Cardiovascular morbidity and mortality in surgically treated hyperthyroidism - a nation-wide cohort study with a long-term follow-up.

OBJECTIVE: Previous studies suggest that patients with hyperthyroidism remain at an increased risk of cardiovascular morbidity even after restoring euthyroidism. The mechanisms of the increased risk and its dependency on the different treatment modalities of hyperthyroidism remain unclear. The aim of this long-term follow-up study was to compare the rate of hospitalizations for cardiovascular causes and the mortality in hyperthyroid patients treated surgically with an age- and gender-matched reference population. PATIENTS AND MEASUREMENTS: A population-based cohort study was conducted among 4334 hyperthyroid patients (median age 46 years) treated with thyroidectomy in 1986-2007 in Finland and among 12,991 reference subjects. Firstly, the hospitalizations due to cardiovascular diseases (CVD) were analysed until thyroidectomy. Secondly, the hazard ratios for any new hospitalization due to CVDs after the thyroidectomy were calculated in Cox regression analysis adjusted with the prevalent CVDs at the time of thyroidectomy. RESULTS: The risk of hospitalization due to all CVDs started to increase already 5 years before the thyroidectomy, and by the time of the operation, it was 50% higher in the hyperthyroid patients compared to the controls (P < 0·001). After the thyroidectomy, the hospitalizations due to all CVDs (HR 1·15), hypertension (HR 1·23), heart failure (HR 1·17) and valvular diseases or cardiomyopathies (HR 1·55) remained more frequent among the patients than among the controls for 20 years after thyroidectomy. The increased morbidity was not clearly related to the aetiology of hyperthyroidism. Despite the increased CVD morbidity among the patients, there was no difference in cardiovascular mortality. CONCLUSIONS: The present study shows that hyperthyroidism increases the risk of hospitalization due to CVDs and the risk is sustained up to two decades after effective surgical treatment. However, there was no excess CVD mortality in the middle-aged patient cohort studied.

Gluten-free diet and autoimmune thyroiditis in patients with celiac disease. A prospective controlled study.

OBJECTIVE: Early diagnosis and dietary treatment with a gluten-free diet might slow down the progression of associated autoimmune diseases in celiac disease, but the data are contradictory. We investigated the course of autoimmune thyroid diseases in newly diagnosed celiac disease patients before and after gluten-free dietary treatment. MATERIAL AND METHODS: Twenty-seven consecutive adults with newly diagnosed celiac disease were investigated at the time of diagnosis and after 1 year on gluten-free diet. Earlier diagnosed and subclinical autoimmune thyroid diseases were recorded and examined. Thyroid gland volume and echogenicity were measured by ultrasound. Autoantibodies against celiac disease and thyroiditis, and thyroid function tests were determined. For comparison, 27 non-celiac controls on normal gluten-containing diet were examined. RESULTS: At the time of diagnosis, the celiac disease patients had more manifest (n = 7) or subclinical (n = 3) thyroid diseases than the controls (10/27 vs. 3/27, p = 0.055). During the follow-up, the thyroid volume decreased significantly in the patients with celiac disease compared with the controls, indicating the progression of thyroid gland atrophy despite the gluten-free diet. CONCLUSIONS: Celiac patients had an increased risk of thyroid autoimmune disorders. A gluten-free diet seemed not to prevent the progression of autoimmune process during a follow-up of 1 year.

Increased long-term cardiovascular morbidity among patients treated with radioactive iodine for hyperthyroidism.

OBJECTIVE: Previous studies suggest that hyperthyroid patients remain at increased risk of cardiovascular morbidity after restoring euthyroidism. The aim of this study was to compare the rate and causes of hospitalization of hyperthyroid patients treated with radioactive iodine (RAI) with those of an age- and gender-matched reference population in a long-term follow-up study. PATIENTS AND MEASUREMENTS: A population-based cohort study with a median follow-up time of 9 years was conducted among 2611 hyperthyroid patients treated with RAI between 1969 and 2002 in Tampere University Hospital, and among 2611 reference subjects. Information on hospitalizations was obtained from the nationwide Hospital Discharge Registry. New events were analysed as the main outcome, including only the first hospitalization due to a given indication. RESULTS: The rate of hospitalization due to cardiovascular disease (CVD) was higher among patients with hyperthyroidism than among the control population [637.1 vs. 476.4 per 10 000 person-years, rate ratio (RR) 1.12, 95% confidence interval (CI) 1.03-1.21]. The risk remained elevated up to 35 years after the RAI treatment. Hospitalizations due to atrial fibrillation (RR 1.35), cerebrovascular disease (RR 1.31), diseases of other arteries and veins (RR 1.22), hypertension (RR 1.20) and heart failure (RR 1.48) were more frequent in the patients than controls, while no such difference was found for coronary artery disease. Hospitalizations due to cancer, infectious and gastrointestinal diseases, and fractures were also more common in patients than in controls. CONCLUSIONS: Hyperthyroidism increases hospitalizations due to CVDs. The excess risk is sustained decades after treatment. Patients treated for hyperthyroidism constitute a high-risk group for CVD and may benefit from preventive interventions.

