Endocrine late effects of cancer treatment.

BACKGROUND: Endocrine disorders are one of the common late complications of cancer treatment in childhood and adulthood. The incidence is more common in individuals who underwent oncology treatment in childhood in whom the estimated prevalence of these disorders is 20-50%. With improving treatment, there is an increasing number of people with a history of cancer treatment and thus persons who are potentially at risk of developing endocrine disorders. In adults, the prevalence of disorders is lower compared to those who had treatment in their childhood; however, endocrinological complications are relatively common even here, although the dia-gnosis is given less attention in adults compared to children. Endocrine disorders are possible complications of practically all treatment modalities used in oncology (radiotherapy, chemotherapy and immunotherapy). In terms of the type of disorders, these mainly include hypofunction or - more rarely - hyperfunction of the endocrine glands and secondary endocrine neoplasms, especially radiotherapy-induced thyroid tumors. The disadvantages of endocrine disorders are often non-specific and slowly developing symptoms. In addition to a clinical examination with an assessment of the presence of possible clinical manifestations, regular laboratory tests should also be performed to allow for early detection. The level of risk of developing endocrine disorders varies and depends on a number of factors, including the age at which the individual underwent treatment as well as the type of treatment: radiation dose, type of chemotherapy, etc. Based on these data, individualized monitoring plan for the individual needs should be made, allowing an early detection of these disorders. The advantage of endocrinological consequences is the fact that if properly and timely dia-gnosed, they are relatively easy to treat and the treatment often allows for full restitution of the condition. PURPOSE: The purpose of this article is to present a brief overview about broad spectrum of various possible endocrine complications of cancer treatment, how to dia-gnose and treat them, aiming to increase awareness about this topic among the health care professionals who treat these patients.

[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.

An alternatively activated macrophage marker CD163 in severely obese patients: the influence of very low-calorie diet and bariatric surgery.

CD163 is a marker of macrophages with anti-inflammatory properties and its soluble form (sCD163) is considered a prognostic predictor of several diseases including type 2 diabetes mellitus (T2DM). We explored sCD163 levels at baseline and after very low-calorie diet (VLCD) or bariatric surgery in 32 patients with obesity (20 undergoing VLCD and 12 bariatric surgery), 32 obese patients with T2DM (22 undergoing VLCD and 10 bariatric surgery), and 19 control subjects. We also assessed the changes of CD163 positive cells of monocyte-macrophage lineage in peripheral blood and subcutaneous adipose tissue (SAT) in subset of patients. Plasma sCD163 levels were increased in obese and T2DM subjects relative to control subjects (467.2+/-40.2 and 513.8+/-37.0 vs. 334.4+/-24.8 ng/ml, p=0.001) and decreased after both interventions. Obesity decreased percentage of CD163+CD14+ monocytes in peripheral blood compared to controls (78.9+/-1.48 vs. 86.2+/-1.31 %, p=0.003) and bariatric surgery decreased CD163+CD14+HLA-DR+ macrophages in SAT (19.4+/-2.32 vs. 11.3+/-0.90 %, p=0.004). Our data suggest that increased basal sCD163 levels are related to obesity and its metabolic complications. On the contrary, sCD163 or CD163 positive cell changes do not precisely reflect metabolic improvements after weight loss.

Can the gold standard be beaten? How reliable are various modifications of the Synacthen test compared to the insulin tolerance test.

