Search

The high incidence of childhood thyroid cancer in Belarus is suspected to be due to radiation exposure after the Chernobyl reactor accident. To clarify the clinical and histological characteristics of childhood thyroid cancer in Belarus, we therefore compared these patients to a radiation non-exposed control series in Japan. In Belarus, 26 thyroid cancers in subjects aged 15 or younger were diagnosed among 25,000 screened between 1991 and 1995 by Chernobyl-Sasakawa Health and Medical Cooperation Project. The clinical and morphologic features of these 26 cases were compared to 37 childhood thyroid cancers in Japan diagnosed between 1962 and 1995. The age distribution at operation in Belarus showed a peak at 10 years old, with a subsequent fall in numbers. In contrast, the age distribution at operation in Japan showed a smooth increase between the ages of 8 and 14. The mean tumor diameter was smaller in Belarus than that in Japan (1.4 +/- 0.7 vs. 4.1 +/- 1.7 cm, P < 0.001). The sex ratio, regional lymph node metastasis, extension to surrounding tissues or lung metastasis did not differ significantly. Histologically, all cases in Belarus were papillary and in Japan 33 cases were papillary and 4 cases were follicular carcinomas. Among papillary carcinomas, the frequency of a solid growth pattern, a criteria for classifying a tumor as poorly differentiated, was higher in Belarus than that in Japan (61.5 vs. 18.2%, P < 0.001). The difference between the features of childhood thyroid cancer in Japan and Belarus may be due to the difference in the process of carcinogenesis, but more direct evidence and further analysis by molecular epidemiology are needed in Belarussian cases.

Preoperative therapy with octreotide, a long-acting somatostatin analog, suppresses GH hypersecretion, shrinks GH-producing tumors and leads to an improvement in subsequent surgical remission in acromegalic patients. A continuous infusion of octreotide has demonstrated more persistent suppression of GH secretion than intermittent injections, and only a few studies were reported on the effect of the tumor shrinkage with a continuous infusion of a small dose of octreotide. We therefore investigated the preoperative effects of small doses of octreotide (120-240 micrograms/day) administered continuously (with a subcutaneous infusion pump) over a short period (2 or 4 weeks) in nine untreated acromegalic patients. Octreotide therapy resulted in suppression of serum GH and IGF-1 concentrations in 8 out of 9 patients and reduction in pituitary tumor size measured by MRI in all patients (by 7.9 to 38.5%). In particular, considerable reduction in tumor size (more than 20%) occurred in 6 of 9 patients. In three patients assessed serially throughout the preoperative period, reduction in tumor size was noted within only one week after the start of octreotide therapy and reduction rate more than 20% was obtained within the first two weeks. In one patient, suprasellar tumor expansion totally disappeared after such therapy. Our results indicate that short-term continuous subcutaneous infusion of a small dose of octreotide results in not only inhibition of GH hypersecretion but also shrinkage of tumor size prior to surgery.

A 40-year-old woman with adrenal insufficiency was clinically diagnosed and examined with human corticotropin releasing hormone (CRH). This patient with secondary hypo-adrenalism has shown a normal serum cortisol response to exogenous ACTH administration and has been examined with CRH, lysine-vasopressin (LVP) and insulin tolerance test (ITT), respectively. Success in secreting ACTH in response to both CRH and LVP tests, but not ITT, suggests that this disorder was possibly due to a hypothalamic CRH deficiency rather than pituitary corticotroph dysfunction. A combination of the CRH test and ITT has come to play an increasingly significant role in the diagnosis and differential diagnosis of isolated ACTH deficiency syndrome.

