[Genetic background of adrenal cortex tumours--news]. / Genetické pozadie nádorov kôry nadobliciek--aktuality.

This review has summarized the current knowledge of the genetic background of tumors originating from adrenocortical tissue, manifested as a part of inherited or familial syndromes, as well as specific forms of sporadic tumors caused by aberrant expression of G-protein coupled receptors.

[Genetic background of tumors originating from adrenomedullar and extraadrenal chromaffin tissue--update]. / Genetické pozadie nádorov adrenomedulárneho a extraadrenálneho chromafinného tkaniva--aktuality.

It is anticipated that an inherited/familial forms of pheochromocytomas cause approximately 20% of all pheochromocytomas. Therefore, the classic "rule of 10" axioma used to remember the key features of disorder is invalid. Various mutations in several genes have been identified, which underly syndromes with paragangliomas and/or pheochromocytomas. The more candidate genes, the less numbers of patients with apparently sporadic forms of the disorder. This review has summarized the current knowledge of the genetic background of tumors orginating from adrenomedullar and extra-adrenal chromaffin tissue.

[Treatment with sunitinib and hypothyroidism--a case report and overview of literature]. / Liecba sunitinibom a hypotyreóza--kazuistika a prehl'ad literatúry.

In the article the authors present the case of a patient with clear cell renal carcinoma, where after nephrectomy local metastases appeared. The treatment of choice was sunitinib. After 20 cycles of therapy heavy hypothyroidism was verified which required substitution by thyroxine. Elevated levels of TSH appeared in up to 70% and hypothyrodism in up to 40% of thus treated patients. Also described is the mechanism of action of sunitinib. There seems to exist a correlation between the "adverse effects" of the drug and a better result of the therapy of cancer, however, prospective studies are absent. Most experts agree that the thyroid function during treatment with sunitinib needs to be monitored.

[Adrenocortical disorders in pregnancy]. / Adrenokortikálne choroby v gravidite.

Adrenocortical disorders in pregnancy are rare, but unrecognized of them are associated with higher maternal and fetal morbidity. The diagnosis is more complicated because of physiologic changes hormones and frequently lacking normative datas during pregnancy. Therefore increased attention could allow early diagnosis and treatment, that improve prognosis for both the mother and fetus.

[Primary aldosteronism in gravidity]. / Primárny aldosteronizmus v gravidite.

Endocrinology and obstetrics have one thing in common--diagnosis and treatment endocrine diseases in gravidity. These are modified by physiological changes in gravidity, often missing data and tests in normal condition and the influence of diagnosis and treatment on the pregnant female and fetus have also to be taken into consideration. If diagnosis of primary aldosteronism is suspected, suprimed plasmatic renin activity is determinant indicator (disregarding arterial hypertension, hypokaliaemia, hyperkaliuresis and proteinuria) as well as ultrasound diagnostics or adrenal gland diagnostics means magnetic resonance imaging. Aldosteron produced adenomas may by treated by adrenalectomy in the second trimester, late diagnosed adenoma and hyperplastic forms are treated by the administration of the respective medicaments.

[From the history of endocrinology: reminiscence of the discovery of adrenocortical hormones]. / Z histórie endokrinológie: reminiscencia okolností objavovania hormónov adrenokortexu.

