Screening of six risk exons of the RET proto-oncogene in families with medullary thyroid carcinoma in the Czech Republic.

Medullary thyroid carcinoma (MTC) occurs as a sporadic form (75%) or as an autosomal dominant inherited familial disorder (25%) called familial MTC (FMTC) or as multiple endocrine neoplasia type 2 (MEN2) syndromes. Germ-line mutations in the rearranged during transfection (RET) proto-oncogene in exons 10, 11, 13, 14, 15 and 16 are known to be a cause of most of the familial forms. In this paper we report molecular genetic testing of 106 families with MTC (358 tested persons) from the Czech Republic in which we directly sequenced these six exons of the RET proto-oncogene.

[Ret proto-oncogene mutation found in the Czech population and its predictive value for offspring of patients with medullary carcinoma of the thyroid gland].

The authors completed a total of 23 pedigrees with the clinical diagnosis of medullary thyroid carcinoma (5 MEN 2A pedigrees, 11 FMTC pedigrees and 7 MTC pedigrees). Using the method of polymerase chain reaction (PCR), it was possible to define the rate of the most frequent mutations in exons 10, 11 and 16 of Ret-protooncogene present in the Czech population. The most frequent hereditary mutation found in MEN 2A and FMTC groups is substitution of thymine for cytosine in position 2095 of the transmembranous domain of the Ret-tyrosine kinase gene.

[The effect of gender on prevalence and survival in thyroid carcinoma].

Based on their own experience with a large group of patients with thyroid cancers, the authors confirm the higher prevalence of differentiated thyroid cancers both papillary and follicular (1 : 3,5) in females, while the differences in anaplastic and medullary cancers are much less prominent. Survival of females in univariate studies is much higher in both papillary and follicular cancers compared to males, in multivariate studies these differences lose their significance and only in papillary cancers under the age of 40 years at diagnosis and in a subgroup of papillofollicular cancers the differences retain their significance. The authors therefore deduce that differences found in univariate studies are significantly influenced by other factors such as age at the diagnosis and the spread of disease at the diagnosis.

[Changes in bone metabolism in girls with Turner's syndrome].

Background: Data of the prevalence of osteoporosis in girls with Turner's syndrome are not uniform, and its causes have not been fully elucidated. Information on the mineralization of osseous tissue is controversial. The objective of the present work was to examine some more recent indicators of bone metabolism in a group of girls with Turner's syndrome.

Osteocalcin in congenital adrenal hyperplasia.

Osteocalcin in the serum reflects bone turnover. It is known that prolonged therapy with glucocorticoids inhibits bone turnover. The aim of this study was to evaluate the osteocalcin level in children with congenital adrenal hyperplasia treated by glucocorticoids and mineralocorticoids and to assess the influence of 1,25(OH)2D3.

[Use of immunoreactive calcitonin and sonography in the diagnosis of medullary carcinoma of the thyroid gland].

In a group of 94 patients with a histologically verified medullary thyroid carcinoma were 59 patients with the sporadic form and 35 patients with the familial form. After radical surgery and subsequent actinotherapy in all patients the values of immunoreactive calcitonin were monitored along with the sonographic examination. In all with calcified thyroid residues confirmed on sonography, or when metastases were detected in the liver, elevated or high levels of immunoreactive calcitonin were found.

Chromosome sensitivity to bleomycin in patients with dominantly inherited and sporadic tumors.

G2 chromosomal sensitivity to bleomycin (30 micrograms/ml) was tested in PHA-stimulated lymphocytes of healthy subjects and in patients with familial and sporadic tumors. These were multiple endocrine neoplasias (MEN) types 1, 2A and 2B, familial medullar thyroid cancer, Recklinghausen neurofibromatosis type I, sporadic and hereditary malignant tumors, and a preleukemic disorder, the myelodysplastic syndrome. Control subjects were either young (15-20), middle-aged (28-49) or old (70-83 years).

[Multiple endocrine neoplasia type 2: familial variant of medullary carcinoma of the thyroid gland].

