Biochemical studies and bone tissue biopsy in primary hyperparathyroidism

Insomnia in 11 general hospital in-patients was treated by a placebo. The conditions of administration of the placebo were experimentally varied, and a hypothesis derived from Festinger's cognitive dissonance theory was tested. Consistent with this hypothesis, it was found that patients who were required to make meaningful decisions concerning their treatment derived significantly greater hypnotic (therapeutic) value from it than did patients whose treatment was simply administered to them and who were not required to make such decisions. The power of cognitive dissonance theory to explain the placebo effect, and the therapeutic potential of this approach are discussed.     

Body weight and bone mineral density in postmenopausal women with primary hyperparathyroidism

OBJECTIVE: To assess bone mineral density and body composition in postmenopausal women with primary hyperparathyroidism. DESIGN: Cross-sectional study with an age-matched control group. SETTING: University teaching hospital. PATIENTS: 41 postmenopausal women with mild primary hyperparathyroidism and 43 eucalcemic, age-matched controls. MEASUREMENTS: Total body, lumbar spine, and proximal femoral (femoral neck, Ward's triangle, and trochanter) bone mineral density; body composition; and fat distribution were measured using dual-energy x-ray absorptiometry. RESULTS: Women with primary hyperparathyroidism were heavier (75.5 kg compared with 66.3 kg; difference, 9.2 kg [95% CI, 3.7 to 14.7 kg]; P = 0.002), had a higher fat mass (33.3 kg compared with 26.1 kg; difference, 7.2 kg [CI, 3.0 to 11.4 kg]; P = 0.001), and had a more android pattern of fat distribution (android-to-gynoid fat ratio, 1.05 compared with 0.84; difference, 0.21 [CI, 0.1 to 0.32]; P = 0.0004) than the controls. Unadjusted bone mineral density was similar in patients and controls at all sites: total body, 0.990 compared with 1.023 g/cm2 (difference, 0.033; CI, -0.004 to 0.070); posteroanterior lumbar spine, 1.032 compared with 1.018 g/cm2 (difference, 0.014; CI, -0.031 to 0.059); lateral lumbar spine, 0.569 compared with 0.528 g/cm2 (difference, 0.041; CI, -0.022 to 0.104); femoral neck, 0.799 compared with 0.825 g/cm2 (difference, 0.026; CI, -0.072 to 0.124); Ward's triangle, 0.653 compared with 0.677 g/cm2 (difference, 0.024; CI, -0.035 to 0.089); trochanter, 0.734 compared with 0.733 g/cm2 (difference, 0.001; CI, -0.024 to 0.026); and arms, 0.720 compared with 0.739 g/cm2 (difference, 0.019; CI, -0.015 to 0.053). After adjustment for body weight, bone mineral density in women with primary hyperparathyroidism was lower than that in controls for total body (P = 0.0004), femoral neck (P = 0.001), Ward's triangle (P = 0.01), trochanter (P = 0.02), and arms (P = 0.0006). Spinal bone mineral density did not differ between groups. CONCLUSIONS: Body weight, total body fat mass, and proportion of android fat are increased in postmenopausal women with primary hyperparathyroidism; these unexplained factors may be relevant to the increased incidence of cardiovascular disease in this condition. Unadjusted bone mineral density values are similar in patients with primary hyperparathyroidism and in controls, suggesting that this condition is not associated with an increased risk for fracture.     

Indications for surgery in patients with minimally symptomatic primary hyperparathyroidism

Although childhood anxiety appears to aggregate in families, transmission could be explained by both genetic and shared environmental factors. Twin studies can be used to disentangle genetic and environmental effects. In this study, a systematically ascertained sample of twins was used to investigate whether anxiety symptoms are heritable. Parent-rated anxiety symptoms could best be explained by an additive genetic model with heritability estimated at 59%. However, when self ratings were analysed (in the adolescent subsample), familial transmission could be accounted for by shared environmental factors only.     

