[Show abstract][Hide abstract] ABSTRACT: Radiation therapy is one of the treatment options for pituitary adenomas. The most common side effect associated with Leksell gamma knife (LGK) irradiation is the development of hypopituitarism. The aim of this study was to verify that hypopituitarism does not develop if the maximum mean dose to pituitary is kept under 15 Gy and to evaluate the influence of maximum distal infundibulum dose on the development of hypopituitarism.
We followed the incidence of hypopituitarism in 85 patients irradiated with LGK in 1993-2003. The patients were divided in two subgroups: the first subgroup followed prospectively (45 patients), irradiated with a mean dose to pituitary <15 Gy; the second subgroup followed retrospectively 1993-2001 and prospectively 2001-2009 (40 patients), irradiated with a mean dose to pituitary >15 Gy. Serum TSH, free thyroxine, testosterone or 17β-oestradiol, IGF1, prolactin and cortisol levels were evaluated before and every 6 months after LGK irradiation.
Hypopituitarism after LGK irradiation developed only in 1 out of 45 (2.2%) patients irradiated with a mean dose to pituitary <15 Gy, in contrast to 72.5% patients irradiated with a mean dose to pituitary >15 Gy. The radiation dose to the distal infundibulum was found as an independent factor of hypopituitarism with calculated maximum safe dose of 17 Gy.
Keeping the mean radiation dose to pituitary under 15 Gy and the dose to the distal infundibulum under 17 Gy prevents the development of hypopituitarism following LGK irradiation.
European Journal of Endocrinology 11/2010; 164(2):169-78. DOI:10.1530/EJE-10-0733 · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IGF-I gene polymorphisms might alter IGF-I level resulting in decreased foetal and postnatal growth and increased risk for diabetes mellitus type 2 and cardiovascular diseases in adulthood.
We analyzed the association between Cytosine-Adenosine (CA)10-24 repeats polymorphism in promoter region of the IGF-I gene and early growth in infants with birth weight appropriate for gestational age (AGA) and small for gestational age (SGA). Design and
All neonates were born at term, 196 of them were AGA and 26 SGA. Blood for DNA analyses was obtained from placental part of umbilical vein. Genotyping was performed using fragment analyses of IGF-I gene promoter region. The data about postnatal growth in the group of AGA children were obtained at the age of 18 months, in SGA children at 12 months.
No differences in the frequency of wild type allele with (CA)19 repeats and polymorphisms with (CA)<19 or (CA)>19 repeats were observed between AGA and SGA children. The average birth weight and length in AGA wild type (CA)19 homozygotes were lower in comparison with AGA carriers of various (CA)n polymorphisms but all observed anthropometric differences disappeared at the age of 18 months. In SGA children, no differences were found between number of (CA)n repeats and anthropometric parameters both at birth and at the age of 12 months.
Although (CA)n repeats polymorphism in IGF-I gene might affect prenatal growth in AGA children, our results have not shown any impact of variable number of (CA) n repeats in IGF-I gene on postnatal growth.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to measure plasma fibroblast growth factor 21 and 19 (FGF21 and FGF19) levels in patients with Cushing's syndrome (CS) and to compare it with those of lean control subjects (C) and patients with obesity (OB). Fourteen untreated patients with CS, 19 patients with OB and 36 controls were included in the study. Plasma FGF21 and FGF19 levels were measured by ELISA kits, other hormonal and biochemical parameters were measured by standard laboratory methods. Plasma FGF19 did not significantly differ among the studied groups. Plasma FGF21 levels were significantly higher in both CS and OB groups relative to C group but they did not differ between CS and OB groups. In a combined population of all three groups FGF21 levels positively correlated with BMI, waist circumference and percentage of total and truncal fat mass. Less prominent inverse relationship with these parameters was found for FGF19. Neither FGF21 nor FGF19 were significantly related to cortisol concentrations. Increased FGF21 concentrations in both patients with CS and OB relative to lean subjects suggest that excessive body fat and/or related metabolic abnormalities rather than direct effects of cortisol are responsible. In contrast neither obesity nor hypercortisolism significantly affected FGF19 concentrations.
Physiological research / Academia Scientiarum Bohemoslovaca 09/2009; 59(3):415-22. · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Presently the laparoscopic adrenalectomy (LA) becomes most popular since 1992 when it was performed for the first time by laparoscopic method by Gagner. Typical indication for LA is the aldosteron-secreting adenoma, Cushing's syndrome, feochromocytoma or scarcity tumors such as adrenal cyst or myelolipomas.
The evaluation of the laparoscopic adrenalectomy as safe method for adrenals tumout's extirpation to the sizes 10 cm.
