ACTA ENDOCRINOLOGICA (BUC)

Context. Infertility affects more and more younger patients nowadays. Life-saving cancer treatments - chemotherapy and radiation therapy unfortunately damage oocytes and reduce the window of fertility in women. There were an estimated 14.1 million cases of cancer worldwide in 2012, of which 6.7 million were in women. Aim. We are reviewing fertility options and treatments for women fighting oncological diseases. It is important to promote that there is a possibility for these patients to know all they can do in order to preserve their fertility and our government should help all these young patients. The trend of delayed childbearing has increased worldwide duet o increased life costs, difficulty of finding a suitable partner and carier options, while the number of women facing a cancer diagnosis is rising. Material and methods. We describe a review regarding the impact of these treatments for the fertility of these patients. Results. Show that informed patients can better cope with their diagnostic and have a better prognosis. Conclusions. Improving survival rates and current data have created a new medical field oncofertility. The term was first introduced in 2015 and is being used all over clinics that treat young patients nowadays.

Context. Hyperparathyroidism-jaw tumour (HPTJT) syndrome is a rare autosomal dominant cause of familial hyperparathyroidism associated with ossifying fibromas (OF) of the maxillofacial bones and increased risk of parathyroid carcinoma, caused by inactivating germline mutation of the cell division cycle 73 (CDC73) gene. Objective. To report the first Romanian family with HPT-JT and genetic screening of CDC73 gene. Subjects and Methods. Mutational analysis of the CDC73 gene and genetic screening of the family of a proband with HPT-JT. Histological diagnosis of parathyroid tumors (WHO criteria) and immunohistochemistry (parafibromin) were performed. Results. Three of the six screened family members had evidence of PHPT and surgically proven parathyroid tumours. Two of the three affected members had parathyroid carcinomas and one had two parathyroid adenomas. Genetic screening of CDC73 gene revealed that 4 of 6 patients showed a heterozygous germline deletion of one nucleotide: c.128-IVS1+1 delG. All the three affected patients, resulted to be carriers of the CDC73 mutation, but each one bearing a different CDC73 polymorphism. Conclusions. We identified a new CDC73 germline mutation in a Romanian family of HPT-JT. Analysis of clinical phenotypes in the four mutated individuals confirmed the incomplete penetrance and the variable clinical expression of the disease.

The detection of thyroid nodules in a patient with Graves’ disease is not a rare event.\r\nThe management of these cases still represents a controversial problem for clinical practice.\r\nThis paper describes the case of a patient with Graves’ disease and a concurrent\r\nfollicular thyroid carcinoma, presenting as a clinical palpable nodule in the right lobe.\r\nThyroid function tests confirmed thyrotoxicosis. Immunological investigations showed high\r\nlevels of TSH-R antibodies. Thyroid ultrasound revealed an increased thyroid volume with\r\na diffuse low echogenicity of parenchyma and in the right lobe a single homogeneous\r\nhypoechoic nodule. The scintiscan indicated the presence of a “cold nodule” in the right lobe\r\nand increased uptake in the rest of parenchyma. Antithyroid drug therapy was\r\nrecommended. Cytological exam indicated an “indeterminate” smear. After euthyroidism\r\nwas achieved, surgical therapy was recommended and near total thyroidectomy was\r\nperformed. The morphopathological exam revealed an invasive follicular carcinoma on a\r\ndiffuse thyroid hyperplasia (Graves’ disease). This case report is followed by a discussion\r\nabout the incidence of malignancy in thyroid nodules concurrent with Graves’ disease. The\r\ncriteria that raised concern about a possible malignancy of the nodule are presented.\r\nIn conclusion, we recommend that patients with Graves’ disease should undergo a\r\nregular examination of the thyroid gland for an early detection of possible malignant\r\nnodules. The intervention of choice in these cases should be near total or total\r\nthyroidectomy, if malignancy cannot be excluded by preoperative evaluation.