In the article authors describe the milestones in history of discoveries of the adrenocortical hormones. Preparation of the adrenal extract cortine was the first experimental contribution. Cortine prolonged life of animals whose adrenals have been removed and had beneficial effects in patients with Addison disease (AD). It was mixture of compounds comprising carbon, hydrogen and oxygen that belong to the steroids. From those deoxycorticosterone had impact on mineral metabolism, substances that Kendall termed as compounds A, B, E, and F influenced metabolism of saccharides and proteins. In 1929 Dr. Hench had observed that the painful symptoms of rheumatoid arthritis (RA) were relieved in a patient who developed jaundice and in 1931 he remarked favourable effects of pregnancy to the course of RA. He suggested that some agent (substance X) was present during jaundice and in pregnancy through that the symptoms of RA were relieved. In 1941 interest concerned to the compound A, however, this was almost ineffective in patients with AD. In 1948 compound E was successfully administered to patients with AD and RA for the first time. Concerning the relation between vitamin E Kendall and Hench gave compound E distinctive name cortisone. Consequently it was confirmed that compound F (hydrocortisone) is the final product of the adrenal cortex. Appreciating the work of the most significant groups was awarding the Nobel Prize to Edward Kendall, Tadeusz Reichstein and Philip Hench in 1950.

Increased thyroid volume and prevalence of thyroid disorders in an area heavily polluted by polychlorinated biphenyls.

OBJECTIVE: To evaluate whether long-term exposure to heavy environmental pollution with polychlorinated biphenyls (PCBs) could result in impairment of thyroid status as evaluated by an epidemiological field survey. METHODS: Thyroid volume (ThV) was measured by ultrasound in 238 employees of a factory (EMP) which previously produced PCBs and 454 adolescents from the surrounding area polluted by PCBs. Controls (C) were 572 adults and 965 adolescents from much less polluted areas. In the 238 EMP and various numbers (shown in parentheses) of adult C the levels of thyroid-stimulating hormone (TSH) (n = 498), thyroxine (n = 498), thyroglobulin (n = 278) and thyroid antibodies (anti-peroxidase (TPO Ab), n= 517; anti-thyroglobulin (Tg Ab), n=455; anti-TSH receptor (TSHR Ab), n=238) were estimated in serum, while only TSH and TPO Ab were measured in 269 and 171 adolescents from polluted and control areas respectively. In several subjects in whom thyroid disease was suspected, total tri-iodothyronine or free thyroxine and tri-iodothyronine were measured. In a total of 362 adults and adolescents the urinary iodine was estimated. RESULTS: Using the Mann-Whitney test, ThV in EMP (mean+/-S.E. = 18.85+/-0.69 ml, median= 17.3 ml, upper quartile=22.9 ml, n=238) was significantly higher (P< 0.001) than that in C (13.47+/-0.48 ml, 11.5 ml, 15.3 ml, n = 486 respectively). Similarly, ThV in adolescents from the polluted area (9.37+/-0.17 ml, 8.9 ml, 11.0 ml, n = 454 respectively) was significantly higher (P< 0.001) than that in C (8.07+/-0.10 ml, 7.6 ml, 9.6 ml, n = 965 respectively). In adults, a significantly increased prevalence of TPO Ab (P<0.05) was found (using the chi-square test) in EMP women of all ages (54/190) vs C women (70/282), in EMP women aged 31-50 years (40/117 vs 70/282 respectively) and those aged 41- 50 years (28/77 vs 54/215 respectively). Compared with C, there was also a higher prevalence of Tg Ab in EMP women aged 31-60 years (36/169 vs 50/342 respectively) and of TSHR Ab (P< 0.001) in the group of EMP men and women (25/238) vs sex- and age-matched C (6/238). No difference between EMP and C was found in the level of thyroxine (mean+/-S.D = 116.1+/-31.2 nmol/l, n = 238 vs 112.2+/-37.0 nmol/l, n = 460 respectively), TSH in the range 0.1-4.5 mU/l(1.56+/-0.86 mUl/l, n = 219 vs 1.51+/-0.84 mU/l, n = 460 respectively), prevalence of TSH >4.5 (14/238 vs 28/498 respectively) and <0.1 mU/l(5/238 vs 10/498 respectively). The prevalence of individuals without any defined clinical or laboratory signs of thyroid disorders among EMP who had worked in the factory for 21-35 years (43/128, 33.6%) was significantly lower than that in twice as many matched C (118/256, 46.1%, P< 0.025) or in EMP who had worked for only 11-20 years (36/73, 49.3%, P< 0.05). In adolescents, no difference was found in the prevalence of TPO Ab or TSH >4.5 mU/l between the polluted (17/269, 6.3%, and 2/243, 0.8% respectively) and C areas (15/171, 8.5% and 4/140, 2.8% respectively). The median values of urinary iodine were in the optimal range (microg per dl/number of cases) and about the same in polluted (12.6/90 and 11.4/55) and C areas (14.1/80, 13.2/82 and 13.4/55). CONCLUSIONS: Since iodine intake in Slovakia is considered sufficient as a result of 45 years of well-monitored iodine prophylaxis, the increased ThVand prevalence of thyroid disorders in the polluted areas presumably results from long-term exposure to toxic substances rather than from a difference in life-long iodine intake. The increased prevalence of some thyroid antibodies may be related to the known immunomodulatory effects of PCBs.

