S Zacharieva

Medical University of Sofia, Ulpia Serdica, Sofia-Capital, Bulgaria

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Publications (73)165.5 Total impact

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    ABSTRACT: Background Mortality in acromegaly strictly depends on optimal control of GH and IGF-I levels. Modern medical therapy with somatostatin analogs (SSA) and GH-receptor antagonist (GHRA) is not available in many countries due to funding restrictions. This retrospective, comparative, cohort study investigated the impact of different treatment modalities on disease control (GH and IGF-1) and mortality in acromegaly patients. Methods Two cohorts of patients with acromegaly from Bulgaria (n=407) and Campania, Italy (n=220) were compared, and mortality rates were evaluated during a 10 year period (1999-2008). Results: The major difference in treatment approach between cohorts was higher usage of SSA and GHRA in Italy, leading to a decreased requirement of radiotherapy. Significantly more Italian than Bulgarian patients had achieved disease control (50.1% vs. 39.1%, p=0.005) at the last follow-up. Compared with the general population, the Bulgarian cohort had decreased life expectancy with standardized mortality ratio (SMR) of 2.0 (95% CI 1.54-2.47) that was restored to normal in patients with disease control - SMR 1.25 (95% CI 0.68-1.81). Irradiated patients had higher cerebrovascular mortality - SMR 7.15 (95% CI 2.92 -11.37). Internal analysis revealed an independent role of age at diagnosis and last GH value on all-cause and radiotherapy on cerebrovascular mortality. Normal survival rates were seen in the Italian cohort: SMR 0.66 (95% CI 0.27-1.36). Conclusions: Suboptimal biochemical control was associated with higher mortality in the Bulgarian cohort. Modern treatment options that induce a strict biochemical control and reduce the necessity of radiotherapy might influence life expectancy. Other factors, possibly management of comorbidities, could contribute to survival rates.
    European journal of endocrinology / European Federation of Endocrine Societies. 05/2014;
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    ABSTRACT: Aim To evaluate the clinical features, hormonal activity and natural evolution of adrenal incidentalomas (AI) in patients investigated in a single endocrinological centre and compare the prevalence of metabolic disorders and hypertension between subjects with AI and the general population. Patients and methods 515 patients with AI evaluated between 1995 and 2010 were retrospectively included in the study. Their anthropometric, clinical, metabolic and hormonal parameters were analyzed. Follow-up data was available for 142 patients. Results Mean age of all participants was 53.45 ± 13.4 years (range 13 — 84) with strong female predominance — 376 (73%) vs. 139 (27%) males. Median size of AI was 28 mm (range 10 — 190 mm). Hormonal investigations revealed that 82.9% of patients harboured non-functioning adenomas, subclinical hypercortisolism was detected in 5.94%, overt Cushing’s syndrome — in 2.7%, pheochromocytoma — in 1.9% and primary aldosteronism was diagnosed in 1% of patients. Adrenal carcinoma was identified in 1.7%. The prevalence of metabolic abnormalities and hypertension did not differ between patients with subclinical Cushing’s syndrome and non-functioning adrenal adenomas. When compared to the general population, however hypertension, type 2 diabetes and metabolic syndrome were significantly more common in patients with hormonally inactive tumours. During the course of follow-up progression to overt hormonal hypersecretion was not observed. Conclusion These results confirm other contemporary studies reporting lower rates of hormonally active and malignant lesions among AI as well as increased prevalence of hypertension and metabolic abnormalities in patients with non-functioning adrenal adenomas.
    Central European Journal of Medicine 04/2014; · 0.26 Impact Factor
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    ABSTRACT: 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.To investigate the levels of circulating ADMA and sVCAM-1 in patients with pheochromocytoma.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.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.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.
