Silvia Vandeva

Background: Polycystic ovarian syndrome (PCOS) and the non-classic form of congenital adrenal hyperplasia (NC-CAH) are hyperandrogenic conditions with overlapping clinical symptoms but different genetic backgrounds. The possible interrelationships between the two conditions remain unclear; thus, the present study aims to investigate the prevalence of CYP21A2 exon 7 genetic variants in patients with PCOS and to explore the possible associations of the polymorphisms with adrenocortical hormonal production. Methods: The CYP21A2 exon 7 region was genotyped in 80 unrelated female patients with PCOS and 12 women with NC-CAH. The associations between genetic variants, clinical characteristics, and adrenocortical hormones were investigated. Results: The pathogenic CYP21A2 NC-CAH variant c.844G>T; p.(Val282Leu) was found in 66.7% (8/12) of patients with NC-CAH but in none of the individuals with PCOS. The benign rs1554305325, rs6465, rs6472, and rs6477 genetic polymorphisms were not related to clinical hyperandrogenism. The rs6472 polymorphic alleles were associated with increased adrenocorticotropic hormone (ACTH) (5.5 vs. 3.4 pmol/L, p = 0.022) and cortisol (460.5 vs. 366.5 nmol/L, p = 0.016) levels. The rs6465 variant alleles were significantly associated with lower pregnenolone (1.43 vs. 3.1 ng/mL, p = 0.031) and ACTH (2.5 vs. 4.5 pmol/L, p = 0.030) levels in the unadjusted model but not after adjustment for potential confounders (p > 0.05). Conclusions: The p.(Val282Leu) variant is very common among Bulgarian patients with NC-CAH but it has not been found in our cohort of women with PCOS. The CYP21A2 exon 7 polymorphisms might be associated with cortisol levels in the patients with PCOS. Further larger studies are needed to confirm or reject the current findings in different ethnic groups.

Acromegaly is a rare disease that significantly affects patients’ quality of life (QoL) – especially appearance, pain, depression, energy and vitality. The aim is to assess and compare the acromegaly patients’ QoL related to the type of pharmacotherapy using specific and generic QoL measuring instruments. A cross-sectional questionnaire-based study among 163 hospitalized acromegaly patients was conducted. QoL was measured by Acromegaly Quality of Life Questionnaire (AcroQol), Short-Form Health Survey (SF-36) and EQ-5D-3 L. Women had lower AcroQol values than men 50 vs. 66 (p < 0.05). Lower values for octreotide than octreotide + pegvisomant were found with all questionnaires: 57 vs. 67 AcroQol (p = 0.0405), 0.699 vs. 0.7586 EQ-5D (p = 0.0595) and 57.94 vs. 66.06 SF-36 scores (p > 0.093) . A significant correlation between AcroQoL, SF-36 and EQ-5D-3 L scores (rs> 0, р < 0.00001) was revealed. AcroQol, EQ-5D and SF-36 are reliable questionnaires applicable for Bulgarian population with acromegaly. This pilot study confirmed that combination therapy which includes biological therapy is related to higher physical appearance AcroQol scores than nonbiological monotherapy – a conclusion which should be further confirmed.

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.

Various factors influence quality of life (QoL) in acromegaly. Whether disease control and treatment approach are related to QoL is still a matter of debate. The aim of the present study was to evaluate QoL in patients with acromegaly using the disease-specific Acromegaly Quality of Life Questionnaire in respect to disease activity, treatment modalities, and other factors. We studied 212 patients with acromegaly in a cross-sectional manner over a 6-year period in a single tertiary center. As a second step, seventy of the patients who were with active disease at baseline were followed up prospectively and 45 of them were in remission at re-evaluation. In regard to the cross-sectional group, active acromegaly independently predicted worse appearance scores. Prior radiotherapy and older age were independent negative predictors of all scales. Female gender negatively predicted all scales except the appearance domain. Longer duration of remission predicted worse personal relations scores in biochemically controlled patients. The use of somatostatin analog (SSA) was associated with worse personal relations scores, while higher IGF-1 index predicted worse appearance scores in patients with active acromegaly. In the prospective group, achievement of remission independently predicted improvement of the total scale. Lower corresponding baseline scores predicted improvement of the total, physical, and appearance scales, while the absence of hypopituitarism independently predicted improvement of the appearance scale. The use of SSA was associated with improvement of the total and appearance scores. In conclusion, QoL is a multifactorial issue that needs an individualized approach for detection and management.