The RET proto-oncogene is expressed in human medullary thyroid carcinoma and pheochromocytoma. Recently germline mutations of the RET proto-oncogene were reported in four syndromes (MEN 2A, MEN 2B, familial medullary thyroid carcinoma and Hirschprung's disease) and somatic mutation was also found in sporadic medullary thyroid carcinoma. To determine the incidence of RET mutations in medullary thyroid carcinoma in Japan, we investigated 14 medullary thyroid carcinomas (comprising 1 case of MEN 2A, 1 case of MEN 2B, 2 cases of familial medullary thyroid carcinoma and 10 cases of sporadic). Tumors from all cases were screened by PCR-SSCP on exons 10 and 11. DNA sequencing on these exons was performed for the hereditary medullary thyroid carcinoma cases. The PCR products of exon 16 from tumor DNA were analyzed by means of Fok1 restriction enzyme digestion analysis and mutations confirmed by DNA sequencing. We found no structural abnormalities in either exon 10 or exon 11 in any of the cases examined, but in four of 10 sporadic cases we detected a common point mutation at codon 918 (ATG to ACG) in exon 16, where methionine was replaced with threonine. Our results support the theory that a point mutation of exon 16 of the RET proto-oncogene may be related to the oncogenesis of sporadic medullary thyroid carcinomas. However, further studies on the entire RET proto-oncogene are needed to clarify the relationship between its expression and thyroid tumorigenesis.

This study is an endemic goiter survey of 3476 school children in 13 Local Government Councils (LGCs) and 1004 subjects in a whole community of one LGC, Plateau State, Northern Nigeria, to determine the prevalence of goiter as well as to identify some of the etiological agents involved. Results of the survey showed that the disease is highly endemic in the area with prevalence varying in places from 1 to 23% of these subjects. Females showed a markedly higher prevalence of goiter. Analysis of 729 urine samples indicated that iodine excretion ranged from 3.5 to 1.3 microgram/dl (32-154 microgram/g creatinine) and was similar to that in iodine deficient areas in the world, but no relation was observed between the prevalence of goiter and urinary iodine. Urinary thiocyanate levels were less than 0.5 mg/dl, suggesting that the role of the thiocyanate as a goitrogen is not important in the region. Thyroid hormone parameters in village subjects with goiter were similar to those in goiter endemia except serum thyroxine (T4). An interesting result found in village subjects was very high serum thyroxine binding globulin, which leads to an increase in serum T4. This study indicated that Northern Nigeria is an area of endemic goiter. Although some areas in Plateau State are iodine deficient zones, we could not conclude that the etiology of endemic goiter in this area is associated with iodine deficiency. There may be an interplay of multiple factors of etiological importance.

In the present studies, the long term effects of IFN alpha on thyroid function and thyroid autoantibodies were evaluated in 42 patients with chronic viral hepatitis type C treated with IFN alpha for at least 4 months. Before IFN treatment, 41 patients tested were all euthyroid. Five (12%) out of 24 patients tested had positive tests for thyroid autoantibodies. MCHA/TPOAb was detected in all 5 and TGHA/TGAb in 3 out of these 5 patients. Six to 10 x 10(6) units (U) of recombinant or natural IFN alpha were given intramuscularly daily for the first 2 to 4 weeks, followed by 3 to 10 x 10(6) U thrice weekly for the subsequent 14 to 22 weeks. Thyroid dysfunction and/or rises in titers of thyroid autoantibodies were observed in 6 patients during IFN alpha treatment; clinically overt thyroid dysfunctions, destructive thyroiditis and thyrotoxicosis of unidentified etiology, developed in 2 patients 4 to 5 months after start of IFN treatment, subclinical hypothyroidism with a slight increase in serum TSH concentrations but no serum thyroid hormone alternations was observed in 2 patients, and increases in titers of thyroid autoantibodies without thyroid dysfunction were found in 2 patients. Thus, IFN alpha exacerbated thyroid autoimmunity exclusively in all patients with positive tests for thyroid autoantibodies prior to treatment, but did not induce thyroid autoimmunity in thyroid autoantibody-negative patients. These data suggest that the prolonged IFN alpha therapy can lead to exacerbation of thyroid autoimmunity in susceptible (thyroid autoantibody-positive) patients.

The topic "Thyroid and Radiation" is both an old and a new area to be solved by human beings. The thyroid is an organ that is usually susceptible to exposure to ionizing radiation, both by virtue of its ability to concentrate radioiodine (internal radiation) and by routine medical examination: Chest X-ray, Dental X-ray, X-irradiation of cervical lymphnodes etc. (external radiation). Iodine-131 is widely used for the therapy of Graves' disease and thyroid cancers, of which the disadvantage is radiation-induced hypothyroidism but not complications of thyroid tumor. The thyroid gland is comparatively radioresistant, however, the data obtained from Hiroshima, Nagasaki and Marshall islands indicates a high incidence of external radiation-induced thyroid tumors as well as hypothyroidism. The different biological effects of internal and external radiation remains to be further clarified. Interestingly, recent reports demonstrate the increased number of thyroid cancer in children around Chernobyl in Belarus. In this review, we would like to introduce the effect of radiation on the thyroid gland at the molecular, cellular and tissue levels. Furthermore the clinical usefulness of iodine-131, including the safety-control for radiation exposure will be discussed.

