Technetium-99m-sestamibi subtraction scintigraphy vs. ultrasonography combined with a rapid parathyroid hormone assay in parathyroid aspirates in preoperative localization of parathyroid adenomas and in directing surgical approach

OBJECTIVE: To determine the sensitivity and positive predictive value (PPV) of subtraction scintigraphy (SS) vs. ultrasonography (US) of the neck combined with rapid intact parathyroid hormone (iPTH) assay in US-guided fine-needle parathyroid aspirates in preoperative localization of parathyroid adenomas and in directing surgical approach. DESIGN: The results of SS for localization of parathyroid adenoma were determined in 121 patients with primary hyperparathyroidism (pHPT) and compared with findings at surgery and with the results of US alone (in patients without nodular goitre) and US in combination with the iPTH assay in US-guided fine-needle aspirates (FNAs) of suspicious parathyroid lesions (in patients with concomitant nodular goitre). PATIENTS: All 121 patients had biochemically documented pHPT; all were referred for first-time surgery. MEASUREMENTS: SS was performed with 99mTc-sestamibi and 99mTc-pertechnetate. High-resolution US of the neck was performed by a single endocrine surgeon and combined with US-guided FNAs of suspicious parathyroid lesions in all patients with nodular goitre (n = 43). RESULTS: The sensitivity and PPV of SS were significantly higher in patients without vs. with goitre (89.3% and 95.7%vs. 74.3% and 76.5%, respectively; P < 0.001). The sensitivity and PPV of US were significantly higher in patients without vs. with goitre (96% and 97.3%vs. 67.7% and 71.9%, respectively; P < 0.001). The iPTH assay of US-guided FNAs of suspicious parathyroid lesions in patients with nodular goitre significantly improved both the sensitivity and PPV of US imaging (90.7% and 100%, respectively), allowing for an accurate choice of surgical approach in 118 (97.5%) of 121 patients. SS was more accurate than US alone in detection of ectopic parathyroid adenomas. However, US alone was characterized by a higher sensitivity in detection of small parathyroid adenomas (< 500 mg) at typical sites (P < 0.01). CONCLUSIONS: Both the sensitivity and PPV of SS and US alone are comparable, with significantly less accurate results obtained in patients with goitre. In cases of equivocal results of US and/or in patients with concomitant goitre, an iPTH assay in US-guided FNAs of suspicious parathyroid lesions may be used to establish the nature of the mass, distinguish between parathyroid and nonparathyroid tissue (goitre, lymph nodes) and improve the accuracy of US parathyroid imaging, allowing for successful directing of surgical approach in a majority of patients.     

Ultrasonographic changes of major salivary glands in primary Sjogren's syndrome. Diagnostic value of a novel scoring system

OBJECTIVES: To reveal typical ultrasonographic (US) changes in major salivary glands associated with Sjogren's syndrome (SS) and to determine the diagnostic value of a novel US scoring system. METHODS: In 218 consecutive patients with suspected SS, US of both parotid and submandibular salivary glands was performed besides the regular diagnostic procedure following the American-European Consensus Group criteria of 2002. Five US parameters were assessed: echogenicity, inhomogeneity, number of hypoechogenic areas, the hyperechogenic reflections and clearness of the borders of the salivary gland. The grades of these five parameters for all four salivary glands were summed. The final US score ranged from 0 to 48. RESULTS: SS was established in 68 patients. The remaining 150 subjects, in whom SS was not confirmed, constituted our control group. All five US parameters were significantly associated with SS. The patients with SS had significantly higher US scores than those not diagnosed with SS (P<0.01). Setting the cut-off US score at 17 resulted in the best ratio of specificity (98.7%) to sensitivity (58.8%). CONCLUSIONS: Well-defined US changes in the major salivary glands summarized in our novel scoring system were typical of SS patients. Advanced structural changes found on US imaging almost invariably represent SS salivary gland involvement.     