The measurement of urinary amino-terminal telopeptides of type I collagen to monitor bone resorption in patients with primary hyperparathyroidism

This study was carried out in order to evaluate clinical usefulness of cross-linked N-telopeptides (NTx) of type I collagen determination, in patients with primary hyperparathyroidism. Twenty-six consecutive patients (6 males and 20 females, aged 56.3 +/- 15.0, SD, yrs) with primary hyperparathyroidism were studied in basal conditions and, ten of them, after surgical cure of the disease. Cross-linked collagen peptides were measured by enzyme-linked immunosorbent assay and conventional markers of bone turnover according to standard procedures. Bone densitometry at the lumbar spine and proximal femur was performed using dual-energy X-ray absorptiometry. Bone mineral density, was also assessed at the junction of the distal and middle third of the radius and at the ultradistal radius of the non-dominant arm by a dual photon densitometer. Mean urinary NTx values (194.2 +/- 121.9 pmoles bone collagen equivalents/mumoles creatinine) were significantly higher (p < 0.001) in respect to those found in normal subjects. The mean increase of Z score values of both serum tartrate resistant acid phosphatase activity (1.4 +/- 1.8) and the fasting hydroxyproline/creatinine ratio (1.45 +/- 2.0) was significantly lower (p < 0.02) in respect to that of NTx Z score values (3.3 +/- 3.3); the latter values were not significantly different than mean Z score values of serum osteocalcin (4.0 +/- 3.9), serum alkaline phosphatase activity (2.6 +/- 2.6) and urinary calcium/creatinine ratio (3.2 +/- 3.3). We found a significant inverse correlation between NTx values and both lumbar spine (p < 0.01) and ultradistal radius bone mineral density (p < 0.05); a modest inverse correlation was also observed between serum tartrate resistant acid phosphatase activity and lumbar spine bone mineral density (p < 0.04). Following successful adenoma removal, the percentage decrease of both NTx and hydroxyproline was similar in patients with increased bone turnover rate; major discrepancies were observed in patients with normal values of NTx, the telopeptide reduction being greater than that of hydroxyproline. Finally, in a hypercalcemic patient with metastatic parathyroid cancer, telopeptide excretion was shown to be more sensitive in respect to urinary hydroxyproline when evaluating the effects of antiresorptive therapy. Our results seem to indicate that amongst the markers with good sensitivity, NTx is the only one that is inversely related with bone mineral density at two different skeletal sites. This assay should therefore have a place in both the initial screening and medical follow-up of patients with this glandular disorder; in fact, in both situations an increased urinary excretion of this marker should warn about the possibility of hidden bone loss.     

Prediction of outcome of patients with life-threatening ventricular arrhythmias treated with automatic implantable cardioverter-defibrillators using SPECT perfusion imaging

BACKGROUND: In the present study, we examined the predictors of outcome of 103 patients with coronary artery disease and left ventricular dysfunction who had life-threatening ventricular arrhythmias and were treated with implantable cardioverter-defibrillators with the use of single-photon emission computed tomography (SPECT). METHODS AND RESULTS: During a mean follow-up of 29 months, there were 29 cardiac deaths. In comparison with patients who died, survivors had less diabetes mellitus (45% versus 19%, P < .007), higher left ventricular ejection fraction (23 +/- 9% versus 27 +/- 11%, P = .04), and fewer perfusion defects as determined with stress SPECT (15 +/- 5 versus 12 +/- 5, P < .004). Most of the perfusion defects were fixed, indicative of scarring; the extent of reversible defects did not differ (2 +/- 3 in survivors and 3 +/- 4 in nonsurvivors). Multivariate Cox survival analysis identified the number of fixed defects as the only independent predictor of death (chi 2 = 10, P = .002). There were six deaths among 42 patients (14%) with < 8 fixed defects compared with 23 deaths among 61 patients (38%) with > or = 8 defects (P = .005). The 4-year survival was better in patients with < 8 segmental fixed defects than in those with > or = 8 fixed defects (80% versus 36%) (chi 2 = 8, P = .005). CONCLUSIONS: The myocardial perfusion pattern is an important determinant of outcome in patients with life-threatening ventricular arrhythmias who are treated with a implantable cardioverter-defibrillator. The extent of scarring separates patients into high- and low-risk groups with a 2.7-fold difference in death rate.     

Technetium 99m tetrofosmin parathyroid imaging. Results with double-phase study and SPECT in primary and secondary hyperparathyroidism

