Prognostic role of stress thallium test in patients with significant coronary artery disease.

OBJECTIVE: The benign outcome of patients with a normal exercise thallium-201 myocardial perfusion study has been well established. The aim of the study was to examine the prognostic implications of normal exercise tomographic thallium images in medically treated patients with angiographic evidence of coronary artery disease (CAD). METHODS: There were 68 patients in Group A with significant angiographic CAD (54 male and 14 female) aged 52 +/- 12 years, 42 had one, 18 had two and eight had three vessel CAD (50% diameter stenosis 1, Group B had 70 patients who had normal coronary arteries at cardiac catheterization. RESULTS: Exercise test was submaximal in 40 (50.82%) patients, ST segment depression during exercise occurred in 28 patients (41.1%) and angina during exercise in 24 patients (35.2%). Majority of patients (76.47%) were on anti-anginal therapy. During a mean follow up of 30 months only two patients had cardiac events in group A patient. One died of cardiac causes and one had non fatal myocardial infarction (event rate 0.96%/year). None of these 2 patients had positive ST response during exercise. In group B only one patient had non-fatal myocardial infarction. CONCLUSION: Medically treated CAD patients including those with multivessel CAD have a benign prognosis in the presence of normal exercise thallium images. These results have long term important implication in management of such patients and cost of health delivery.

Solitary nodular goiter. Review of cytomorphologic features in 441 cases.

OBJECTIVE: To study the cytomorphologic features of solitary nodular goiters (SNG). STUDY DESIGN: May-Grünwald-Giemsa-stained smears in 441 SNG diagnosed by ultrasonography and fine needle aspiration (FNA) and found to have optimum cellular material at review were subjected to detailed cytologic assessment. The age of the patients ranged from 11 to 75 years, with a median of 35. Male: female ratio was 69:372. The parameters for cytologic assessment included cellularity, colloid content, acinar formation, papillary formation, intranuclear cytoplasmic inclusions, nuclear grooves, marginal vacuoles, Hürthle cells and various inflammatory cells. Histopathology reports on thyroidectomy specimens were available in 27 cases from two Delhi hospitals. RESULTS: Hyperplastic nodules (68 cases) differed significantly from colloid goiters (269 cases) by having more cases with excessive cellularity, acinar formation and marginal vacuoles (P < .001). There was also a significant difference with respect to papillary formation and moderate-to-excessive colloid content (P < .001). As compared to hyperplastic nodules, neoplasms (60 cases) had a significantly higher number of cases with papillary formation, intranuclear inclusions and nuclear grooves but lower number of cases with marginal vacuoles (P < .01-.001). Among neoplasms, usual papillary carcinoma (19 cases) differed from follicular neoplasms (20 cases) with respect to acinar formation, papillary formation and nuclear grooves (P < .001). A significant difference was also observed with respect to colloid content and nuclear inclusions. Follicular variant of papillary carcinomas (FVPC) (10 cases) emerged as a distinct cytologic entity following review and differed from usual papillary carcinomas in having a higher number of cases with acinar formation, tubular formation and marginal vacuoles (P < .01-.001) and lower number of cases with nuclear grooves (P = .05). FVPC also differed from follicular neoplasms with respect to papillary formation, tubular formation, intranuclear inclusions and nuclear grooves (P < .01-.001). Overall cytohistologic agreement was achieved in 24 of 27 (88.9%) cases. CONCLUSION: Detailed cytologic assessment of FNA smears-in SNG was helpful in highlighting parameters that differentiate between various types of goiters.

Response to exercise and ambulatory blood pressure monitoring in essential hypertension.