Criteria for the evaluation of the insulin tolerance test (ITT) and Synacthen test are still a matter of debate. The objective of the study was to make a comparison of serum and salivary cortisol during four stimulation tests. Sixty four healthy volunteers underwent the ITT, the Synacthen test with 1 (LDST), 10 (MDST) and 250 (HDST) microg dose of ACTH. Maximum serum cortisol response was observed at the 90 min of the ITT (49 %), HDST (89 %) and MDST (56 %) and at the 40 min of the LDST (44 %). Results expressed as 95 % confidence intervals: 408.0-843.6 and 289.5-868.1 nmol/l in the IIT at 60 and 90 min. In the HDST and the MDST serum cortisol reached the maximum at 90 min 542.6-1245.5 and 444.2-871.3 nmol/l. Levels of salivary cortisol followed the same pattern as serum cortisol. Salivary cortisol reached the maximum response in the HDST and the MDST at 90 min and at 40 min in the LDST. We confirmed good reliability of all tests with respect to timing of response and maximum response compared to the ITT. We proved that the MDST test can provide the similar response in serum cortisol to the HDST. Measuring either salivary cortisol or ACTH levels did not provide any additional benefit then measuring serum cortisol by itself.

The possible role of mRNA expression changes of GH/IGF-1/insulin axis components in subcutaneous adipose tissue in metabolic disturbances of patients with acromegaly.

We explored the effect of chronically elevated circulating levels of growth hormone (GH)/insulin-like-growth-factor-1 (IGF-1) on mRNA expression of GH/IGF-1/insulin axis components and p85alpha subunit of phosphoinositide-3-kinase (p85alpha) in subcutaneous adipose tissue (SCAT) of patients with active acromegaly and compared these findings with healthy control subjects in order to find its possible relationships with insulin resistance and body composition changes. Acromegaly group had significantly decreased percentage of truncal and whole body fat and increased homeostasis model assessment-insulin resistance (HOMA-IR). In SCAT, patients with acromegaly had significantly increased IGF-1 and IGF-binding protein-3 (IGFBP-3) expression that both positively correlated with serum GH. P85alpha expression in SCAT did not differ from control group. IGF-1 and IGFBP-3 expression in SCAT were not independently associated with percentage of truncal and whole body fat or with HOMA-IR while IGFBP-3 expression in SCAT was an independent predictor of insulin receptor as well as of p85alpha expression in SCAT. Our data suggest that GH overproduction in acromegaly group increases IGF-1 and IGFBP-3 expression in SCAT while it does not affect SCAT p85alpha expression. Increased IGF-1 or IGFBP-3 in SCAT of acromegaly group do not appear to contribute to systemic differences in insulin sensitivity but may have local regulatory effects in SCAT of patients with acromegaly.

Prediction of adrenocortical insufficiency after pituitary adenoma surgery using postoperative basal cortisol levels.

Our aim was to analyze the correlation of early postoperative cortisol levels in patients after transsphenoidal pituitary adenoma surgery compared to the standard dose ACTH test and Insulin tolerance test (ITT) several months later. We retrospectively reviewed data from 94 patients operated for pituitary adenoma in years 2009-2012. The comparison of day 7 (median) postoperative basal cortisol levels and 3.6 months (median) after pituitary adenoma surgery stimulation test - standard dose 250 microg 1-24ACTH test in 83 patients or ITT in 11 patients were performed. All 16 patients with early postoperative cortisol levels >500 nmol/l proved a sufficient response in the stimulation tests. At basal cortisol levels of 370-500 nmol/l the sufficient response was found in 96 % (27/28) of patients. In the postoperative basal cortisol levels 200-370 nmol/l we found a preserved corticotroph axis later on in 88 % (28/32) of cases. Patients with basal cortisol levels 100-200 nmol/l had a maintained corticotroph axis function in 8/11 cases - 73 %. All patients with an early postoperative basal cortisol level above 500 nmol/l proved in the stimulation tests a preserved corticotroph axis function. The interval 370-500 nmol/l showed a minimal risk of postoperative adrenal insufficiency.

Response of cortisol metabolites in the insulin tolerance test and Synacthen tests.