Increased cancer incidence after radioiodine treatment for hyperthyroidism.

BACKGROUND: Concerns remain about risk of cancer after radioactive iodine (RAI) treatment for hyperthyroidism, especially in organs that concentrate iodine. The objective was to assess the long-term cancer risk from RAI treatment for hyperthyroidism. METHODS: A total of 2793 hyperthyroid patients treated with RAI at Tampere University Hospital between 1965 and 2002, and 2793 age- and sex-matched reference subjects were followed for an average of 10 years through the Finnish Cancer Registry. RESULTS: Cancer incidence among hyperthyroid patients treated with RAI was higher than in the population-based control group (118.9 vs 94.9 per 10,000 person-years, rate ratio [RR], 1.25; 95% confidence interval [CI]: 1.08-1.46). Furthermore, incidence of stomach (RR, 1.75, 95% CI: 1.00-3.14), kidney (RR, 2.32; 95% CI: 1.06-5.09), and breast (RR, 1.53; 95% CI: 1.07-2.19) cancer was increased among RAI-treated patients. The relative risk of cancer increased with higher RAI dose administered. The increase in cancer incidence was statistically significant in patients treated at the age of 50-59 (RR, 1.44; 95% CI: 1.05-1.97) or older than 70 years (RR, 1.39; 95% CI: 1.05-1.82). There was a 5-year latent period after the RAI treatment before the cancer incidence began to differ between the RAI-treated hyperthyroid patients and the control group. CONCLUSIONS: Cancer incidence, especially cancer of the stomach, kidney, and breast, was higher in patients treated with RAI for hyperthyroidism.

Increased cardiovascular and cancer mortality after radioiodine treatment for hyperthyroidism.

CONTEXT: Patients treated with radioiodine (RAI) for hyperthyroidism have been reported to be at increased risk for death. It is not clear whether the increased mortality is due to hyperthyroidism itself or the effect of RAI. OBJECTIVE: Our objective was to compare the mortality of hyperthyroid patients treated with RAI with that of an age- and gender-matched reference population. DESIGN: We conducted a population-based cohort study. PARTICIPANTS: A total of 2793 patients who received RAI treatment for hyperthyroidism in Tampere University Hospital between 1965 and 2002, and 2793 reference subjects were followed for a median of 9 yr. RESULTS: Record linkage with Statistics Finland identified all-cause mortality of 453 vs. 406 per 10,000 person-years in the patients and controls [rate ratio (RR) 1.12; 95% confidence interval 1.03-1.20]. Cerebrovascular diseases accounted for most of the increased mortality among patients (RR 1.40), and mortality from cancer increased (RR 1.29) as well. The risk of death increased in patients older than 60 yr at treatment. Mortality increased with the dose of RAI and was elevated in patients with nodular thyroid disease, but not in those with Graves' disease. Previous treatment with partial thyroidectomy decreased, whereas antithyroid medication did not affect mortality. In Cox regression analysis, RAI-treated hyperthyroidism (RR 1.56) and age (RR 1.10/1 yr) increased, and the development of hypothyroidism (RR 0.52) reduced mortality significantly. CONCLUSIONS: Hyperthyroidism per se probably accounts for the increased cerebrovascular mortality after RAI treatment. Our results of increased cerebrovascular and cancer mortality emphasize the need for long-term vigilance concerning patients treated with RAI.

Fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography as a tool to localize an insulinoma or beta-cell hyperplasia in adult patients.