    Experimental and Clinical Endocrinology & Diabetes 09/2013; · 1.56 Impact Factor
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    ABSTRACT: Data on the incidence, mortality and causes of death in patients with Cushing's syndrome (CS) are scarce, due to the rarity of CS. The aim of the study was to analyze mortality rates in CS in a large cohort of patients of all etiologies and to determine the cause of death. This was a retrospective study of patients with CS, treated over a period of 45 years in the main tertiary referral center in Bulgaria. 386 patients with CS of all etiologies were included. The main outcome measures were the standardized mortality ratio (SMR) and the cause of death. Mean (± SD) age at diagnosis was 38±13 years; 84% of patients were women; mean follow up was 85 months (range: 0-494 months). The SMR in the CS cohort was 4.05 (95% confidence interval (CI) 2.50-5.80) (p<0.0001). The following subgroups did not have a significantly increased SMR: patients with Cushing's disease SMR - 1.88 (95%CI 0.69-4.08), adrenal adenomas 1.67 (95%CI 0.20-6.02) and ACTH-independent bilateral adrenal hyperplasia 1.14 (95 %CI 0.21-6.34). Patients with adrenal carcinomas, ectopic CS and those with CS of undetermined etiology had significantly increased SMR: 48.00 (95%CI 30.75-71.42), 13.33 (95%CI 0.00-24.59) and 4.00 (95%CI 0.48-14.45), respectively (p<0.0001). The significant predictors for mortality were active disease at death, age, male sex, etiology of the disease, the overall duration of active disease. The major causes of death were vascular events (40%) -cardiovascular 29% and cerebrovascular 11%, followed by infections (12%). Patients with CS have increased mortality due to vascular events and infections.
    European Journal of Endocrinology 08/2013; · 3.14 Impact Factor
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    ABSTRACT: Transforming growth factor-β1 (TGF-β1) signaling pathway is crucial for both human fibrogenesis and tumorigenesis. Objective: to investigate the usefulness of TGF-β1 and MMP-2 as potential circulating markers for fibrotic valvular heart disease (FVHD) and invasiveness as well as of Fetuin A as a marker of calcification in patients with prolactinomas. Design: Study population consisted of 147 subjects enrolled into 4 groups: 30 DA-treated prolactinoma patients with proven FVHD and 3 control groups with normal echocardiography: 43 DA treated pts; 26 naïve patients and 48 healthy subjects. Results: We observed significantly higher serum TGF-β1 levels in all three patients groups compared to healthy subjects (21.4 ± 8.86 vs. 19.1 ± 9.03 vs. 20.7 ± 11.5 vs. 15.8 ± 7.2 ng/ml; p=0.032). Moreover, TGF-β1 levels were significantly higher in patients with macro- and invasive prolactinomas in comparison to micro- and non invasive tumors respectively. In addition, a strong positive linear relationship between TGF-β1 levels and the score of invasiveness (ρ=0.924; p<0.001) and a moderate correlation between TGF-β1 and the tumor volume (r=0.546; p<0.002) in invasive prolactinomas were found. In contrast, PRL levels showed a better correlation with the tumor volume (r=0.721; p<0.001) then with the invasive score (ρ=0.436; p<0.020). No significant difference was observed in Fetuin A levels between patients with FVHD and healthy controls. Results concerning MMP-2 were unclear. Conclusions: TGF-β1, MMP-2 and Fetuin A are not reliable biomarkers for valvular fibrosis and calcification in DA-treated patients with prolactinomas, but TGF-β1 may represent a usefull serum marker for invasiveness. The simultaneous evaluation of TGF-β1 and PRL could improve the noninvasive assessment of prolactinoma behaviour.