In addition to a brief characteristic of the syndrome of multiple endocrine neoplasia type 2 and medullary thyroid carcinoma with a familial incidence which is a prerequisite of the syndrome, the authors submit an account on a group of 53 patients who were on the authors' records during the past 12 years. During this period the disease is systematically searched for in the families of newly diagnosed patients by examining the immunoreactive calcitonin level of relatives. Familial variants account for 28% of all medullary thyroid carcinomas.

[Medullary carcinoma of the thyroid gland. Personal experience].

The authors present their experience with the diagnosis and treatment of medullary thyroid carcinoma (MTC) in a group of 175 patients in the records of the RI in Motol. From the above number 106 are alive, 69 of the patients who died were diagnosed at the time of the clinical manifestation of the disease, frequently an advanced stage of the disease. Of the living patients one third was treated by total thyroidectomy after active screening.

[Medullary carcinoma of the thyroid gland and the APUD system].

Medullary thyroid carcinoma, MTC, accounts for 8-10% of all thyroid malignancies. It occurs in the sporadic form (70-75%) and the familial variant (25-30%). In familial MTC the autosomal dominant type of heredity is involved.

[Determination of serum calcitonin using a non-commercial RIA method].

A radioimmunoanalytical determination of the immunoreactive calcitonine in the humen serum was worked out using the authors' own specific antiserum, the preparation and properties of which are reported in the present paper. The precision and reliability of the analytical procedure is within the usual limits (the intraserial variation coefficient was 8.6%, the calculated sensitivity was 6 pg/ml).

[Diagnostic significance of osteocalcin levels in the classification of senile osteoporosis].

The authors investigated the osteocalcin (BGP) serum level in 55 women with the senile type of osteoporosis. According to BGP values they divided the group into three sub-groups. Lower values were recorded in 27 subjects (50%), normal values comparable with a control group of 13 healthy women of equal age were recorded in 21 subjects (38%) and in a small sub-group of 7 women (12%) the BGP level was raised or high.

[Present experience with surgical treatment of medullary carcinoma of the thyroid gland].

Between June 1 1975 and Dec. 31 1989 at the surgical clinic for adults in Prague-Motol 44 patients were operated on account of medullary cancer of the thyroid gland (MCT). In the great majority total thyroidectomy (TTE) was performed which in this disease is an absolute indication.

Application of non-commercial methods for estimation of immunoreactive serum calcitonin in clinical practice (comparison of two methods).

The authors compared the results of two radioimmunological methods for the estimation of immunoreactive calcitonin in human serum. Parallel with the commercial RIA kit the estimation was made by the authors' own modification of this process with their own specific antiserum and radioligand prepared in the laboratory. The results in a large group of patients with medullary carcinoma of the thyroid gland (MCT) in different stages of the disease revealed that although the values obtained by the two methods differ, there is a statistically significant correlation between the values and the clinical evaluation is also comparable.

[Osteocalcin].

Osteocalcin, non-collagenous vitamin K dependent bone protein is as a biochemical indicator of osteoblastic activity and metabolic turnover in bone, valuable in the diagnosis of several diseases and in investigations of the dynamics of osseous changes (processes) during treatment of osteopathies. Elevated osteocalcin levels are normal in childhood and adolescence. In the diurnal rhythm the peak is recorded in the early hours.

[The effect of streptozotocin-induced diabetes treated with insulin on the metabolism of calcium, magnesium and phosphorus].

In a group of rats with streptozotocin induced diabetes the excretion of calcium, magnesium, phosphorus and creatinine in urine was investigated and the calcium, magnesium and phosphorus content of bone in relation to the duration of the disease. The authors observed that in diabetic rats the urinary losses of calcium, magnesium and phosphorus increase significantly. The creatinine excretion is also significant but lower in relation to calciuria and therefore the value of Nordin's index in diabetic rats rises markedly.

Plasma somatostatin activity in medullary cancer of the thyroid.

In a group consisting of 50 adults and 5 children with diagnosed or suspected medullary cancer of the thyroid, plasma somatostatin levels were measured in 77 samples with a sensitive radioimmunoassay. Only 2 patients had clearly enhanced plasma somatostatin immunoreactivity, both with highly active aggressive tumors. Other patients had plasma somatostatin levels of under 20 ng/l or undetectable ones.