LA is provided with transperitoneal lateral approach most frequently then in back side position. Retroperitoneal approach is used less commonly.
Since 2006, firstly at the 1st Surgical department of 1st Medical School of Charles University and General Faculty Hospital and lastly at the Surgical department 2nd Medical School of Charles University and Central Military Hospital, has been performed on the whole 120 LA in 114 patients. The bilateral LA was performed in 6 patients. The conversion from the laparoscopic to open adrenalectomy was necessary by reason of the king size of the tumor (13/14 cm) in two cases. The lateral position and transperitoneal approach was used in all cases. The harmonie scalpel was used with advantage. Average length of the operation was 82 minutes (40-154 min), respective 180 minutes (130-270 min) in the case of the bilateral LA. The median size of the adrenal tumor was 4.9 cm (1.5-12.5 cm) with average weight 44 g (18-421 g). All of the patients after LA were monitored for 24 hours in the Intensive care units. The average time of the hospitalization was 3.7 days (2-6 days).
Laparoscopic adrenalectomy presently becomes as the "gold standard" for the treatment of adrenal tumors to the size 10 cm namely and in the event of malignancy. The harmonie scalpel is useful and sparing advice for the LA.
Rozhledy v chirurgii: měsíčník Československé chirurgické společnosti 08/2009; 88(8):439-43.
[Show abstract][Hide abstract] ABSTRACT: Pharmacological treatment with dopaminergic agonists (DA) is the treatment of choice for prolactinomas. Surgical and radiation treatment is also indicated in certain situations. We describe our 12-year experience in treating prolactinomas with the Leksell gamma knife (LGK).
We followed 35 prolactinoma patients (25.7% microprolactinomas, 74.3% macroprolactinomas) treated with LGK irradiation. The mean follow-up period was 75.5 months. Prior to LGK irradiation, patients were treated with DA and 10 of them (28.6%) underwent neurosurgery. Indications for LGK irradiation were: DA intolerance (31.4%), DA resistance (45.7%) and efforts to reduce the DA dose or shorten the period of administration (22.9%). Pituitary function was monitored regularly at 6-month intervals. The central radiation dose range was 40-80 Gy (median 70 Gy), and the minimal peripheral dose was 20-49 Gy (median 34 Gy).
Normoprolactinaemia was achieved in 37.1% of the patients who discontinued DA and in 42.9% of patients who continued DA treatment after LGK irradiation. The median time to prolactin normalization after discontinuation of DA was 96 months. No relapse was seen in any patient. After LGK irradiation, the prolactinoma stopped growing or decreased in size in all but one patient (97.1%).
LGK treatment resulted in normoprolactinaemia in 80.0% of the patients, all of whom had failed pharmacological treatment due to DA resistance or intolerance. After achieving normoprolactinaemia, no relapse of hyperprolactinaemia was observed in any patient. The size of the adenoma decreased even in those patients in whom it was not changed by previous DA treatment.
[Show abstract][Hide abstract] ABSTRACT: Visceral obesity, insulin resistance and increased cardiovascular morbidity and mortality are strongly related. Development of visceral obesity and regulation of body fat distribution in general are influenced by many factors. This article is a summary of current knowledge about pathogenesis of insulin resistance in different endocrinopathies, particularly in the Cushing's syndrome and acromegaly, as they are both connected with the pathological conditions mentioned above.
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to evaluate skin microvascular reactivity (MVR) and possible influencing factors (fibrinolysis, oxidative stress, and endothelial function) in patients with Cushing's syndrome. Twenty-nine patients with active Cushing's syndrome (ten of them also examined after a successful operation) and 16 control subjects were studied. Skin MVR was measured by laser Doppler flowmetry during post-occlusive (PORH) and thermal hyperemia (TH). Malondialdehyde and Cu,Zn-superoxide dismutase were used as markers of oxidative stress. Fibrinolysis was estimated by tissue plasminogen activator (tPA) and its inhibitor (PAI-1). N-acetyl-beta-glucosaminidase, E-selectin, P-selectin, and ICAM-1 were used as markers of endothelial function. Oxidative stress and endothelial dysfunction was present in patients with hypercortisolism, however, increased concentration of ICAM-1 was also found in patients after the operation as compared to controls (290.8+/-74.2 vs. 210.9+/-56.3 ng.ml(-1), p<0.05). Maximal perfusion was significantly lower in patients with arterial hypertension during PORH and TH (36.3+/-13.0 vs. 63.3+/-32.4 PU, p<0.01, and 90.4+/-36.6 vs. 159.2+/-95.3 PU, p<0.05, respectively) and similarly the velocity of perfusion increase during PORH and TH was lower (3.2+/-1.5 vs. 5.2+/-3.4 PU.s(-1), p<0.05, and 0.95+/-0.6 vs. 1.8+/-1.1 PU.s(-1), p<0.05, respectively). The most pronounced impairment of microvascular reactivity was present in patients with combination of arterial hypertension and diabetes mellitus.