To evaluate the relationship of ambulatory blood pressure (ABP) recording and blood pressure response to exercise, 58 essential hypertensive patients, not taking any drugs, had symptom-limited treadmill stress test (TST) within 48-96 hours of ABP, TST time, blood pressure increase, decrease, mode of increase and decrease, were independent of ABP systolic (SBP) and diastolic blood pressure (DBP) over 24 hours, day time and night time (p = ns). SBP decrease immediately after exercise were independent of ABP data. TST achieved heart rate was related to both 24 hours SBP (r = -0.64, p = 0.00005) and DBP (r = -0.55, p = 0.00001) in both day (r = -0.64, p = 0.00001 and r = -0.54, p = 0.002) and night (r = -0.52, p = 0.0001 and r = -0.46, p = 0.003) time periods. Therefore patients with achieved heart rate < 100% (n = 18) had higher 24 hour SBP (148 vs 132 +/- 2 mm Hg, p = 0.0006) and DBP (92.4 +/- 6.4 vs 84 +/- 6.2 mm Hg, P = 0.006) day and night. It is concluded that there is no overlap of diagnostic information using blood pressure. Values in TST or ABP although achieved heart rate in exercise is inversely related to severity of hypertension.

Role of radionuclide perfusion study in cold solitary thyroid nodule for diagnosis of malignancy: a complimentary diagnostic modality to fine needle aspiration cytology.

One hundred and forty eight subjects with euthyroid solitary thyroid nodules (STN) were taken up for radionuclide perfusion study. They were found to have a cold STN on 99mTc thyroid static scan. All had fine needle aspiration cytology (FNAC), and except for subjects with chronic lymphocytic thyroiditis, were subjected to surgery for tissue diagnosis by histopathology. The diagnostic findings in these patients of solitary thyroid nodules were correlated with the histopathology. Radionuclide perfusion study is considered useful to differentiate benign from malignant cold thyroid solitary nodules with high degree of sensitivity (95%) and specificity (87.9%).

Prognostic significance of thyroid antibodies in hyperthyroid patients treated with antithyroid drugs.

Lymphocytic infiltration of the thyroid gland in patients with hyperthyroidism is associated with the presence of serum antithyroidal microsomal antibodies (TMA) and serum antithyroglobulin antibodies (TGA). The aim of this study was to evaluate the clinical significance of TMA and TGA during and after treatment of hyperthyroidism with antithyroidal drugs. One hundred and fifty-four hyperthyroid patients were treated for 18 months with methimazole and then followed up for 18 months or more (mean, 24.8 +/- 12.6 months). Patients were classified into three group. group I, patients negative for TGA and TMA before and during 18 months of treatment, group II patients positive for TMA but negative for TGA before and during 18 months treatment and group III patients who were positive for both TGA and TMA before and during treatment. The relapse rates after discontinuation of treatment in these group were 44.7% (17 of 38), 29% (18 of 62) and 11.1% (6 of 54), respectively. The value in group I was significantly higher than that in group III (P < 0.01). These results show that presence of TMA and TGA influence the prognosis of patients with hyperthyroidism treated with methimazole with regard to relapse. Those patients who had both antibodies were least likely to have a relapse and those who had neither antibody before and during treatment were most likely to have a relapse of hyperthyroidism.

Early development of transient hypothyroidism after I131 therapy for thyrotoxicosis.

295 patients of Graves' disease were studied for early development of transient hypothyroidism (TH) and its prognostic value following I131 therapy. 278 patients received I131 < 10 mci (6.4 +/- 1.7 mci) and 17, a dose of > 10 mci (12.6 +/- 2.6). TH was diagnosed on the basis of low T4 regardless of TSH within the first year after I131 therapy followed by normal T4 and TSH. 32 patients developed TH following administration of < 10 mci I131 and it was symptomatic in 10 patients. No instance of TH after high dose of I131 was noted. I131 uptake > 60% at 2 hours before treatment was a risk factor for developing TH (odds ratio 2.6, 95% confidence interval 0.8-9.6). At diagnosis of TH basal TSH was high in 53%, normal in 32%, or low in 15%; Hypothyroidism recognized during the first six months with basal TSH of 50 microU/ml or higher ruled out TH. Development of TH and its hormonal profile did not influence long term thyroid functions. As no prognostic factors predicted TH before I131 therapy or at the time of diagnosis, re-evaluation of thyroid functions later is essential to avoid unnecessary chronic replacement therapy, if hypothyroidism has been diagnosed within a few months of I131 treatment.

