Analysis of pheochromocytomas / paragangliomas from Eastern Slovakia.

This multi centre observational cohort study gives a view about the occurrence, clinical and laboratory presentation, localization, histological type and genetic background of pheochromocytoma (PHEO) and paraganglioma (PGL) in Eastern Slovakia. It included 28 patients (18 women + 10 men), of which 23 were diagnosed to have PHEO (82,1%) and 7 patients (25%) suffered from PGL with retroperitoneal, inguinal/pelvic and mediastinal distribution. Arterial hypertension was the major symptom present in 86 % with slight dominance of paroxysmal form (58%). In 3 cases (10,7%), the diagnosis was gained after differentiation of adrenal incidentaloma in asymptomatic patients. Five patients (17,8%) were classified to have malignant form of the disease. 9 patients (32,1%) were confirmed to have hereditary form - five of them (17,8%) with familiar medullar thyroid cancer (FMTC) and mutations in RET gene classified as multiple endocrine neoplasia 2A and 4 patients (14,3%) with germline mutations of SDHB gene, respectively. There was found a relatively high occurrence of other co-morbidities: thyroid disease in 20 patients (71,4%), impairment of glucose metabolism in 11 patients (39,3%) and apart from FMTC, 4 patients (14,3%) suffered also from other malignancy. Together with a bigger size of the primary tumor (6,6 cm), higher concentrations of metanephrines and prevalence of extra-adrenal tumors, malignant and hereditary forms, we suppose genetic and environmental factors of Eastern Slovakia may play a role in the etiopathogenesis of the tumors.

Transient ischemic attack in the vertebro-basilar circulation due to a hemodynamically significant variation - kinking of the extracranial section of the left vertebral artery.

We present a case report of a 74-year old female patient with the clinical diagnosis of transient ischemic attack (TIA) in the vertebro-basilar (VB) circulation, in whom we found bilateral variation of the extracranial section of vertebral arteries on ultrasound, on the left side to the extent of kinking. This finding was later confirmed by magnetic resonance angiography (MRA). We discuss the presumed hemodynamic significance of this variation and its etiological relation to the patient's clinical picture. Ultrasound examination of the carotid and vertebro-basilar circulations is an important examination technique contributing to an early detection of possible aetiology of the cerebral circulation disorders (Fig. 7, Ref. 18).

Adrenal metastases.

The adrenal gland is a frequent location for metastatic spread of a various number of malignant tumors. Among all tumors, carcinoma of lung, breast, ovary and malignant melanoma count to the most frequent ones. In nononcological and unselected populations, the prevalence of adrenal metastases is 0-21 %. The metastases are mostly discovered in patients during their follow-up carried out in consequence of their antecedent malignant disease. A malignant disease in adrenal gland may occasionally manifest as a solitary metastasis referred to as adrenal incidentaloma. If the malignant disease is disseminated at the time of adrenal mass diagnosis, no further differentiation of lesion is necessary as it does not influence the further therapeutic process. If the dissemination is not present, further differentiation of adrenal lesion is essential. CT and MRI characteristics of the adrenal mass play the key role in the differential diagnosis. The examination of adrenal overproduction is not necessary in case of known adrenal metastasis except when performing tests in order to rule out the catecholamine overproduction. In case of bilateral metastases, adrenal insufficiency should be also excluded. Surgical treatment is indicated in cases of solitary metastasis. The further management of patients with adrenal metastases belongs to the oncologist. The prognosis of the disease is usually very poor with average survival rate of three months (Fig. 2, Ref. 34).

The Association Between Three Adipocytokines (Adiponectin, Resistin and Visfatin) And Thyroid Status in Patients With Type 2 Diabetes Mellitus and Autoimmune Thyroiditis.

Autoimmune thyroiditis (AIT) and type 2 diabetes mellitus (DM2) are the most common endocrinological diseases worldwide. Relation between these diseases explains several hypotheses. One of them is influence of some adipocytokines. This study evaluated association between three adipocytokines (adiponectin, resistin and visfatin) and thyroid and glycid status in patients with DM2 and AIT compared to the control group (CG). The group consisted of four subgroups: patients with DM2 without thyreopathies, patients with AIT on substitution therapy without diabetes and prediabetes, patients with DM2 and AIT on substitution therapy and healthy subjects as the CG. We investigated parameters of thyroid and glucose metabolism and serum levels of three adipocytokines. The mean level of resistin in the group of patients with diabetes and thyroiditis was significantly higher than in patients with thyroiditis without diabetes and than in the CG. We found a weak negative correlation between visfatin and fasting glucose levels in patients with thyroiditis without diabetes. We detected a weak negative correlation between resistin and glycated haemoglobin and a weak negative correlation between visfatin and thyroid gland volume in patients with diabetes without thyroiditis. In the CG we determined a weak positive correlation between visfatin and free thyroxin. Our results are consistent with several studies, which confirmed association between AIT and adipocytokines.