The molecular cloning of the thyrotropin (TSH) receptor cDNA has led to advances in understanding the structure and function of the molecule and the pathogenesis of autoimmune thyroid disease. The recombinant TSH receptors expressed on mammalian cells are now available for TSAb and TBIAb assays. TBI assay in this system is much more sensitive than the conventional method. The binding sites for TSH and TSAb/TBIAb have been studied with epitope library, synthetic peptides, anti-peptide sera and mutagenesis. Some of these data, however, are confusing and undefined. The binding sites for TSH and TSAb/TBIAb are very likely to span the entire region of the extracellular domain of the TSH receptor with discontinuous contact points, and seem to be different from each other on N-terminal half, but similar on C-terminal half, of the extracellular domain of the receptor. However, the determination of the precise amino acids involved may be very difficult without monoclonal anti-TSH receptor antibodies.

We report here on a patient who was unilaterally adrenalectomized for Cushing's syndrome, and who developed antibodies to 1-24 ACTH. A 49-year-old nurse had undergone right adrenalectomy for adrenal adenoma. After surgery, she was treated with 0.5 mg of 1-24 ACTH-Z together with glucocorticoid replacement therapy for 40 days. Thereafter she was given 0.25-0.5 mg of ACTH-Z every other day for 4 months. ACTH-Z was then stopped for a year but glucocorticoid therapy was continued. About one year prior to this admission, 1 mg of ACTH-Z was again initiated 1 to 2 times a week. Glucocorticoid therapy was not withdrawn during the four years after adrenalectomy. She was admitted for the purpose of withdrawal of glucocorticoids. Her serum was found to bind labeled ACTH. This labeled ACTH was competitively displaced from binding by unlabeled hormones. Finally, reaction with specific antihuman Ig demonstrated an antibody of the IgG class. The titer of the antibodies gradually decreased after the discontinuation of ACTH-Z, but it is still present in measurable quantity in her serum. The clinical significance of the circulating anti-ACTH antibody in her serum is discussed.

Unlabelled: Despite the fact that subacute thyroiditis (SAT) is a common disease, its pathogenesis is still uncertain. At present, viral infection is simply thought to be a possible pathogenic factor. In Caucasians and Chinese, however, a strong association has recently been found between HLA-Bw35 and SAT. Therefore, genetic factors are also thought to participate in the onset of SAT. In this study we have further attempted to clarify the pathogenesis of this disease in this regard., Protocol: HLA typing for A, B and C loci (class I antigens) was performed on 89 patients with SAT (males: 7, females: 82) aged from 23 to 66 years, and DR and MT loci (class II antigens) were investigated in 55 patients. In 12 patients, viral antibody titers were measured as soon as possible after onset and two weeks later. The viral antibodies evaluated were those of Influenza A and B, Coxsackie A9, B1, B2, B3, B4, B5 and B6, Echo 3, 7, 11 and 12, Parainfluenza 1, 2, 3 and 4, and Adeno 8 virus. The following results were obtained: In class I HLA typing, the frequency of HLA-Bw35 in SAT was 67.4%, which was significantly (p less than 0.0001) higher than that in the control (14.1%). On the other hand, the frequency of Cw1 in SAT (14.6%) was significantly (p less than 0.01) lower than that of the control (32.1%), and that of Cw3 (65.2%) was significantly (p less than 0.01) higher than that of the control (46.5%). In class II HLA typing, the frequency of DRw8 in SAT was 38.2%, which was significantly (p less than 0.05) higher than that of the control (21.9%). Other antigens showed no significant changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Testosterone secreted from the testis is converted to dihydrotestosterone (DHT) in target tissues by 5 alpha-reductase and DHT exerts its action on the nucleus. Since skin is one of the target tissues of androgen we established a system for culturing human skin fibroblasts, and we investigated the conversion of testosterone to DHT in genital and nongenital skin fibroblasts obtained from males as well as from females. In our system, fibroblasts were incubated with 0.1 microM 1, 2-3H testosterone, and labeled metabolites were separated by thin layer chromatography. DHT formation was linear for 6 hours and the rate of DHT formation correlated with the growth phase of the fibroblasts. In the course of serial subculture, DHT formation did not change between the 3rd and 10th subculture in four cell strains. DHT formation in nongenital skin fibroblasts did not differ significantly between males and females. Fibroblasts obtained from male genital skin produced significantly greater amounts of DHT than those from male or female nongenital skin. Furthermore, DHT formation in genital skin fibroblasts did not differ between normal males and hypogonadal males. These data suggest that genital skin is the target tissue where testosterone strongly converts to DHT and the difference of male secondary sexual characteristic appearance between males and females may not depend on the sensitivity of the target tissues to androgen but on the secretion rate of androgen.