Daily blood pressure profile in Cushing's syndrome before and after surgery.

No significant difference has been demonstrated in the altered circadian blood pressure pattern between the pituitary-dependent and adrenal forms of Cushing's syndrome before surgery. The effect of therapy, however, proved to be different. The mesor was normalized in the pituitary-dependent Cushing's syndrome more conspicuously for systolic than for diastolic blood pressure. In Cushing's syndrome due to adrenal adenoma, systolic and diastolic blood pressure mesors have been even significantly "overnormalized" after treatment, being 11 to 27 and 2 to 13 mmHg (95% confidence) lower than corresponding mesors in controls. There was no difference between forms in the effect of treatment on blood pressure amplitudes, which remained significantly lower than in controls. Finally, acrophase patterns were partly normalized after treatment of the pituitary-dependent form only for diastolic blood pressure, while both systolic and diastolic blood pressure acrophases were normalized in the treated adrenal form. In conclusion, complete normalization of the pattern of daily blood pressure profile has not been achieved in either form of the syndrome. This may be one of the reasons for the reduced long-term survival after surgical cure of hypercortisolism, than expected.

Daily variation of serum cortisol, 17-hydroxyprogesterone and five androgens in healthy women.

Serum cortisol, 17-hydroxyprogesterone and five androgens (androstenedione, 11-hydroxyandrostenedione, dehydroepiandrosterone and its sulphate, and testosterone) were measured by radioimmunoassay at 8:00, 16:00, 20:00 and 24:00 h and again at 8:00 h on the next day in eight healthy female subjects aged 16-40 years in the midfollicular phase of the menstrual cycle. Regression analysis revealed a significant (alpha = 0.05) circadian periodicity, with estimated peaks between 8:00 a.m. (testosterone) and 2:00 p.m. (dehydroepiandrosterone sulphate), and with estimated amplitudes between 76% (11-hydroxyandrostenedione) and 33% (17-hydroxyprogesterone, testosterone and dehydroepiandrosterone sulphate) of the rhythm adjusted mean. The inferential statistical approach illustrated here should contribute significantly to the diagnostic elucidation of adrenocortical disorders.

Risk factors for glucose intolerance in active acromegaly.

In the present retrospective study we determined the frequency of glucose intolerance in active untreated acromegaly, and searched for risk factors possibly supporting the emergence of the diabetic condition. Among 43 patients, 8 (19%; 95% CI: 8-33%) had diabetes mellitus and 2 (5%; 1-16%) impaired glucose tolerance. No impaired fasting glycemia was demonstrable. The frequency of diabetes was on average 4.5 times higher than in the general Slovak population. Ten factors suspected to support progression to glucose intolerance were studied by comparing the frequency of glucose intolerance between patients with present and absent risk factors. A family history of diabetes and arterial hypertension proved to have a significant promoting effect (P<0.05, chi-square test). A significant association with female gender was demonstrated only after pooling our data with literature data. Concomitant prolactin hypersecretion had a nonsignificant promoting effect. In conclusion, the association of active untreated acromegaly with each of the three categories of glucose intolerance (including impaired fasting glycemia, not yet studied in this connection) was defined as a confidence interval, thus permitting a sound comparison with the findings of future studies. Besides a family history of diabetes, female gender and arterial hypertension were defined as additional, not yet described risk factors.