Physiological research / Academia Scientiarum Bohemoslovaca 02/2008; 57(1):13-22. · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The A-ZIP/F-1 transgenic mouse is a model of lipoatrophic diabetes with severe insulin resistance, hyperglycemia and hyperlipidemia. Recently, a regulatory role of adipose tissue on adrenal gland function and blood pressure has been suggested. To further explore the importance of adipose tissue in the regulation of adrenal function and blood pressure, we studied this mouse model of lipodystrophy. A-ZIP/F-1 mice exhibit significantly elevated systolic and diastolic blood pressure values despite lack of white adipose tissue and its hormones. Furthermore, A-ZIP/F-1 lipoatrophic mice have a significant reduction of adrenal zona glomerulosa, while plasma aldosterone levels and aldosterone synthase mRNA expression remain unchanged. On the other hand, lipoatrophic mice present elevated corticosterone levels but no adrenocortical hyperplasia. Ultrastructural analysis of adrenal gland show significant alterations in adrenocortical cells, with conformational changes of mitochondrial internal membranes and high amounts of liposomes. In conclusion, lipodystrophy in A-ZIP/F-1 mice is associated with hypertension, possibly due to hypercorticosteronemia and/or others metabolic-vascular changes.
[Show abstract][Hide abstract] ABSTRACT: The hormones with a strong influence on the lipid spectrum and the development of atherosclerosis include cortisol, growth hormone and oestrogens. Cortisol accelerates atherosclerosis both through dyslipidemia and through an increase in visceral fat, hypertension, increased insulin resistance and the development of reduced glucose tolerance which may result in diabetes mellitus. Even when a cortisol excess disappears, as is the case of patients cured of Cushing syndrome, arterial walls remain permanently vulnerable to the atherosclerotic process. In conditions involving a lack of growth hormone, dyslipidemia develops and increases the burden on the cardiovascular system if not treated in a timely manner by the substitution of growth hormone. Oestrogens have a double effect: they have an anti-atherogenic effect on artery walls that are not yet damaged by an atherosclerotic process, but where atherosclerosis has already developed they have a prothrombotic effect and destabilise the atheromatous plaques. If oestrogen is to be used as protection against the onset of atherogenesis, it is necessary to start in a period when the atherosclerotic process has not yet begun to damage the woman's arterial walls and it is best to use natural hormones (estradiol) and to prevent endometriosis it should be combined with crystalline progesterone applied locally--inravaginally. Oestrogens should be given in small doses, preferably parenterally. Even this will not prevent genetic oestrogen effects though.
[Show abstract][Hide abstract] ABSTRACT: Computer tomography (CT) and magnetic resonance imaging (MRI) quite often detect unexpected cases of enlargement in the hypothalamus-hypophysial region, without the above methods being indicated for clinical manifested symptomatology provoked by the tumour. This is not surprising if we consider that autopsies show the presence of hypophysial adenomas of 10-15% of population on an average. X ray, CT or MRI are indicated in the case of head traumas, lateral nasal cavity inflammations, headaches, strokes, neurological diseases and other disorders. A number of tumours of diverse etiology occur in the hypothalamus-hypophysial region, but hypophysial adenomas are by far the most frequent among all (above 90 %). Among other primary enlargements, the most frequent are craniopharyngeomas and meningeomas, while other enlargements are by fare less common. Such randomly detected tumours are mostly asymptomatic, but targeted anamnesis may show some of the symptoms quite clearly. The symptomatology can be linked with possible slight hormonal overproduction of hypophysial adenomas, a deficit of hypophysial hormones or local manifestations of expansion. Exact assessment of MRI results, of hormonal activity of the enlargement, of the relation to surrounding structures, especially the optic nerves, and the assessment of hypophysial functions are important for the therapeutic decision. Depending on the type and extension of the tumour the options considered are pharmacotherapy (the treatment of choice in the case of prolactinomas), surgery, radiotherapy (today prevailingly using the gamma knife), and if no intervention is necessary, follow up with regular MRI examinations. Tumorous growth is more often observed in "macroadenomas" than in "microadenomas" (up to 10 mm).
