Histologically Proven Bronchial Neuroendocrine Tumors in MEN1: A GTE 51-Case Cohort Study.

OBJECTIVE: To evaluate the natural history of MEN1-related bronchial endocrine tumors (br-NETs) and to determine their histological characteristics, survival and causes of death. br-NETs frequency ranges from 3 to 13% and may reach 32% depending on the number of patients evaluated and on the criteria required for diagnosis. METHODS: The 1023-patient series of symptomatic MEN1 patients followed up in a median of 48.7 [35.5-59.6] years by the Groupe d'étude des Tumeurs Endocrines was analyzed using time-to-event techniques. RESULTS: br-NETs were found in 51 patients (4.8%, [95% CI 3.6-6.2%]) and were discovered by imaging in 86% of cases (CT scan, Octreoscan, Chest X-ray, MRI). Median age at diagnosis was 45 years [28-66]. Histological examination showed 27 (53%) typical carcinoids (TC), 16 (31%) atypical carcinoids (AC), 2 (4%) large cell neuroendocrine carcinomas (LCNEC), 3(6%) small cell neuroendocrine carcinomas (SCLC), 3(6%) TC associated with AC. Overall survival was not different from the rest of the cohort (HR 0.29, [95% CI 0.02-5.14]). AC tended to have a worse prognosis than TC (p = 0.08). Seven deaths were directly related to br-NETs (three AC, three SCLC and one LCNEC). Patients who underwent surgery survived longer (p = 10-4) and were metastasis free, while 8 of 14 non-operated patients were metastatic. There were no operative deaths. CONCLUSIONS: Around 5% of MEN1 patients develop br-NETs. br-NETs do not decrease overall survival in MEN1 patients, but poorly differentiated and aggressive br-NETs can cause death. br-NETs must be screened carefully. A biopsy is essential to operate on patients in time.

PSYCHO-SOCIAL ASPECTS OF QUALITY OF LIFE IN WOMEN WITH ENDOMETRIOSIS.

OBJECTIVES: The objective of this study was to assess the impact of endometriosis on the quality of life. PATIENTS AND METHODS: Study group of 205 women, aged between 18-45 years old, hospitalized in the "Cuza-Voda" Hospital of Iasi, between 2013-2015. We used the Fertility Problem Inventory, the Endometriosis Health Profile and the Beck Depression Inventory. RESULTS: We first realized a descriptive analyses of patients' health related quality of life - 60% of women reported higher infertility distress associated with relationship issues caused by difficulties to conceive. The descriptive analysis over the quality of life in patients with endometriosis suggests that the high level of stress related factors, are: the loss over the control of the symptoms, dyspareunia and altered emotional status. Regarding the sexual aspect of life, almost a quarter of the women complained about an altered sexual status, due to both fear of failing in conceiving and dyspareunia caused by the endometriosis. The descriptive analysis over the infertility related stress suggests that the factors associated with a high level of stress are: sadness, pessimism, feeling of failure, irritability, lack of confidence, self-hatred and fatigue. CONCLUSIONS: Patients with endometriosis are dealing daily with a large spectrum of symptoms, including pain, dyspareunia, emotional instability and high levels of stress, which have a negative impact upon the quality of life, by lowering it on different levels. Also, within the present study we showed a significant presence of high infertility stress in patients of all ages that lead to depression and social anxiety.

THE VOLUME OF SOLITARY PARATHYROID ADENOMA IS RELATED TO PREOPERATIVE PTH AND 25OH-D3, BUT NOT TO CALCIUM LEVELS.

PURPOSE: To correlate the volume of parathyroid adenomas with the hormonal and metabolic profile at patients diagnosed with primary hyperparathyroidism (pHPTH). PATIENTS AND METHODS: Cross-sectional multicentric study, enrolling 52 patients with pHPTH from two medical institutions. Serum calcium and PTH were evaluated in all patients before surgery, whereas 25OHD3 was measured only in the 33 patients recruited form one medical unit. The volume of parathyroid adenoma was measured by using the formula of a rotating ellipsoid. RESULTS: We observed a significant correlation of the volume of parathyroid adenomas with PTH at patients from the two units and in the whole group (p < 0.0001), but not with serum calcium (p = 0.494). Twenty-five out of the 33 patients at whom 25OHD3 was measured had levels in the range of deficiency. 25OHD3 was not correlated with PTH or calcium levels, but was negatively correlated to the adenoma volume and positively to the PTH/volume ratio (p = 0.041 and p = 0.048, respectively). CONCLUSIONS: The volume of parathyroid adenoma seems to be related to preoperative PTH and 25OHD3, but not to calcium level. Vitamin D deficiency is frequently found at patients with pHPTH and may contribute to particular disease profiles, including larger parathyroid adenomas.

