A. Prodanova, P. Popivanov, M. Boyanov, M. Protich
 

The role of growth hormone (GH) in promoting linear bone growth throughout childhood and adolescence is a well established fact. However, in adults too GH maintains a broad spectrum of actions which are impaired in hypopituitary patients. Nowadays, growth hormone deficiency (GHD) in adults is recognized as a distinct nosological entity with effects on cardiovascular risk factors (hyperlipidemia, decreased fibrinolysis, increased atherosclerosis), abnormal bodycom-position (decreased lean body mass, increased body fat, reduced extracellular water), abnormal cardiac structure and function, reduced exercise performance, decreased bone mineral density due to bone formation reduction and increase in bone resorption.

As shown by the results of clinical trials in the early 90ies, GH replacement therapy has markedly expressed benefits in adults. According to the consensus guidelines for diagnosing and treating adults with GHD, formulated by the Growth Hormone Research Society (GRS), GHD in adults should be defined biochemically within the framework of an appropriate clinical context. Dynamic tests of GH secretion should be considered in patients presenting evidence of hypothalamic-pituitary disease, exposure to cranial irradiation and GHD onset in childhood.

All patients with documented severe GHD are eligible for GH replacement. The objective of treatment is to attain maximum benefit against the background of minimum side effects, necessitating individualization of the GH dose consistent with differences in responsiveness, and monitoring of the treatment efficacy using biochemical markers of GH action.
 

A.-M. Borisova
 

Menopause taken alone is by no means a disease, but rather a period during which preconditions are created promoting the development of a number of pathological changes. Parallel to the decline of estrogens and aging, postreceptor insulin response deterioration takes place along with further reduction of insulin secretion and hepatic insulin clearance. This is the mechanism of metabolic syndrome developmeat during menopause, including a number of conditions, such as: hyperinsulinemia, android obesity, arterial hypertension, lipid disorders (elevated total cholesterol, LDL cholesterol, TGL and decreased HDL cholesterol), elevated coagulation factors (fibrinogen, factor VII, plasminogen activator inhibitor) and homocysteine.

Hormone replacement therapy (HRT) contributes greatly to eliminate the aforementioned metabolic disturbances, with additional effects exerted on:

1. Cardiovascular svstem ­ as a vasodilator enhancing nitric oxide and prostacyclin production, decreasing endothelin 1 production and blocking Ca channels.

2. Brain ­ as a modulator of serotonin synthesis and release, promoting in turn the overcoming of depression. It is a well established fact that estrogens reduce beta-amiloid deposition in the senile plaques of brain, characteristic of Alzheimer’s disease.

3. Skeletal sistem ­ as a prophylaxis against and treatment of osteoporosis through bone resorption inhibition.
The positive changes in the metabolic syndrome, cardiovascular and CNS status and bone mineral density are elements of the quality of life throughout menopause, provided for by hormone replacement therapy.
 

K. Hristozov
 

Cell mediated immune reactions have an essential bearing on the pathogenesis of autoimmune thyroid diseases (ATD). CD4+T-cells obtained from thyroid infiltrates in ATD patients lead to transfer of thyroiditis into experimental animals. Mononuclear cells obtained from ATD patients are capable to secrete spontaneously thyroid antibodies. This are processes largely dependent upon T-cell cooperation. Intrathyroidal infiltrates consist mainly of T-cells with a CD4+ and CD8+ phenotype, with predominance of the respective type consistent with the pattern of ATD. In Hashimoto's thyroiditis patients the function of T-cells is characterized by a direct cytotoxicity mainly whereas in Graves' disease the T-cell zones are made up of CD4+ and CD8+ lymphocytes at a 2­3: l ratio. The functional characterization of mononuclear cells in such infiltrates reveals a reduced suppressor/inducer activity of T-cells which, along with the augmented number of activated B cells, is the most likely underlying couse of abnormal antibody production. Cytokines IL-2, TNF-a and INF-g give rise to hyperexpression of HLA class II molecules and adhesion molecules type ICAM-1 on the surface of thyrocytes. Adhesion molecules ICAM-1 and their ligand LFA-1 play a major role in T-cells interaction with thyrocytes, and are thereby considered as a likely cause of mononuclear infiltration of the thyroid gland.
 

T. Tzotzas, M. Bougoulia, H. Efthymiou, G. Koliakos, Th. Konstantinidis, A. Triantos, G. E. Krassas
 

Background and Aim: Nutrient substances like carbohydrates and fat may influence acutely leptin levels regardless of body weight variation. The aim of this study was to investigate possible changes in leptin levels after a fat load in obese and normal weight women in reproductive age.

Methods and Results: We performed an oral fat tolerance test meal (breakfast which included 40  g/sq.m. fat, 35­40 g carbohydrates, 60 g protein) in 17 obese women aged 33,5±4,9 years and 12 normal weight women aged 31,8±5,2 years. Basal serum lipid levels (total cholesterol, triglycerides and HDL), insulin and leptin, as well as levels of leptin and triglycerides were measured, at 2, 4 and 6 hours postprandially. The variations of leptin and triglycerides after the test were calculated from the areas under the curve (AUC) and from the difference from their baseline levels (D max). In both groups basal levels of triglycerides correlated inversely with basal leptin levels, and in normal weight women basal insulin concentrations correlated positively with basal leptin levels. No statistically significant changes were found in leptin levels during the test in both groups, while triglyceride concentrations were increased significantly at a maximum reached 4 hours after the fat meal.