Hyperfunctioning parathyroid tumours in patients with thyroid nodules. Sensitivity and positive predictive value of high-resolution ultrasonography and 99mTc-sestamibi scintigraphy

A series of 112 consecutive patients with primary hyperparathyroidism who underwent both high-resolution neck ultrasonography (US) and 99mTc-sestamibi/99mTc-pertechnetate subtraction scintigraphy (SS) prior to successful parathyroidectomy was reviewed. There were 29 (25.9%) men and 83 (74.1%) women, with a median age of 58 years (range 13-78 years). Patients were divided into two groups, according to the preoperative US findings: group A (87 patients, 77.7%) without thyroid diseases, and group B (25 patients, 22.3%) with either multinodular goitre or a solitary nontoxic thyroid nodule. In group B patients partial or total thyroidectomy was also performed, according to the intraoperative findings and frozen-section examination results. Final histopathology showed 99 (88.4%) solitary parathyroid (PT) adenomas and 3 (2.7%) PT carcinomas, while 10 (8.9%) patients had a multiglandular disease. The sensitivity and positive predictive value (PPV) were (group A vs group B) 79.8% vs 70.8% (P=0.25) and 95.7% vs 94.4% (P=0.58) for US, and 83.3% vs 87.0% (P=0.47) and 95.9% vs 90.9% (P=0.32) for SS respectively. Better but similar (P=not significant) results were obtained in patients with solitary PT tumours: 81.5% vs 77.8% (US) and 85.0 vs 94.1% (SS) sensitivity; 97.1% vs 93.3% (US) and 95.8% vs 88.9% (SS) PPV. Overall, the combination of US and SS was 92.9% sensitive (group A=93.1%, group B=92.0%; P=0.55), and the PPV reached 100% in each group. In conclusion, in patients with primary hyperparathyroidism the results of both US and SS are independent of coexistent thyroid disease, especially in patients with solitary PT tumours.     

Noninvasive localization procedures in ectopic hyperfunctioning parathyroid tumors

In primary hyperparathyroidism (pHPT), parathyroidectomy is the treatment of choice, but anatomic variations of ectopic glands may cause surgical failure. Reliable preoperative noninvasive localization procedures would have a positive impact on the operative time and increase recovery rate. We retrospectively evaluated 186 patients with pHPT who were studied before successful parathyroidectomy by double tracer scintigraphy (99mTc-pertechnetate+201TI chloride or 99mTc-pertechnetate +99mTc-sestamibi, 160 patients), ultrasonography (148 patients) and computerized tomography (CT) scan (92 patients). During bilateral neck exploration, 159 (85.5%) single adenomas, 6 (3.2%) parathyroid carcinomas, and 3 (1.6%) double adenomas were found. Moreover, 18 (9.7%) patients had diffuse chief cells parathyroid hyperplasia. Removed parathyroid glands were in ectopic sites in 41 (22.0%) cases, mainly localized in the upper mediastinum or behind the esophagus. The overall sensitivity was 83.5 and 85.2% for 99mTc-pertechnetate+201TI chloride and 99mTc-pertechnetate+99mTc-sestamibi scintigraphy respectively, 80.4% for CT scan and 81.1% for ultrasonography. In patients with ectopic glands, sensitivity was 81.2, 79.5, 73.3 and 81.6% respectively. In 36 out of 41 patients with ectopic glands in whom the removed parathyroids were correctly localized, mean operative time was 95 min, and in 5 patients without preoperative localization it was 260 min. In conclusion, in pHPT, preoperative localization of an enlarged parathyroid is helpful, especially in ectopic adenomas and in anatomic variations in location, and it has been proved to reduce operative time and morbidity rate.     

Preoperative evaluation of parathyroid lesions in patients with concomitant thyroid disease: role of high resolution ultrasonography and dual phase technetium 99m sestamibi scintigraphy

The aim of this study was to evaluate the sensitivity and usefulness of high resolution ultrasonography (US) and dual phase technetium-99m sestamibi (Tc-MIBI) scintigraphy in the preoperative localization of parathyroid lesions in patients with or without thyroid disease and to define the impact of the presence of thyroid disease on these methods. Preoperative US and scintigraphy were performed on 52 patients with primary hyperparathyroidism. Age, gender, preoperative parathyroid hormone level, serum calcium level, serum phosphate level, diameter, location, associated with thyroid abnormality, and results of parathyroid exploration were determined in all patients. The results of US and Tc-MIBI imaging were analyzed and compared with surgical and histopathologic findings. At surgery, 56 parathyroid lesions were found in 52 patients (9 men, 43 women), the parathyroid lesion was solitary (47 adenomas, two hyperplasias), in 2 patients double adenomas were present, in 1 patient three glands was affected by hyperplasia. Twenty-seven patients had concomitant thyroid disease. The overall sensitivity of US and Tc-MIBI scintigraphy was 84% and 73%, respectively. In patients without thyroid disease, the sensitivity of these techniques was 90% and 75%, respectively. In patients with thyroid disease, the sensitivity was 78% and 70%, respectively. In patients with thyroid disease, the combined sensitivity of these techniques was 89%. These results allow the conclusion that, in experienced hands, US is a highly sensitive technique. Especially in patients with no thyroid pathology and typical located gland, US alone should be used as a first step for preoperative localization of parathyroid lesions. When negative, Tc-MIBI scintigraphy is suggested. In patients with concomitant thyroid disease, the combination of US and Tc-MIBI scintigraphy represents a reliable localization technique.     