Investigations of thyroid diseases--an update on diagnostic methods.

Iodine deficiency disorders (IDD) are an important public health problem in India. It requires further refinement and improvements in thyroid disease diagnosis, especially in the early diagnosis of thyroid malfunctioning and risk assessment of autonomously functioning thyroid tissue. Scintigraphy with technetium-99m pertechnetate under exogenous or endogenous thyroid stimulating hormone (TSH) suppression provides the best results. There has been significant improvement in methodology in various laboratory investigations that have resulted from the application of newer luminescent techniques and gene technology in various thyroid function tests. TSH measurement especially by using second or third generation assays has ensured diagnostic accuracy and thyrotropin releasing hormone (TRH) test now almost always unnecessary. Determination of glycosaminoglycans in urine may become a helpful tool in the follow up of endocrine ophthalmopathy. The differentiation of blocking and stimulating TSH receptor antibodies is relevant when discrepant results are obtained with respect to thyroid function. Some newer imaging agents have been used in thyroid disease scintigraphy such as octreotide or in thyroid diseases diagnosis such as fluorodeoxyglucose. Both improve the detectability of thyroid cancer metastasis especially if radioiodine scan is negative.

Clinical, biochemical and cytomorphological observations in juvenile chronic lymphocytic thyroiditis.

OBJECTIVE: To determine the clinical, biochemical, ultrasonological and cytomorphological features in goitrous juvenile chronic lymphocytic thyroiditis(CLT). SETTING: Tertiary referral center for thyroid disorders. SUBJECTS: A total of 455 children were evaluated for goiter. Of these 122 children had features of CLT in FNAC and were further studied. METHODS: All subjects were subjected to detailed clinical examination. The thyroid functional status was assessed by estimation of serum concentration of thyroid hormones (thyroxine and triiodothyronine) and thyrotropin (TSH). In addition the antithyroid antibody titers were measured. Ultrasonological and cytomorphological characteristics in these patients were also evaluated. RESULTS: The mean age at presentation was 12.5 years (SD 3.93). The male: female ratio was 1:7.7. Thyroid functional status as assessed by serum thyroxine and thyrotropin levels revealed, euthyroidism in 67 (54.9%), hypothyroidism in 30 (24.6%), subclinical hypothyroidism in 22 (18%) and hyperthyroidism in 3 (2.5%). Thyroid antimicrosomal antibodies were detected in significant titers in 90 (73.8%) and antithyroglobulin was positive in 71 (58.2%). The positivity of the antimicrosomal and antithyroglobulin antibodies were much higher in subjects with hypothyroidism and was detected in 86.5% and 69.2%, respectively. The mean urinary iodine excretion was 74.1 micrograms/g of creatinine (SD 31.4) indicating mild iodine deficiency. Fine needle aspiration cytoloty (FNAC) revealed features of chronic lymphocytic thyroiditis. Hurthle cell changes was seen in only 12% of the cases. The epithelium was more often hyperplastic and vacuolation of the cytoplasm and peripheral vacuolations were seen frequently. Giant cells and epithelioid cells were seen in many cases. CONCLUSIONS: In any child presenting with firm goiter, a diagnosis of CLT should be excluded. Many subjects with juvenile CLT have biochemical evidence of hypothyroidism but only few symptoms or clinical features.

Effects of long-term thyroid hormone suppressive treatment on the cardiac functions.