Gastrointestinal effects of estrogens are emerging as an important topic in colorectal cancer management. Current research demonstrated the link between inflammation and this malignancy, so important estrogen dependent mediators of the inflammatory response have been identified. Radioresistance and chemoresistance still represent an important cause of therapeutic failure in colorectal cancer and lead to further studies of colorectal carcinogenesis and predictive markers.

Background. People chew betel nut (Areca catechu) for physical work and stress reduction, but it contains arecoline, which has both therapeutic value and untoward effects on endocrine and gonadal functions. Objective. Aim of the present study is to investigate its role on adrenal with its target in metabolic stress in mice. Materials and methods. Mice were deprived of water / food, each for 5 days / treated with arecoline (10 mg / kg body wt daily for 5 days) / arecoline after water or food deprivation, for 5 days each. Results. Water or food-deprivation caused adrenocortical hyperactivity, evident from abundance of enlarged mitochondria and smooth endoplasmic reticulum (SER) with elevation of corticosterone level (C: 68.31 ± 2.30, WD: 159.31 ± 4.10 / FD: 194.12 ± 3.40 μg/ mL). Arecoline treatment alone or in water deprivation (C: 68.31 ± 2.30, AR: 144.50 ± 4.33, AR+WD: 194.42 ± 3.35 μg/ mL) / food deprivation (AR + FD: 180.89 ± 4.51 μg/ mL) stress also stimulated adrenocortical activity as recorded in metabolic stress. In contrast, adrenomedullary activity was not altered following water/ food deprivation. Arecoline treatment alone or in metabolic stress suppressed adrenomedullary activity by showing depletion of chromaffin granules (E/NE?), epinephrine (E) and norepinephrine (NE) concentrations. Both the stress decreased blood glucose and liver glycogen levels. Arecoline treatment decreased blood glucose level, with a rise in liver glycogen level, but elevated blood glucose level in water deprivation unlike in starvation. Conclusion. Arecoline alone or in metabolic stress involves adrenal and probably other endocrine glands (pancreas, posterior pituitary and rennin-angiotensin system) to maintain homeostasis in metabolic stress in mice.

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The appearance and normal development of the anterior pituitary gland requires several signalling molecules and specific transcription factors. Gene mutations of these\r\npituitary transcription factors may lead to different degrees of combined pituitary hormone deficiency (CPHD) associated or not with morphological changes of the hypothalamicpituitary region. We present the first Romanian case of progressive CPHD in two brothers from a consanguineous family. Clinical, hormonal and MRI follow-up were performed during 20 years. Growth hormone deficiency was certified at the age of 5, respectively 3 years, followed by gonadotropin deficiency diagnosed at the age of 21, respectively 19 years, and by central hypothyroidism diagnosed at the age of 23, respectively 21 years.\r\nSubstitutive treatment rhGH was commenced, followed by testosterone and later thyroxin, in adequate doses. Adrenal function was normal during the follow-up. MRI revealed\r\nanterior pituitary hypoplasia in both siblings, with a partially empty sella in the younger brother and a thick midline septum in the sphenoid sinus in both siblings, which was not described in previous reports. The progressive CPHD suggested a PROP 1 deficiency, which was confirmed by genetic analysis. The c.301-302delAG homozygous mutation in the PROP 1 gene was identified, resulting in a complete loss of promoter binding and\r\ntranscriptional activation of the mutant protein.