The role of colour Doppler ultrasonography in the preoperative localization of parathyroid adenomas

The aim of the present study was to evaluate the diagnostic accuracy and imaging patterns of colour Doppler ultrasonography (US) and compare it with grayscale US, 99m-Tc methoxyisobutylisonitrile (MIBI) scans, and combined US and MIBI scans in the preoperative diagnosis of parathyroid adenomas in patients with primary hyperparathyroidism (pHPT). From June 2007 to June 2011, 36 consecutive patients (seven men and 29 women) with pHPT underwent grayscale US, colour Doppler ultrasonography (CDUS), and 99m-Tc MIBI scans prior to parathyroidectomy with traditional unilateral neck dissection. All 36 patients with pHPT underwent parathyroidectomy at our university hospital. According to histopathology results, the sensitivity, specificity, and accuracy of MIBI and US scan were 88%, 94%, and 91%, and 70%, 100%, and 85%, respectively. The overall sensitivity and specificity of combined US and MIBI was 97% and 100% respectively. The overall sensitivity, specificity, and accuracy of CDUS in the correct diagnosis of parathyroid adenoma were 97%, 100%, and 98.6%, respectively. The sensitivity and specificity of US in the detection of parathyroid adenoma and differentiating it from other cervical masses reached up to 97% and 100%, respectively, by combining CDUS with grayscale evaluations of parathyroid adenoma.     

Ultrasonography for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism: comparison with (99m)technetium sestamibi scintigraphy

OBJECTIVE: To determine the utility of ultrasonography for the preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism, and to compare this method with (99m)technetium sestamibi scintigraphy. DESIGN: The results of ultrasonography for localization of enlarged parathyroid glands were determined in 120 consecutive patients with primary hyperparathyroidism and compared with findings at surgery (n = 86) and with the results of (99m)technetium sestamibi scintigraphy (n = 99). PATIENTS: All patients had biochemically documented primary hyperparathyroidism based on elevated serum calcium and 'intact' parathyroid hormone measured by immunoassay. Patients with prior parathyroid surgery or secondary hyperparathyroidism were excluded. MEASUREMENTS: High-resolution ultrasonography was performed by a single observer. (99m)Technetium sestamibi scintigraphy was performed using early and delayed (2-h) views, and correlated with simultaneous thyroidal 123I uptake in most patients. RESULTS: Ultrasonography detected putative enlarged parathyroid glands in 92 of 120 unselected patients (77%). It correctly predicted surgical findings in 64 of 86 patients undergoing surgery (74%), including 61 of 72 patients with solitary eutopic parathyroid adenomas (84%), but only two of eight patients with solitary ectopic adenomas, and only one of six patients with multigland parathyroid disease. Sestamibi scintigraphy was positive in 87 of 99 unselected patients (88%), a higher proportion than ultrasonography (P < 0.05), reflecting superior sensitivity for the detection of ectopic parathyroid adenomas. For 74 patients undergoing parathyroid surgery who underwent both imaging tests there was no statistically significant difference between ultrasonography and sestamibi scintigraphy in ability to correctly predict surgical findings (74%vs. 82%, respectively) or in positive predictive value (93%vs. 90%, respectively). However, sestamibi scintigraphy was clearly more sensitive for ectopic parathyroid adenomas, providing correct localization in 8/8 cases. When one test was negative, testing with the second method was usually positive, improving the likelihood of a positive result to 98% when both tests were employed. CONCLUSIONS: Ultrasonography can be a sensitive and accurate method for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism, comparable in overall utility to sestamibi scintigraphy. These results suggest that a strategy of initial testing with one or the other method, followed by the alternate imaging test if the first test is negative, would provide correct parathyroid imaging in most patients without prior parathyroid surgery.     

