R. Robeva, Ph. Kumanov
The Prolactin and Non-endocrine Diseases
 Original Articles
J. Gerenova, Y. Vulkov, S. Boeva, K. Halacheva
Diagnostic and Prognostic Value of Antithyroid Antibodies and Serum Thyroglobulin Levels 
During Treatment of Graves' Disease with Methimazole
E. Karakhanian, H. Dimitrov, L. Tincheva, B. Anavi, D. Staykov
Hyperthyrotropinemia without Hypothyroidism ­ Report on a Family Presenting 
Receptor Insensitivity to Thyrotropin?

G. Grozeva, B. Lozanov, I. Atanassova
Autoimmune Polyglandular Syndrome Type III ­ A in Patients with Thyroid 
Autoimmune Diseases
M. Petkova,  M. Boyanov, M. Protich, D. Krivoshiikova, G.Vutova
Long-term  Effects of Dietary Protein Restriction and ACE-inhibitors on Micro-albuminuria 
in Normotensive Type 1 Diabetics

 Clinical Case
J. Gerenova, A. Kojchev, P. Gojcheva, Y. Vulkov
Pheochromocytoma Running a Course Characterized by Reversible Severe 
Multiple Organ Failure ­ Case Report

 Instructions to Authors

The Prolactin and Non-endocrine Diseases
R. Robeva, Ph. Kumanov
Clinical Center of Endocrinology and Gerontology, 
Medical University ­ Sofia

Prolactin is a hormone stimulating milk secretion and reproductive function. Its biological activity is mediated by specific receptors making part of cytokine receptor family. Prolactin effect on the immune system and oncogenesis is still not well enough clarified. In this review literature data concerning the role played by prolactin in the genesis and development of some autoimmune disorders and tumors are summarized. Its action at endocrine, as well as at auto- and paracrine levels is discussed.
As shown by the results, changes in prolactin secretion against the background of autoimmune diseases and tumors involving breast, prostate, rectum etc may have both diagnostic and therapeutic implications.
Further studies along this lines are needed to clarify whether or not prolactin may be considered as a marker of pathological processes, or a factor promoting their occurrence and development with a view to undertake eventual medical treatment.
KEY WORDS: prolactin, autoimmune diseases, cytokine receptors, oncogenesis, breast cancer.

Diagnostic and Prognostic Value of Antithyroid Antibodies and Serum Thyroglobulin Levels During Treatment of Graves' Disease with Methimazole
J. Gerenova, Y. Vulkov, S. Boeva, K. Halacheva
Department of Internal Medicine, Medical Faculty
Thracian University, Stara Zagora ­ Bulgaria

It is the purpose of the study to assay the clinical relevance of antithyroid antibodies presence, serum thyroglobulin (hTg) concentrations, and their changes in the course of methimazole (M) treatment in diagnozing and prognosticating Graves' disease (GD) patients from the region of Stara Zagora. Thyrotropin-receptor antibodies (TRAb), thyroid peroxidase antibodies (TPO Ab) and antibodies to thyroglobulin (TgAb) are measured in 51 hyperthyroid patients with GB. Serum hTg concentrations are also evaluated in 39 patients without TgAb.
Following M treatment over 12­24 months, the patients are retrospectively distributed in two groups depending on whether or not the remission after M treatment persists. Group A ­ 25 cases with remission after M treatment, and group B ­ 26 cases presenting relapses within 15 months of its suspension. Patients are studied prior to treatment (IA, IB), at 6 months after the beginning of therapy (IIA, IIB), and 2 months after M therapy discontinuation (IIIA, IIIB).
During the active hyperthyroid stage of GD, 76,5% of the patients under study are positive for TRAb, 86,3% ­ for TPO Ab, and 43,1% ­ for TgAb; 43,6% are with serum hTg values>75 ng/ml. There is no statistically significant difference between IA and IB groups in terms of the parameters being examined. In group IB the percentage of antiTg-positive patients is statistically significantly higher. The patients in group IIIB show statistically significantly higher serum levels of the parameters under study relative to group IIIA. Two months after suspending the antithyroid drug, serum hTg>75 ng/ml and TRAb>30 U/l show sensitivity 60% and 42,3% respectively, and 100% specificity for both parameters. TgAb and TPO Ab levels have good specificity, but low sensitivity.
In conclusion, the obtained data demonsrtate that the presence of TRAb or TPO Ab is sufficient to confirm the autoimmune character of GD hyperthyroidism. For financial (cost-effective) reasons measurement of TPO Ab only may be used in practice. In patients presenting relapses and in those with early remission the dynamic patterns of changes in antithyroid antibodies and serum hTg after 6-month-long M therapy are different. At termination of thyrostatic therapy and after its discontinuation, the serum levels of hTg>75 ng/ml and TRAb>30 U/l are accepted as markers predicting GD recurrence.
KEY WORDS: Graves' disease, antithyroid antibodies, serum thyroglobulin, remission, relapse.