controversial. Aim. This study retrospectively reviews the tumor evolution in patients with NFA macroadenomas treated with surgery and conventional RT, as compared to surgery alone. Methods. Of 107 unselected patients with operated NFA (aged 19 - 77 years), evaluated between 1977 - 2008, 71 patients were follow-up without RT (group A), while 36 patients were submitted to RT (group B). Patients submitted to radiosurgery were not included. Both groups underwent serial imaging studies with computed tomography or magnetic resonance. Tumor evolution was conventionally defined as a change of minimum 25% of diameter. Results. The surgical approach was transfrontal in 47% of patients, transsphenoidal in 43% or both in 10% of patients, similar in both study groups. In group B, 30 patients underwent highvoltage RT (mean total dose 50.5 Gy) and 6 patients low-voltage RT (mean emission dose 16,775 R). Mean follow-up after surgery in group A was 3.4 years (range 6 months - 10 years) and after RT in group B it was 6.8 years (range 2 &#8211; 24 years), p < 0.001. In group A, 16 out of 71 patients had no visible tumor remnants. In this subgroup, 2 patients (12.5%) showed tumor recurrence. Fifty-five out of 71 patients had residual tumors, 21 with extrasellar extension after surgery. In this subgroup, 21 patients (38%) showed tumor re-growth and 7 (13%) showed tumor decrease. In group B (n=36) all patients had tumor remnants after surgery with extrasellar extension in 30 patients. After RT, tumor re-growth occurred in 5 out of 36 patients (14%) as compared to subgroup A with residual tumors (p< 0.05) and tumor decrease in 14 out of 34 (41%), as compared to the same subgroup A (p < 0.01). The 5 year-tumor re-growth free survival rate of 88% in irradiated patients was significantly better than in non-irradiated patients with residual tumors (31%, log-rank test, p < 0.01, Kaplan-Meier analysis), but similar to that in patients without remnants (87.5%). Age, sex, tumor parasellar extension and size of residual tumor were not predictors of recurrency. Conclusion. Postoperative radiotherapy provides a significant improvement of local control in patients with residual NFA compared to surgery alone. It is necessary a long term follow-up due to recurrency noticed up to 8 years postsurgery. In patients without tumor remnants, a wait-and-see policy is indicated after surgery.

Context. Ghrelin is a hormone secreted primarily from stomach that can affect growth by its somatotropic and orexigenic activities. Objective. The aim of this study was to investigate the relationship of ghrelin and growth in children and adolescents with idiopathic short stature. Subjects and Methods. After thorough clinical examination, 56 subjects including 31 with normal weight and height and 25 with short stature were evaluated for fasting total (TG) and acylated (active) ghrelin (AG) levels. All the parameters of growth including growth hormone and IGF-1 levels, bone age and body mass index were also investigated. Appetite was also assessed and all the studied subjects were also divided into two groups, poor or good appetite. Results. TG and AG levels were not significantly different in the two groups. There was not any significant correlation between ghrelin and parameters of growth. On the other hand, TG concentration was significantly higher in subjects with poor appetite, but AG was not significantly different. Conclusions. The results of this study show that ghrelin is not significantly altered in idiopathic short stature. Although TG is increased in children with poor appetite its acylation is not increased concomitantly.

Objective. Mean platelet volume (MPV) and platelet function analysis have been studied before in acromegaly, but the effect of treatment on both parameters has not been evaluated. We aimed to investigate MPV and platelet function analysis in acromegalic patients after sixmonths of treatment. Methods. Forty patients with active acromegaly and 36 healthy subjects were included in the study. Plasma glucose and lipids, fibrinogen, GH, IGF-1 levels, MPV and platelet function analysis were measured. All patients with acromegaly were re-evaluated six months after treatment. Results. Fasting blood glucose (FBG), GH, IGF- 1, fibrinogen levels and MPV values were significantly higher in acromegalic group compared with the control. Platelet function was enhanced significantly (pcol-ADP: 0.002, pcolepinephrine: 0.002). After 6 months of treatment FBG, serum GH, IGF-1, fibrinogen and MPV decreased and collagen/ADP- and collagen/epinephrine-closure times (CT) were increased. Acromegalic patients that were in remission with long-acting SSA after surgery had significantly higher fibrinogen levels and MPV and decreased collagen/ epinephrine-CT with respect to the controls (pfibrinogen: 0.001, pMPV: 0.026, pcol-epinephrine: 0.037). Conclusion. Acromegaly was associated with increased MPV and enhanced platelet activity. Although growth hormone hypersecretion was controlled by surgery and medical treatment, these parameters did not improve – indicating a still increased risk for cardiovascular events.