Ultrasonography of salivary glands in primary Sjogren's syndrome. A comparison with magnetic resonance imaging and magnetic resonance sialography of parotid glands

Objectives. To evaluate ultrasonography (US) of salivary glandsin primary Sjögren's syndrome (SS) and to compare US withparotid magnetic resonance (MR) imaging and MR sialography. Methods. US examination of parotid, submandibular and sublingualglands was performed on 27 patients with primary SS, 27 healthycontrols and 27 symptomatic controls without SS. The resultswere compared with parotid MR imaging and MR sialography andthe clinical features of the patients. Results. Salivary gland abnormalities, parenchymal inhomogeneityor adipose degeneration, were visualized in 21 (78%) SS patients,in one healthy control and in two symptomatic controls by US.Eighteen (67%) patients had changes in the parotid and submandibularglands and 8 (30%) changes in the sublingual glands. In thecomparison, MR sialography was found to be the most sensitivemethod (96%), followed by MR imaging (81%) and US (78%), indetecting glandular changes. The specificity of US was 94%.The US and MR results were related to anti-Ro/SSA positivitybut not to saliva secretion. The focus scores were related onlyto parotid MR imaging findings. Conclusions. US, MR imaging and MR sialography with modern technologyhave reached such a good accuracy in visualizing glandular structuralchanges that they are promising alternatives to the conventionalinvasive examinations in the diagnostics of SS. KEY WORDS: Diagnostics, Submandibular glands, Sublingual glands     

Technetium-99m tetrofosmin parathyroid imaging in patients with primary hyperparathyroidism

OBJECTIVE: To confirm the clinical significance of 99mTc-tetrofosmin imaging for the localization of hyperfunctioning parathyroid glands in patients with primary hyperparathyroidism. METHODS: All patients were imaged with 99mTc-tetrofosmin at 10 minutes and 2 hours after radiotracer injection, and with ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI). The parathyroid/thyroid uptake ratio of 99mTc-tetrofosmin (P/T uptake ratio) was calculated. PATIENTS: Twenty patients with primary hyperparathyroidism were referred to our clinic, underwent surgical neck exploration or mediastinotomy and were diagnosed as having parathyroid adenoma. These patients were investigated for the preoperative localization by 99mTc-tetrofosmin scintigraphy. RESULTS: 99mTc-tetrofosmin imaging demonstrated focal uptake in 19 out of 20 patients with parathyroid adenoma. Two of the lesions were ectopic. US identified 17 parathyroid glands. CT and MRI initially detected 17 parathyroid glands. However, two additional parathyroid glands were localized on repeated CT and MRI in tandem with the results of the 99mTc-tetrofosmin imaging. Thus, the sensitivity and specificity of tetrofosmin imaging were 95% (19/20) and 95% (19/20); US, 85% (17/20) and 94% (16/17); initial CT, 85% (17/20) and 94% (16/17); and initial MRI, 88% (17/20) and 94% (16/17), respectively. The P/T uptake ratio at 2 hours after tetrofosmin injection was correlated with the serum concentration of intact PTH (rs=0.47, p<0.05) and the resected tumor weight (rs=0.53, p<0.05). CONCLUSION: 99mTc-tetrofosmin scintigraphy is useful for localization of parathyroid adenoma. Tetrofosmin uptake depends on the tumor weight and serum intact PTH levels.     

Diagnosis and treatment of extrahepatic cholangiocarcinoma: results in a series of 124 patients

AIM: The aim of the study was to evaluate the diagnostic methods and therapeutical results in patients with extrahepatic cholangiocarcinoma admitted between 2000 and 2003 and to assess the efficacy of various imaging methods. MATERIAL AND METHOD: We included 124 consecutive patients with suspected cholangiocarcinoma who underwent endoscopic retrograde cholangiopancreatography (ERCP) between 2000 and 2003. Every patient underwent an ultrasound (US) examination before ERCP. ERCP was considered as the "gold standard" for diagnosis. The therapy applied consisted of endoscopic stenting, US guided biliary drainage or surgery. The sensitivity, specificity and accuracy were calculated for every tumour localisation and also globally for all tumours. RESULTS: The sensitivity, specificity and accuracy of US were 85.9 %, 76.9 %, and 84.4 % for hilar localization, 59.1 %, 50 % and 57.1 % for the mid bile duct (CBD) and 33.3 %, 42.8 % and 36.8 % for the distal CBD tumours. The global performances for US in diagnosing extrahepatic cholangiocarcinoma were 73.5 %, 61.5 % and 70.9 %. In 73 cases (74.5%) an endoscopic stent was placed. In 11 cases (11.2%) we performed an US guided biliary drainage and in 14 cases (14.2%) surgery was recommended. CONCLUSIONS: Ultrasonography proved to be a reliable method for the diagnosis of cholangiocarcinoma in spite of its low accuracy for distal localization. The combination of the two investigations (US and ERCP) was very efficient in the management of these patients. Endoscopic stenting for hilar localization is a good therapeutical option.     