CONTEXT AND OBJECTIVE: Fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET) is a promising method in localizing neuroendocrine tumors. Recently, it has been shown to differentiate focal forms of congenital hyperinsulinism of infancy. The current study was set up to determine the potential of 18F-DOPA PET in identifying the insulin-secreting tumors or beta-cell hyperplasia of the pancreas in adults. PATIENTS AND METHODS: We prospectively studied 10 patients with confirmed hyperinsulinemic hypoglycemia and presumed insulin-secreting tumor using 18F-DOPA PET. Anatomical imaging was performed with computed tomography (CT) and magnetic resonance imaging (MRI). All patients were operated on, and histological verification was available in each case. Semiquantitative PET findings in the pancreas using standardized uptake values were compared to standardized uptake values of seven consecutive patients with nonpancreatic neuroendocrine tumors. RESULTS: By visual inspection of 18F-DOPA PET images, it was possible in nine of 10 patients to localize the pancreatic lesion, subsequently confirmed by histological analysis. 18F-DOPA uptake was enhanced in six of seven solid insulinomas and in the malignant insulinoma and its hepatic metastasis. Two patients with beta-cell hyperplasia showed increased focal uptake of 18F-DOPA in the affected areas. As compared to CT or MRI, 18F-DOPA PET was more sensitive in localizing diseased pancreatic tissue. CONCLUSION: 18F-DOPA PET was useful in most patients with insulinoma and negative CT, MRI, and ultrasound results. In agreement with previous findings in infants, preoperative 18F-DOPA imaging seems to be a method of choice for the detection of beta-cell hyperplasia in adults. It should be considered for the detection of insulinoma or beta-cell hyperplasia in patients with confirmed hyperinsulinemic hypoglycemias when other diagnostic work-up is negative.

A nationwide survey of mortality in acromegaly.

CONTEXT: Increased mortality in acromegaly has been confined to those with posttreatment basal GH of 2.5 microg/liter or greater, but the impact of IGF-I and pituitary radiotherapy on mortality has remained controversial. OBJECTIVE: The purpose of this nationwide survey was to examine the all-cause mortality of patients with acromegaly and evaluate the impact of treatment outcome and mode of treatment on survival. DESIGN, SETTING, AND PATIENTS: All-cause mortality of all patients with acromegaly diagnosed during January 1980 and December 1999 in the five university hospitals of Finland was followed up by the end of 2002 (12.5 +/- 5.6 yr) and compared with that of the general population by using age- and gender-adjusted standardized mortality ratios (SMRs). Logistic regression analysis was used to investigate factors related to mortality within the survey population. MAIN OUTCOME MEASURE: Mortality was the main outcome measure. RESULTS: Of the 334 patients, 56 (16.8%) had died during follow-up. SMR of the patients was 1.16 [confidence interval (CI) 0.85-1.54, not significant (NS)]. However, patients with basal serum GH concentration 2.5 microg/liter or greater (SMR 1.63, CI 1.10-2.35, P < 0.001) measured 5.2 +/- 4.4 yr after the initial treatment, and those irradiated (SMR 1.69, CI 1.05-2.58, P < 0.001) showed excess mortality. In a multivariate model, the effect of radiotherapy was of borderline significance only (P = 0.083). Posttreatment IGF-I levels, available for 72.2% of the patients, did not have impact on mortality. CONCLUSIONS: The posttreatment basal GH concentration less than 2.5 microg/liter in acromegalic patients is associated with a normal lifespan. Excess mortality is confined to poorly controlled patients and possibly those who have received conventional radiotherapy.

Atrial fibrillation in elderly patients after cardiac surgery: postoperative hemodynamics and low postoperative serum triiodothyronine.

OBJECTIVE: The purpose of this study was to evaluate serum triiodothyronine levels as a trigger of postoperative atrial fibrillation (AF) in elderly patients undergoing cardiac surgery and to study the possible association of serum triiodothyronine levels with preoperative and postoperative hemodynamics. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Forty-six consecutive nonemergency patients 65 years or older undergoing cardiac surgery during 1999 to 2000 in Tampere University Hospital, Tampere, Finland. INTERVENTIONS: Free serum T3 concentration was used as a measure of serum triiodothyronine levels. Samples were taken preoperatively, on the fourth postoperative day, and at the 3-month follow-up. The hemodynamic state of the patients was estimated by whole-body impedance cardiography preoperatively, during the intensive care unit period, daily until the fourth postoperative day, and at the 3-month follow-up. MEASUREMENTS AND MAIN RESULTS: AF occurred in 43% of the patients. The patients in the AF group had significantly more grafts (3.9 v 3.1, p = 0.02), and there was a small difference in age between the AF and non-AF groups (73 years v 69 years, p = 0.06). The free T3 concentration on the fourth postoperative day was significantly lower in the AF group (3.5 nmol/L v 4.6 nmol/L, p = 0.04). In logistic regression analysis, the independent predictors of AF were age, number of grafts, and serum free T3 concentration on the fourth postoperative day. In the group with low T3 concentration, the cardiac index was lower (1.4 v 1.8, p = 0.05) and the systemic vascular resistance index was higher (4,064 v 2,969, p = 0.04) but only immediately after the operation. Although the AF mostly appeared during the second to fourth postoperative days, there were no longer any differences in the hemodynamic state at that time. CONCLUSIONS: In a group of elderly patients undergoing cardiac surgery, there was a strong association between a postoperative decrease of serum triiodothyronine levels and atrial fibrillation. The decrease of serum triiodothyronine levels was related to the changes of hemodynamic parameters only in the immediate postoperative period.