Hyperthyrotropinemia without Hypothyroidism ­ Report on a Family Presenting Receptor Insensitivity 
to Thyrotropin?
E. Karakhanian, H. Dimitrov, L. Tincheva, B. Anavi*, D. Staykov*
Higher Medical Institute ­ Plovdiv
Department of Pediatrics
*Department of General and Clinical Pathology

Mass screening examination of neonates for congenital hypothyroidism contributes greatly to detect uncommon parrerns of deviation in the level of thyroid (T3 and T4) and thyrotropic (TSH) hormones. Hyperthyrotropinemia at normal T3 and T4 concentrations is not infrequently found in neonates, usually interpreted as an expression of subclinical hypothyroidism attributable to slight degree enzymatic defects, or thyroid gland ectopia. In the last five years, reports have been published on resistance to TSH, becoming manifest with euthyroid hyperthyrotropinemia.
This is a report on the first observation of euthyroid hyperthyrotropinemia in this country, documented in seven members from two genrations in a single family. In one of the children there are ocular anomalies, and in four ­ idiopathic arterial calcinosis. The results of neonatal screening for hypothyroidism among children with elevated TSH levels at normal FT3 and FT4 prompted the detection of anomalies. It is of interest to note that hyperthyrotropinemia persists in rather advanved age: analogical changes are likewise discovered in two members of the preceding generation.
The assumption is warranted that it is a matter of TSH resistance due to receptor insensitivity. The latter may be related to mutation of the gene responsible for regulation of TSH receptors, and conditions hyperthyrotropinemia development in case of normal location and function of the thyroid gland.
KEY WORDS: familial hyperthyrotropinemia, thyroid hormones, resistance to TSH.   

Autoimmune Polyglandular Syndrome 
Type III ­ A in Patients with Thyroid Autoimmune Diseases
G. Grozeva, B. Lozanov, I. Atanassova
Clinical Center of Endocrinology and Gerontology
Medical University ­ Sofia

Autoimmune polyendocrine syndrome type III-A (APS III-A) represents a constellation of autoimmune thyroid disease (ATD) and diabetes mellitus type 1. The aim of the study is to gain better insight into the characteristic features and clinical course of ATD and diabetes mellitus as components of APS III-A. Twenty-four patients presenting ATD + diabetes mellitus type 1 (21 women and 3 men at mean age 41,2±7 years) ­ 8 with Graves' disease and 16 with Hashimoto's thyroiditis ­ are covered by the study. There is a markedly expressed predominance of the female gender among APS III-A patients (7-to-1 female-to-male ratio). The peak incidence in terms of manifestation of the conditions making part of the syndrome is recorded in the age group 30 to 40 years. In most instances (90%) autoimmune hyperthyroidism precedes diabetes mellitus, whereas euthyroid and hypothyroid forms of Hashimoto's thyroiditis usually succeed diabetes. The earliest clinically expressed condition in APS III-A runs a much severer course compared to the ensuing diseases which become manifest at an older age. Autoimmune endocrinopathies are usually preceded by non-endocrine diseases ­ vitiligo and/or alopecia ­ which may be concidered as a clinical marker of impending APS development. As shown by the obtained results, ATD and diabetes mellitus type 1, as components of APS III-A, exhibit a number of clinical features and specificity of expression at variance from the ones in diabetes and ATD running an independent course.
KEY WORDS: autoimmune polyendocrine syndromes, autoimmune thyroid disease, diabetes mellitus.