Localization of parathyroid tumors using endoscopic ultrasonography in primary hyperparathyroidism

Parathyroid adenomas responsible for primary hyperparathyroidism may be difficult to detect preoperatively. Furthermore parathyroid adenomas may arise behind the (nodular) thyroid gland, in a deep cervical location, and plans should be plane. The purpose of the present prospective study was to evaluate echoendoscopy, and to compare its accuracy to that of non invasive tests. Fourteen consecutive patients with primary hyperparathyroidism were prospectively studied. All patients underwent echoendoscopy, ultrasonography (US), CT scanning or magnetic resonance imaging (MRI) and Tc 99m sestamibi scanning before undergoing initial neck exploration. The parathyroid pathology was a solitary adenoma in 13 patients and a 4 glands hyperplasia in one. All tests were corroborating in 5 cases. Four adenomas were localized to the correc tside (33%), and no test accurately localized all hyperplastic glands. EUS, sestamibi and CT scanning or MRI correctly identified 10 parathyroid tumors in 14 cases (71%). US correctly localized only 5 adenomas (sensitivity 36%). The sensitivity of EUS to detect parathyroid adenomas is superior to US (p<0.05) and comparable to that of other non invasive tests. We conclude that EUS may be an useful tool to localize parathyroid lesions. This method may replace US prior to initial neck exploration with further miniaturization of probes, or find an intermediate place among invasive and noninvasive preoperative localization procedures in patients with persistent or recurrent PHPT.     

Reduced p18INK4c, p21CIP1/WAF1 and p27KIP1 mRNA levels in tumours of primary and secondary hyperparathyroidism

OBJECTIVE: Hyperparathyroidism (HPT) refers to states of excessive production of parathyroid hormone (PTH). The eukaryotic cell cycle is driven forward by cyclins and their cyclin-dependent kinase (CDK) partners. Cyclin-dependent kinase inhibitors (CKIs), which generally inhibit cell cycle progression, modulate the activity of cyclin-CDK complexes. DESIGN: In order to quantify the expression of the CKI genes p18, p21, and p27 semiquantitative RT-PCR with mRNA specific-primers was performed on four normal parathyroid biopsies, 31 parathyroid adenomas of primary HPT and 13 hyperplastic glands from uraemic patients with secondary HPT. PATIENTS: Parathyroid adenomas and secondary hyperplastic glands were obtained from 31 and 13 randomly selected patients undergoing parathyroidectomy in the clinical routine, respectively. Four normal parathyroid gland biopsies were obtained at surgery for pHPT or from normocalcemic patients undergoing thyroidectomy for goitre. RESULTS: The relative p27 expression (p27/GAPDH) was significantly reduced in parathyroid adenomas compared to normal parathyroid gland biopsies. Furthermore, 42% and 53% of the parathyroid adenomas displayed undetectable p18 and p21 expression levels, respectively. All 13 adenomas that lacked p18 expression showed undetectable p21 expression. The p18 expression was significantly lower in tumours of uraemic sHPT as compared to normal parathyroids and an undetectable expression level was observed for p21 and p27 in 61% and 53%, respectively. CONCLUSION: Parathyroid adenomas and secondary hyperplastic glands exhibit aberrant reduced expression of the CKIs p18, p21, and p27. This suggests that deranged collaboration of different CKIs may contribute to the development of both primary and secondary HPT.     

Thyroid evaluation in patients with primary hyperparathyroidism

We evaluated the efficacy of preoperative high-resolution ultrasonography (US) for diagnosing possible concomitant thyroid disease which affects the surgical management in patients with primary hyperparathyroidism (pHPT). One hundred and nine patients with sporadic pHPT underwent US with or without ultrasound-guided fine-needle aspiration biopsy (US-FNAB). Diagnosis of concomitant thyroid nodules by US and US-FNAB were compared with the histopathological findings. Of the 109 patients, 19 (17.4%) had malignant thyroid nodules, 26 (23.9%) had benign thyroid nodules alone, and 12 (11.0%) had diffuse goiter. The sensitivity, specificity, and accuracy of diagnosing 72 thyroid nodules were 91.3%, 91.8%, and 91.7% for US, 57.9%, 94.3%, and 81.5% for US-FNAB, and 95.7%, 91.8%, and 93.1% for combined US and US-FNAB, respectively. True positive/false negative ratio of US-FNAB diagnosis was significantly lower in nodules of 5-9 mm than nodules of 10 mm or more. Four unexpected thyroid cancers existed at a different site in 3 of the 39 patients with palpable thyroid disease. Five thyroid cancers were histopathologically confirmed in 5 (7.1%) of 70 patients without palpable thyroid disease. Eight (88.9%) of the 9 non-palpable thyroid cancers were accurately diagnosed by combined US and US-FNAB. Preoperative US is useful for evaluation of possible concomitant thyroid disease, especially for prediction of malignancy.     

