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Journal Article 2008; 29(6): 1038-144 PubMed PMID: 19112390 Citation  Keywords:  Acromegaly:blood, Adenoma:complications, Adult, Aged, Follow-Up Studies, Humans, Insulin-Like Growth Factor I:analysis, Male, Middle Aged, Pituitary Neoplasms:complications, Somatostatin:analogs & derivatives, Treatment Outcome,.   

OBJECTIVE: The aim of our study was to investigate the characteristics of acromegalic patients diagnosed at a tertiary University Hospital and to evaluate the results of the recommended treatment protocols.

PATIENTS AND METHODS: All our acromegalic patients were included (n=48; 27 women). Demographic, hormonal, visual and imaging data at diagnosis and during follow-up were recorded, as well as the treatments applied.

RESULTS: In 73.0% of the patients, acromegaly was due to a pituitary macroadenoma. From those under periodic surveillance, 68.2% underwent surgery and 36.4% had radiotherapy. At the time of the study 88.6% of the patients were receiving medical therapy, 28.2% of them as first-line treatment. Applying current criteria, only one patient was cured by surgery. Considering normal age and sex-matched concentrations of IGF-I as a control criteria, surgery resulted in disease control in 10% of the patients who had surgery, while medical treatment controlled the disease in 76.9% (P <0.05). Of those who receive medical therapy as first-line treatment, tumour size decreased in 45.5%, while in the rest no significant changes were observed during follow-up.

CONCLUSIONS: Not all centres obtain the results reported in the literature in terms of disease control and morbidity after surgical treatment of growth hormone-secreting tumours. It is possible that in some hospitals first-line medical treatment should be chosen, unless the patient has visual disturbances, as long as it is not clear that partial surgical removal of the tumour significantly improves response to medical therapy or reduces its costs....

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Comparative Study 2008; 29(2): 222-229 PubMed PMID: 18404140 Citation  Keywords:  Birth Weight, Body Height, Female, Gestational Age, Humans, Infant, Newborn:blood, Infant, Newborn, Diseases:blood, Infant, Premature:blood, Infection:blood, Insulin-Like Growth Factor I:analysis, Male, Pregnancy, Pregnancy Complications, Infectious:blood.   

OBJECTIVES: IGF-I is believed to be a key factor in fetal growth dynamics It is widely known, that serious early-onset infection in the newborn is a risk factor for further developmental disturbances in a child. However, effect of congenital infection as well as an influence of infectious and non-infectious perinatal risk factors on circulating IGF-I concentrations in newborns has not been examined, yet.

DESIGN: Thus, the aim of this study was: 1) evaluation of IGF-I venous blood serum concentration in full-term and premature infants considering their sex, occurrence of intrauterine infection and perinatal risk factors; 2) establishing the relationship between IGF-I serum concentrations and chosen anthropometric parameters values in infected and healthy newborns.

SETTING: The study involved 112 newborns appropriate for gestational age. Taking into consideration occurrence of early onset infection and gestational age we divided examined children into 4 groups: I group--infected, full-term newborns; II group--infected premature newborns; III group--healthy full-term newborns; IV group--healthy premature newborns. In all infants immediately after birth anthropometric measurements were performed (birth weight, body length, circumference of head and circumference of chest) and serum IGF-I concentration was determined.

RESULTS: We demonstrated that full-term infants with intrauterine infection have statistically significantly higher concentration of IGF-I in blood serum than infected premature infants and healthy full-term infants. Analysis of correlation revealed a significant positive linear correlations between IGF-I serum concentration and gestational age and anthropometric parameters values.

CONCLUSIONS: We conclude that intrauterine infection increases serum IGF-I concentration in full-term infants, but not in preterm infants, that may be a result of immaturity. We suggest serum IGF-I concentration may be considered an additional element of developmental and nutritional state assessment in infected newborn....

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Journal Article 2007; 28(5): 596-603 PubMed PMID: 17984943 Citation  Keywords:  Acromegaly:etiology, Acylation, Adenoma:complications, Blood Glucose:metabolism, Body Mass Index, Case-Control Studies, Fasting:blood, Female, Ghrelin:blood, Glucose Tolerance Test, Humans, Insulin-Like Growth Factor I:analysis, Male, Matched-Pair Analysi.   

