Reviews
G. Kirilov, B. Lozanov
Clinical and Laboratory Strategy for Thyroid Status Assessment
A.Tomova, O. Koseva, Ph. Kumanov
Inhibin - the Predicted Hormone
M. Yaneva, S. Zacharieva
Ectopic and Abnormal Hormone Receptors in Adrenal Cushing's Syndrome 28
Z. Abadjieva, G. Kirilov, Ph. Kumanov
A Reliable Simple Method of Bioavailable Testosterone Assessment
S. Vladeva
Microelements and Diabetes Mellitus - Realities and Expectations

 Original Articles
Zh. Boneva, Vl. Christov
Reductil (Sibutramine Hydrochloride) Effect in Treating Obese Patients
 

Clinical and Laboratory Strategy for Thyroid Status Assessment
G. Kirilov, B. Lozanov
Clinical Center of Endocrinology and Gerontology
Medical University - Sofia

Abstract

Improvements in sensitivity and specificity of biochemical thyroid tests account for considerable progress in clinical strategies for diagnosing and treating thyroid disorders. This is a survey paper designed to present an updated overview of the potentials and shortcomings of the in vitro thyroid tests most commonly used in clinical practice. Regardless of recent methodological progress along this line, current thyroid tests still exhibit wide variability and a number of technical drawbacks physicians are not infrequently unaware of. It is a matter of problems relating to binding protein abnormalities affecting the results of FT4 tests, thyroglobulin autoantibodies interfering with serum Tg measurements, medication, or severe nonthyroid diseases giving rise to unexpected results of thyroid tests. It is recommended to maintain active laboratory/physician team-work with a view to ensure that quality and cost-effectiveness of the analyses would be practically implemented in a logical sequence for assaying the results at variance, and gaining better insight into existing incompatibilities. Discrepancies along this line should be interpreted with great caution against the background of close cooperation between laboratory and physicians.

KEY WORDS: thyroid tests, thyroid hormones, TSH, thyroglobulin, thyroid autoantibodies, calcitonin.
 

Inhibin - the Predicted Hormone
A.Tomova, O. Koseva, Ph. Kumanov
Clinical Center of ?ndocrinology and Gerontology
Medical University - Sofia

Abstract

This is a survey paper outlining the endocrine role of gonadal inhibin A and inhibin B in the human. McCullagh in 1932 reported that an aqueous testicular extract interferes with the formation of "castration cells" in the rat pituitary, and thus the existence of a nonsteroidal gonadal secretory product from testes was presumed for the first time. Inhibin is a glycoprotein hormone secreted by the Sertoli cells of testis, and the granulose and theca cells of ovary. It is made up of an a-subunit disulfide-linked to one of two b-subunits, the bA-subunit to form inhibin A or the bB-subunit to form inhibin B. Inhibin B controls FSH secretion through a negative feedback mechanism. In the adult inhibin B production depends both on FSH and spermatogenic status. Serum inhibin B levels exhibit clearcut positive correlation with testicular volume and sperm counts. Inhibin B and FSH jointly are a more sensitive and specific marker for spermatogenesis than either one alone. The role played by inhibin in female reproductive physiology has been explored, including determination of specific inhibin subunits in the ovary, as well as concentration of circulating inhibins across the menstrual cycle. According to updated concepts for inhibin physiology and pathophysiology in humans, inhibin B may serve as a marker of Sertoli cell function in infertile men, and as a prognostic indicator in women undergoing ovulation induction therapy.

KEY WORDS: inhibin, follicle-stimulating hormone, spermatogenesis, hypogonadism.
 

Ectopic and Abnormal Hormone Receptors in Adrenal Cushing's Syndrome
M. Yaneva, S. Zacharieva
Clinical Center of Endocrinology and Gerontology
Medical University - Sofia

Abstract

Cortisol secretion mechanisms in the so-called primary adrenal Cushing's syndrome where ACTH level is lowered are unknown, and so far presumed to be due to an "autonomous" secretion. Nowadays, in vitro and in vivo studies by a number of investigators are successful in demonstrating that part of cortisol- and other steroid-producing adrenal tumors or hyperplasias are controlled by ectopic and/or aberrant membrane hormone receptors. The latter include ectopic receptors for gastric inhibitory polypeptide (GIP), b-adrenergic agonists, LH/hCG and eutopic receptors with impaired activity, such as the ones for vasopressin, serotonin and probably leptin. Usually these ectopic/aberrant receptors are functionally coupled to G-proteins, thereby activatinge adenyl cyclase and steroidogenesis. The molecular mechanisms to which these processes are attributed are still not well enough clarified. Their understanding may eventually lead to new pharmacological therapeutic approaches as an alternative to adrenalectomy. Thus far, a long-term control of ectopic b-adrenoreceptors and LH/hCG-dependent Cushing's syndrome is achieved by propranolol and leuprolide acetate. Further researches along this line will most likely identify a greater diversity of abnormal receptors in adrenals and other endocrine and nonendocrine tissues. Elucidation of the molecular mechanisms underlying abnormal hormone receptors expression will probably contribute to gain better insight into the the regulation of tissue-specific expression of genes.