99mTc MIBI THYMIC SCINTIGRAPHY IN DIAGNOSIS AND THERAPEUTIC DECISION MAKING: WHAT IS BEHIND THE IMAGE?

CONTEXT: Despite CT being generally used in thymic pathology, in the case of regions with the same tissue density, only functional radioisotopic imaging can hint towards malignity. OBJECTIVES: To assess the usefulness of 99mTc MIBI scintigraphy for diagnosis and treatment planning in thymoma, in relation with the radiotracer uptake mechanism. PATIENTS AND METHODS: 99mTc MIBI thymic scans for 19 patients diagnosed with thymic disorders were assessed using tumor uptake ratio (UR). Specimens of thymectomies were examined and cytological assessments were correlated with the UR. RESULTS: The UR of all surgical patients was higher than 1.2, with a 1.5 cutoff between lymphoid hyperplasia and thymoma. The UR values were correlated with the histopathologic diagnosis (Pearson correlation 0.91, significant at p<0.01). The highest UR was 3.24, found in the case of an AB thymoma where the rate lymphocytes/epithelial cells (L/E) was 1.6. In B1 thymoma UR was 1.14 and L/E was 2.46. CONCLUSION: Phenotype differences between thymoma types correlate with 99mTc MIBI cellular uptake: lower rate L/E corresponds to higher UR, higher malignity potential and invasiveness. A thymic 99mTc MIBI UR higher than 1.5, corresponding to a CT tumoral image, is suggestive for a thymoma, requiring surgical treatment first.

DEVELOPMENT OF SYNTHETIC GROWTH CHARTS FOR ROMANIAN POPULATION.

There are no new national growth references for the Romanian population and the current recommendations for short stature evaluation is the use of the Swiss growth charts developed based on a longitudinal study.The aim of the present paper is to present the new synthetic growth references for Romanian children. MATERIAL AND METHODS: We used local Romanian data from 9 studies with information on height and weight obtained between 1999 and 2016. Based on their plausibility and methodology six studies were selected for generating the National Synthetic Growth References for Romanian Children based on the specific methodology described previously. The selected studies included 8407 subjects measured in schools/kindergartens. Age is reported in years covering a range from 3-18 years. Height and weight were measured at a precision of 0.1 cm and 0.1 kg. All children were measured at normal temperature, in light clothes, without footwear. RESULTS: We present the charts and tables with the common centiles for height, weight and body mass index for boys and girls. CONCLUSION: We suggest synthetic growth references based upon recent growth data from 6 different Romanian regions as new National Growth Charts for Romanian children.

Dicentric Chromosome 14;18 Plus Two Additional CNVs in a Girl with Microform Holoprosencephaly and Turner Stigmata.

We report a 20-year-old female with features evocative of Turner syndrome (short stature, broad trunk, mild webbed neck), dysmorphic face, minor features of holo-prosencephaly (HPE), small hands and feet, excessive hair growth on anterior trunk and intellectual disability. Cytogenetic analysis identified a pseudodicentric 14;18 chromosome. Genome wide single nucleotide polymorphism (SNP) array showed a terminal deletion of approximately 10.24 Mb, from 18p11.32 to 18p11.22, flanked by a duplication of approximately 1.15 Mb, from 18p11.22 to 18p11.21. In addition, the SNP array revealed a duplication of 516 kb in 16p11.2. We correlated the patient's clinical findings with the features mentioned in the literature for these copy number variations. This case study shows the importance of microarray analysis in the detection of cryptic chromosomal rearrangements in patients with intellectual disability and multiple congenital anomalies.

Ageing and reproduction: is polycystic ovary syndrome an exception?