Conclusions: Acute administration of a fat rich meal does not produce any significant change in leptin levels postprandially.
 

K. Hristozov, L. Koeva, S. Balev, Tz. Odjakova
 

The thyroid gland is an organ readily accessible to direct examination by fine-needle aspiration biopsy (FNAB), allowing for serial assessment of immune regulation disorders in Graves' disease (GD) and their response to treatment. Using flow-cytometric technique for immunophenotyping of surface markers, enabling simultaneous analysis of two surface antigens with the respective monoclonal antibodies, mononuclear cells from peripheral blood (PB) and intrathyroidal (IT) punctures are studied in twenty-six patients with GD in active stage of the disease and after discontinuation of thyrostatic treatment. IT lymphocytes are obtain through serial FNAB. In the group of untreated patients a statistically significant increase in the number of IT activated T cells, B cells and CD4/CD8 ratio, by comparison with lymphocytes in PB, is recorded. Thyrostatic treatment with Metizole results in normalization of the number of B lymphocytes, activated T lymphocytes along with T-helper/suppressor ratio reduction at the expense of an increase in T-suppressor/cytotoxic cells. Retrospective analysis of lymphocyte subsets in three patients with hyperthyroidism relapse one year after thyrostatic treatment suspension shows that there are no changes whatsoever in the levels of B lymphocytes, activated T lymphocytes and in the redistribution of CD4+ and CD8+ cells prior to and after treatment.
 

L. Dakovska, B. Lozanov, R. Kovatcheva, R. Ivanova, I. Atanassova, G. Kirilov, A. Michailova
 

Nowadays the organ-specific autoimmune pathogenesis of thyroid-associated ophtalmopathy (TAO) is unversally accepted but the choice of reliable diagnostic tests predicting the outcome of treatment in this contingent of patients is still disputable.
The study is designed to asses the predictive value of a constellation of clinical criteria and antibodies against eye muscle membrane in the course of glucocorticoid therapy in TAO patients.

Twenty patients (14 f, 6 m, aged 18­65 y) presenting TAO cl. 3­6 (clinical activity score; OI ­ 5­7) of which 14 with Graves' disease and 6 with Hashimoto's thyroiditis are covered by the study. Immunosuppressive therapy (methyl prednisolone i.v. 125 mg/24 h over 3 consecutive days followed by prednisolone 30­15 mg/24 h over 3 months) is applied. Clinical observations and laboratory testing (TSH, FT3, FT4, TgAb, TMAb and urinary glucosaminoglycans) are carried out at the beginning and at 30 and 90 days of treatment. Antibodies reactive with pig eye muscle membrane antigens (PEMM-Abs) are determined by SDS-PAGE and Western blotting according to Salvi's et al method as modified by the authors.
In 6/20 patients Abs reactive mainly with 64 kDa PEMM-antigen are detected. Proceeding from changes in PEMM-reactivity in the course of treatment (0 and 90 days) the patients are divided up into three groups ­ A, B and C. For subgroup A, PEMM-Abs (-) to (-), the decrease in mean OI amounts to 28,2%. For subgroup B, PEMM-Abs change from (+) to (-), the improvement is the most clearcut ­ with decrease in OI by 43,4%. Patients in subgroup C show the least decrease in OI (14%); PEMM-Abs reactivity in their sera persists by the 90th day and the patients are characterized by the highest mean age, greater number of thyroid disease relapses and previous history of corticosteroid therapy. A close interrelationship between shanges in PEMM-Abs and clinical characteristics (expressed as OI after summing up) for all three subgroups is observed.

As shown by the obtained results there is a good correlation between the clinical evaluation of ocular changes and PEMM-Abs as a parameter aptly mirroring the pathogenetic process.

The inference is reached that assessment of PEMM-Abs and their dynamic patterns, patient's age and TAO duration may be successfully used as reference points in predicting the effect of immunosuppressive therapy in TAO patients.
 

B. S. Lozanov
 

A wide spectrum of highly sensitive and specific diagnostic methods are currently available in thyroidology allowing for greater precision in assaying thyroid function, morphological patterns of the gland and involvement of immunogenetic factors, as well as dynamic study of the evolution of disorders with a special reference to the long-term prognosis of the treatment undertaking. The ultrasensitive methods for TSH assessment which have virtually replaced the in vivo functional tests for inhibition and stimulation, the TRH test inclusive, play a crucial role in diagnosing hyper-  and hypothyroidism. Practical implementation of the "Gammacoat two-steps" procedures and immunometric methods for FT3, FT4 and sTSH noticeably increase the sensitivity of assays, contributing in turn to make exact and prompt diagnosis of the subclinical and atypical forms of thyroid dysfunction.

The testing of humoral and cell-mediated thyroid autoimmunity by assaying TPO-Ab, TSH-R-Ab (TRAK), circulating eye-muscle antibodies and specific lymphoproliferative tests for T/B cells afford important information on the nature of pathological damage. Their study in dynamics throughout the treatment course has an essential practical bearing on evaluating the evolution of the process and eventual correction of therapy with a view to attain a long-term remission.

Doppler-ultrasonography, fine-needle biopsy with immunochemical cytodiagnostic procedures, 111Indii-Octreotide scan, hrTSH-stimulating test and the like broaden the scope of updated thyroid diagnostics.

Emphasis is laid on the necessity of strict comliance with the requirements for practical implementation of the tests in view of eliminating the influence of eventual additional or side phenomena. Interpretation of the obtained laboratory data should be comprehensive and consistent with the clinical picture, a basic rule in good medical practice.