa) and hypercalcemic (HCa) groups based on 6-month postoperative serum calcium data (n = 328). HCa incidence at 6 months did not differ significantly between the LG (5%) and NLG (3%). A localizing scan had a PPV of 95% for normocalcemia at 6 months. A nonlocalizing scan had a PPV of 21% for HCa at 6 months. CONCLUSIONS: Nonlocalizing sestamibi scans were more common in primary hyperparathyroidism with MGD and were associated with smaller-volume abnormal glands found at operation. Preoperative sestamibi scan-results did not predict HCa at 6 months.     

Pitfalls of intraoperative quick parathyroid hormone monitoring and gamma probe localization in surgery for primary hyperparathyroidism

HYPOTHESIS: Intraoperative quick parathyroid hormone (qPTH) monitoring and gamma probe (GP) localization greatly aid the surgeon. DESIGN: Prospective case series of patients undergoing parathyroidectomy (PTX) with preoperative localization studies, operative data (including intraoperative qPTH values and GP localization), and outcomes. Follow-up was complete (mean, 4.2 months). SETTING: University teaching hospital. PATIENTS: We studied 57 consecutive patients with primary hyperparathyroidism from December 1, 1999, through November 30, 2000. Of these, 51 underwent first-time PTX, and 6, reoperative PTX (rePTX). MAIN OUTCOME MEASURES: Cure rate and morbidity after PTX or rePTX; sensitivity and accuracy of preoperative localization studies; prediction of cure from results of qPTH monitoring (comparing Nichols [>50% fall from the highest baseline level and lower than the lowest baseline] or normal-limit [>50% fall from first baseline level and lower than upper limit of the reference range] criteria); and value of GP localization. RESULTS: Patients were cured in 50 (98%) of 51 PTX and 6 (100%) of 6 rePTX for single adenomas (n = 49), double adenomas (n = 4), and multigland hyperplasia (n = 3). Nichols criteria for qPTH monitoring correctly categorized 45 (92%) of 49 cured single adenomas 10 minutes after excision. Only 35 (71%) of these adenomas were correctly categorized as cured by means of the normal-limit criteria. In double adenomas, both sets of criteria in the 10-minute samples indicated unresected glands in only 2 of 4 cases. Preoperative sestamibi parathyroid scans correctly localized 38 (76%) of 50 single adenomas. The GP was used in 54 of 57 cases. All adenomas measured greater than 20% of background ex vivo, but 6 thyroid nodules also measured greater than 20% ex vivo. In double adenomas, the GP helped locate the second adenoma in only 1 of 4 cases. The GP was graded as crucial in 2 cases with dense scar (both rePTX), helpful in 12 (22%) of 54 cases (particularly in retroesophageal glands), confirmatory in 32 (59%), and not helpful in 8 (15%). The GP helped localize 3 (43%) of 7 glands not seen on sestamibi parathyroid scans. CONCLUSIONS: Intraoperative qPTH monitoring confirmed cure in most cases. For single adenomas, use of the Nichols criteria for qPTH assessment allowed more accurate and faster confirmation than the normal-limit criteria. The GP was less useful but was crucial in 2 rePTX cases; it was not specific for parathyroid tissue. Both techniques have potential pitfalls that could result in surgical failure.     

Incidence and location of ectopic abnormal parathyroid glands

BACKGROUND: Ectopic parathyroid glands are a cause for failed parathyroid exploration. METHODS: Patients with hyperparathyroidism and ectopic parathyroid glands were identified from a parathyroid database. Laboratory data, gland weights, and surgical outcomes were obtained. The locations of the ectopic glands were correlated with results of technetium-99m-sestamibi imaging. RESULTS: Of 231 patients operated on for hyperparathyroidism, 37 (16%) had ectopic parathyroid glands. Ectopic inferior glands (N = 23 [62%]) were intrathymic, n = 7 (30%); anterosuperior mediastinal, n = 5 (22%); intrathyroidal, n = 5 (22%); within the thyrothymic ligament, n = 4 (17%); and submandibular, n = 2 (9%). Ectopic superior glands (N = 14 [38%]) were in the tracheoesophageal groove, n = 6 (43%); retroesophageal, n = 3 (22%); posterosuperior mediastinal, n = 2 (14%); intrathyroidal, n = 1 (7%); in the carotid sheath, n = 1 (7%); and paraesophageal, n = 1 (7%). Sestamibi scans were true-positive in 81%, identifying 13 of 16 retrosternal glands, and false-negative in 19%. CONCLUSIONS: A 16% incidence of ectopic parathyroid glands and a 100% positive predictive value of sestamibi scintigraphy underscore the importance of sestamibi imaging in patients with primary hyperparathyroidism.     