It is generally believed that in the long-term observation of chronic thyroiditis, the goiter decreases in size with thyroid hormone therapy and the thyroid function drops gradually. On the other hand, the histological changes in so-called Hashimoto's thyroiditis have been recognized to show progressive loss of epithelium and increased fibrosis. In this study, goiter size, thyroid function, thyroid microsomal and thyroglobulin antibodies and histology in needle biopsy were investigated in 75 patients with chronic thyroiditis during an interval of more than ten years. Among 75 cases, 8 (11%) were hypothyroid at the first medical examination. Among 21 cases who received no treatment, 7 (33%) became hypothyroid during the period of more than ten years. Among 54 cases with thyroid hormone therapy, 16 (30%) showed a remarkable reduction in size of goiter, but among 21 cases without thyroid hormone therapy only 3 (14%) showed a remarkable reduction. This paper discusses changes in titers of thyroidal antibodies in 47 cases. Among these 47 cases, 21 increased titer of thyroglobulin antibody during the period of more than ten years. 10 (48%) out of these 21 cases showed a remarkable reduction in size of goiter. But among 11 cases with a decrease of titer of thyroglobulin antibody, only one (9%) showed a remarkable reduction in size of goiter. On the other hand, titer of thyroid microsomal antibody increased in 33 cases. 9 (27%) out of these 33 cases showed a remarkable reduction in size of goiter. Only one (13%) of 8 cases, which decreased titer of thyroid microsomal antibody, showed a remarkable reduction in size of goiter.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-protein bound testosterone is considered to represent an active androgen in blood, and it reflects in androgenicity. We measured the dializable free testosterone (AFT) in various disorders. The values of plasma testosterone (T), fractional free testosterone (%FT) and AFT were 560 +/- 151 (mean +/- SD) ng/dl 1.9 +/- 0.4% and 10.7 +/- 3.3 ng/dl in normal males (n = 43, aged 25-58), 51 +/- 12 ng/dl, 1.2 +/- 0.3% and 0.6 +/- 0.2 ng/dl in normal females (n = 30, aged 21-41), and 63 +/- 26 ng/dl, 0.6 +/- 0.3% and 0.4 +/- 0.2 ng/dl in pregnancy (n = 20, second and third trimester), respectively. Those values in normal females and pregnancy were significantly lower than those in normal males (p less than 0.001). In male, the concentrations of T and AFT in patients with primary (n = 43, aged 18-50) and secondary hypogonadism (n = 16, aged 22-66) were significantly decreased (p less than 0.001 vs normal males), respectively. The plasma concentration of total testosterone (T) was increased 1032 +/- 269 ng/dl in chronic hepatitis (p less than 0.001) (n = 21, aged 28-52) and 1455 +/- 366 ng/dl in hyperthyroidism (p less than 0.001) (n = 44, aged, 18-52). However, %FT in those disorders was significantly decreased 1.2 +/- 0.3% in chronic hepatitis (p less than 0.001) and 0.8 +/- 0.3% in hyperthyroidism (p less than 0.001), and plasma levels of AFT in both disorders were not different as compared with that in normal males.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to evaluate the validity of the direct radioimmunoassay of plasma cAMP level by using Yamasa cyclic AMP assay kit, we determined the cyclic AMP concentration of normal human plasma before and after purification through anion-exchange chromatography. We found that 1) the direct assay before purification gave almost the same values as the indirect assay after purification by anion-exchange chromatography, 2) hemolysis did not affect the results of the direct assay, 3) the plasma cAMP was stable for up to 12 weeks when 5 mM EDTA was added to the blood at the time of sampling and stored below -20 degrees C and 4) the cAMP concentration did not decrease by repeated freeze-thawing of the plasma samples for up to 10 times. These results indicate that the direct radioimmunoassay of plasma cAMP concentration in normal subjects can give the same values as those obtained after purification by anion-exchange chromatography. Although further investigation is needed to clarify whether these results can be equally applied to patient's plasma with various diseases, the direct assay offers a convenient and accurate method to determine plasma cAMP concentration.

