Tina Dušek

Analysis and prospects for curricular reform of medical schools in Southeast Europe.

Aim  To analyse the curricula of 16 medical schools in 6 countries in Southeast Europe in order to establish a prevailing standard curriculum against which a prospective curriculum reform could formulate its objectives.

Hypercoagulable state in Cushing's syndrome is reversible following remission.

Hypercoagulability is a commonly described complication in patients with Cushings syndrome (CS). The aim of this study was to assess the long‐term effects of surgical remission from CS on serum levels of coagulation and fibrinolytic markers.

A Novel AAAS Gene Mutation (p.R194X) in a Patient with Triple A Syndrome

Objective: The clinical and molecular data of a patient with triple A syndrome are reported. Patient: A 21-year-old male who was diagnosed for adrenal insufficiency at the age of 2 years after a severe attack of adrenal crisis. At the age of 4 years, achalasia and alacrima were diagnosed. Puberty started at the age of 17 years. At the same time, symptoms of central, peripheral, and autonomic nervous system dysfunction were noted. Later on, at the age of 20 years, a bone age delay of 6 years and severe osteoporosis was diagnosed. Results: A compound heterozygous AAAS mutation consisting of two mutations was found: a C > T transition in exon 7 resulting in a change of arginine at amino acid position 194 into a stop codon (Arg194X) at one allele, and a C > T transition in exon 12 resulting in a change of glutamine at amino acid position 387 into a stop codon (Gln387X) on the other allele. Conclusion: The mutation in exon 7 (p.R194X) of the AAAS gene is a novel mutation which has not been found in any other family so far, whereas the second was already found in some other families. This case adds to the clinical and molecular spectrum of triple A syndrome and may provide a new insight into the functions of AAAS gene.

Clinical features and therapeutic outcomes of patients with acromegaly: Single-center experience

The aim of this study was to review the outcome of acromegaly treatment, as well as co-morbidity and mortality in a series of patients with acromegaly attending a single center in the last 10 yr. In that period, 53 patients were treated for acromegaly. Transsphenoidal operation was applied as the first-line therapy in 94.3% of patients and it led to disease remission in 59.2% of them. The remission criteria included a nadir GH<1 µg/l after glucose load, and normal age-related IGF-I levels. The remission rate after transsphenoidal surgery was significantly higher in the group of patients with microadenoma (76.9%), than in the group of patients with macroadenoma (52.8%). Patients with invasive tumors had remission rate of 16.7% after transsphenoidal surgery. There were no perioperative deaths. As the second-line treatment somatostatin analogues, radiotherapy, and dopaminergic agonists were used. Hypertension and diabetes were the most frequent co-morbidities in the group of patients. After successful treatment, 30% of patients with diabetes or impaired glucose tolerance had significant improvement of glycemic control. Transsphenoidal surgery is the appropriate first-line therapy in patients with somatotropinoma. Medical and radio-therapy should be reserved as the second-line therapy after surgery failure.

Decreased peak bone mass is associated with a 3-bp deletion/insertion of the CYP19 intron 4 polymorphism: Preliminary data from the GOOS study

Finding that estrogen plays an important role in bone homeostasis in men prompted research on relationship of polymorphism at the CYP19 gene and the bone mass. Therefore, influence of 3-bp deletion/insertion polymorphism of CYP19 (TTTA)7 allele on the peak bone mass attainment in males was studied. Fifty-eight unrelated male participants, aged 21–35, were selected depending on the presence of (TTTA)7 (no.=19) or (TTTA)7−3 (no.=39) alleles from the initial cohort of 92 young males. Heterozygotes (TTTA)7/(TTTA)7−3 (no.=13) were not included in the analysis. Serum levels of estradiol, free testosterone, 25-hydroxyvitamin D, bone alkaline phosphatase, osteocalcin, and β-crosslaps were measured. Bone mass was measured by DXA at the hip and at the spine. (TTTA)7−3 allele was associated with significantly lower femoral neck bone mineral density (BMD) (p=0.02). Logistic regression model indicated strong association of (TTTA)7−3 allele with low BMD in the range of osteopenia/osteoporosis (p=0.014, odds ratio 12.36, confidence intervals 1.65–92.46). In the present study association of 3-bp deletion polymorphism of the (TTTA)7 allele with decreased peak bone mass in males is reported for the first time. However, further studies are necessary to elucidate the functional relevance of this polymorphism.

A Rapid Biochemical and Radiological Response to the Concomitant Therapy with Temozolomide and Radiotherapy in an Aggressive ACTH Pituitary Adenoma

Background and Importance. In the last eight years temozolomide (TMZ) has been used as the last-line treatment modality for aggressive pituitary tumors to be applied after the failure of surgery, medical therapy, and radiotherapy. The objective was to achieve a rapid control of tumor growth and hormone normalization with concurrent chemoradiotherapy in a patient with very aggressive ACTH pituitary adenoma. Clinical Presentation. We describe a patient with an aggressive ACTH-producing adenoma treated with concurrent temozolomide and radiotherapy. The patient suffered from an aggressive ACTH adenoma resistant to surgical and medical treatment. After two months of concurrent temozolomide and radiotherapy, cortisol normalization and significant tumor shrinkage were observed. After 22 months of follow-up, there is still no evidence of tumor recurrence. Conclusion. Concurrent treatment with temozolomide and irradiation appears to be highly effective in the achievement of the tumor volume control as well as in the control of ACTH secretion in aggressive ACTH adenoma.

Hypopituitarism after gamma knife radiosurgery for pituitary adenoma

ABSTRACT Purpose: The aim of the study was to investigate the incidence of and risk factors for hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenoma. Materials and Methods: We conducted a retrospective analysis of the pituitary function of 90 patients who underwent GKRS for pituitary adenoma at the University Hospital Centre Zagreb between 2003 and 2014. Twenty seven of them met the inclusion criteria and the others were excluded from the study due to pituitary insufficiency which was present before GKRS. Eighteen patients had non-functioning and 9 patients had secretory adenomas. Median patients’ age was 56 years (24–82). GKRS was performed using the Leksell gamma knife Model C. The median prescription radiation dose was 20 Gy (15–25) and the median tumor volume size was 3.4 cm3 (0.06–16.81). New onset hypopituitarism was defined as a new deficit of one of the three hormonal axes (corticotroph, thyreotroph, or gonadotroph) ≥3 months following GKRS. SPSS was used for statistical analysis, with the significance level at P<0.05. Results: During the median follow-up period of 72 months (range 6–144), 30% of patients developed new hypopituitarism after GKRS. This corresponds to incidence of one new case of hypopituitarism per 15 patient-years. Age, gender, tumor function, tumor volume, suprasellar extension, prescription dose of radiation, as well as dose-volume to the pituitary gland, stalk and hypothalamus were not predictive factors for the development of hypopituitarism. Conclusions: In our cohort of patients with pituitary tumors who underwent GKRS, 30% developed new hypopituitarism during the follow-up period.

Transsphenoidal surgery for pituitary adenoma: indications and outcomes.

To the Editor: We read with great interest the article by Maric et al (1) on the outcomes of pure endoscopic transsphenoidal surgery (PEETS). Since PEETS is a relatively new surgical technique, data on its effectiveness and safety are very valuable, which makes this article an important contribution to the field. However, we have some concerns about the protocol of the study regarding the biochemical criteria for remission of acromegaly, assessment of pituitary function, and the indications for surgical treatment of prolactinoma.