Hormonal and metabolic evaluation of adrenal incidentalomas.

The biochemical and hormonal data in patients with adrenal incidentalomas were evaluated to compare the differences between adrenal adenomas and other benign lesions and to find the relationship between metabolic parameters and adrenal hormones. Ninety two patients (29men, age 20-90 years) with incidentally discovered unilateral or bilateral adrenal masses detected on CT were included in this study for the reasons others than adrenal pathology. Glycemia, cholesterolemia, triglyceridemia, hormonal evaluation including plasma ACTH, plasma aldosterone, plasma renin acitivity, overnight dexametasone test, ACTH test, free plasma metanephrines, urinary catecholamines were determined. In the group of patients with adrenal masses the prevalence of arterial hypertension was three fold higher, the prevalence of DM was approximately five fold higher and the prevalence of the overweight and obesity two fold higher than is reported in the general population. The most frequent adrenal masses were nonfunctional masses, the occurence of functional lesions was as follows: steroid enzymopathies (an exaggerated response of 17-OHP indicating a possible 21-hydroxylase deficiency), subclinical Cushing syndrome, primary aldosteronism and pheochromocytoma (5%, 2%, 2% and 1% respectively). There were no significant differences in evaluated data between patients with adenomas and hyperplasia and also no significant difference in evaluated data between lesions smaller than 3 cm and lesions greater than 3 cm. We did not find any correlations between plasma cortisol and lipid values. In this study we confirmed a higher prevalence of symptoms characteristic for different metabolic syndromes in these patients with adrenal incidentalomas, which indicate systematic screening for the metabolic syndrome including evaluation of the insuline resistance in this patients.

The prevalence of 21-hydroxylase deficiency in adrenal incidentalomas - hormonal and mutation screening.

UNLABELLED: The aim of the present study was to evaluate and compare the response of 17 OHP to ACTH stimulation in patients with various types of adrenal incidentalomas and to examine the occurence of germline CYP21 mutation in these patients. SUBJECTS AND METHODS: 40 patients (27 females, 13 males) with unilateral and bilateral masses were screened for fi ve most common mutations of the CYP21 in peripheral blood DNA samples. A hormonal evaluation, i.e. baseline plasma values of 17OHP, DHEAS as well as plasma 17OHP and DHEA after ACTH stimulation, was performed in all patients. 21 of them had unilateral adrenal adenoma, 13 patients had adrenal hyperplasia (six of them unilateral) and 6 patients had CT characteristics of other tumors (myelolipomas, cysts, adrenocortical carcinoma). RESULTS: There were no significant differences in plasma 17OHP, DHEAS and plasma cortisol between all three groups. Stimulated plasma values of DHEA and 17OHP after ACTH administration were significantly higher in patients with adenomas (p < 0.05 and p < 0.01) and with hyperplasia (p < 0.05 and p < 0.05) compared with those with other tumors. An exaggerated response of 17 OHP was found in 5 (12 % ) patients. However, mutation screening in peripheral blood samples revealed no CYP21 mutation in all examined groups. SUMMARY: Although 12 % of patients with adrenal incidentalomas had an exaggerated response of 17 OHP after ACTH administration indicating a possible 21-hydroxylase deficiency, these findings are not associated with CYP21 mutation estimated in peripheral blood samples. There was found no germline CYP21 mutation in all patients with various adrenal incidentalomas.

Adrenal incidentalomas and the metabolic syndrome--are there any differences between adenoma and hyperplasia?