Short-term outcomes of parathyroidectomy in patients with or without 25-hydroxy vitamin D insufficiency

BACKGROUND: 25-OH Vitamin D (VitD) plays a role in serum calcium (Ca) and parathyroid hormone (PTH) homeostasis. VitD insufficiency in patients with primary hyperparathyroidism (HPT) may be associated with greater disease severity and a higher incidence of multi-gland disease and postoperative normocalcemic PTH elevation. MATERIALS AND METHODS: One hundred ten patients with HPT undergoing parathyroidectomy had preoperative VitD levels as follows: levels were insufficient (< or =20 ng/mL) in 55 patients (group 1) and sufficient (>20 ng/mL) in 55 patients (group 2). All patients had preoperative localizing sestamibi scans and/or ultrasounds and postoperative serum Ca and PTH levels. A focused approach was performed when possible, and intraoperative PTH monitoring (IPM) was used in all patients. RESULTS: Patients with VitD insufficiency had significantly higher preoperative Ca (11.3 +/- 1.2 versus 10.8 +/- 0.9 mg/dL, P = 0.012) and PTH levels (204 +/- 138 versus 156 +/- 179 pg/mL; P = 0.006) as well as higher bone specific alkaline phosphatase (P = 0.006). Localization studies were similar. IPM levels were significantly higher in group 1 at all time intervals. Both groups were similar in operative time, conversions to bilateral explorations, number of glands removed, and number of frozen sections. The glands in group 1 were larger (1757 versus 524 g; P = 0.005). Postoperative Ca levels, PTH levels, rates of eucalcemia, and rates of eucalcemic PTH elevation were all similar. CONCLUSION: Patients with HPT and VitD insufficiency may have significantly more severe disease based on preoperative serum Ca and PTH levels, bone markers, and gland size. IPM levels in these patients are higher but can be used to predict postoperative eucalcemia, an outcome which appears be independent of VitD status.     

Can localization studies be used to direct focused parathyroid operations?

BACKGROUND: There is considerable controversy today concerning the most appropriate surgical approach for patients with primary hyperparathyroidism. The conventional surgical operation involves a bilateral neck exploration through a collar incision with identification of all parathyroid tissue and removal of abnormal parathyroid glands while the patient is under general anesthesia. The success rate of this operation is about 95% or greater in the hands of an experienced endocrine surgeon. Preoperative localization techniques are generally considered to be unnecessary before initial parathyroid operations. The purpose of this investigation was (1) to evaluate the individual and combined accuracy of ultrasonography and technetium 99m sestamibi scans in localizing abnormal parathyroid glands and (2) to determine whether such scans could be used to direct a focused operation. METHODS: We retrospectively studied 338 patients with sporadic primary hyperparathyroidism who had preoperative neck localization studies, ultrasonography and/or technetium 99m sestamibi scans, and parathyroid exploration (238 patients or, reexploration, 60 patients) from January 1996 to April 2000 at the University of California San Francisco/Mount Zion Medical Center. The preoperative localization studies were recorded as true-positive, false-positive, and false-negative and compared with the surgical and pathologic findings and with the outcome of the operation. RESULTS: All of the abnormal parathyroid glands were correctly identified by ultrasonography in 184 of 303 patients (60.7%) and by technetium 99m sestamibi scanning in 183 of 237 patients (77.2%). The sensitivities of ultrasonography and sestamibi were 65% and 80%, respectively. Among the 202 patients who received both ultrasonography and sestamibi scans, a parathyroid tumor was identified at the same site in 105 (52%) of them. When both techniques identified a parathyroid tumor at the same site, the tests were correct in 101 of 105 patients and the sensitivity increased to 96%. CONCLUSIONS: When both the ultrasonography and sestamibi scans identified the same, solitary parathyroid tumor in patients with sporadic primary hyperparathyroidism, this was the only abnormal parathyroid gland in 96% of the patients. A focused parathyroidectomy could therefore be performed in such patients with an acceptable ( approximately 95%) success rate.     

Surgery for hyperparathyroidism: does morphology or function matter most?

BACKGROUND: With minimally invasive parathyroidectomy (MIP) not all enlarged parathyroid glands are necessarily removed, and intraoperative measurement of parathyroid hormone levels (IO-PTH) does not necessarily predict multiple enlarged glands. The aim of this study was to compare morphology with function, using Ca(2+)-regulated PTH secretion. METHODS: PTH secretion was determined by perifusion: (1) cells from 12 normal parathyroids were compared with 14 parathyroid adenomas; (2) functional characteristics (PTH secretion, sestamibi uptake, IO-PTH decrease) were correlated with morphologic characteristics; (3) PTH secretion as a predictor of IO-PTH decrease was determined in 7 patients with 2 enlarged parathyroids. RESULTS: (1) There were significant differences between normal and pathological parathyroid cells consistent with reduced sensitivity to Ca(2+). Maximum secretion rates for normal and adenomatous cells were, respectively, 3.9 +/- 0.4 fg min(-1) cell(-1) and 2.0 +/- 0.4 fg min(-1) cell(-1) (P = .002) and minimum secretion rates, 0.7 +/- 0.1 fg min(-1) cell(-1) and 0.4 +/- 0.1 fg min(-1) cell(-1) (P = .008). However, the IC(50) value for Ca(2+) was elevated in adenomatous cells indicating an apparent loss of extracellular Ca(2+) sensitivity being 1.1 +/- 0.02 mmol/L for normal and 1.2 +/- 0.02 mmol/L for adenomatous cells (P = .02). (2) There was no overall correlation between PTH secretion and gland morphology. (3) In 5 of 7 cases, PTH secretion correctly predicted the decrease in IO-PTH. CONCLUSION: Parathyroid adenomas generally exhibit abnormal PTH secretory function; however, enlarged parathyroid glands that do not contribute to the biochemical changes of hyperparathyroidism do exist, and, in these cases, cellular secretory function is a useful predictor of IO-PTH dynamics.     