KEY WORDS: Cushing's syndrome, receptors, ectopy.
 

A Reliable Simple Method of Bioavailable Testosterone Assessment
Z. Abadjieva, G. Kirilov, Ph. Kumanov
Clinical Center of Endocrinology and Gerontology
Medical University - Sofia

Abstract

It is the purpose of this survey paper to gain better insight into free testosterone determination and evaluation methods. A fraction of total testosterone circulates in the plasma, specifically bound to the sex hormone-binding globulin (SHBG), another fraction is non-specifically bound to albumin, and merely a small amount is the biologically active free form accounting for exerting androgenous effect on target tissues. Accurate assessment of the latter has important practical implications on the clinical evaluation of androgenous status, and clarification of the clinical and laboratory incompatibilities, not infrequently noted when total testosterone is used. This is particularly valid for women with hirsutism and elder men. The updated procedures for free testosterone measurement through equilibrium dialysis (the most accurate method but difficult for practical implementation), the analogue-ligand method, and the free testosterone index are analyzed. Special attention is focused on the mathematical method for calculating bioavailable testosterone by the formula: FT = (T-N.FT) / [kt.(SHBG-T+N.FT)], where total testosterone and SHBG levels, determined by immunoassay, are emloyed. Free testosterone calculated by the suggested formula shows high correlation with the aforementioned methods, and what is more, it proves a reliable and precise indicator for androgenous status assay.

KEY WORDS: free testosterone, sex hormone-binding globulin (SHBG), hirsutism, androgenous status.
 

Microelements and Diabetes Mellitus - Realities and Expectations
S. Vladeva
Clinic of Endocrinology
Higer Medical Institute - Plovdiv

Abstract

Over the past few years, a number of experimental and clinical studies contribute greatly to gain better insight into the effect exerted by microelements on the human organism. As shown by the results, they have an essential practical bearing on a number of biochemical processes. Special emphasis is laid on assaying their relationship with cancerigenesis, oxidative stress, diabetes mellitus and cardiovascular diseases.
In the present review microelements particularly closely related to the pathogenesis of diabetes mellitus and development of diabetic complications are discussed, namely zinc, chromium, manganese, vanadium and selenium. The assumption is warranted that their simultaneous participation in antioxidant protection of the organism has important implications on the therapeutic outlooks of this condition.

KEY WORDS: diabetes mellitus, microelements, antioxidants.
 

Reductil (Sibutramine Hydrochloride) Effect in Treating Obese Patients
Zh. Boneva, Vl. Christov*
Department of Endocrinology, Hospital of the Ministry of Internal Affairs - Sofia
* Clinic of Endocrinology, Alexandrov's Hospital - Sofia

Abstract

Effective treatment of obesity may reduce substantially the risk of overweight comorbidities, and accordingly result in mortality rate decrease. Sibutramine hydrochloride (Reductil) is a serotonin (5-HT) and noradrenalin (NA) reuptake inhibitor (SNRI). It conditions dose-dependent weight loss among obese patients by a dual mechanism of action: food intake reduction and energy expenditure increase.
The aim of the present study is to assay Reductil effect in treating obese patients indicated for pharmacotherapy.
Patients and methods: 35 patients with overweight and obesity are covered by a prospective 12-week open study. The patients are given Reductil at 15 mg daily dose, and distributed into 3 groups, as follows:
I group - patients with BMI ?30 kg/m2 free of concomitant diseases;
II group - patients with BMI ?27 kg/m2 with glucose tolerance (IGT) impairment;
III group - patients with BMI ?27 kg/m2  with diabetes mellitus type 2.
Results: At the end of the first and third month, the average body weight decrease is 4,22±2,2 kg and 9,46±4,2 kg, respectively (P<0,00001). 88,57% of the patients lose more than 5% of baseline body weight and 40% - more than 10% (P<0,00001). BMI decreases significantly from 36,33±6,82 to 33,09±5,91 (P<0,0000001). As shown by bioimpendance study body weight reduction occurs mainly at the expense of fat mass. The latter decreases significantly from 44,02±15,5 to 36,66±14,3 kg (P<0,00001). Also there is statistically significant decrease in waist circumference, OGTT, HbA1c and lipid parameters. No significant side effects are recorded.
Conclusion: Sibutramine (Reductil) is ? drug yielding optimal effect in obesity treatment, especially in patients presenting metabolic syndrome.

KEY WORDS: obesity, fat mass, metabolic syndrome, Sibutramine hydrochloride.