Authors evaluated the prevalence of symptoms of the metabolic syndrome and insulin resistance in 25 patients with adrenal incidentalomas (10 men, 15 women) of the mean age 57.9+/-15 years. 15 patients had adrenal adenoma determined by CT or MR scan and 10 had unilateral or bilateral hyperplasia. The prevalence of obesity was 72%, arterial hypertension 60%, diabetes mellitus or impaired glucose tolerance 28%, hyperlipidemia 56% and hyperuricemia 20%, respectively, which is more frequent occurrence than that in normal human population. Patients with adrenal adenomas had mildly but significantly higher body mass index (BMI, p<0.05) and insulin resistance calculated as HOMA IR (p<0.05) and FIRI (p<0.05) and significantly higher values of serum ferritin (p<0.01). Plasma cortisol values were slightly but not significantly higher in the group with adrenal adenomas. Authors conclude that adrenal adenomas are probably more related to the metabolic syndrome than adrenal hyperplasia.

A study of the renal sodium excretion during the normal menstrual cycle using method of passive leg rising.

12 healthy women (age 18-38 years) were examined using the 2-hour's method of passive leg rising (PLR) in follicular (FP) and luteal (LP) phases of normal ovulatory cycle. Renal and hormonal response to PLR was investigated. There was a significant increase of diuresis (from 53 +/- 9 ml/h to 298 +/- 27 ml/h in FP, from 69 +/- 12 to 324 +/- 28 ml/h in LP) and natriuresis (from 4.5 +/- 0.9 to 9.8 +/- 1 mmol/h in FP, from 5.7 +/- 0.3 to 12.1 +/- 1.1 mmol/h in LP), simultaneously with a decrease of plasma renin activity (PRA) and plasma aldosterone (PA) in both FP and LP. Baseline PRA was mildly and PA was significantly higher in LP compared to FP. Urinary osmolarity, heart rate and systolic blood pressure dropped significantly. Renal and hormonal response to PLR were identical in the two phases of the menstrual cycle. Authors conclude that 1/PLR causes significant diuresis and natriuresis due to central volume expansion and may be used as a simple stimulating test of renal sodium excretion, 2/renal sodium retention does not occur in the LP of normal ovulatory cycle.

Adrenal myelolipoma. 6 cases and a review of the literature.

Adrenal myelolipoma is an uncommon, benign and hormonally inactive tumor. Most lesions are asymptomatic and usually are discovered incidentally at autopsy studies. Authors report on 6 patients (5 women, 1 man) with adrenal myelolipomas (5 right, 1 left), analyze their morphological findings and association with an adrenal hormonal overproduction. Five of the patients underwent surgery because of tumor size, in 3 of them histological evaluation confirmed myelolipoma and in 2 cases an adrenocortical adenoma with foci of myelolipoma. All the patients were asymptomatic and in 4 cases hormonal overproduction was not found. One female patient has oveproduction of dehydroepiandrosteron-sulphate (DHEAS) indicating a 3beta hydroxylase deficiency in this tumor and 1 patient has primary aldosteronism with a histological finding of an association of adrenocortical adenoma with foci of myelolipoma. Neither Cushings syndrome nor congenital adrenal hyperplasia were present in our group of patients.

[Adrenal incidentalomas]. / Adrenálne incidentalómy.

The extensive use and progress in the improvement of imaging techniques brings about the growing incidence of incidentalomas, i.e. adrenal lesions accidentally revealed during the imaging of the abdominal cavity which was originally focused on the visualisation of organs other than adrenal glands. Despite the fact than the majority of incidentalomas (55-91%) represent benign adrenocortical adenomas, it is necessary to focus the diagnostic approach on the exclusion of malignity and hormonal activity. However, no common consent has been yet achieved in the management of incidentalomas. The authors review the literature data on the prevalence, diagnosis (namely hormonal assessments as well as imaging methods) and the current suggestion of the necessity of further investigation and treatment of adrenal incidentalomas. (Tab. 1, Fig. 5, Ref. 64.)

Prolactin and interleukin 2 concentrations before and after i.v. TRH application in primary hypothyroidism and in controls.

The authors evaluated serum level of prolactin (PRL) and interleukin 2 (IL-2) before and after i.v. application of tyreoliberin (TRH) 0.2 mg in 10 women as controls and 10 women with primary hypothyreoidism. In controls, there was a significant increase of IL-2 20 min following application of TRH (IL-2 0 min: 17.95 +/- 11.69, IL-2 in 20 min: 33.36 +/- 17.73 fmol/l), in patients with hypothyreoidism the serum level of IL-2 decreased (IL-2 0 min: 31.32 +/- 19.0, IL-2 in 20 min: 19.11 +/- 17.8 fmol/l). The basal concentration of IL-2 in patients with hypothyreoidism was significantly higher as in controls (p < 0.01). The presented finding indicated relation between the neuroendocrine and immune system but its value is not yet apparent. (Tab. 4, Fig. 1, Ref. 7.)