Long-term  Effects of Dietary Protein Restriction and ACE-inhibitors 
on Micro-albuminuria in Normotensive 
Type 1 Diabetics  
M. Petkova,  M. Boyanov*, M. Protich*, D. Krivoshiikova, G.Vutova
Diagnostic and Consultative Center ôSt. Luka" ­ Sofia 
*Clinic of Endocrinology, Alexandrov's Hospital ­ Sofia 

Potein intake restriction in type 1 diabetes patients with microalbuminuria (MA) has been found to reduce elevated glomerular filtration rate and albuminuria regardless of glycemic control and blood pressure. ACE inhibitors given to normotensive individuals also account for delayed progress of diabetic renal damage and blunted increases in MA.
A randomized parallel study is conducted to evaluate the effect of 3-year-long protein restriction and ACE inhibitor treatment on MA in normotensive type 1 diabetes patients. Twenty-four diabetics (10 men and 14 women) are randomly selected, and distributed in groups as follows: low protein diet (group 1), given ACE inhibitor (2), or intensive insulin regimen (3). The mean age of the patients is: 40,5±8,1, 42,2±8,1, and 45,8±13,0 years, respectively for group 1, 2 and 3.
Food intake is assayed by 24-hour diet recalls, with the reported protein intake validated by urine urea nitrogen.
After 36-month observation, reported protein intake is 0,75 g/kg bw in group 1, 0,92 g/kg bw in group 2, and 0,89 g/kg bw in group 3. Albumin excretion rate at endpoint: 94,5 mg/min, 72,0 mg/min, and 83,0 mg/min for the three groups, respectively ­ without any significant differences between the groups. Blood pressure remains stable throughout the study period. Glycemic control, evaluated by HbA1c level: 9,46±2,0%, 9,7±2,3%, and 8,2±1,3% respectively, for the three groups.
The patients reported a sufficient reduction of protein intake, but it failed to result in a significant MA reduction. Presumably, the patients being examined were unable to comply with the diet prescribed for a continuous period of time.
The obtained results are in support of the hypothesis that ACE inhibitors reduce MA independently of glycemic control.
KEY WORDS: microalbuminuria, protein restriction, ACE inhibitors, diabetes mellitus type 1, normotension.

Pheochromocytoma Runing a Course Characterized by Reversible Severe Multiple Organ Failure ­ Case Report
J. Gerenova, A. Kojchev, P. Gojcheva, Y. Vulkov
Department of Internal Medicine, Medical Faculty, 
Thracian University ­ Stara Zagora

This is a report on a male patient aged 46 years, admitted to the clinic in a critical condition against the background of consecutive hypertonic attack, presenting the picture of serious pulmonary edema of noncardiogenic and cardiogenic type and acute renal failure (ARF) from rhabdomyolysis due to catecholamine-mediated vasoconstriction and ischemia of skeletal muscles. The elevated amylase levels, attributable to pulmonary endothelium damage and abdominal pain mimick acute pancreatitis. Following active resuscitation measures and conservative therapeutic approach, the functions of respiratory and cardiovascular systems, kidneys, pancreas, and deviations in electrolyte and CPK blood levels are completely restored and returned to normal.
When pheochromocytoma is diagnosed, it should be promptly operated to preclude the aforementioned life-threatening complications.
KEY WORDS: pheochromocytoma, multiple organ failure.