Long-term follow-up study of radioiodine treatment of hyperthyroidism.

OBJECTIVE: To determine the cumulative incidence of hypothyroidism during long-term follow-up in patients treated for hyperthyroidism by radioactive iodine (131)I (RAI) therapy, the significance of clinical factors in predicting the development of hypothyroidism, and the outcome after a fixed 7 mCi (259 MBq) dose of RAI. DESIGN: Prospective cohort study of patients treated for hyperthyroidism by RAI. PATIENTS AND MEASUREMENTS: Since 1965, details on 2043 patients treated by RAI therapy in Tampere University Hospital were entered into a computerized register. Following RAI treatment, thyroid status was monitored every 1-3 months during the first year, and subsequently at 1-3-year intervals until June 2002 or until the patient died or moved out of the Tampere University Hospital district. results The cumulative incidence of hypothyroidism in patients with Graves' disease and toxic multinodular goitre at 1, 10 and 25 years was 24%vs. 4%, 59%vs. 15% and 82%vs. 32%, respectively. In a Cox regression model, previous partial thyroidectomy [risk ratio (RR) = 1.63 in patients with Graves' disease and RR = 1.59 in those with toxic multinodular goitre] and age at the first RAI treatment (RR = 0.998 and RR = 0.996 per year) were statistically significantly associated with the development of hypothyroidism both in patients with Graves' disease and in those with toxic multinodular goitre. Antithyroid medication preceding RAI therapy (RR = 0.47) decreased and female gender (RR = 1.53) increased the risk of hypothyroidism only in patients with Graves' disease. Administration of a single dose of RAI resulted in the control of hyperthyroidism in 75% of patients, while two to six RAI treatments were needed in 25% of patients to achieve either a hypothyroid or a euthyroid state in both groups. None of the clinical factors studied was associated with the remission rate either in patients with Graves' disease or in those with toxic multinodular goitre. The remission rate did not differ between the patients who received a dose of RAI calculated according to the uptake of RAI and thyroid size and those who received an empirical dose of RAI. The fixed 7 mCi (259 MBq) dose of RAI cured 80% of patients. CONCLUSION: RAI treatment is effective in treating hyperthyroidism in patients with Graves' disease, but hypothyroidism will develop in 82% of patients in 25 years. Because the development of hypothyroidism seems to be inevitable and unpredictable by any clinical factors, the objective of RAI treatment should be to minimize the persistence of hyperthyroidism with the simplest possible form of treatment. We recommend a fixed 7 mCi dose of RAI to be used as the first empirical dose in the treatment of hyperthyroidism, at least in Graves' disease.

Imaging of adrenal incidentalomas with PET using (11)C-metomidate and (18)F-FDG.