    European Journal of Endocrinology 06/2013; · 3.14 Impact Factor
  • Journal of endocrinological investigation 05/2013; · 1.65 Impact Factor
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    ABSTRACT: Data on the prevalence of macroprolactinemia in patients with prolactinomas is quite limited as the presence of high-molecular prolactin forms is suspected mainly in subjects with mild hyperprolactinemia and negative pituitary imaging.The main objective of this observational case-control study was to assess the prevalence and clinical significance of macroprolactinemia among patients with prolactinomas.The study population consisted of 239 subjects: 131 prolactinoma patients and 108 sex-, age- and ethnicity- matched healthy controls. Macroprolactinemia was defined by a PRL recovery after PEG precipitation of<40%.The prevalence of macroprolactinemia among newly diagnosed prolactinoma patients did not differ statistically from the prevalence in the control group (3.5 vs. 3.7%; p=1.000) but was lower although non-significantly than the subgroup of patients treated with dopamine agonists (DA) (3.5 vs.10.8%; p=0.072). Significant association between disruptions of ovarian function and serum levels of the monomeric as well as high-molecular prolactin isoform was found.In few cases, the presence of typical hyperprolactinemia-related clinical symptoms and their disappearance after treatment with DA suggests biological activity of macroprolactin comparable with that of monomeric prolactin isoform. Decrease of macroprolactin levels after DA treatment could suggest tumoral origin of the high-molecular isoform in these rare cases. Although macroprolactinemia is considered a benign condition, pituitary imaging, DA treatment, and prolonged follow-up may be necessary in certain cases. An individualized approach to the management of patients with macroprolactinemia should be applied.
    Experimental and Clinical Endocrinology & Diabetes 04/2013; 121(4):201-5. · 1.56 Impact Factor
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    ABSTRACT: Background. Macroprolactin, the high-molecular prolactin isoform, is considered to be an inactive in vivo product with extrapituitary origin. Patients with macroprolactinemia are usually asymptomatic, with negative pituitary imaging. Based on these data, most authors do not recommend treatment and long-term followup in subjects with macroprolactinemia. However, there is evidence for overlapping clinical features among subjects with hyperprolactinemia due to monomeric or "big big" PRL isoform. Case Presentation. We present a 35-year-old female patient with secondary amenorrhea, mild obesity, hirsutism, headache and blurred vision. Hormonal evaluation revealed an extreme hyperprolactinemia (PRL = 10 610 mIU/L) almost exclusively due to macroprolactin isoform (MPRL = 10 107 mIU/L; recovery after PEG precipitation 4.7%) and hypogonadotropic hypogonadism. An invasive pituitary macroadenoma was visualized on MRI, and cabergoline therapy was initiated. Disappearance of clinical signs and symptoms, normalization of gonadotropin levels, and restoration of regular ovulatory menstrual cycles after 1 year of treatment are arguments in favor of preserved-macroprolactin bioactivity in this case. The significant decrease in MPRL levels and tumor volume in response to dopamine agonist therapy is suggestive for the tumoral origin of this isoform. Conclusions. Although macroprolactinemia is considered to be a benign condition, pituitary imaging, dopamine agonist treatment, and prolonged followup should be recommended in some particular cases.
    Case reports in endocrinology. 01/2013; 2013:634349.
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    ABSTRACT: In contrast to cabergoline, evidence-based information about a possible profibrotic effect of bromocriptine in prolactinoma patients is extremely limited. To assess the prevalence of valvular lesions among patients on long-term bromocriptine or cabergoline therapy. Case-control study. A transthoracic echocardiographic evaluation was performed in 334 subjects divided into four groups: 103 cabergoline treated, 55 bromocriptine treated, 74 naïve patients, and 102 controls. Clinically relevant valve regurgitations were equally prevalent in all investigated groups whereas subclinical valve fibrosis was significantly more frequent in both bromocriptine- and cabergoline-treated patients (40 vs 43.6 vs 21.6 vs 23.5%; P=0.004). The odds ratio (OR) for developing valvular fibrosis was 2.27 (95% CI 1.17-4.41; P=0.016) for cabergoline and 2.66 (95% CI 1.22-5.78; P=0.014) for bromocriptine groups compared with subjects not exposed to dopamine agonists (DAs). A significantly higher pulmonary arterial pressure corresponding to the longer treatment duration was observed among patients taking bromocriptine compared with cabergoline-treated subjects. Long-term treatment with cabergoline and bromocriptine seems not to be associated with an increased risk of clinically significant valve disease but possible subclinical lesions should be expected. An echocardiographic examination is recommended at the beginning and periodically during therapy with DAs acting as full or partial agonists of 5-hydroxytrytamine 2B receptors (cabergoline and bromocriptine). Bromocriptine seems not to be a safe alternative for patients receiving cabergoline treatment who have preexisting or diagnosed abnormalities suggesting valvular, interstitial myocardial, or pulmonary fibrosis. Further studies are needed to investigate the possible impact of DA treatment on pulmonary arterial pressure.