Long-term effects of thyroid hormone suppressive therapy on the heart were evaluated in 45 patients by non-invasive techniques. Fifteen patients were athyreotic after surgery for differentiated thyroid cancer and 30 had diffuse or nodular goiter. Mean age of the group was 42 +/- 12 years. Twenty-four age- and sex-matched subjects were taken as controls. Mean daily dose of levothyroxine was 158 +/- 36 micrograms. Plasma thyroid stimulating hormone (TSH) levels were within normal range. Mean serum T4 and free T4 were significantly higher (p < 0.001) whereas mean serum T3 and free T3 did not differ from the control levels. Non-invasive cardiac assessment was done by a standard 12 lead electrocardiogram (ECG), ambulatory electrocardiographic (Holter) monitoring and echocardiographic study. Six patients had left ventricular hypertrophy in ECG. Holter monitoring demonstrated a higher average heart rate in patients compared to controls (86 +/- 10 vs 72 +/- 6 beats/min; p < 0.001). Supraventricular premature beats were more frequent in patients than in the control group (98% vs 60%; p < 0.06). Echocardiogram showed an increased left ventricular (LV) mass index in patient group (98 +/- 28 vs 78 +/- 16 gm/m2; p < 0.02). LV systolic function was increased with higher values of fractional shortening (40 +/- 8% vs 34 +/- 6%; p < 0.05) and rate-adjusted velocity of shortening (1.4 +/- 0.12 vs 1.02 +/- 0.16 circumferences/sec; p < 0.01). It is concluded that long-term levothyroxine suppressive therapy has significant effects on the cardiac functions.

Technetium-99m dextran: a promising new protein-losing enteropathy imaging agent.

The purpose of this study was to evaluate technetium-99m dextran (99mTc-Dx; molecular weight 81000) as a prospective protein-losing enteropathy (PLE) imaging agent. Twenty-two patients with diseases commonly associated with PLE and 12 healthy control subjects underwent intravenous 99mTc-Dx scintigraphy. All of the 22 test patients showed significant radiotracer accumulation in the intestines within 3-4 h post injection. The focal, regional or generalised nature of the enteropathy and involvement of the large or small intestine could be identified in most cases. Four of the 12 apparently healthy subjects also showed minimal accumulation in the abdominal area occurring late in the study period. This could have been physiological, related to food habits or due to unsuspected intestinal worms. We attribute the high sensitivity of 99mTc-Dx to its relatively fast blood (background) clearance. The radiotracer may have several other advantages over 99mTc-labelled human serum albumin in imaging PLE.

Predictor of outcome of hyperthyroidism due to Graves disease: serum triiodothyronine/thyroxine ratio.

There is a proportionally greater increase in the serum T3 than Serum T4 concentration in patients with hyperthyroidism due to Grave's disease which results in an elevation of serum T3 to T4 ratio. The study was undertaken to investigate the alteration of serum T3 to T4 ratio in relation to the outcome of antithyroid drug therapy. 98 patients of hyperthyroid Grave's disease were studied and 78 patients had T3 to T4 ratio greater than 20 ng/microgram before therapy (normal range 14-20; mean 16.0) In 16 out of 78 patient T3 to T4 ratio remained high during a 18 months course of antithyroid drug therapy and in 13 of them (81%) hyperthyroidism recurred after stoppage of treatment. In the remaining 62 patients, the initial high T3 to T4 ratio became normal (< 20) during treatment and 34 of them (54.9%) had a remission of the disease after stoppage of the drug. Of the 20 patients in whom the initial T3 to T4 ratios were within normal range, the ratio remained normal during treatment and 16(80%) had a remission. Goiter size was larger in patients with high serum T3 to T4 ratio and reduction of goiter size occurred in some patients (59%) with decreasing T3 to T4 ratios. It is concluded that serum T3 to T4 ratio is a single and a useful predictor of the outcome of antithyroid drug therapy in patients with hyperthyroidism due to Grave's disease. A ratio greater than 20 throughout therapy indicates that the chances of relapse is high and a ratio below 20 either initially or during therapy is an indication of prolonged remission.

Evaluation of long-term results of two schedules of treatment for toxic multinodular goitre with radioiodine therapy (I 131).