Minimal Incision Parathyroidectomy: Cure, Cosmesis, and Cost

The goals of operative treatment of primary hyperparathyroidism are (1) cure; (2) minimal invasion; and (3) cost-effectiveness. The optimal strategy is controversial. Retrospective review of was undertaken 66 previously unoperated patients having minimal-incision, full-neck exploration by one surgeon over 29 months. A group of 51 women and 15 men had open full neck exploration under general anesthesia through a small (25–40 mm) incision using specifically selected instruments; patients remained hospitalized overnight. Preoperative sestamibi scans were obtained before referral for 17 patients: 11 had localized disease, and 6 did not (65% sensitivity). Four parathyroid glands were identified in 98% of patients; intraoperative frozen section was used selectively on a median of one gland per patient. About 76% of patients had single-gland disease, 6% had two-gland disease, and 18% had four-gland hyperplasia. One patient had four normal cervical parathyroid glands and an aortopulmonary window parathyroid adenoma resected at thoracotomy 1 week later; preoperative sestamibi scans failed to localize his disease. There were no nerve injuries and a 98% cure rate after initial cervical exploration. Excluding the cost of the sestamibi scans, there was no difference between those who had preoperative localization and those who did not; 60% of hospital costs were operating room time-related. Minimal-incision parathyroidectomy is effective for curing hyperparathyroidism and has excellent cosmetic results with negligible scar. Preoperative sestamibi scanning had no impact on cure or treatment costs. Strategies to improve cost-effectiveness must address the substantial costs of anesthesia and operating room services.     

Mild hypercalcemia: an indication to select 4-dimensional computed tomography scan for preoperative localization of parathyroid adenomas

Background

Technetium sestamibi scanning is the most accepted method of imaging used for preoperative localization of parathyroid adenomas. Four-dimensional computed tomography (4D-CT) scanning is a relatively new localization technique that has not been as rigorously evaluated.

Methods

One hundred thirty-five consecutive patients who underwent preoperative sestamibi scanning, 4D-CT scanning, and parathyroidectomy for primary hyperparathyroidism were evaluated. Patient characteristics, parathyroid gland weights, and the probability of having positive preoperative localization were examined.

Results

Four-dimensional computed tomography scanning was significantly more accurate than sestamibi (73% vs 62%, P = .016). In those with serum calcium levels less than 10.8 mg/dL, 4D-CT scanning was significantly more accurate than sestamibi scanning for the quadrant (45% vs 29%, P = .013) and hemisphere (66% vs 48%, P = .012). Also, 4D-CT scanning was more accurate among patients with parathyroid gland weights less than 500 mg (69% vs 45%, P < .001).

Conclusions

Four-dimensional computed tomography scanning provides better preoperative localization than sestamibi scanning, particularly in patients with mild hypercalcemia and smaller parathyroid adenomas.     

An analysis of sestamibi-positive versus -negative patients with primary hyperparathyroidism.

We performed this study to evaluate two patient groups with primary hyperparathyroidism depending on whether their abnormal gland(s) could be preoperatively imaged with sestamibi. Patients with primary hyperparathyroidism evaluated by preoperative sestamibi examination from January 1999 to June 2000 were divided into two groups depending on the ability of sestamibi to localize their disease. Records were reviewed to determine pre- and postoperative biochemical data, weight of the excised glands, and total operating room time. When the sestamibi imaging was positive a minimally invasive parathyroidectomy was performed; however, when sestamibi scanning was negative patients underwent a formal bilateral neck exploration. All 40 patients in the sestamibi-positive group and 17 of 18 patients in the sestamibi-negative group were cured of their primary hyperparathyroidism as a result of surgery. Sestamibi scanning with a minimally invasive parathyroidectomy shortens operating room time and is most effective when adenomas are large. The results of this study suggest that strategies to preoperatively increase the activity of adenomas may improve the sensitivity of sestamibi scan localization of parathyroid adenomas.