Epidemiological studies in children of a low-endemic region, a high-endemic region, and dwellers of a leprosy colony: evaluation of anti-ND-BSA antibodies and lepromin response.

Children residing in a low-endemic region (LER), a high-endemic region (HER), and a leprosy colony contact population (CP) were evaluated for lepromin response as well as reactivity to the Mycobacterium leprae-specific synthetic antigen, ND-BSA. The mean reactivity to ND-BSA in the LER group (OD 0.03 +/- 0.03, N = 71) was significantly lower (p < 0.001) than that in the contact population (OD 0.14 +/- 0.09, N = 140) as well as the population residing in the HER (OD 0.09 +/- 0.08, N = 1340). ELISA-positive results were the highest (21.4%) with the CP group and lowest (0.0%) in the LER group, suggesting that it was a measure of the extent of exposure of M. leprae. In the contact population, females showed a preponderance for ELISA positivity over males (p < 0.005), a finding not observed with the HER population. The Mitsuda responses showed a Gaussian-type distribution in all of the three populations examined with the mean response being highest in the LER (6.0 mm +/- 2.9) and lowest in the HER (4.5 mm +/- 2.0) groups. The percent positivity for the Mitsuda reaction was found to be highest in the LER (93.0%) and lowest in the HER (88.3%) groups. The Mitsuda response thus appears to be independent of M. leprae exposure, and its interpretation in a given population needs consideration of several factors, such as nutritional, environmental, etc.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical utility of serum thyroglobulin in metastatic disease.

We examined the usefulness of serum thyroglobulin (Tg) levels in 196 patients with metastatic disease. Of these, 51 patients had a thyroidal primary (40 differentiated, 7 medullary and 4 undifferentiated), 35 patients had a nonthyroidal primary and in 110 patients the primary site was not known. Serum Tg was raised in 74.5 per cent (38 of 51) patients with carcinoma of the thyroid and in 92.5 per cent (37 of 40) patients with differentiated thyroid carcinoma (DTC). Twelve (34.3%) patients with proved nonthyroidal malignancies and 34 (30.9%) patients with unknown primary origin had elevated serum Tg levels. Of the 110 patients with unknown primary site thyroidal primary in 10 patients (all with elevated serum Tg levels) and nonthyroidal primary in 38 patients (7 had raised serum Tg levels) could be established. The sensitivity (for DTC) and the specificity (for nonthyroidal primary) of serum Tg estimation were 94.0 per cent (47 of 50) and 74.0 per cent (54 of 73) respectively and for patients with distant metastases were 100 (29 of 29) and 85.1 per cent (40 of 47) respectively. The positive and the negative predictive values of serum Tg were 71.2 (47 of 66) and 94.7 per cent (54 of 57) respectively and for patients with distant metastases were 80.6 (29 of 36) and 100 per cent (40 of 40) respectively. Our findings suggest that for patients presenting with metastases (particularly distant metastases) of an unknown primary site, serum Tg estimation is of great value to identify or rule out the involvement of the thyroid as the primary organ.

Significance of antithyroglobulin autoantibodies in differentiated thyroid carcinoma.

The incidence of antithyroglobulin autoantibodies (ATA) was 17.7% in 963 patients (who attended the clinic from 1981 to 1990) with differentiated thyroid carcinoma (DTC). Another 12 patients developed ATA for a transient period after the treatment with radioiodine. The prevalence of ATA in females (21.5%, 123/572) was significantly higher (p < 0.001) than that seen in males (12.0%, 47/391). Age-dependent occurrence of ATA was not seen for the various age decades. The ATA was more prevalent (p < 0.01) with the papillary type of tumor (118/564) as compared to the follicular variety (51/398). ATA did not influence the metastatic spread of the tumor at the initial presentation (105/170 for the ATA-positive group and 445/793 for the ATA-negative group). However, within the group with metastases, 82.9% (87/105) of patients had local spread into the neck in the presence of ATA, which was significantly higher (p < 0.01) than that seen for patients without ATA (63.8%, 284/445). For assessment of the influence of ATA on the outcome of the disease, the data from 222 patients (46 positive and 176 negative for ATA), with a minimum follow-up of 5 years (mean follow-up of 7.4 years), was considered suitable for analysis. The outcome of the disease was comparable in the presence and the absence of ATA (38/46 and 137/176 patients became disease-free in ATA-positive and -negative groups, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

TSH receptors in human thyroid tumours.

