Reviews
M. Yaneva
Differential Diagnosis between Cushing's Disease and Pseudo-Cushing States. Desmopressin Test  4
M. Nikolov, V. Christov
A Method for Assessment of Long-term Control of Diabetes Mellitus by Means
of an Intensively Blue Colour ed Derivative of the Boronic Acid 12

 Original Articles
Shin-Ichi Noguchi, Ichiro Iwamoto, Shoichiro Kosha,Toshinori Fujino, Yukihiro Nagata
The Effects of Testosterone and Aromatase Inhibitor on Bone: Action Mechanisms of Androgens  17
V. Iotova, V. Madjova, V. Tzaneva
Does Size at Birth Influence the Development of Microalbuminuria in Young Patients
with Type 1 Diabetes Mellitus 23
A. Kurtev, D. Fisher, J. Nelson, E. Iliev
Estimation of the Thyroid, Pancreatic b-cells and Adrenal Functions and Organ-Specific
Autoimmunity in Children and Adolescents with Alopecia Areata 30
A. Kurtev,  D. Fisher, J. Nelson, A. D?urmishev
Vititligo in Childhood and Adolescence and Autoimmune Endocrine Diseases -
Accidental Combination or Regularity? 36

New Items  43
New Monographs  44
Instructions to Authors  45
 
 

Differential Diagnosis between Cushing's Disease and Pseudo-Cushing States. Desmopressin Test
M. Yaneva
Clinical Center of Endocrinology and Gerontology
Medical University - Sofia

Abstract

Pseudo-Cushing (PC) states affect patients with severe affective and eating disorders, alcoholism and alcohol-withdrawal syndrome, severe central obesity, poorly controlled noninsulin-dependent diabetes mellitus and stress. Patients with PC states are characterized by all or at least some of the clinical features of Cushing's disease (CD) itself, and demonstrate hypercortisolism. A summarized hormonal profile of PC patients includes increased cortisol production, increased basal level of plasma cortisol with abnormal circadian rhythm; elevated cortisol excretion in the urine and altered Dexamethasone suppressibility. The hormonal cha-racteristics of CD are quite similar. For this reason precise methods for differentiation of these two diseases have been elaborated. It is generally accepted that the PC state has resulted from the functional activation of the pituitary-adrenal axis, caused by the corticotropin releasing hormone (CRH). The Desmopressin (DDAVP) test is based on the stimulation of ACTH release by the vasopressin analogue in patients with CD, but not in the majority of normal, obese and patients with PC states. The i.v. administration of 10 mg DDAVP provokes a marked ACTH rise in CD; a small, but significant ACTH rise in normal and obese subjects and no reaction in patients with PC state. The cortisol reaction during DDAVP administration is similar, though few differences exist. There is a marked cortisol elevation in CD patients, while those with PC, obese and healthy people do not respond. The mechanisms of these reactions remain still largely unknown. In conclusion, the Desmopressin test may be a useful tool for the differentiation of mild CD from PC states.

KEY WORDS: pseudo-Cushing state, Cushing's disease, Desmopressin, test
 
 

A Method for Assessment of Long-term Control of Diabetes Mellitus by Means
of an Intensively Blue Coloured
Derivative of the Boronic Acid
M. Nikolov, V. Christov*
Medical University - Sofia
Preclinical University Center, Department of Chemistry and Biochemistry
*Department of Internal Diseases, Clinic of Endocrinology

Abstract

The glycohaemoglobin with its structure, kinetics of formation and degradation is an objective marker of the long-term glycaemia in the patients with diabetes mellitus. Its level reflects the mean glycaemia over the previous six to eight weeks. Trough regular determinations of the glycoHb by means of reliable laboratory methods is possible to correct on time and it eliminate the metabolic disorders and so to prevent the severe late complications of diabetes.
The affinity chromatography method with its positive aspects - determination of stable ketoamines only, a weak influence of changes of the pH of the buffer and temperature, lack of interference of HbF is considered in details in the present review. Xylene cyanol-diaminopropanol-carboxyphenyl-boronic acid is synthezed in the Norway branch of the Axis-Shield Group. This blue conjugate of the boronic acid binds specifically the cis-diols of the glycoHb making them coloured, while the rest of Hb remains unchanged. The percentage of the HbA1c can be determined reflectometrically by means of a small and light portable apparatus NicoCard Reader. This method called NicoCard HbA1c is based on an affinity binding and evaluation of the glycoHb by reflectometer. This method is not a chromatographic one but nevertheless it has all positive features of the affinity chromatography. The test is rapid - within three minutes, utilizes 5 ml whole blood and can be done at the patient's bed. It is relatively cheap and is now accessible in Bulgaria.