UNLABELLED: Our aim was to evaluate the use of PET with (11)C-metomidate and (18)F-FDG for the diagnosis of adrenal incidentalomas. METHODS: Twenty-one patients underwent hormonal screening before dynamic imaging of the upper abdomen with (11)C-metomidate, and for 19 of these 21 patients, static (18)F-FDG imaging followed. Uptake of (11)C-metomidate and (18)F-FDG in incidentalomas was quantified and correlated with the hormonal work-up and the mass size on CT (median, 2.5 cm; range, 2-10 cm). RESULTS: The final diagnoses were hormonally active adenoma (n = 7), nonsecretory adenoma (n = 5), adrenocortical carcinoma (n = 1), pheochromocytoma (n = 2), benign noncortical tumor (n = 2), normal adrenal (n = 1), and malignant noncortical tumor (n = 3). Diagnosis was established at surgery (n = 9), percutaneous biopsy (n = 4), or follow-up (n = 8). The highest uptake of (11)C-metomidate, expressed as standardized uptake value (SUV), was found in adrenocortical carcinoma (SUV = 28.0), followed by active adenomas (median SUV = 12.7), nonsecretory adenomas (median SUV = 12.2), and noncortical tumors (median SUV = 5.7). Patients with adenomas had significantly higher tumor-to-normal-adrenal (11)C-metomidate SUV ratios than did patients with noncortical tumors. (18)F-FDG detected 2 of 3 noncortical malignancies but failed to detect adrenal metastases from renal cell carcinoma. All inactive and most active adenomas were difficult to detect with (18)F-FDG against background activity, whereas both pheochromocytomas and adrenocortical carcinoma showed slightly increased uptake of (18)F-FDG. There was no correlation between uptake of (11)C-metomidate or (18)F-FDG and mass size. CONCLUSION: (11)C-Metomidate is a promising PET tracer to identify incidentalomas of adrenocortical origin. (18)F-FDG should be reserved for patients with a moderate to high likelihood of neoplastic disease.

Is bile flow reduced in patients with hypothyroidism?

BACKGROUND: Disturbances in the sphincter of Oddi (SO) function may prevent normal bile flow and thus enhance the probability of common bile duct stone (CBDS) formation. We have previously shown increased prevalence of diagnosed hypothyroidism in CBDS patients, thyroxine (T(4)) -induced inhibition of the SO contractility both in animal and in human experiments ex vivo, and reduced bile flow to duodenum in hypothyroid rats. The aim of the present study was to investigate human biliary dynamics in relation to altered thyroid gland function. METHODS: Eight female patients, 1 with diagnosed untreated hypothyroidism and 7 with total thyroidectomy performed due to thyroid cancer, were studied in hypothyroid stage and again after thyroxine replacement therapy in euthyroid stage, with quantitative (99m)Tc HIDA cholescintigraphy (QC), biliary ultrasonography, and serum determinations. Each patient served as her own control in the 2 stages of the study. RESULTS: In QC, maximal uptake of (99m)Tc HIDA was not changed in hypothyroidism compared to euthyroidism. The first appearance of radioactivity to large bile ducts at the hepatic hilum remained unchanged in the 2 stages of the study. Hepatic clearance of (99m)Tc HIDA was decreased at 45 minutes (28% [11-38] vs 50% [33-54]; P =.028; median and range) and at 60 minutes (55% [28-80] vs 69% [61-79]; P =.028; median and range) and hilum-duodenal transit time increased by 31% compared to euthyroid stage. In US no changes were seen in gall bladder or bile ducts in the 2 stages of the study. Serum hypercholesterolemia was observed in the hypothyroid stage. CONCLUSIONS: We conclude that hypothyroidism may result in delayed emptying of the biliary tract, as studied with QC. In addition to the changes in bile composition and excretion rate suggested before to take place in hypothyroidism, according to the present study changes in biliary emptying also may be included in the probable causes for the increased prevalence of CBDS in hypothyroidism. This may be due to the absence of the prorelaxing effect of thyroxine on SO, which we have shown before to exist ex vivo.

Prevention of bone loss by clodronate in early postmenopausal women with vertebral osteopenia: a dose-finding study.