RATIONALE AND OBJECTIVES: The aim of our study was to evaluate the sensitivity, specificity, and positive predictive value (PPV) of technetium 99m (99mTc) tetrofosmin double-phase scintigraphy and single-photon emission computer tomography (SPECT) in preoperative localization of parathyroid adenoma in case of primary and secondary hyperparathyroidism (HPT). METHODS: Sixty-eight consecutive patients biochemically or sonographically suspected of parathyroid adenoma were included in our study. Apart from biochemical analysis of serum calcium, phosphate, and intact parathyroid hormone, double-phase scintigraphy was performed in each patient 5 and 45 minutes after injection of 370 MBq 99mTc tetrofosmin, followed by SPECT imaging. In consciousness of the scintigraphic results, ultrasound of the neck was performed as well to exclude false-positive results due to thyroid adenomas. RESULTS: Depending on the results of the biochemical analysis in combination with the results of the scintigraphic and ultrasound examination, the patients were classified retrospectively into three groups: group A with primary HPT (n = 35), group B with secondary HPT (n = 13), and group C without any biochemical suspicion of primary or secondary HPT (n = 20). In group A, double-phase study localized 25 of 36 (69.2%) parathyroid adenomas (one double adenoma) as against 34 of 36 (94.4%) with SPECT. Nine adenomas could be visualized only by SPECT. The reason for nonvisualization on planar scans was suspected to be an ectopic location in 2 cases (retrotracheal dislocation, retrovascular dislocation), a maximal diameter less than 15 mm (9-13 mm) in 6 cases, and oxyphilic-cell-poor cellularity in 1 case. Four false-positive retention (3 thyroid adenomas and 1 papillary thyroid carcinoma) were observed. SPECT showed a sensitivity of 94.4%, a specificity of 85%, and a PPV of 91.9% in biochemically suspected primary HPT. In group B, planar scintigraphy demonstrated 12 hyperplastic glands in 5 of 13 patients, and SPECT demonstrated 20 hyperplastic parathyroid glands in 8 out of 13 patients, which corresponds to a sensitivity of 38% and 61.5%, respectively. CONCLUSIONS: Technetium 99m tetrofosmin seems to be a promising alternative tracer with similar capabilities to 99mTc sestamibi in localization of parathyroid adenoma. SPECT showed clear advantages in terms of sensitivity over planar scintigraphy and should be used at least in cases with poor or no uptake in double-phase study. In endemic goiter areas, ultrasound of the neck should be performed to exclude false positive retention in thyroid adenomas. Technetium 99m tetrofosmin, like 99mTc sestamibi, is not ideal for localization of hyperplastic glands in secondary hyperparathyroidism because of low sensitivity.     

Duration of the effects of intravenous alendronate in postmenopausal women and in patients with primary hyperparathyroidism and Paget's disease of bone

The effect of a single intravenous (i.v.) infusion of 5 mg alendronate was studied in ten patients with Paget's disease, six patients with primary hyperparathyroidism and ten osteopenic postmenopausal women. Urinary hydroxyproline excretion significantly decreased within few days in all patients (from 113 +/- 67.9 to 58 +/- 35 mmol/mol Cr in Paget's disease, from 21.8 +/- 9 to 12.9 +/- 6 mmol/mol Cr in hyperparathyroidism, from 18.7 +/- 9.5 to 8.5 +/- 4.3 mmol/mol Cr in postmenopausal women). In the patients with Paget's disease urinary hydroxyproline remained suppressed over the 6 months of follow-up, whereas it rose toward pretreatment values within 4 and 6 weeks in the patients with primary hyperparathyroidism and in postmenopausal osteopenic women, respectively. Plasma alkaline phosphatase significantly fell only after 4-6 weeks in patients with primary hyperparathyroidism and in Pagetic patients. In the latter group alkaline phosphatase continued to decline thereafter and a plateau became apparent after 2 months. In postmenopausal women the serum alkaline phosphatase remained unchanged. Thus, the same dose of alendronate induces comparable fractional decreases of bone resorption in the three groups of patients, but the effect is persistent only in Paget's disease. This is consistent with the hypothesis that alendronate inhibits osteoclastic activity only at the level of the existing resorption sites. In osteoporotic and primary hyperparathyroid patients, as soon as the treatment is withdrawn, the appearance of new sites of resorption is not inhibited and bone turnover is resumed to pre-treatment values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bone mineral recovery after parathyroidectomy in patients with primary and renal hyperparathyroidism