KEY WORDS: glycohaemoglobin, affinity binding, reflectometric determination, long-term control of diabetes.
 

The Effects of Testosterone and Aromatase Inhibitor on Bone: Action Mechanisms of Androgens
Shin-Ichi Noguchi, Ichiro Iwamoto, Shoichiro Kosha,
Toshinori Fujino*, Yukihiro Nagata
Faculty of Medicine, Kagoshima University - Kagoshima, Japan
Department of Obstetrics and Gynecology
*School of Health Sciences

Abstract

Objective: To investigate the mechanisms of the effects of androgens on bone.
Methods: The effect of testosterone with or without an androgen receptor blockade, flutamide on proliferation and production of bone metabolic markers in a human osteoblastic cell line, Saos-2 cells was investigated. The effect of an aromatase inhibitor, fadrozol hydrochloride, together with testosterone on bone mineral density (BMD) in castrated rats was also examined.
Results: Testosterone treatment enhanced the proliferation of Saos-2 cells and increased the production of osteocalcin (Gla-OC) and TGF-b in the cells (p<0,05).  These effects were inhibited by the androgen receptor blockade. The aromatase inhibitor together with testosterone decreased BMD in castrated male rats.
Conclusions: Testosterone exerts its protective effects on bone through enhancing the proliferation and production of Gla-OC and TGF-b in osteoblasts at least partly by binding to androgen receptor. Besides, androgens may also have a bone-protective effect by being converted to estrogens.

KEY WORDS: androgens, testosterone, human osteoblast-like cell line, aromatase inhibitor, rats.
 

Does Size at Birth Influence the Development of Microalbuminuria in Young Patients
with Type 1 Diabetes Mellitus
V. Iotova, V. Madjova*, V. Tzaneva
Medical University - Varna
Department  of  Paediatrics and Medical Genetics
*Department of  General Medicine

Abstract

The good metabolic control is mandatory for the diabetic nephropathy (DN) prevention. Nevertheless, there are well controled cases, in whom DN develops relatively early. On the other hand, the impaired intrauterine development has been recently suggested as a risk factor for a number of adult diseases manifesting yet earlier. The aim of the present work is to compare the size at birth of adolescents with type 1 diabetes mellitus (DM), positive for micrroalbuminuria (+MAU) and negative for MAU (-MAU) in an attempt to evaluate their role in the development of initial DN. 25 females and 22 males with type 1 DM and +MAU, mean age 20,9±2,6 years, mean diabetes duration 13,6±2,9 years and diabetes duration prior to MAU - 8,35±3,3 years were studied. The results are compared to a group of 24 females and 19 males without MAU, aged 19,4±3,4 years, with diabetes duration 12,9±3,8 years. The +MAU males were born lighter than the controls - 3348±470 g vs. 3792±430 g (?<0,02), as were +MAU females - 3335±558 g vs. 3870±332 g (?<0,01). The boys were also shorter at birth - 51,2±1,8 cm vs. 52,4±1,2 cm (?<0,05). The +MAU girls gained more weight till the end of their first year - 8805±875 vs. 7140±786 g (?=0,01), as did +MAU boys - 8666±1125 vs. 7348±1050 g (?<0,01). As a whole, 66,7% of the born lighter than ­2 SD developed MAU against 22,2% of the born heavier than +2 SD. The results suggest the possible role of the impaired intrauterine development of the kidneys as a precipitating factor for the early start of nephropathy in young people with diabetes.

KEY WORDS: type 1 diabetes mellitus, initial diabetic nephropathy, size at birth.