Determination of response of cortisol and its metabolites to different stimuli may be important for adrenal gland disorders. To date, only one metabolite, cortisone, has been followed in stimulation tests of the adrenal gland. We aimed to describe a response of cortisol metabolites to the standard short Synacthen test (HDST), insulin tolerance test (ITT), low dose Synacthen test (LDST) and medium dose Synacthen test (MDST). Sixty healthy subjects were investigated: 30 men and 30 women. Plasma for measurements of cortisol and its metabolites was obtained before and 30th and 60th min after Synacthen and insulin administration. The cut-off 500 nmol/l of cortisol was reached after stimulation in all of tests, the maximal stimulation level was reached in 60th min in all of the tests except for LDST. The response of cortisol and its metabolites at 30th and 60th min strongly correlated in all of the tests except for LDST. Cortisol and its metabolites increased after stimulation; in contrast, cortisone and its metabolites decreased. We showed that the response of the cortisol metabolites during the Synacthen tests and ITT well correlated, and the MDST showed similar response compared to HDST. The decrease in cortisone metabolites may correspond to the regeneration of cortisol from cortisone in response to stimulation test.

Comparison of partial body weight-supported treadmill gait training versus aggressive bracing assisted walking post stroke.

PURPOSE: To test the hypothesis that partial body weight-supported treadmill training (PBWSTT) provides more effective gait training than an equally supportive but less physiologic aggressive bracing assisted walking (ABAW) program. METHODS: Following informed consent, patients participating in an inpatient rehabilitation program with significant leg weakness and need for at least moderate assistance for walking, without orthostatic hypotension, symptomatic dyspnea, or angina pectoris were randomized to receive PBWSTT vs. ABAW. PBWSTT was provided by a commercially available, overhead motorized hoist attached to a parachute-type body harness, which provided partial support of the patient's weight over a treadmill. Therapists assisted with weight shifting, leg advancement, and foot placement as needed. ABAW included aggressive early therapist-assisted ambulation using knee-ankle combination bracing and hemi-bar if needed. Treatment sessions of up to 45 minutes per day, five days per week were given as tolerated for the duration of the inpatient stay or until patients could walk over-ground unassisted. All patients had an additional 45-minute session of functionally oriented physical therapy each day with or without bracing as judged appropriate by the patient's individual therapist. RESULTS: Fifty-six patients a mean age of 71 +/- 1 SEM were enrolled 40 +/- 3 days post stroke. Although the outcome of the two groups as a whole did not differ, a subgroup with major hemispheric stroke defined by the presence of hemiparesis, hemianopic visual deficit, and hemihypesthesia who received more than 12 treatment sessions showed significantly better over-ground endurance (90 +/- 34 vs. 44 +/- 10 meters) and speed scores (12 +/- 4 vs. 8 +/- 2 meters/minute) for PBWSTT vs. ABAW, respectively. CONCLUSIONS: PBWSTT and ABAW are equally effective gait training techniques except for a subset of patients with major hemispheric stroke who are difficult to mobilize using ABAW alone.

Serum cortisol seems to be a more appropriate marker for adrenocortical reserve evaluation in ACTH test in comparison to salivary cortisol.

Salivary cortisol reflects the free fraction of serum cortisol. Monitoring salivary cortisol may be a promising alternative method for assessing serum cortisol in some clinical situations. We aimed to compare the reliability of salivary vs. serum cortisol during ACTH test. 84 subjects (mean age 63.2; 24-89 years; n=66 males) suspected for adrenocortical insufficiency underwent an ACTH test. Patients were divided based on peak serum cortisol into hypocortical group with cortisol <500 nmol/l and to reference group cortisol >500 nmol/l. Median serum cortisol levels in reference group were 445, 766, and 902 nmol/l at 0, 30, and 60 minutes, respectively, and in hypocortical group were 256, 394, and 453 nmol/l. Median salivary cortisol levels were 19.02, 40.02, and 62.1 nmol/l in reference group, and 9.60, 14.08, and 13.28 nmol/l in hypocortical group. Obtained values showed good correlation between serum and salivary cortisol (p<0.0001). The percentage of explained variability R(2) (coefficient of determination for linear model) representing a measure of agreement between experimental values and predictions for repeated measures ANOVA, was significantly higher (p=0.021) for serum cortisol (R2=93.4 %) when compared to the salivary cortisol (R2=89.3 %). A stronger discriminating power of serum versus salivary cortisol suggests that it seems to be slightly, but statistically significantly more appropriate marker of adrenocortical reserve in ACTH test.