Ultrasonography of salivary glands -- a highly specific imaging procedure for diagnosis of Sjögren's syndrome

OBJECTIVE: To verify ultrasonographic criteria for examination of the major salivary glands in diagnosis of primary and secondary Sj?gren's syndrome (SS). METHODS: Three hundred sixteen consecutive patients with rheumatic diseases were selected according to the European Consensus Study Group diagnostic criteria for SS. Fifty-seven had primary SS, 33 had secondary SS, 78 had Sicca symptoms, and 148 patients served as asymptomatic controls. This cohort was analyzed for size and parenchymal echogenicity of the major salivary glands by ultrasonography. RESULTS: Evident parenchymal inhomogenicity in 2 or more major salivary glands was detected by ultrasonography in patients with primary and secondary SS with a sensitivity of 63.1% and 63.6%, respectively. The specificity of this imaging approach in our cohort was 98.7%. The volume of submandibular glands was reduced in patients with primary and secondary SS by about 30% compared to patients with sicca symptoms and asymptomatic controls. In receiver-operating characteristic (ROC) curve analysis, the detection of reduced volumes of both submandibular glands in patients with primary and secondary SS had a specificity of 93% and a sensitivity of 48% at the cutoff point of 3.0 ml. Of note, the volume of the parotid glands did not differ between the groups of patients. In patients with primary SS, parenchymal inhomogenicity of the salivary glands was strongly associated with positivity for anti-Ro and/or anti-La antibodies. CONCLUSION: Ultrasonographic detection of parenchymal inhomogenicity of the major salivary glands and observation of reduced volume of the submandibular glands resulted in high specificities for diagnosis of primary and secondary SS. The data indicate that ultrasonography of major salivary glands is a noninvasive imaging procedure with high diagnostic value for the diagnosis of primary and secondary SS.     

Insulin secretion, insulin sensitivity and hepatic insulin extraction in primary hyperparathyroidism before and after surgery

OBJECTIVE: Primary hyperparathyroidism (pHPT) is associated with hypertension, hyperinsulinaemia, and insulin resistance. The present study investigated the causes of these metabolic disturbances by quantifying insulin sensitivity and glucose effectiveness, and by assessing the time course of beta-cell insulin secretion and hepatic insulin extraction, during a dynamic condition such as after an intravenous glucose load. In addition, we evaluated the possible link between metabolic disorders and high blood pressure. SUBJECTS: We studied 16 patients with pHPT, before and 12 weeks after parathyroidectomy; eight of these patients were re-evaluated one year after surgery. The control group consisted of 18 healthy volunteers. DESIGN AND MEASUREMENTS: All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. The data from the intravenous glucose tolerance test were analysed by means of the minimal model technique which yields relevant parameters to comprehend the metabolic status of the single individual. RESULTS: The glucose intolerance condition was characterized by a severely impaired insulin sensitivity in pHPT (3.2 +/- 0.5 vs 9.5 +/- 1.5 x 10(4)/min/(microU/ml) of control subjects; P < 0.001), as well as by a reduced glucose effectiveness, (0.02 +/- 0.002 vs 0.03 +/- 0.003/min of control subjects; P < 0.04). Total insulin secretion during the 4 hours of the test was almost twofold elevated in comparison to the control subjects (32795 +/- 4769 vs 16864 +/- 1850 pM, P < 0.004) and its basal component significantly correlated with the high blood pressure. Hepatic extraction of insulin was significantly increased in pHPT (85 +/- 2 vs 76 +/- 2%, P < 0.03), possibly as a compensatory mechanism of hypersecretion, which however did not prevent peripheral hyperinsulinaemia in pHPT. Patients with pHPT were divided into two subgroups with normal and impaired glucose tolerance. The patients with impaired glucose tolerance had a significant reduction of first phase insulin response, although their basal and stimulated insulin levels were higher. Tissue insulin sensitivity and glucose effectiveness did not significantly differ between the two subgroups. After surgery, all the biochemical parameters (former hypercalcaemia, hypophosphataemia, elevated parathormone levels) were normalized, insulin sensitivity significantly improved (6 +/- 1 x 10(4)/min/(microU/ml), P < 0.001), whereas glucose effectiveness remained completely unchanged. Basal and stimulated insulin responses were insignificantly lowered after surgery, and hepatic extraction did not change either. CONCLUSIONS: Patients with pHPT exhibited decreased insulin sensitivity and insulin hypersecretion. The latter is only partially ameliorated by increased hepatic insulin extraction. After surgery, although the biochemical abnormalities were fully reversible, the metabolic changes improved only partially.     