    European Journal of Endocrinology 04/2012; 167(1):17-25. · 3.14 Impact Factor
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    ABSTRACT: Pituitary adenomas represent a group of functionally diverse neoplasms with relatively high prevalence in the general population. Most occur sporadically, but inherited genetic predisposing factors are increasingly recognized. Familial isolated pituitary adenoma is a recently defined clinical entity, and is characterized by hereditary presentation of pituitary adenomas in the absence of clinical and genetic features of syndromic disease such as multiple endocrine neoplasia type 1 and Carney complex. Familial isolated pituitary adenoma is inherited in an autosomal dominant manner and accounted for approximately 2-3% of pituitary tumors in some series. Germline mutations in the aryl-hydrocarbon interacting protein gene are identified in around 25% of familial isolated pituitary adenoma kindreds. Pituitary adenomas with mutations of the aryl-hydrocarbon interacting protein gene are predominantly somatotropinomas and prolactinomas, but non-functioning adenomas, Cushing disease, and thyrotropinoma may also occur. These tumors may present as macroadenomas in young patients and are often relatively difficult to control. Furthermore, recent evidence indicates that aryl-hydrocarbon interacting protein gene mutations occur in >10% of patients with sporadic macroadenomas that occur before 30 years of age, and in >20% of children with macroadenomas. Genetic screening for aryl-hydrocarbon interacting protein gene mutations is warranted in selected high-risk patients who may benefit from early recognition and follow-up.
    Clinics (São Paulo, Brazil) 01/2012; 67 Suppl 1:37-41. · 1.59 Impact Factor
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    ABSTRACT: ABSTRACT The European Registry on Cushing's syndrome (ERCUSYN) is designed to collect prospective and follow-up data at EU level on Cushing's syndrome (CS). Baseline data on 481 CS patients (390 females, 91 males; mean age (±s.d.): 44±14 years) collected from 36 centres in 23 countries, including new patients from 2008 and retrospective cases since 2000. Patients were divided into four major aetiologic groups: pituitary-dependent CS (PIT-CS) (66%), adrenal-dependent CS (ADR-CS) (27%), CS from an ectopic source (ECT-CS) (5%) and CS from other aetiologies (2%). Proportion of men in the ECT-CS group was higher than in the other groups (P<0.05). The ADR-CS group was older than the PIT-CS (P<0.05). Prevalence of hirsutism (92%) and diabetes (74%) in ECT-CS was higher than in the other groups (P<0.05 and P<0.01 respectively). PIT-CS had more skin alterations, menstrual irregularities and hirsutism than ADR-CS (P<0.01). Reduced libido was more prevalent in men than women (P<0.01). Prevalence of spine osteoporosis was higher in men than women (P<0.05), and males had more vertebral and rib fractures than females (52 vs 18% for vertebrae; P<0.001 and 34 vs 23% for ribs; P<0.05). ECT-CS consulted a diabetologist more frequently than ADR-CS (P<0.05), while a gynaecologist was consulted more often by women with PIT-CS or ADR-CS than with ECT-CS (P<0.05). Overall, weight gain was more common in women than men (P<0.01). CushingQoL and EuroQoL visual analogue scale scores did not differ between the groups. The ERCUSYN project demonstrates a heterogeneous clinical presentation of CS at a European level, depending on gender and aetiology.