[Hormonal and morphologic characteristics of adrenal incidentalomas]. / Hormonálna a morfologická charakteristika adrenálnych incidentalómov.

The authors analyse hormonal and morphological characteristics of adrenal incidentalomas, i.e. pathological adrenal masses accidentally found on CT scan performed due to extraadrenal causes of other causes of adrenal pathology. The group of patients was consisted by 42 patients at the age 24-79 years (27 females and 15 males). The most frequent clinical symptoms included arterial hypertension, diabetes mellitus and obesity. CT examinations revealed 36 cases of unilateral lesions (in 21 cases the lesions were localised on the right and in 15 cases on the left) and 6 bilateral lesions. The size of adrenal masses ranged from 7 mm to 12 cm. The CT examination helped in characterising myelolipomas in 3 cases, cysts in two cases, and pre-assuming malignity in 6 cases. Hormonal analyses have revealed primary aldosteronism in 2 cases, subclinical hypercortisolism in 1, steroid enzymopathy in 2 and secondary hyperaldosteronism in 2 patients. No patient had catecholamine overproduction. 19 patients were indicated for adrenalectomy with the following histological findings.: adenoma (n = 5), cyst (n = 2), myelolipoma (n = 3), carcinoma (n = 3), feochromocytoma, ganglioneuroma, metastases, lymphoma, sarcoidosis and pseudodrenal structure--Gravitz tumor (n = 1, respectively). The size of all neoplasms exceeded 3 cm, therefore the authors recommend adrenalectomy in incidentalomas with hormonal activity exceeding 3 cm in size. (Tab. 2, Fig. 1, Ref. 17.)

[Effect of passive leg lifting on sodium excretion in patients with liver cirrhosis]. / Vplyv pasivneho zdvihnutia dolnych koncatin na exkreciu sodika u chorych s cirhozou pecene.

18 healthy subjects and 15 patients with liver cirrhosis were examined using a 2-hour method of passive leg rising (PLR). Renal and hormonal responses to PLR were investigated. There was a significant increase in diuresis (p < 0.01) and sodium excretion (p < 0.01) simultaneously with a decrease in plasma renin activity (p < 0.01) and plasma aldosterone (p < 0.01) in the group of healthy subjects. Similarly, in the group of patients with liver cirrhosis a significant increase in diuresis (p < 0.01), natriuresis (p < 0.05) together with a decrease in plasma renin activity (p < 0.05) and aldosterone (p < 0.01) were detected. 3 of 15 patients were nonrespondents. We conclude that PLR leads to central volume expansion which causes suppression of sodium retaining factors, and the increase in diuresis and natriuresis not only in healthy objects but also in cirrhotics. This simple method may be used as the first therapeutic regimen in patients with cirrhosis and edemas. (Tab. 2, Fig. 3, Ref. 13.)

[Incidence of primary hyperaldosteronism in hospitalized patients with hypertension]. / Výskyt primárneho hyperaldosteronizmu u hospitalizovaných hypertonikov.

AIMS: To detect the incidence of primary hyperaldosteronism (PH) in hospitalized hypertensive patients. METHODS: Authors assessed plasma renin activity (PRA) and plasma aldosterone (PA) in 100 patients with arterial hypertension hospitalized at the II. department of Internal medicine in Kosice because of resistance to ambulatory treatment, eventually with the aim of differential diagnosis of arterial hypertension. RESULTS: From 100 hypertensive patients 90 (90%) have had essential hypertension (EH), 8 (8%) PH, 2 (2%) renovascular hypertension and 1 patient (1%) pheochromocytoma. Aldosterone-renin ratio was in PH patients 10-fold higher comparing with EH patients. From the 8 patients with PH 4 have had adenoma and in 3 patients hyperplasia was diagnosed with the use of CT or histology, 1 case was idiopathic hyperaldosteronism without CT hyperplasia evidence. In all PH patients the level of kalemia was less than 4 mmol/l, i.e. kalemia 4.0 mmol/l has 100% sensitivity for PH detection. CONCLUSION: Introduction of PRA and PA examinations in the diagnostic process of arterial hypertension led to more frequent diagnosis of PH, which may probably represent the most frequent form of endocrine hypertension. Although ARR is a reliable test for PH screening, routine ARR examinations in ambulatory practice are technically complicated and connected with high costs. Increasing the threshold level of kalemia for PH detection led to higher sensitivity and that is why the authors consider ARR examination rational in every patient with kalemia level less than 4 mmol/l. (Tab. 4, Ref. 18.)