Insulin resistance is not coupled with defective insulin secretion in primary hyperparathyroidism

Aims An increased frequency of both impaired glucose tolerance and Type 2 diabetes mellitus (DM) has been reported in primary hyperparathyroidism (pHPT), thus we sought to investigate insulin sensitivity and insulin secretion in a large series of pHPT patients. Subjects and methods One hundred and twenty‐two consecutive pHPT patients without known DM were investigated [age (mean ± sd ) 59.3 ± 13.6 years, body mass index (BMI) 25.7 ± 4.2 kg/m²; serum calcium 2.8 ± 0.25 mmol/l; PTH 203.2 ± 145.4 ng/l]. Sixty‐one control subjects were matched, according to the degree of glucose tolerance, in a 2 : 1 patient:control ratio. Fasting‐ and oral glucose tolerance test‐derived estimates of insulin sensitivity and secretion were determined by means of the quantitative insulin sensitivity check index (QUICKI) and the insulin sensitivity index (ISI) composite. Results Both the QUICKI and ISI composite were lower in pHPT patients than control subjects (P < 0.03 and P < 0.05, respectively) after adjusting for age, systolic blood pressure and BMI. Conversely, all insulin secretion estimates were significantly increased in pHPT patients than in control subjects (P < 0.04 and P < 0.03, respectively) and after adjusting for age, systolic blood pressure and BMI. Log serum calcium levels were negatively associated with the QUICKI and log ISI composite (R = ?0.30, P = 0.001; R = ?0.23, P = 0.020, respectively) in pHPT patients. Serum calcium levels significantly and independently contributed to impaired insulin sensitivity in multivariate analysis (QUICKI as dependent variable: β = ?0.31, P = 0.004, R² = 0.15; log ISI composite as dependent variable: β = ?0.29, P = 0.005, R² = 0.16). Conclusions Our study confirms a reduction in both basal and stimulated insulin sensitivity in primary hyperparathyroidism, in spite of increased insulin secretion. Moreover, our data show for the first time a significant relationship between hypercalcaemia and insulin sensitivity in this condition.     

Ultrasonography in detection of single and multiple abnormal parathyroid glands in primary hyperparathyroidism: comparison with radionuclide scintigraphy and surgery

BACKGROUND: Among the parathyroid imaging techniques, ultrasonography (USG) has the advantage of convenience, easy availability and low cost. OBJECTIVE: To study the role of USG in localization (side and/or site) of abnormal parathyroid glands in primary hyperparathyroidism (PHPT) and to compare with radionuclide scintigraphy and the 'gold standard', surgery. METHODS: Forty-six consecutive patients undergoing USG of the anterior neck for a diagnosis of PHPT in whom a nuclear scan (technetium-99m sestamibi and/or thallium-201/technetium-99m pertechnetate scintigraphy) was also performed, were studied. The results of imaging were independently interpreted and correlated with reference to surgical findings. RESULTS: Forty-six patients had 52 abnormal parathyroid glands on surgical exploration and surgery was successful in all but one. Forty-one patients had a single adenoma, four had multigland disease and one had a paraganglioma. USG correctly localized the abnormal gland in 30 (73%) and scintigraphy was positive in 40 (98%) out of 41 patients with a single adenoma as confirmed on surgical exploration. Scintigraphy showed a positive concordant test in all 30 patients with a single abnormal gland detected on USG and picked up 10 out of 11 abnormal glands where USG was negative. The sensitivity and positive predictive value of USG for detecting a single abnormal gland was 73% and 100%, respectively, whereas the sensitivity and positive predictive value for scintigraphy was 98%. In patients with multigland disease, USG missed 3 (30%) out of 10 and scintigraphy missed 6 (60%) out of 10 abnormal parathyroid glands as confirmed on surgical exploration (P < 0.05). However, in two patients who had ectopic parathyroid gland, both the modalities localized the lesion in one (paraganglioma), whereas in the other neither test was helpful (left retro-esophageal). CONCLUSION: USG is a convenient, affordable and useful modality to localize abnormal enlarged parathyroid glands in the majority of patients with PHPT. However, when USG is negative, scintigraphy is complementary to it.     