Primary aldosteronism caused by aldosterone-producing adenoma in pregnancy--complicated by EPH gestosis.

Pregnancy in conjunction with primary aldosteronism is an unusual occurrence. We report a 28-year-old woman who presented with mild hypertension and hypokalemia as manifestations of primary aldosteronism caused by an aldosterone-producing adenoma in the left adrenal gland during pregnancy. Although the diagnosis was straightforward, the patient refused to undergo the proposed operation during the second trimester of her pregnancy. She was not admitted to hospital until she developed EPH gestosis in the 27th week of gestation, which had an unfavourable outcome for the infant who died nine days after delivery. The patient underwent a laparoscopic adrenalectomy which resulted in normalization of blood pressure and blood potassium levels. In cases of aldosterone-producing adenoma, surgery in the second trimester is the most appropriate option to avoid a poor obstetric outcome.

Tumours of the adrenal cortex.

The authors report their experience of 34 benign and 17 malignant tumours of the adrenal cortex. Both occurred more frequently in women (79.4% of cortical adenomas and 70.6% of adrenocortical carcinomas). Moreover, females were significantly younger (average age: adenomas: females 44.9 years and males 54.4 years, adrenocortical carcinomas: females 34.1 years and males 58.3 years). Some tumours presented in the form of increased hormone production, while others were hormonally inactive and did not cause clinical signs until later. Pain was the first symptom in the cases of malignant adrenocortical tumours. Adenomas occurred as frequently twice in the left adrenal gland (24 versus 12), whereas carcinomas were more than twice are frequent on the right (10 versus 7). Ultrasonography and CT were appropriate and fully sufficient methods for the diagnosis of adrenal tumours. Arteriography was valuable in the differential diagnosis of large upper abdominal masses when the organ of origin could not be identified by CT and for determination of anatomic conditions and subsequent surgical tactics. For small tumours of the adrenal cortex, the classic lumbar approach through the bed of the resected eleventh rib is adequate. For larger tumours, extended lumbotomy, laparotomy or thoracotomy is necessary.

[Problems posed by asymptomatic pheochromocytoma and malignant tumors of the adrenal medulla]. / Problèmes posés par les phéochromocytomes asymptomatiques et les formes malignes de tumeurs de la médullo-surrénale.

The authors analyse a group of 38 patients with a diagnosis of pheochromocytoma, in particular the topics of atypical symptomatology and malignancy. Three patients did not suffer from any subjective symptoms or other signs of pheochromocytoma ("incidentalomas"). Another three patients, although having giant tumours, only complained of atypical symptoms. Signs suspicious of malignancy were detected in 6 out of 38 patients. The authors recommend a practical approach to modern diagnostic and imaging tools for early primary diagnosis and for the early diagnosis of local recurrence and distant metastases.

[Cushing's syndrome is still a potentially fatal disease]. / Cushingov syndróm je este stále potenciálne smrtiacou chorobou.

The paper summarizes the studies documenting the outlasting of increased cardiovascular mortality in patients with Cushing's syndrome even after the hypercortisolism resolution. Despite the hypercortisolism resolution the mortality during the subsequent period of life is up to four-fold higher than in the comparable population as a whole. The pathogenesis of this cardiovascular risk is based on arterial hypertension, steroid cardiomyopathy and hyperlipidaemia with subsequent atherosclerosis. The post mortem material bears a parallel of the extent of atheromatous changes and duration of hypercorticolism. The prevention has to its disposition two mutually complementing means. The first is represented by clinical screening of hypercorticolism which enables an early recognition and therapy of the Cushing's syndrome. The successive measure resides in increased attention to the cardiovascular system even after hypercorticolism resolution. (Tab. 1, Fig. 1, Ref. 25.).