Patients with hyperparathyroidism (HPT) generally display reduced bone mass due to excessive PTH activity. The effect of parathyroidectomy on bone mass changes in different types of HPT, however, is not well understood. Bone mineral density (BMD) was measured in the distal radius, total body, femoral neck, and lumbar spine by dual energy x-ray absorptiometry in four groups of patients with different hyperparathyroid conditions: primary symptomatic HPT (n = 54), primary asymptomatic (mild) HPT (n = 24), HPT associated with hemodialysis (n = 20), and HPT associated with renal transplant (n = 30). Subsets of patients with primary symptomatic HPT (n = 52), HPT associated with hemodialysis (n = 19), and HPT associated with renal transplant (n = 15) underwent parathyroidectomy, and bone density was measured longitudinally for 3 yr. Patients with primary asymptomatic (mild) HPT did not undergo surgery and were followed prospectively. Before surgery, all groups showed a greater reduction of bone mineral density in cortical bone (distal radius) than in predominantly trabecular bone (lumbar spine). In primary symptomatic HPT, the BMD z-score of the distal radius was -1.80 +/- 0.21 (+/-SEM), and the corresponding figures for the total body, femoral neck, and lumbar spine were -0.60 +/- 0.15, -0.54 +/- 0.14, and -0.53 +/- 0.18 compared with those of an age- and sex-matched reference group. In renal HPT BMD z-scores were -2.51 +/- 0.38 (hemodialysis patients) and -2.83 +/- 0.43 (renal transplant patients) for the distal radius and between -0.81 and -1.46 for the other measured sites. After parathyroidectomy, BMD increased by 1-8% at all sites in patients with primary symptomatic HPT and HPT associated with renal transplant. The largest increase in bone mass was observed in patients with HPT associated with hemodialysis, in whom the improvement amounted to 7-23%. In patients with primary HPT and HPT associated with hemodialysis, this increase in bone density resulted in virtual recovery from their preoperative bone loss. The majority of patients with asymptomatic primary HPT disease (n = 21) maintained their bone density during the follow-up period and have not shown evidence of increases in serum calcium or PTH levels, but three patients followed conservatively underwent parathyroidectomy due to progressive deterioration of BMD. We conclude that, regardless of the etiology, a large proportion of HPT patients show reduced bone density. In patients with primary symptomatic HPT and patients with HPT associated with hemodialysis, bone density increases after parathyroidectomy to an extent that largely restores the preoperative bone loss. However, no anabolic effect of parathyroidectomy on bone mass was observed in patients with HPT associated with renal transplant, probably because of their immunosuppressive therapy.     

Anemia in primary hyperparathyroidism

Although anemia has not been widely appreciated as a complication of primary hyperparathyroidism, 5.1% of the individuals with this disorder seen at the Massachusetts General Hospital since 1962 had a normochromic, normocytic anemia that could not be related to blood loss,a deficiency state, or uremia. The anemic group had more advanced bone disease and higher levels of serum calcium, alkaline phosphatase, and parathyroid hormone than the nonanemic group. Results of bone marrow biopsies performed in five patients showed variable degrees of myelofibrosis. However, none of the patients had hepatosplenomegaly, a myelophthisic peripheral blood smear, leukopenia, or thrombocytopenia. Removal of the abnormal parathyroid glands led to improvement or correction of the anemia.     

Surgery in primary hyperparathyroidism

Data were reviewed on 26 patients suffering from primary hyperparathyroidism (PHPT). The diagnosis of PHPT is increasing in frequency, due to greater awareness and better methods of detection. Delay in recognition has gradually decreased, thus permitting earlier treatment. No single test or any combination of tests can be considered satisfactorily pathognomonic of PHPT. Hypercalcemia is the most satisfactory finding suggestive of PHPT. Cervical exploration should be an integral part of the diagnostic work-up. Removal of a distinct adenoma is adequate therapy if the other parathyroid glands are normal. Subtotal parathyroidectomy should be performed only in cases of hyperplasia of all parathyroid glands.     

Cerebral blood flow study using SPECT in patients with memory disorders

INTRODUCTION: Global amnesia (AG) is a dysfunction of memory, in which there is a sudden incapacity to remember recent events and assimilate new information. The aetiology is currently under discussion. The main hypotheses under consideration are an ischemic mechanism and an epileptic mechanism. OBJECTIVE: To study the cerebral blood flow in patients with temporary global amnesia (AGT) or permanent global amnesia (AGP) using functional neuroimaging techniques. MATERIAL AND METHODS: Four patients were studied. Two had severe alterations of fixation memory which had been present for months. The other two had a sudden loss of recent memory, although space-person orientation and immediate memory remained normal. In all cases the cerebral blood flow (FSC), was assessed by single photon emission tomography (SPECT), using Tc-HMPAO as the radio tracer. RESULTS: We describe 4 patients, 2 men and 2 women aged between 42 and 64.2 with AGT and the others with AGP. On SPECT there was temporal hypoperfusion in all 4 patients. In 2 cases there was associated parietal hypoperfusion and in 1 case there was frontal hypoperfusion. CONCLUSIONS: These findings suggest that AGT and AGP are of vascular origin and that SPECT is a useful diagnostic technique in patients with AG.     