To evaluate the binding of human TSH (h-TSH) to various human thyroid tumours using radio receptor assay technique, 26 thyroid tumour specimens were examined. Five specimens did not show displacement by stable h-TSH. A wide variation was observed in B0, non specific binding, affinity and capacity of TSH in all the tumours examined. The Scatchard analysis of the binding of h-TSH to thyroid membranes suggested the presence of the receptors in 57.7 per cent (15 of 26, Ka much greater than 10(9)) and more than one component in 46 per cent (12 of 26) of the tumours studied. There was no consistent pattern of the binding of TSH for thyroid tissue with respect to its pathology. However, with 35 pairs of observations log affinity appeared to be linearly related to log capacity with a slope -0.95, intercept 9.96 and r value -0.93.

Monoclonal antibodies to human thyroglobulin: production and characterization.

Human thyroglobulin was used as an antigen for the development of monoclonal antibodies by the hybridoma technique. Spleen cells of BALB/c mice immunized with human thyroglobulin were fused with SP2/0 mouse myeloma cells. Seven clones secreting specific monoclonal antibodies to thyroglobulin were established. Two of these monoclonal antibodies have been purified and characterized. Their equilibrium association constants (Ka) as determined by Scatchard analysis were 0.24 X 10(11) L/M and 1.4 X 10(11) L/M respectively. The specificity of both these antibodies was validated by immunohistochemical staining of human tissues (normal human thyroid, brain, salivary gland, skeletal and smooth muscle, mucous membrane, parathyroid, adrenal) obtained from autopsy material. Only follicles and follicular cells of thyroid tissue were stained by both the monoclonal antibodies. H10 I monoclonal antibody was used for constructing a standard curve for in vitro immunoassay using a solid phase ELISA technique. The minimum amount detectable was 7.8 ng/ml. Thirty six sera from patients of various thyroid disorders were evaluated using ELISA and compared with conventional RIA. A good agreement was seen (r = 0.92) between the two techniques. These specific monoclonal antibodies may prove to be valuable for in vitro immunoassays and in vivo immunoscintigraphy.

Immunoreactive thyroglobulin-like material derived from saliva.

The presence of an immunoreactive thyroglobulin-like material in saliva from normal subjects and from 35 patients with thyroid carcinoma was detected by radioimmunoassay. The levels of this material in saliva were markedly elevated in patients with extensive metastases. Concentrated saliva samples from normal subjects and from patients with thyroid carcinoma were fractioned on Sepharose-6B and each fraction was assayed from thyroglobulin content by RIA. Several protein peaks of varying molecular size with thyroglublin-like immunoreactivity were observed. The physiological significance of these molecules in saliva remains to be established.

Serum thyroglobulin differentiated thyroid carcinoma: histological and metastatic classification.

Serum thyroglobulin (tg) levels were measured in 112 patients with proved differentiated thyroid carcinoma (6 pre-operative, 32 post-operative and 74 in whom thyroidectomy was followed by radioiodine treatment). The tg levels were within the normal range in patients who had a residual mass in the neck region after surgery and who were in remission. The patients with metastases showed a wide range (undetectable to microgram quantities) of tg in circulation. The analysis of serum tg with respect to histology showed that the follicular variety of carcinoma tends to show higher tg in serum than the papillary type. Metastatic involvement of bone was associated with much higher serum tg levels than other sites such as lung and lymph node. Thirteen patients with bone metastases of non-thyroidal primary origin had tg levels within the normal range. Serum tg estimation is useful in excluding thyroid as a primary site in patients with bone metastases of unknown primary origin.