ECHOCARDIOGRAPHIC MYOCARDIAL CHANGES IN ACROMEGALY: A CROSS-SECTIONAL ANALYSIS IN A TERTIARY CENTER IN BULGARIA.

CONTEXT: Cardiomyopathy is the most frequent cardiovascular complication in acromegaly. OBJECTIVE: We aimed to compare some echocardiographic markers in acromegaly patients with controls and find a correlation with disease duration, disease activity, levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). DESIGN: We conducted a cross-sectional case-control study for the period of 2008-2012. SUBJECTS AND METHODS: Acromegaly patients altogether 146 (56 men and 90 women), were divided into four groups according to disease activity and the presence of arterial hypertension (AH). The control group included 83 subjects, matching the patient groups by age, gender and presence of AH. GH was measured by an immunofluorometric method, while IGF-1 by IRMA method. All patients and controls were subjected to one- and two-dimensional transthoracic echocardiography, color and pulse Doppler. RESULTS: We found a thickening of the left ventricular walls and an increase in the left ventricular mass. However, these changes were not statistically significant in all groups and no correlation with disease duration could be demonstrated. As markers of diastolic dysfunction, increased deceleration time and isovolumetric relaxation were registered, which were dependent mainly on age in a binary logistic regression analysis, but not GH or IGF-1. Using absolute values, ejection and shortening fractions were increased in some groups. Using cut-off values, a higher percentage of systolic dysfunction was demonstrated in patients compared to their corresponding controls. Engagement of the right heart ventricle was also found - increased deceleration time and decreased e/a tric ratio. CONCLUSIONS: In conclusion, functional impairments of both ventricles were present, with a predominance of left ventricular diastolic dysfunction.

Treatment outcome results from the Bulgarian Acromegaly Database: adjuvant dopamine agonist therapy is efficient in less than one fifth of non-irradiated patients.

OBJECTIVE: We described biochemical outcome in regards to different treatment modalities in patients with acromegaly in Bulgaria. PATIENTS AND METHODS: It was a retrospective analysis using data from the Bulgarian Acromegaly Database. Patients with eligible data on at least one treatment modality were included in the study. Disease control was assessed by both GH and IGF-1 values or by GH/IGF-1 alone in cases with one marker. Last follow-up was median 7.0 (range 0.5-51) years after diagnosis. RESULTS: We identified 534 patients with interpretable data, 65.4% of whom were females. Overall surgical cure rate was 28.8%. Adjuvant bromocriptine and cabergoline treatment was analyzed in 133 and 70 patients with disease control achieved in 18.8% and 31.4% respectively. Patients without prior radiotherapy had 16.3% and 18.2% control rates respectively. Predictors of response to dopamine agonist (DA) therapy were disease activity, radiotherapy and medication dose. Adjuvant somatostatin analog (SSA) treatment led to biochemical control in 38.6% of 70 patients. Combination of SSA and cabergoline led to remission in 25% of 20 patients. Growth hormone receptor antagonist (GHRA) alone or in combination resulted in remission in 61.5% of 13 patients. Approximately one third of the patients were cured median 10 years after irradiation. Overall disease control was observed in 51.4% of our patients increasing to 70.3% in the last 5 years of the study period. CONCLUSION: DAs are efficient in less than 20% of non-irradiated patients. They are a good cost-effective alternative for carefully selected patients.

Asymmetric dimethylarginine (ADMA) and soluble vascular cell adhesion molecule 1(sVCAM-1) as circulating markers for endothelial dysfunction in patients with pheochromocytoma.

BACKGROUND: Endothelial dysfunction is a common feature of hypertension and is associated with reduced nitric oxide bioavailability. The endogenous inhibitor of nitric oxide syntase, asymmetric dimethylarginine (ADMA), and soluble adhesion molecules such as vascular cell adhesion molecule 1 (sVCAM-1) have been established as markers of endothelial dysfunction in a number of pathologic conditions including essential hypertension. There is little information, however, about these markers in endocrine hypertension. OBJECTIVE: To investigate the levels of circulating ADMA and sVCAM-1 in patients with pheochromocytoma. PATIENTS AND METHODS: Serum ADMA and sVCAM-1 concentrations were assayed by ELISA technique in 18 patients with pheochromocytoma, 18 patients with essential hypertension (EH) and 18 healthy subjects serving as a control group. RESULTS: ADMA and sVCAM-1 levels were significantly elevated in pheochromocytoma patients compared to normotensive healthy controls (0.479 ± 0.072 vs. 0.433 ± 0.054 µmol/l, p=0.037 and 690 ± 181 vs. 577 ± 108 ng/ml, p=0.03, respectively). Patients with EH also had higher ADMA concentrations than the control group, but the difference was not significant (0.476 ± 0.075 vs. 0.433 ± 0.054 µmol/l, p=0.06). No associations were found between the levels of ADMA, sVCAM-1 and some potential risk factors for endothelial dysfunction. CONCLUSION: Endothelial function is impaired in patients with pheochromocytoma as indicated by the elevated circulating levels of ADMA and sVCAM-1. The lack of association of these markers with cateholamines, glucose and lipid abnormalities together with their comparable levels in EH patients suggests that endothelial dysfunction is most likely related to hypertension itself.

Familial pituitary adenomas.

Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern because of hormonal overproduction or compression symptoms of adjacent structures. Most arise in a sporadic setting with a small percentage developing as a part of familial syndromes such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and the recently described familial isolated pituitary adenomas (FIPA) and MEN-4. While the genetic alterations responsible for the formation of sporadic adenomas remain largely unknown, considerable advances have been made in defining culprit genes in these familial syndromes. Mutations in MEN1 and PRKAR1A genes are found in the majority of MEN1 and CNC patients, respectively. About 15% of FIPA kindreds present with mutations of the aryl hydrocarbon receptor-interacting protein (AIP) gene. Mutations in the CDKN1B gene, encoding p27(Kip)¹ were identified in MEN4 cases. Familial tumours appear to differ from their sporadic counterparts not only in genetic basis but also in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, they are more aggressive and affect patients at younger age, therefore justifying the importance of early diagnosis. In this review, we summarize the genetic and clinical characteristics of these familial pituitary adenomas.

[Paraneoplastic endocrine syndromes: diagnosis and management]. / Syndromes paranéoplasiques endocriniens: diagnostic et prise en charge.

Paraneoplastic endocrine syndromes define a group of secondary signs and symptoms associated to a neoplasia, independently from the location of the primary tumor or its metastases. Paraneoplastic or ectopic endocrine syndromes usually result from aberrant hormone precursors or hormone-like substances by tumours. Knowledge of paraneoplastic endocrine complications is important both for the early diagnosis of neoplasia and the prognosis of the patient. In this review we discuss almost all reported paraneoplastic endocrine syndromes. We analyze their prevalence, etiology, laboratory diagnosis and treatment.