Diabetes mellitus in primary aldosteronism.

BACKGROUND: Information concerning diabetes mellitus associated with primary aldosteronism is scarce. OBJECTIVES: To determine the prevalence of diabetes mellitus in its two main pathogenetic forms of primary aldosteronism and to evaluate its association with several clinical variables. PATIENTS: Fifty in-patients (31 female and 19 male, aged 16-66), diagnosed during the years 1980-1998 as aldosterone producing adenoma (n = 26) or as idiopathic hyperaldosteronism (n = 24). METHODS: Morning fasting plasma glucose was measured by glucoso oxidase method in all patients. In the presence of higher values, confirmatory measurements were performed on the next day. The results were evaluated retrospectively by the diagnostic criteria of American Diabetes Association, 1997. Statistical significance of the association between diabetes mellitus and clinical variables was evaluated by chi-square test. RESULTS: Diabetes mellitus was ascertained in 6 patients out of 50 (12%; interval of 95% confidence 5-24%). Diabetes was accompanied significantly more often with idiopathic hyperaldosteronism (10-47%) than with aldosterone producing adenoma (0-13%). Patients with the family history of diabetes suffered more often (9-76%) from this disease than those without the history (1-19%). Obesity, longer (> 5 years) duration of hypertension and hypokalaemia did not affect the occurrence of diabetes. CONCLUSIONS: The occurrence of diabetes in primary aldosteronism was connected significantly with its idiopathic subtype and positive family history of diabetes. (Tab. 2, Ref. 11.)

[The polycystic ovary syndrome and insulin resistance]. / Syndróm polycystických ovárií a inzulínová rezistencia.

The insulin resistance syndrome and the polycystic ovary syndrome (PCOS) appear to have some following coincidences: the existence of subclinical acanthosis nigricans in PCOS hyperinsulinemic women, correlation of insulin levels and free testosterone, insulin-like growth factor I binding protein (IGFIBP), and sex-hormone binding globulin. Insulin and IGFI act synergically with luteinizing hormone increasing the activity of cytochrome P450c17 and its enzymatic activity in the adrenals. The decrease in IGFI level and IGFI receptors in the ovarian granulosa cells reduce the steroids aromatisation. The increased expression of IGFI receptors in the theca cells favours the androgens' synthesis. Long-term insulin therapy results in an increase in ovary volume and the blood androgens levels. The deterioration of insulin resistance in PSOC women progresses also by the reduction of type I of skeletal muscle fibres which are sensitive to insulin, and the increase of type II fibres which are resistant to insulin in hyperandrogenemia. Testosterone deteriorates the skeletal as well as hepatic insulin sensitivity by both its facilitating effect on lipolysis and the increase of free fatty acids. Abdominal obesity seen in PCOS and insulin resistance is composed by adipocytes with glucocorticoid receptors, which after cortisol stimulation activate the lipoprotein lipase and fat accumulation. Gynoid obesity with the preferential aromatisation of steroids is not evolved because of the low estrogens and progesterone levels in PCOS. Low progesterone levels (with anticortisol effect) support the development of abdominal obesity. Ultimately, the early peak of insulin secretion (4-8 min) in PCOS is higher. This fact should testify a certain diabetic disposition. (Ref. 37.)

[Primary aldosteronism--personal experience with diagnosis and surgical treatment of adenomatous forms]. / Primáry aldosteronizmus--vlastné skúsenosti s diagnostikou a chirurgickou liecbou jeho adenómových foriem.