[Show abstract][Hide abstract] ABSTRACT: Adrenal incidentalomas are called as a disease of modern technology because increased availability and accuracy of imaging techniques lead to increased incidence of incidentally discovered adrenal masses. Adrenal incidentalomas are found in about 0.35-4.36% of abdominal CT scans performed for purpose other than suspicion of adrenal diseases. However, in autoptic studies the percentage of incidentally discovered adrenal tumours in much higher, in some of then being even more than 20%. Important component of differential diagnosis is endocrinological examination aimed to reveal potential autonomous hormonal overproduction. Approximately more than 10% of adrenal incidentalomas is characterized by autonomous cortisol production, 5-10% is phaeochromocytomas and 5-7% is aldosteron producing adenomas. Vast majority of adrenal incidentalomas are nonfunctioning tumours, mainly adenomas. Rational ways and recommendations for screening of hormonal activity of adrenal incidentalomas is discussed. Very important issue is to distinguish between benign and malignant lesions and between adenomas and non-adenomas. The accuracy of CT, MR, and fine needle aspiration cytology in distinguishing between adenomas from non-adenomas is comparable, in general not exceeding 90%. Particular characteristics of particular adrenal tumours are discussed. From the relationship between the tumour size and probability of malignancy, current recommendations are derived, that non-functioning tumours smaller than 4 cm are indicated for further follow-up, size over 6 cm is indication for adrenalectomy and in tumours between 4-6 cm decision process is complex.
[Show abstract][Hide abstract] ABSTRACT: The Leksell gamma knife (LGK) is one of the treatment options for pituitary adenomas. We report on our long-term experience treating acromegaly using LGK.
Since 1993 we have followed 96 acromegaly patients through periods of from 12 to 120 months. The mean follow-up period was 53.7 +/- 26.8 months. Seventy-two patients were treated with neurosurgery prior to LGK; for 24 LGK was the primary treatment. Thirteen patients were irradiated twice, due to persistent activity of the adenoma or its residue. Pituitary functions were tested at 6-month intervals, post-irradiation. The target tumour volume for radiosurgery was between 93.3 and 12 700 mm3 (median 1350 mm3).
Fifty per cent of the patients achieved mean GH < 2.5 microg/l within 42 months, normalized their IGF-I within 54 months, and achieved GH suppression in the oral glucose tolerance test (oGTT) < 1 microg/l with normal IGF-I within 66 months. LGK effectiveness was dependent on initial adenoma hormonal activity (GH and IGF-I serum levels), not on the size of the adenoma. Patients with primary neurosurgery followed by LGK irradiation had better outcomes than those with LGK alone. Irradiation arrested all adenoma growth, causing tumour shrinkage in 62.3% of patients. Twenty-six developed hypopituitarism when irradiated by 15 Gy (or more) on functional peritumoral pituitary tissue. No hypopituitarism appeared using lower doses.
In acromegaly, LGK is a useful adjunct to primary neurosurgery when treating post-surgical residues because it can limit the duration of medical therapy. It can be used as a primary therapy when neurosurgery is not possible.
[Show abstract][Hide abstract] ABSTRACT: Ghrelin is an endogenous growth hormone (GH) secretagogue recently isolated from the stomach. Although it possesses a strong GH releasing activity in vitro and in vivo, its physiological significance in endogenous GH secretion remains unclear. The aim of this study was to characterize plasma ghrelin levels in acromegaly and growth hormone deficiency (GHD). We investigated plasma total and active ghrelin in 21 patients with acromegaly, 9 patients with GHD and 24 age-, sex- and BMI-matched controls. In all subjects, we further assessed the concentrations of leptin, soluble leptin receptor, insulin, IGF-I, free IGF-I and IGFBP-1, 2, 3 and 6. Patients with acromegaly and GHD as well as control subjects showed similar levels of total ghrelin (controls 2.004+/-0.18 ng/ml, acromegalics 1.755+/-0.16 ng/ml, p=0.31, GHD patients 1.704+/-0.17 ng/ml, p=0.35) and active ghrelin (controls 0.057+/-0.01 ng/ml, acromegalics 0.047+/-0.01 ng/ml, p=0.29, GHD patients 0.062+/-0.01 ng/ml, p=0.73). In acromegalic patients plasma total ghrelin values correlated negatively with IGF-I (p<0.05), in GHD patients active ghrelin correlated with IGF-I positively (p<0.05). In the control group, total ghrelin correlated positively with IGFBP-2 (p<0.05) and negatively with active ghrelin (p=0.05), BMI (p<0.05), WHR (p<0.05), insulin (p=0.01) and IGF-I (p=0.05). Plasma active ghrelin correlated positively with IGFBP-3 (p=0.005) but negatively with total ghrelin and free IGF-I (p=0.01). In conclusion, all groups of the tested subjects showed similar plasma levels of total and active ghrelin. In acromegaly and growth hormone deficiency plasma ghrelin does not seem to be significantly affected by changes in GH secretion.
Physiological research / Academia Scientiarum Bohemoslovaca 01/2006; 55(2):175-81. · 1.29 Impact Factor