This double-masked, placebo-controlled study was undertaken to determine the efficacy and safety of oral clodronate in the prevention of bone loss in early postmenopausal women with vertebral osteopenia. Altogether 610 women with a mean age of 53 years were recruited for the study. They were 1-5 years postmenopausal and their lumbar spine bone mineral density (BMD) was at least 1 standard deviation below the mean of premenopausal women ( T-score < or =-1). The subjects were randomized into five study groups to receive either placebo, clodronate 65 mg, 400 mg or 800 mg daily, or intermittent clodronate in 3 month cycles with 400 mg daily for 15 days followed with no treatment for 75 days for 3 years. One hundred and eighty-seven of 509 women who completed the primary study continued in the extension study of 2 years in which previous placebo users were switched to clodronate 800 mg daily, while previous users of 400 mg or 800 mg of clodronate used either placebo or 800 mg of clodronate daily. In the primary study clodronate was administered in the evening, and in the extension 1 h before breakfast on an empty stomach. In the primary study mean changes in lumbar spine BMD were -3.4% in the placebo group and +0.4% in 800 mg clodronate group [difference between groups at 3 years 3.8% (95% CI 2.7% to 4.9%, p<0.0001)], and in the trochanter area BMD -1.1% in the placebo group, and + 0.4% in the 800 mg clodronate group [difference between groups at 3 years 1.5% (95% CI 0.05% to 2.9%)]. During the extension study mean changes in lumbar spine BMD were +1.5% in the clodronate group and -0.2 % in the placebo group [difference between groups 1.7% (CI 0.4% to 3.0%, p = 0.010)] and in trochanter BMD were +2.5% in the clodronate group and no change in the placebo group [difference between groups 2.1% (CI 0.3% to 3.9%, p = 0.007)]. No statistically significant differences between the placebo and 800 mg clodronate groups were found in the femoral neck BMD. In the primary study the urinary excretion of type I collagen aminoterminal telopeptide (NTX) decreased by 44% ( p<0.0001 compared with placebo) and that of deoxypyridinoline by 18% ( p<0.0001) in the clodronate 800 mg group. In the extension study urinary NTX decreased by 51% ( p<0.0001) in those who were switched to 800 mg of clodronate and increased by 67% ( p<0.0001) in those who stopped using that dose. There was no difference in the frequency of gastrointestinal complaints between clodronate- and placebo-treated patients in the primary study, but they were more common among women who received clodronate in the extension phase. Clodronate in daily doses of 400-800 mg caused a slight elevation of aminotransferase levels, usually within the reference range. In bone biopsies no defect in mineralization was found. In conclusion, clodronate in a daily dose of 800 mg prevents early postmenopausal bone loss at the sites of the skeleton in which cancellous bone predominates. It effectively reduces bone resorption and bone turnover rate. Antifracture efficacy of clodronate remains to be established by prospective, placebo-controlled trials.

Endocrinological disorders and celiac disease.

Celiac disease is a permanent intolerance to dietary gluten. Its well known features are abdominal symptoms, malabsorption of nutrients, and small-bowel mucosal inflammation with villous atrophy, which recover on a gluten-free diet. Diagnosis is challenging in that patients often suffer from subtle, if any, symptoms. The risk of clinically silent celiac disease is increased in various autoimmune conditions. The endocrinologist, especially, should maintain high suspicion and alertness to celiac disease, which is to be found in 2-5% of patients with insulin-dependent diabetes mellitus or autoimmune thyroid disease. Patients with multiple endocrine disorders, Addison's disease, alopecia, or hypophysitis may also have concomitant celiac disease. Similar heredity and proneness to autoimmune conditions are considered to be explanations for these associations. A gluten-free diet is essential to prevent celiac complications such as anemia, osteoporosis, and infertility. The diet may also be beneficial in the treatment of the underlying endocrinological disease; prolonged gluten exposure may even contribute to the development of autoimmune diseases. The diagnosis of celiac disease requires endoscopic biopsy, but serological screening with antiendomysial and antitissue transglutaminase antibody assays is an easy method for preliminary case finding. Celiac disease will be increasingly detected provided the close association with autoimmune endocrinological diseases is recognized.

Intraoperative localization of parathyroid glands with gamma counter probe in primary hyperparathyroidism: a prospective study.

BACKGROUND: Technetium 99m-sestamibi imaging might be the best method to localize abnormal parathyroid glands. No studies to date have compared preoperative imaging and intraoperative gamma probe localization in patients with primary hyperparathyroidism. STUDY DESIGN: This prospective study included 20 arbitrarily selected patients with primary hyperparathyroidism, verified by elevated serum ionized calcium and intact parathyroid hormone concentrations and low serum phosphatase level. Each patient underwent both preoperative imaging study of the parathyroid glands with technetium 99m-sestamibi (dose 740MBq) and intraoperative localization with a handheld gamma probe. Full collar exploration served as the gold standard. RESULTS: Hypercalcemia and hypophosphatemia normalized in each patient. A single parathyroid adenoma was confirmed histologically in 16 and hyperplasia (4 abnormal glands) in 4 patients. None of the patients had multiple adenomas. The sensitivity of the preoperative scan was 81% (13 of 16 patients) in adenoma patients and 100% (4 of 4 patients) in hyperplasia. The corresponding specificity was 88% and 100%. Intraoperatively only 8 of 16 adenomas were correctly detected (sensitivity 50%), and none of the hyperplastic glands were correctly detected. CONCLUSIONS: In unselected patients with primary hyperparathyroidism, preoperative technetium 99m-sestamibi imaging is more accurate than intraoperative gamma probe detection in localizing abnormal parathyroid glands.