Radionuclide imaging in primary hyperparathyroidism using 99mTc sestamibi--four case reports

Radionuclide imaging using the 99mTc sestamibi either singly or as a subtraction technique with pertechnetate is a recent and reliable method in localising parathyroid adenomas prior to surgery. This is of use in pre-operative planning, as well as in failed first neck exploration. Four local patients with primary hyperparathyroidism whose parathyroid adenomas were localised by this scintigraphy are presented. The value and limitations of this imaging modality are discussed.     

Alveolar bone loss and restorative dentistry in the primary molars

Stab wounds to the abdomen can present a diagnostic dilemma to the trauma surgeon, especially in the thoracoabdominal region. Patients with lower chest and upper abdominal stab wounds are at risk for both intraabdominal and cardiac injury. Current options in the evaluation of these patients include mandatory laparotomy, diagnostic peritoneal lavage, thoracoscopy, sonography, and observation. Each has its own inherent advantages and disadvantages, but none of them represents the gold standard. Herein is reported a case of a patient with an epigastric stab wound who underwent diagnostic laparoscopy and laparoscopic transdiaphragmatic pericardial window to rule out both peritoneal penetration and cardiac injury.     

Videocervicoscopy in surgery of primary hyperparathyroidism. Preliminary study of 19 patients

The aim of this study was to assess the feasibility of a minimally invasive parathyroidectomy performed by videocervicoscopy. 19 patients were operated. Preoperative localization by ultrasonography and/or technetium 99 m sestamibi scan was performed in 17 patients. The technique was first attempted in two pigs, using three 2.5 mm trocars and a 2.5 mm endoscope. However, this technique failed in the first two human cases because of the lack of optical clarity of the 2.5 mm endoscope. A 5 mm endoscope was subsequently used. Carbon dioxide insufflation was maintained at 10 mmHg with a low 3 L/min flow. Three trocars were inserted in to the cervical space: one 5 mm trocar for the endoscope, two 3 mm trocars for the instruments. A unilateral neck exploration was carried out in 5 cases and a bilateral neck exploration in 14 cases. Enlarged glands were discovered in 13 patients (12 adenomas, 1 hyperplasia of the 4 glands). 8 adenomas were removed via a short midline incision, 4 others via a short lateral incision. Horizontal cervicotomy was required in 7 cases (4 failures to identify the abnormal gland, 1 thyroid cancer discovered incidentally, 1 hyperplasia of 4 glands and 1 anterior jugular vein bleeding). Except for the case of bleeding, no other complication occurred. Subcutaneous emphysema resorbed in 3 hours. 17 patients were discharged within 48 hours and 2 patients were discharged within 24 hours. 18 patients had normal serum calcium two months postoperatively. This study demonstrates that videocervicoscopy is safe and feasible in primary hyperparathyroidism.     

Hypercalcemic cardiomyopathy associated with primary hyperparathyroidism mimicking primary obstructive hypertrophic cardiomyopathy

A 72-year-old woman presented to hospital with rapidly progressive dyspnea and chest pain on exertion. Physical findings included a grade 3/6 systolic murmur increased by the Valsalva manoeuvre. Transthoracic echocardiography revealed concentric left ventricular hypertrophy, systolic anterior motion of the mitral valve and critical dynamic outflow tract obstruction. The myocardium was strikingly heterogeneous with hyperdynamic left ventricular systolic function. Laboratory findings included severe hypercalcemia secondary to primary hyperparathyroidism. The patient's outcome was unfavourable with nephrogenic diabetes insipidus, pancreatitis, shock, severe acidosis and death. Postmortem examination confirmed the presence of severe concentric left ventricular hypertrophy, a narrowed left ventricular outflow tract and localized endocardial fibrosis of the left interventricular septum. Microscopic findings showed diffuse calcium deposits of the myocardium, coronary arteries, kidneys and lungs. This appears to be the first report of two-dimensional and Doppler echocardiographic findings in hypercalcemic cardiomyopathy mimicking obstructive hypertrophic cardiomyopathy.     

Topical diagnostic methods in primary hyperparathyroidism

The efficiency of USI of the neck, scintigraphy of the parathyroid glands (PTG) with selen-methionine and selective catheterization of veins (SCV) of the neck and mediastinum for preoperative determination of the localization of the source of hyperproduction of the parathyroid hormone was analyzed on the basis of results of examination of 149 patients including 51 patients with primary hyperparathyroidism confirmed during the operation. It was noted that none of the methods of topical diagnostics used in the work is thought to be universal for different clinical situations. A method of their complex use is proposed which foresee USI of the neck as the first step. In case of insufficient information of the results of USI the authors propose SCV of the neck and mediastinum as a method of choice which allows the size and level of the altered PTG to become more exact and which makes further search with the help of other methods of topical diagnostics more purposeful and effective.