[Prolactin levels before and after stimulation with thyroliberin in primary hypothyroidism]. / Koncentrácie PRL pred a po stimulácii tyreoliberínom u primárnych hypotyreóz.

The authors examined the concentration of thyrotropic hormone (TSH) and prolactin (PRL) before and after stimulation with synthetic thyroliberine (0.2 mg TRH i.v.) in a group of 72 women with primary hypothyroidism (mean age 45 years, range 17-69 years) and 12 controls (mean age 35 years, range 17-49 years). According to the total thyroxin concentrations (TT4) and TSH they divided the group into three smaller subgroups: developed primary hypothyroidism (n = 8, mean age 50 years, TT4 < 65 nmol/l, basal TSH concentration > 15.0 mIU/l nmol/l), subclinical hypothyroidism, severe grade (n = 23, mean age 36 years, TT4 > 65 nmol/l, basal TSH concentration < 4.5 mIU/l), subclinical hypothyroidism mild degree (n = 39, mean age 42 years, TT4 > 65 nmol/l, basal TSH concentration < 4.5 mIU/l, TSH after TRH stimulation > 25 mIU/l). Mean basal PRL concentrations were in all three patient groups significantly higher than in the control group (P < 0.01) but mutually they did not differ significantly. Poststimulation PRL concentrations were also significantly higher than in controls however the values in developed hypothyroidism were significantly higher than in subclinical patients. No correlation was found between TSH and PRL concentrations.

T45G and G276T adiponectin gene polymorphisms in primary aldosteronism and healthy controls in an East Slovak population.

Metabolic complications are frequent in primary aldosteronism (PA) and adiponectin gene polymorphisms seem to confer a genetic risk for metabolic alterations. Aim of the study was to evaluate the prevalence of metabolic symptoms in patients with PA compared to controls and the prevalence of two single nucleotide polymorphisms (SNPs), T45G and G276T, in the adiponectin gene and their relationship to metabolic syndrome (MS). The study involved 47 patients with PA and 90 controls selected from general population. Body mass index (BMI), and selected biochemical parametres were examined, and the mentioned SNPs were genotyped in all subjects. PA patients had a significantly higher BMI (p<0.0001), blood glucose level (p<0.01), and triglycerides (p<0.0005) compared to controls. There were no significant differences in the prevalence of the studied genotypes of adiponectin gene polymorphisms. The 276GT genotype was linked with lower levels of triglycerides (p

Effect of growth hormone replacement therapy on plasma brain natriuretic peptide concentration, cardiac morphology and function in adults with growth hormone deficiency.

OBJECTIVE: The impact of growth hormone (GH) replacement on plasma brain natriuretic peptide (BNP) in association with cardiac morphology and function in adults with growth hormone deficiency (GHD) was evaluated. SUBJECTS AND METHODS: Fifty nine adult patients with GHD (29 men, age 19-59 years) received a starting dose of 0.1-0.2 mg/day recombinant GH, which was subsequently adjusted to the 50th percentile of normal serum insulin-like growth factor (IGF-1) over a 6 month period. Plasma BNP and IGF-I levels before, 3 and 6 months after treatment were determined, as were the echocardiographic data, such as ejection fraction (EF), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness (IVST), posterior wall thickness (PWT), left ventricular mass (LVM), E/A wave and deceleration time (DT). RESULTS: Mean plasma BNP levels (53.1+/-8 pg/ml) and echocardiographic parameters were within the normal range at baseline, although men had higher LVM, IVST, PWT, LVEDV and LVEDD, respectively. A significant decrease in plasma BNP was observed after 6 months (27+/-5.6 pg/ml, P<0.05). No significant changes in echocardiographic parameters were observed except for a mild tendency to increase in LVM, and a borderline decrease in DT (181+/-8.1 vs. 155+/-9 ms, P<0.01). CONCLUSIONS: Six months GH replacement therapy induced a significant decrease in plasma BNP levels despite the majority of patients having plasma BNP within the normal range at baseline. A borderline decrease in diastolic deceleration time was observed, the clinical significance of which is unclear.