OBJECTIVE: The pathophysiology of ghrelin secretion in acromegaly is unclear. Our aim was to study circulating fasting ghrelin levels and their response to oral glucose in acromegalic patients and normal control subjects.

DESIGN AND PATIENTS: 9 acromegalic patients (4 male, 5 female; 59.4+/-3.6 years; 28.6+/-1.0 kg/m2) and 9 age and BMI matched healthy control subjects (4 male, 5 female; 59.1+/-1.4 years; 26.5+/-0.8 kg/m2) were included. We obtained blood samples for glucose, insulin, GH, total ghrelin and acylated ghrelin at times 0, 30, 60, 90 and 120 minutes after 75 g of oral glucose.

RESULTS: Fasting GH and IGF-I were statistically different between patients and controls: GH (microg/l): 6.7+/-1.4 vs. 0.8+/-0.4, p<0.01; IGF-I (ng/ml): 414+/-75 vs. 86+/-6, p<0.01. Fasting total ghrelin (pg/ml) were similar in the patient and in the control group, 916+/-132 vs. 844+/-169, p=ns. In both groups total ghrelin levels decreased during oral glucose, and nadir total ghrelin was lower than fasting ghrelin: patients: 916+/-132 vs. 747+/-95, p<0.05; controls: 844+/-169 vs. 625+/-90, p<0.05). The AUCs of total ghrelin (pg/ml*min) were not different between the two groups: 98953+/-13052 vs. 83773+/-13096, p=ns). Fasting acylated ghrelin (pg/ml) were similar in the patient and the control group 65+/-13 pg/ml vs.74+/-14 pg/ml, p=ns. In both groups acylated ghrelin levels decreased during oral glucose, and nadir acylated ghrelin levels were lower than basal acylated ghrelin levels: patients: 65+/-13 vs. 42+/-6, p<0.05; controls: 74+/-14 pg/ml vs. 37+/-4 pg/ml, p<0.05). The AUCs of acylated ghrelin (pg/ml*min) were not different between the two groups: patients: 6173+/-992 vs. controls 8648+/-2742, p=ns). In acromegalic patients there was a negative correlation between fasting, both total and acylated, ghrelin and both fasting and post oral glucose insulin levels.

CONCLUSIONS: These data suggest that circulating total and acylated ghrelin in acromegaly is regulated by insulin and not by GH hypersecretion....

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Comparative Study 2007; 28(5): 621-628 PubMed PMID: 17984937 Citation  Keywords:  Acromegaly:blood, Adult, Aged, Aged, 80 and over, Bone Density:physiology, Bone Resorption:blood, Estradiol:blood, Female, Follicle Stimulating Hormone:blood, Human Growth Hormone:blood, Humans, Hypogonadism:blood, Insulin-Like Growth Factor I:analysis, L.   

OBJECTIVES: The aim of our study was to evaluate bone metabolism and bone mineral density (BMD), and to indicate the main determinants of these parameters in a large group of patients with active acromegaly.

METHODS: A group of 121 active acromegalics, aged 23-80 years, from a single endocrinological center was studied. Serum GH, IGF-I, LH, FSH, PRL, estradiol/testosterone, osteocalcin (OC), type I collagen carboxyterminal telopeptide (ICTP) as well as BMD by DXA at spine L2-L4, femoral neck, Ward's triangle and trochanter were measured.

RESULTS: Serum OC and ICTP concentrations were elevated (mean+/-SEM: 31.7+/-2.2 microg/L, p<0.001; 7.3+/-0.5 microg/L, p<0.001, respectively), and positively correlated with each other, as well as with IGF-I. BMD (Z-scores) was increased at L2-L4, femoral neck and trochanter (0.35+/-0.15, p=0.016; 0.60+/-0.11, p<0.001 and 0.59+/-0.13, p<0.001; respectively). The main determinants of Z-scores and ICTP were gonadal status and gender, while of OC was IGF-I. Eugonadal acromegalics had higher than normal serum OC and ICTP, as well as Z-scores at all measured sites. Hypogonadal patients (2/3 of the population) had significantly higher serum ICTP concentrations and lower BMD at all sites, when compared to eugonadal acromegalics. Thirty five percent of hypogonadal subjects had T-score<-1. Men had significantly higher serum ICTP and lower Z-scores than women.