    European Journal of Endocrinology 09/2011; 165(3):383-92. · 3.14 Impact Factor
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    ABSTRACT: Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments. We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age. Overall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas. Germline AIPmut occur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.
    European Journal of Endocrinology 07/2011; 165(4):509-15. · 3.14 Impact Factor
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    ABSTRACT: The European Registry on Cushing's syndrome (ERCUSYN) is designed to collect prospective and follow-up data at EU level on Cushing's syndrome (CS). Baseline data on 481 CS patients (390 females, 91 males; mean age (±s.d.): 44±14 years) collected from 36 centres in 23 countries, including new patients from 2008 and retrospective cases since 2000. Patients were divided into four major aetiologic groups: pituitary-dependent CS (PIT-CS) (66%), adrenal-dependent CS (ADR-CS) (27%), CS from an ectopic source (ECT-CS) (5%) and CS from other aetiologies (2%). Proportion of men in the ECT-CS group was higher than in the other groups (P<0.05). The ADR-CS group was older than the PIT-CS (P<0.05). Prevalence of hirsutism (92%) and diabetes (74%) in ECT-CS was higher than in the other groups (P<0.05 and P<0.01 respectively). PIT-CS had more skin alterations, menstrual irregularities and hirsutism than ADR-CS (P<0.01). Reduced libido was more prevalent in men than women (P<0.01). Prevalence of spine osteoporosis was higher in men than women (P<0.05), and males had more vertebral and rib fractures than females (52 vs 18% for vertebrae; P<0.001 and 34 vs 23% for ribs; P<0.05). ECT-CS consulted a diabetologist more frequently than ADR-CS (P<0.05), while a gynaecologist was consulted more often by women with PIT-CS or ADR-CS than with ECT-CS (P<0.05). Overall, weight gain was more common in women than men (P<0.01). CushingQoL and EuroQoL visual analogue scale scores did not differ between the groups. The ERCUSYN project demonstrates a heterogeneous clinical presentation of CS at a European level, depending on gender and aetiology.
    European Journal of Endocrinology 06/2011; 165(3):383-92. · 3.14 Impact Factor
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    ABSTRACT: To summarize current knowledge on the clinical and genetic characteristics of familial pituitary tumor syndromes. This review is based on a comprehensive search through the English-language literature with use of the following terms: "familial," "pituitary," "adenomas," and "tumors." Familial pituitary tumors are rare and constitute approximately 5% of all pituitary adenomas. Currently, there are 4 recognized inherited syndromes that involve pituitary tumorigenesis-multiple endocrine neoplasia type 1 (MEN 1), multiple endocrine neoplasia type 4 (MEN 4), Carney complex (CNC), and familial isolated pituitary adenomas (FIPA). MEN 1 and CNC have been known for several decades, and their clinical and molecular characteristics have been comprehensively studied. Many familial cases of pituitary adenomas can be attributed to mutations in MEN1 and PRKAR1A genes. The recently defined MEN 4 is extremely rare. Familial pituitary tumors that are not associated with MEN 1 and CNC have been united under a new term introduced in the 1990s-FIPA. About 15% to 25% of patients with FIPA harbor mutations in the AIP gene. Although rare, familial pituitary tumors present an opportunity to study inherited molecular and genetic mechanisms of pituitary tumorigenesis. A comprehensive understanding of their characteristics may provide a basis for early diagnosis and better management of affected patients.