Estimation of Thyroid, Pancreatic
b-cells and Adrenal Functions
and Organ-S pecific Autoimmunity in Children
and Adolescents with Alopecia Areata
A. Kurtev, D. Fisher*, J. Nelson*, E. Iliev**
Clinic of Pediatric Endocrinology, Chair of Pediatrics,
University Pediatric Hospital - Sofia
*Nichols Institute, Quest Diagnostics - CA, USA
**Chair of Dermatology and Venerology, Medical University - Sofia
 

ABSTRACT

Alopecia areata (AA) in children and adolescents is often associated with some autoimmune diseases. The aim of the study is to estimate the function and the presence of some autoimmune disease of the thyroid gland, pancreas and suprarenal glands in children and adolescents with AA. 46 children with AA (23 girls and 23 boys), age 2,2-17,5 years were studed: thyroid: size and function - T3, T4, TSH, TRH test (FIA, DELFIA), antibo-dies (ATA) - TAT, MAT, TBII, TSI, TGSI, ultrasound examination; b-cells: function (OGTT - blood sugar, IRI), antibodies against GAD 65, ICA 512, IA; adrenal glands: function, cortisol rhythm and ACTH test and antiadrenal antibodies. Results: goitre - in 29 children (63%), increased TSH - basal levels in 6 (13,3%) and hypothyroid type stimulated secretion (TRH test) in 2 children; increased TA - TAT in 17 (39,5%) and MAT in 14 children with AA (33,3%); ultrasound examination - picture suspicious or typical for AT in 18 (47,4%); AT in 22 (47,8%); increased stimulated insulin secretion in children with AA and normal blood sugar curves; increased titers of GAD 65 abs - in 1 child and IA - in another; changed stimulated 17 OHP  secretion (ACTH test) - in 3 children.
The changes in the function and autoimmunity mainly in the thyroid gland and to a smaller extent in the pancreatic b-cells and adrenal glands in children and adolescents with AA makes it nesessary to examine the function and antibody formation against these endocrine glands (first of all thyroid) at diagnosis and their regular follow up.

KEY WORDS: alopecia, thyroid, pancreatic b-cells, adrenal glands, function, autoimmunity.
 
 

Vititligo in Childhood and Adolescence
and Autoimmune Endocrine Diseases
- Accidental Combination or Regularity?
A. Kurtev,  D. Fisher*, J. Nelson*, A. D?urmishev**
Clinic of Pediatric Endocrinology, Chair of Pediatrics,
University Pediatric Hospital - Sofia
*Nichols Institute, Quest Diagnostics - CA, USA
**Chair of Dermatology and Venerology, Medical University - Sofia

Abstract

The association between vitiligo (V) and some autoimmune endocrine and systemic diseases is well known. The aim of the present study is to determine the function and autoimmunity in thyroid, pancreatic b-cells and adrenal glands in children and adolescens with V. 61 children and adolescens with V (35 girls and 26 boys) were examined. Goiter was found in 31 children (53,45%), thyroid dysfunction (T4, TSH) in 8 children (13,8%) - hyperthyroidism in 3 and subclinical hypothyroidism in 5 children; hypothyroid answer (TRH test) - in 6 children (27,3%). Antithyroglobulin (??A) and antimicrosomal antibody (A??) titers were elevated  in 29 children (50%), ??II - in 5 children (15,6%). Ultrasound examination showed picture typical or suspicious for ?? in 15 children with V (34,1%) and typical for Grave's disease (GD) in 2 children (4,5%). Autoimmune thyroid disese has been diagnosed in 32 children with V (52,5% - ??:GD=29:3).
Elevated insulin secretion during OGTT was found in children with V and normal blood sugar curves (n=24) and in V and AT (n=15). There was no correlation between changes of IRI and thyroid function. GAD 65 antibodies were with elevated titer in 6 children (18,8%) and I?? 512 in 2 children (7,4%). All except one were with normal blood sugar and insulin secretion. Increased stimulated 17 ??? secretion (???? test) was found in 4 children (33,3%). All examined children were with normal titers of antiadrenal antibodies.
Our study showed increased thyroid dysfunction and autoimmunity, increased stimulated insulin secretion and islet cell autoimmunity as well as increased stimulated 17 OHP secretion (early subclinical adrenalitis?) in children with V. Thyroid and b-cells function and autoimmunity should be checked in children with V at diagnosis and least twice a year thereafter.

KEY WORDS: thyroid, pancreas, adrenal, function, autoimmunity.