CONCLUSIONS: (i) In active acromegaly, enhanced IGF-I-dependent bone turnover and increased BMD is observed. (ii) In hypogonadal acromegalics, high bone resorption decreases BMD and may lead to osteoporosis. (iii) There is a smaller increase in bone resorption and greater increase in BMD in women with acromegaly than in men....

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Journal Article 2007; 28(3): 279-283 PubMed PMID: 17627262 Citation  Keywords:  Child, Child, Preschool, Cyanosis:blood, Female, Heart Defects, Congenital:blood, Human Growth Hormone:blood, Humans, Insulin-Like Growth Factor Binding Protein 3:blood, Insulin-Like Growth Factor I:analysis, Male, Nutritional Status, Regression Analysis,.   

: In this study we aimed to evaluate serum insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and growth hormone (GH) levels in children with congenital heart disease (CHD) and to determine if these parameters have any relationship to the cyanosis, nutritional status and the left ventricular systolic function. This study is prospective-randomized study which conducted in 94 CHD patients (36 girls and 58 boys, aged between one 1-192 months, 19 cyanotic CHD and 75 acyanotic CHD) and age-sex matched 54 children (26 girls and 28 boys) with no CHD. In the study group, 37 out of the 94 CHD patients (39.4%) and 16 out of the 54 controls (29.6%) had malnutrition. The difference between the cyanotic and acyanotic patients in respect to malnutrition was significant (57.9% and 34.6%, p<0.05). Serum IGF-1 levels were lower (41.8+/-3.9 microg/L, 106.9+/-17.9 microg/L respectively, p<0.001) and GH levels were higher (6.43+/-0.9 ng/ml, 3.87+/-0.5 respectively, p<0.05) in CHD patient group than the controls. Serum IGF-1 levels were significantly lower in cyanotic CHD patients than the acyanotic patients (17.2+/-3.2 microg/L, 48.7.0+/-4.6 microg/L respectively, p<0.001) and serum IGF-1 levels were both lower in acyanotic and cyanotic CHD patients than the controls (p<0.001 for both). Serum IGF-1 and GH levels were similar between the well-nourished CHD patients and CHD patients with malnutrition (p>0.05). In total study group, the most effective factors on serum IGF-1 levels was presence of CHD (p<0.001), in CHD patients, the presence of cyanosis is the most effective factor on serum IGF-1 level, the presence of malnutrition is the most effective factor on serum IGFBP-3 levels (p<0.01). In the acyanotic, cyanotic, and the entire CHD patient groups, we find no correlations between the serum IGF-1, IGFBP-3 levels and left ventricular systolic function measurements. But serum GH levels were negatively correlated with diastolic left ventricular interseptum diameter, diastolic left ventricular mass and left ventricular end-diastolic volume measurements in CHD patients. In conclusion, we determined that the most important factor on serum IGF-1 levels is cyanosis. Reduced IGF1 levels and decreased left ventricular mass with an elevated GH levels in CHD patients and these findings are prominent in the cases with cyanosis and malnutrition. For this reason we believe that chronic hypoxia plays a significant role in the pathogenesis of malnutrition and also we believe that IGF-1 deficiency seen in CHD patients may be responsible in the etiology of the decrease in left ventricular mass independently from GH....

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Journal Article 2007; 28(3): 274-278 PubMed PMID: 17627261 Citation  Keywords:  Adolescent, Body Height, Child, Child, Preschool, Female, Growth Disorders:blood, Human Growth Hormone:blood, Humans, Insulin-Like Growth Factor I:analysis, Male,.   

OBJECTIVES: Insulin-like growth factor-I (IGF-I) secretion is growth hormone (GH) dependent. However the data on using IGF-I assessment as a screening procedure in diagnosing GH deficiency are not consistent. The goal of the study was an analysis of the relations between GH secretion in stimulating tests and plasma IGF-I concentration.

PATIENTS & METHODS: The analysis comprised 540 children with short stature in whom two standard GH stimulating tests (GHST) were performed, together with an assessment of plasma IGF-I concentration. The relationships between GH peak in both tests and IGF-I secretion were analysed.