Results of the long term effects of two schedules of radioine therapy (I131) in 130 toxic multinodular goitre patients were evaluated. Seventy five patients (group I) were treated with low doses and 55 patients (group II) with calculated high doses adjusted for thyroid weight (0.5-1 mu ci/g) and radioiodine uptake. Follow up (mean +/- SEM) was 4.5 +/- 0.4 years and 4.8 +/- 0.6 years respectively (p > 0.1). At the end of followup hyperthyroidism was successfully reversed in 87% (Group I) and 82% (Group II). In group I hypothyroidism was present in 5% of patients while it was 12.5% in group II patients. The total dose per gram of thyroid tissue was not significantly different in both the groups (0.058 mu ci +/- 0.0054 VS 0.073 +/- 0.0054 ci/g.) However in group II the number of I131 administration was significantly lower (1.5 +/- 0.2) than in group I (3.2 +/- 0.4) and the percentage of patients who were adequately treated in Group II with single dose was more as compared in group I (62% in group II versus 49% in group I) Hypothyroidism was reached in a shorter time after treatment in group II (median time 0.8 year in group II Vs 1.1 yrs in group I). Patients with positive thyroid antibodies showed a significant earlier development of hypothyroidism within six months. It is concluded that radioiodine is an effective treatment for toxic multinodular goitre with a significant low incidence of post therapy hypothyroidism in patients treated with low doses as compared to higher doses of radioiodine therapy.

Blood mercury in workers exposed to the preparation of mercury cadmium telluride layers on cadmium telluride base.

Study was conducted in a group of 32 persons engaged in liquid phase epitaxial growth of mercury cadmium telluride (MCT) layers for nearly 11 years. Airborne mercury concentrations in work environment have been exceeding the threshold limit value of 0.05 mg/m3 recommended by ACGIHD. Hg concentration in workplace during peak working hours remained between 0.04-0.08 mg/m3. Findings were compared with 32 unexposed referents. Mercury value was estimated 1.60 +/- 0.20 (mean +/- SD) in control, and in Phase I and II, 10.72 +/- 1.34 ng Hg/ml and 8.08 +/- 1.15 ng Hg/ml of blood respectively. Results indicate a fall in blood mercury level during the second phase of study. But the values did not return to normal even after a gap of 3 months. An individual who met with a mercury accident showed 226 ng Hg/ml of blood which decreased to 25 ng/ml after 3 months. It is inferred from the present study that Hg level has increased significantly in MCT workers during working period, and also in non-working period, the values were higher than controls.

Diagnosing protein losing enteropathy. A new approach using Tc-99m human immunoglobulin.

Tc-99m HIG has recently come into prominence as an inflammation seeking radiotracer. The authors describe a novel use of the agent for imaging protein-losing enteropathy. The agent may have certain advantages over Tc-99m HSA, which is currently being used for imaging protein loss.

Long-term results of two schedules of treatment for toxic multinodular goitre with radioiodine therapy.

Results of the long-term effects of two schedules of radioiodine therapy I131 in 130 toxic multinodular goitre patients were evaluated. Seventy five patients (group I) were treated with low doses and 55 patients (group II) with calculated high doses adjusted for thyroid weight (0.5-1 mci/g) and radioiodine uptake. Follow up (mean +/- SEM) was 4.5 +/- 0.4 years and 4.8 +/- 0.6 years respectively (P > 0.1). At the end of follow up, hyperthyroidism was successfully reversed in 78% (Group I) and 82% (Group II). In group I hypothyroidism was present in 5% of patients, while it was 12.5% in group II patients. The total dose per gram of thyroid tissue was not significantly different in both the groups (.058 mci +/- .0054 VS .073 +/- .0054 mci/g). However in group II the number of I131 administration was significantly lower (1.5 +/- 0.2) than in group I (3.2 +/- 0.4). The percentage of patients who were adequately treated in Group II with single dose was more as compared in group I (62% in group II versus 40% in group I). Euthyroidism was reached in a shorter time after treatment in group II (median time 0.8 year in group II Vs 1.1 yrs in group I) It is concluded that radioiodine is an effective treatment for toxic multinodular goitre with a significant low incidence of post therapy hypothyroidism in patients treated with low doses as compared to higher doses of radioiodine therapy.