Parathyroid localization by 201Tl-99mTc subtraction scintigraphy: results in secondary hyperparathyroidism

Subtraction scintigraphy with 201Tl and 99mTc for parathyroid localization was performed preoperatively in 13 patients with chronic renal failure and secondary hyperparathyroidism. Twenty of the 37 examined pathological glands were predicted correctly (sensitivity 54%). In 3 patients with recurrent hyperparathyroidism after surgery all pathological glands found at second operation had been detected correctly by subtraction scintigraphy. We conclude that this localization method has a limited value when used prior to first neck exploration in secondary hyperparathyroidism. In persistent hyperparathyroidism after surgery it may play a useful role in localizing missed and ectopic glands.     

The effect of parathyroidectomy on neuropsychological symptoms and biochemical parameters in patients with asymptomatic primary hyperparathyroidism

Background With increased biochemical screening, primary hyperparathyroidism (pHPT) is often discovered incidentally whilst patients are asymptomatic. Objective To assess the impact of parathyroidectomy on neuropsychological symptoms and biochemical parameters in people with asymptomatic pHPT, whilst controlling for the surgical procedure. Patients/design/measurements Twenty‐four patients with asymptomatic pHPT requiring parathyroidectomy, in accordance with National Institutes for Health recommendations, were recruited prospectively. A control group of 23 subjects was recruited simultaneously from consecutive patients undergoing diagnostic hemithyroidectomy (HT) for benign thyroid nodules. Operations were performed by a single surgeon. Biochemical investigations and neuropsychological symptoms were measured preoperatively and 3 months after surgery. Neuropsychological symptoms were measured using the Hospital Anxiety (HAD‐A) and Depression (HAD‐D) scales and the Mood Rating Scale (MRS). Results Postoperatively, calcium and parathyroid hormone normalized in all patients in the pHPT group. Patients with pHPT showed a significant improvement in neuropsychological symptoms with a pre‐ and postoperative mean change of 2·45 ± 2·57 (P < 0·05) on HAD‐A, 2·79 ± 3·85 (P < 0·05) on HAD‐D, and 3·2 ± 4·57 (P < 0·05) on MRS, parameters that were unaltered in the HT group. The differences between the two groups remained statistically significant after adjustment for age and sex for HAD‐D (mean change 2·8, 95% CI = 0·3, 5·3, P = 0·025) and MRS (mean difference 3·5, 95% CI = 0·4, 6·7, P = 0·027) but not for HAD‐A (mean difference 1·5, 95% CI = ?0·8, 3·8, P = 0·20). For all three mental health scores, there were no significant associations with either age or sex. Conclusions Asymptomatic pHPT is associated with neuropsychological symptoms that improve after parathyroidectomy.     

The threshold of bone mineral density for vertebral fractures in female patients with primary hyperparathyroidism

BACKGROUND AND OBJECTIVE: Primary hyperparathyroidism (pHPT) is one of the causal diseases that induce secondary osteoporosis. Although patients with pHPT have reduced bone mineral density (BMD) especially at the cortical bone, there have been controversies about risk of fracture. Moreover, no reports have been available about the threshold of BMD for fractures in pHPT patients. METHODS: BMD values were measured by dual-energy x-ray absorptiometry at lumbar spine, femoral neck and distal one third of radius. Various indices were compared in 116 female pHPT patients and 716 control subjects. Moreover, we analyzed relationship between the cut-off values of BMD and the prevalence of vertebral fractures in pHPT and control subjects. RESULTS: The prevalence of subjects with vertebral fractures was lower in pHPT patients, compared with that of control subjects. Age and body height were significantly higher and lower in pHPT women with vertebral fractures, respectively. Lumbar spine BMD was significantly lower in pHPT women with vertebral fractures, presumably due to their increased age. There were no differences in femoral neck and radius BMD or in bone metabolic indices between pHPT women with and without vertebral fractures. On the other hand, age-matched BMD was not significantly different between both groups at any measured site. Cut-off values of BMD at lumbar spine and femoral neck were lower in postmenopausal pHPT patients, compared with those of the postmenopausal control group. Moreover, cut-off values of BMD at radius was much lower in postmenopausal pHPT patients, compared with those of the postmenopausal control group (pHPT vs control (g/cm(2)): 0.670 vs 0.706 at lumbar spine; 0.549 vs 0.570 at femoral; 0.394 vs 0.474 at radius). Sensitivity and specificity of vertebral fractures was lower in pHPT patients, compared with those in control group. CONCLUSIONS: The present cross-sectional study demonstrated that thresholds of BMD for vertebral fractures were lower especially at radial bone in female patients with pHPT, compared with those in the control group.