Primary aldosteronism (Conn's syndrome) forms about 2% of disease in patients with arterial hypertension. Primary aldosteronism is in 50% of patients caused by aldosteron producing adenoma. Surgical treatment of these adenomas is excellent, or with complete disappearance of the disease, or with simple drug control of the symptoms after adrenalectomy. In the diagnostic process we can meet also seemingly divergent results of investigations. In these cases diagnosis usually requires the catheterization of adrenal veins with selected sampling of aldosteron level and thus determines the localisation of the tumor. Localised adenomas are indicated for surgical treatment. The best approach seems to be the abdominal transperitoneal incision with removal the whole adrenal gland. In this paper authors describe their experience with 5 patients treated at the F.D. Roosevelt Hospital in Banská Bystrica. (Tab. 1, Fig. 2, Ref. 25.)

[Initial experience with laparoscopic adrenalectomy]. / Prvé skúsenosti s laparoskopickou adrenalektómiou.

We present the first experience with laparoscopic adrenalectomy, which was in Slovakia introduced to the surgical practice on March 3, 1996. We analyse first seven patients who underwent completed laparoscopic adrenalectomy (five leftsided, two right-sided). Four patients had cortex adenoma (clinically 2 incidentalomas and 2 Cishing syndroma), three patients had cortex hyperplasia (clinically Conn syndroma). Average duration of operation was 120 minutes, there were no postoperative complications. Average postoperative hospital stay was 5 days. Our initial experiences are comparable with that of surgical departments which has more than two-years experiences. Laparoscopic adrenalectomy is a perfect method for the small adrenal tumors and it is better than traditional transabdominal approach.

[Present state and perspectives of endocrinology in Czechoslovakia]. / Soucasný stav a perspektivy endokrinologie v CSFR.

The contemporary state of the sub-discipline of endocrinology within the framework of internal medicine is generally considered rather desolate, but so far actual data were lacking. Based on an analysis of data provided by regional specialists in the Czech Republic and by regional (district) specialists in internal medicine in Slovak republic it may be said that in the majority of health institutions the number of endocrinologists does not reach even the unsatisfactory standard (i. e. 1 endocrinologist per 150 to 250,000 population), that specialized training of endocrinologists, specialists in internal medicine and other specialist is not ensured, that there are not adequate numbers of community doctors and factory medical officers, that there are not adequate capacities of specialized laboratory examinations and that adequate collaboration with other disciplines is not ensured (the position is in particular alarming as regards immunological methods and cytological processing of specimens obtained by aspiration biopsy from the thyroid gland. With regard to these data the authors recommend to raise the numbers of endocrinologists so that in institutions corresponding to hospitals with policlinics type II there will be one endocrinologist per 50-100,000 population, to improve the standard and availability of auxiliary examinations, to ensure endocrinological in-patient care at the level of hospitals with policlinics type III and to create specialized centres within the framework of the research base or university hospitals. It is important to resolve the link between endocrinology and other disciplines (paediatrics, gynaecology etc). It is also essential to coordinate closely therapy, education and research, Federal coordination is essential.

[Personal experience with the hypolipidemic agent Olbetam-Acipimox in hyperlipoproteinemia associated with type II diabetes]. / Nase skúsenosti s hypolipemikom Olbetam-Acipimox pri hyperlipoproteinèmii u diabetu II. typu.

The objective of this work was to test in type II diabetics with hyperlipoproteinaemia the action of a new analogue of nicotinic acid--Acipimox (Olbetam, Farmitalia Carlo Erba). The investigation comprised 24 patients of whom 16 took for three months Olbetam (250 mg 3 x per day by the oral route) and 8 patients were given placebo. The investigated biochemical parameters were examined before administration of the preparation was started and 4 and 12 weeks following its administration. Contrary to the group taking placebo, in the group taking Olbetam a significant decline of the triglyceride serum level occurred and a slight decline of total serum cholesterol levels and increase of HDL-cholesterol and the atherogenic risk indexes were thus more favourable. The results indicate that Olbetam is a satisfactory hypolipidemic agent for the treatment of diabetic hyperlipoproteinaemia.