Hypothalamo-pituitary dysfunction in patients with chronic subdural hematoma.

Relatively frequent pituitary hormone deficiencies are observed after traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) and according to the published studies the neuroendocrine consequenses of traumatic brain injury are underdiagnosed. In a cohort of 59 patients (49 males, mean age 68.3 years, 36-88 years) after evacuation of subdural hematoma (SDH) were evaluated hypothalamo-pituitary functions one week after surgery, after three months and after one year. Hypogonadism was present in 26 % of patients in an acute phase, but in the majority had a transient character. Less than half of patients was GH deficient (GHD) according to the GHRH+arginine test. We did not find any serious case of hypocortisolism, hypothyroidism, diabetes insipidus centralis nor syndrome of inappropriate secretion of ADH (SIADH). Transient partial hypocortisolism was present in two cases, but resolved. We did not find relation between extension of SDH or clinical severity and development of hypopituitarism. In conclusion, in some patients with SDH growth hormone deficiency or hypogonadism was present. No serious hypocortisolism, hypothyroidism, diabetes insipidus nor SIADH was observed. The possibility of neuroendocrine dysfunction should be considered in patients with SDH, although the deficits are less frequent than in patients after TBI or SAH.

Anatomic topographical relationship of the intraspinal accessory root to the upper cervical roots and to the vessels of the cranial cervical region.

The object of this investigation was to provide a statistical interpretation of macroscopic anatomic findings in the cranial cervical region, which is very rich in variation. In this way rare nervous and vascular variations could be related statistically. The first cervical posterior root demonstrated the most striking variations, which, according to anlage and connection with the accessory nerve, was divided into four anlage types of formation. In this way it was shown that in only 23% of the cases, no posterior C-1 root had been formed. It was further demonstrable that in at least part of the cases the accessory nerve was sensibly mixed with the first posterior root. Furthermore, nervous structures and peculiarities in the vessels were investigated. Special courses taken by the posterior inferior cerebellar artery, in addition to those already known, were statistically interpreted. Nervous as well as vascular contact and courses were analyzed, especially in relation to their topography to the accessory nerve, in order to provide clinicians with possibilities for explanations of irritations or compressions of this cranial nerve.

[Echinococcosis of the heart]. / Ehinokok srca.

Although echinococcosis in different parts of the world and also in some sheep raising regions of our country belongs to a pretty frequent parasitary entity, the localisation of hydatid cyst in cardiac muscle is relatively rare: according to different authors it amounts only to 0,02-2% of all the echinococcoses. Heyat and al. in their cummulative world statistic up to 1971 collected only 118 surgically treated cases. The problematic of this pathology is presented. Beside a proper in extracorporeal circulation successfully operated case of an echinococcosis of the left ventricle, recent possibilities of exact preoperative localisation with the aid of coronarography and left ventricular cineangiography are presented.

[Fibromyxoma of the left ventricle as a cause of heart aneurysm and recurrent thromboembolism]. / Fibromiksom levega prekata kot vzrok srcne anevrizme in ponavljajocih se tromboembolij.

Primary heart tumours are a rarity but no more an academic curiosity. When recognised they may be successfully surgically treated. A Cardiac tumour is to be suspected in thromboembolism of young people especially in the absence of cardiac symptoms. A short review of possible symptoms and diagnostic methods available in the present is given. A successfully operated case of fibromyxoma of the left ventricle with consecutive cardiac aneurysm and peripheral thromboembolism is presented. Selective coronary angiography and cine-cardioangiography were the deciding investigations. The nature of the tumour is shown by means of classical histology as with the aid of electron microscopy.