Efficacy of hepatobiliary scintigraphy in demonstrating cholangio-colic fistulae. Is formation of internal biliary fistula related to external leak closure?

The authors present four cases of internal biliary fistulae (IBF) identified on hepatobiliary scintigraphy. All of the cases share common history of external biliary leak closure. Scintigraphy in all four cases showed a similar pattern of direct visualization of transverse colon without any significant small bowel activity. This suggests an increased frequency of IBF formation in cases with external fistulous tract closure. Retrospectively, it appears that spontaneous closure of external leak may be pathological consequence of formation of IBF involving hepatic flexure.

Efficacy of standard ten millicurie dose of radio-iodine in management of autonomously functioning toxic thyroid nodules.

Therapeutic effect of radio-iodine treatment on thyroid patients with autonomously functioning toxic thyroid nodule was evaluated. Fifty one patients were given a standard dose of 10 mci of radioiodine (I-131) and were followed up for 2-3 years. The failure rate (relapse after 10 mci of radioiodine) of this regime was 10%. It was found that the nodules less than or equal to 3 cms. in size were completely cured after a dose of 10 mic. of radio-iodine therapy, over a follow up period of next 6 months. Patients having nodules larger than 3 cms. relapsed after first dose of 10 mci of radio-iodine, but were cured completely after the second dose of 10 mci of radio-iodine therapy. Tri-iodothyronine (T3) and thyroxine (T4) values were both found to be high before giving treatment in all the cases. Only one case developed hypothyroidism after radioiodine therapy.

Evaluation of the healing process in fractures using early and delayed bone scanning.

Fifty-two fracture sites were evaluated by bone scintigraphy after acquiring similar views of the lesions at 4 and 24 h following technetium-99m methylene diphosphonate administration. After calculating 24/4 h radio-uptake ratio (RUR) and using 1.15 as the critical point of separation, fresh healing lesions could be separated from old healed fractures persisting as 'hot spots' with a sensitivity of 100% and specificity of 82%. The 24/4 h RUR technique is a new approach in measuring the osteoblastic activity at the lesion site. The technique appears to have clinical significance in the detection and follow up of the healing status of occult fractures where radiological procedures are of limited value.

Thyrotoxicosis--treatment by I131 therapy and early prediction of hypothyroidism following this therapy.

This study was undertaken in 68 thyrotoxic patients to assess the predictive value of various post treatment biochemical and immunological tests for early hypothyroidism after I131 therapy and to determine whether pretreatment with carbimazole protects against post I131 therapy hypothyroidism. Early changes observed in serum T3, T4, TSH, thyroid microsomal and thyroglobulin antibody levels were found to be of no predictive value. A sharp increase in TRAb levels around 3 months following I131 therapy indicated that hypothyroidism was likely to occur as this rise reflected a greater degree of thyroid damage. Lower levels of thyroglobulin in patients who became hypothyroid by 12 months after treatment would support this view. Carbimazole pretreatment for eight weeks did not appear to protect against hypothyroidism, in our study.

Effect of some chemical radioprotectors on mouse bone marrow.

Effect of HT, AET and Se on mice bone marrow has been studied by counting bone marrow micronucleated cells and endogenous spleen colony count (CFU-S). Combination of HT and AET used as a radioprotector has not caused any significant variation in any of the parameter studied when administered once, it increases bone marrow micronucleated cells and decreases CFU-S slightly after daily administration for 7 days. The individual constituent of the combination administered singly does not increase micronucleated cell number. Seven consecutive doses of HT + AET and same in combination with Se enhances micronucleated cells to a higher level. Daily injection of Se alone up to 7 days also causes an increase in micronucleated cells upto same level. CFU-S pool does not show any significant change in number of bone marrow cells through out the study except in the groups where animals were treated with Se.