Blood-free testosterone indices were measured among 28 normal men (age; 24-48 yrs.), 20 normal women (20-36 yrs.), 18 pregnant women (22-31 yrs.), 17 males with hypogonadism (23-56 yrs.), 17 males with chronic hepatitis (20-42 yrs.), 24 males with liver cirrhosis (29-68 yrs.), 34 males with hyperthyroidism (20-42 yrs.) and 7 hirsute women (18-31 yrs.), and these were compared with the plasma concentrations of free testosterone. The testosterone index was obtained by multiplying the plasma concentration of testosterone by the percent of sex hormone-binding globulin (SHBG), non-bound testosterone precipitated by dextran-coated charcoal. A significant increase of plasma testosterone was observed in patients with chronic hepatitis (p less than 0.001) and hyperthyroidism (p less than 0.001) as compared with normal men and was also observed in pregnant (p less than 0.01) and hirsute women (p less than 0.01) as compared with normal women. The close negative correlation between plasma levels of testosterone and the percent of SHBG non-bound testosterone (r = -0.87, n = 79, p less than 0.001) was observed among normal men, male patients with chronic hepatitis and hyperthyroidism. The sex hormone binding capacity was increased from two to three fold in patients with chronic hepatitis and hyperthyroidism. The patients with compensated liver cirrhosis had increased plasma testosterone and a decreased percent of SHBG non-bound testosterone, and those with decompensated liver cirrhosis had decreased plasma testosterone and a normal percent of SHBG non-bound testosterone. The plasma concentration of free testosterone was normal in patients with chronic hepatitis and hyperthyroidism. It decreased in pregnancy (p less than 0.01) and increased in hirsute women (p less than 0.01). The blood free testosterone index was slightly high in one third of the patients with chronic hepatitis and hyperthyroidism as compared with that in normal men. However, a close correlation of the percent of SHBG non-bound testosterone and fractional free testosterone (%) measured by equilibrium dialysis (gamma = 0.82, p less than 0.001) was obtained in all subjects (n = 170). These data suggest that the blood free testosterone index parallels the plasma concentration of free testosterone and is useful to evaluate the status of androgenicity.

Changes in serum TSH, T4 and T3 concentrations after complete thyroidectomy were observed for 4 weeks in 9 euthyroid patients with thyroid carcinoma. Completeness of the thyroidectomy was confirmed by a 131 I scintigram performed one or two months after the operation. Serum TSH levels rose progressively during the 4 weeks of observation, and a significant increase was noticed as early as 3 days after the thyroidectomy. Serum T4 and T3 concentrations decreased significantly 3 days and 18 hrs, respectively, after the thyroidectomy. A sharp decrease in serum T3 concentrations within 18 hrs without a significant change in serum T4 levels and possibly without a significant change in the amount of T3 derived from T4 suggests that the amount of T3 secreted from the thyroid is large enough to affect serum T3 concentrations. The rate of decrease of serum T4 (t 1/2: 16 days) or serum T3 (t 1/2: 23 days) after the 3rd day of the thyroidectomy was much slower than the rate of disappearance of labeled T4 or T3 reported previously. The slow decrease rate of serum T3 is probably due to the conversion of T4 to T3 in peripheral tissues, and that of serum T4 may be due to either the decrease in T4 disposal rate in hypothyroidism or due to the release of T4 from peripheral tissues to serum.