    Endocrine Practice 05/2011; 17 Suppl 3:41-6. · 2.49 Impact Factor
  • New England Journal of Medicine 03/2011; 364(10):907-17. · 51.66 Impact Factor
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    ABSTRACT: Prolactinomas are the most common hormonally active pituitary tumors and are usually successfully treated with dopamine agonists. A small proportion, however, appears not to respond to such treatment and such cases are termed resistant prolactinomas. Resistance is generally defined as failure to achieve normoprolactinemia and inability to induce tumor shrinkage. Reduced dopamine receptor density on lactotroph cells is currently considered the major underlying mechanism of resistance. Treatment options in resistant cases usually include substitution with another dopamine agonist, increasing the dose of the drug, as well as surgery, radiotherapy, and experimental medical therapies.
    Journal of endocrinological investigation 03/2011; 34(4):312-6. · 1.65 Impact Factor
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    ABSTRACT: This paper presents experiments in automatic Information Extraction of medication events, diagnoses, and laboratory tests form hospital patient records, in order to increase the completeness of the description of the episode of care. Each patient record in our hospital information system contains structured data and text descriptions, including full discharge letters. From these letters, we extract automatically information about the medication just before and in the time of hospitalization, especially for the drugs prescribed to the patient, but not delivered by the hospital pharmacy; we also extract values of lab tests not performed and not registered in our laboratory as well as all non-encoded diagnoses described only in the free text of discharge letters. Thus we increase the availability of suitable and accurate information about the hospital stay and the outpatient segment of care before the hospitalization. Information Extraction also helps to understand the clinical and organizational decisions concerning the patient without increasing the complexity of the structured health record.
    Studies in health technology and informatics 01/2011; 166:260-9.
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    ABSTRACT: Pituitary adenomas are benign intracranial neoplasms and clinically apparent pituitary adenomas have a prevalence of approximately 1:1,000 individuals. They usually arise sporadically, but familial pituitary adenomas comprise about 5% of all cases, more than half of which include multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). The other half is represented by familial isolated pituitary adenomas (FIPA), a clinical entity described in the late 1990s. Recently, interest has been focused on the genetic pathophysiology of familial pituitary adenomas. MEN1 is due to mutations in MEN1 gene. CNC is related to PRKAR1A mutations and still unknown disruptions on 2p16. Mutations of CDKN1B in MEN1-like patients without MEN1 mutations allowed the differentiation of the condition as MEN4. About 15% of FIPA kindreds are associated with aryl hydrocarbon receptor-interacting protein (AIP) gene mutations, which suggests that this is a genetically heterogeneous condition. Overall, familial pituitary adenomas represent a small proportion of pituitary tumors, but are particularly significant as affected individuals may be younger, and adenomas may be relatively difficult to treat. KeywordsMultiple endocrine neoplasia type 1-MEN4-Carney complex-Familial isolated pituitary adenomas
    12/2010: pages 137-150;
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    ABSTRACT: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. This study was an international, multicenter, retrospective case collection/database analysis. The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility.
    The Journal of clinical endocrinology and metabolism 11/2010; 95(11):E373-83. · 6.50 Impact Factor
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    ABSTRACT: 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.
    Annales d Endocrinologie 10/2010; 71(6):479-85. · 1.02 Impact Factor

Publication Stats

462 Citations
165.50 Total Impact Points

Institutions

  • 1998–2014
    • Medical University of Sofia
      • Clinical Center of Endocrinology and Gerontology
      Ulpia Serdica, Sofia-Capital, Bulgaria
  • 2012
    • University Children's Hospital Sofia Bulgaria
      Ulpia Serdica, Sofia-Capital, Bulgaria
  • 2010–2012
    • Centre Hospitalier Universitaire de Liège
      Luik, Walloon Region, Belgium
  • 2010–2011
    • University of Liège
      • Department of Endocrinology
      Liège, WAL, Belgium
  • 2009
    • Università degli Studi dell'Aquila
      • Department of Experimental Medicine
      Aquila, Abruzzo, Italy
  • 2001
    • National Oncological Hospital, Sofia
      Ulpia Serdica, Sofia-Capital, Bulgaria