RESULTS: There was no correlation either between GH peaks in different tests or between GH and IGF-I secretion in particular patients. Moreover, both the mean IGF-I concentration was similar in the patients with normal and subnormal results of GHST and the mean GH peak in GHST presented similar in the groups of children with normal and decreased IGF-I secretion.

CONCLUSIONS: Assessment of IGF-I secretion fails to be a screening procedure for the results of GHST. The lack of correlation between the results of two GHST should be taken into account when evaluating the significance of GHST and IGF-I assessment in diagnosing GH deficiency....

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Journal Article 2006; 27(6): 828-832 PubMed PMID: 17187024 Citation  Keywords:  Acromegaly:blood, Adenoma:blood, Adult, Aged, Aged, 80 and over, Bromocriptine:therapeutic use, Female, Follow-Up Studies, Hormone Antagonists:therapeutic use, Human Growth Hormone:blood, Humans, Insulin-Like Growth Factor I:analysis, Male, Middle Aged, P.   

OBJECTIVES: Acromegaly is a rare disease with increased mortality rate. The aim was to present our centre experience in the diagnosis and treatment of a series of patients suffering from acromegaly.

METHODS: 130 patients (55 men, 75 women) aged 19-84 years presenting with clinical and hormonal features of acromegaly, attending Department of Endocrinology and Out-patient Clinic between 1990 and 2004 were studied. They were analyzed their GH and IGF-1 levels, CT and MRI scans, and they were administered medical therapy, neurosurgery and radiotherapy.

RESULTS: We have observed 106 macro-, 16 microadenomas and 1 case of ectopic GHRH. 115 patients were operated, as cured were recognized 74 of them. Pituitary irradiation was applied to 11 patients, in 4 of them it did not cure the disease. Medical therapy was efficacious in 12% patients treated with bromocriptine, 73% with long-acting lanreotide and 58% with long-acting octreotide. In 7 patients other malignant neoplasm were detected. 11 patients died during the follow-up.

CONCLUSIONS: There is possible underdiagnosis of acromegaly in our region, especially in males. We have observed better diagnostic opportunities in recent years when MRI was available. It was accompanied by better outcome of surgical and pharmacological treatment and better control of the complications of the disease....

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Comparative Study 2006; 27(5): 639-643 PubMed PMID: 17159821 Citation  Keywords:  Acromegaly:blood, Adenoma:complications, Adult, Aged, Colonic Polyps:complications, Colonoscopy:methods, Colorectal Neoplasms:complications, Female, Fluorescence, Growth Hormone:blood, Humans, Insulin-Like Growth Factor I:analysis, Male, Middle Aged, Pitu.   

OBJECTIVES: Acromegalics have an increased risk of colorectal neoplasm. The aim of this study was to establish the association between acromegaly and colorectal lesions.

MATERIALS AND METHODS: The study included 51 patients with active acromegaly: 30 women and 21 men (average age 52.95 +/- 13.49 years). Growth hormone (GH), insulin-like growth factor I (IGF-I), prolactin (PRL), thyreothropin (TSH), thyroxine (FT4) were measured in the serum when patients were hospitalized for their first diagnosis of acromegaly, before starting the treatment. All patients underwent colonoscopy--in the first phase conventional in white light; in the second phase fluorescence colonoscopy. Autofluorescence of colonic mucosa was assessed by illumination with monochromatic light. Green fluorescence is characteristic for normal colonic mucose, whereas red fluorescence occur in pathological lesions. Material to histopathological examination was taken from every pathological colorectal lesion.

RESULTS: Using conventional colonoscopy we detected colonic polyps in 21 acromegalic patients (41.17%). Polyps with red fluorescence were found in 7 (13.7%) acromegalics and with green fluorescence in 16 (31.37%) cases of these patients. Histological diagnoses of colorectal lesions are adenoma, hyperplastic and inflammatic polyps. The number of colorectal polyps was dependent on IGF-I, fT4 and sex.

CONCLUSIONS: Acromegaly is associated with high prevalence of colorectal pathology, mainly hyperplastic polyp and adenoma. There is a relationship between number of colorectal polyps and serum IGF-I levels in acromegaly. Adenomas and hyperplastic polyps were associated with higher levels of IGF-I....

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