BACKGROUND: Polycystic ovary syndrome (PCOS) is a frequent cause of infertility. Despite an impressive number of reports, few have evaluated the influence of age upon fertility. We present the outcomes of three infertile women with PCOS who achieved spontaneous pregnancies when ageing. CASE REPORTS: Three patients with PCOS were monitored for more than 20 years. PCOS was confirmed by clinical data (oligo/amenorrhoea, infertility, hirsutism), hormonal measures and ovarian ultrasonography. All three infertile patients were treated for several years using numerous ovulation induction protocols with varying responses. When ageing, they gained more regular cycles and spontaneously became pregnant at 39, 40 1/2 and 36 years of age, more than 5 years after induction treatment was stopped, and in spite of increasing weight in each of them. CONCLUSIONS: These clinical observations suggest improved fertility in some PCOS ageing women. The positive impact of ageing on cycle regularisation in PCOS has recently been claimed but the fertility outcome was not evaluated. Ovary ageing results in diminution of the follicular cohort in both normal and PCOS women, associated with decreased inhibin B and anti-müllerian hormone (AMH) levels. Lower inhibin B levels induce FSH enhancement, with a rise in FSH rate per follicle which may determine better follicle maturation, regular and ovulatory cycles in PCOS ageing women. The best proof of this improved fertility was the occurrence of spontaneous pregnancies which never occurred previously.

Pseudomalabsorption of thyroid hormones: case report and review of the literature.

Many causes of thyroxine malabsorption are described in the literature, but the most common cause of failure of thyroxine therapy is poor patient compliance, or pseudomalabsorption. We describe the case of a female patient who underwent total thyroidectomy for Basedow-Graves disease. Post-operatively, several treatment regimens were employed to achieve euthyroidism, but only injectable thyroxine was found to be effective. To exclude levothyroxine malabsorption, the patient was hospitalized in a hypothyroid state while a single oral test dose of levothyroxine (1000 microg) was administered. Within 4 hours a decrease of TSH level (from 59.7 to 55.6 microUI/ml) and a significant increase in free T4 levels (from 0.8 to 15.5 pg/ml) was observed, eliminating a malabsorption problem. The cause of resistance to thyroid hormone therapy was poor patient compliance, leading to the designation of this as a case of pseudomalabsorption.

[Fine needle puncture--method of treatment in nodular pathology of the thyroid]. / La ponction à aiguille fine--méthode de traitement dans la pathologie nodulaire de la thyroïde.

Fine needle biopsy (FNB) has been used as a therapeutic method in different nodular lesions of the thyroid. Between 1989-1995, 295 subjects with thyroid cysts, 235 women and 60 men have been treated by FNB. The treatment of cysts was performed by: one or multiple aspirations in 207 cases, sclerosis by injection with tetracycline in 77 cases and by ethanol washing in 11 cases. 263 (89.11%) cases have been cured and we have lost track of 32 cases in the survey. Of the 207 cases treated by aspiration, 177 (86.5%) have been cured after one or more aspirations. Of the 77 cases treated by injections with tetracycline, 75 (97.26%) displayed sclerosis after one or more injections. All 11 cases treated by ethanol washing method displayed sclerosis. Between 1993-1995 we used percutaneous ethanol injection (PE1) in 6 cases, as an alternative to the classic treatment, in order to induce necrosis of toxic adenoma. After 1 to 9 injections all cases were cured, with the appearance of the entire image of the gland on the scintigram. In 4 cases of cold nodules with benign cytology PEI, induced a significant decrease of volume appreciated by sonography.

[The Wermer syndrome]. / Sindromul Wermer.

The difficult diagnostic and therapeutic management of patients having gastrinoma with multiple endocrine neoplasia type I (MEN I) has been discussed by reference to the literature and a personal experience of 2 patients with Wermer syndrome. The syndrome is often familial and might be inherited as an autosomal dominant trait with a high but variable degree of penetrance. Pancreatic islets, parathyroid glands and adenohypophyseal [correction of antehypophyseal] cells are the three localization main for endocrine involvement in MEN I syndrome.

[Endocrinological disorders in association with alopecia areata-a 27 patients study]. / Boli endocrine asociate cu alopecia areata--studiu pe un lot de 27 pacienti.

Alopecia areata is a dermatological disease, characterized by the loss of hair, which affect men, women and children and can evaluate alone or in association with a variety of other disorders. Between these endocrinological diseases, especial thyroid disorders, have a high incidence. Twenty-seven patients with alopecia areata (12 women and 15 men) aged between 3 and 46 years were endocrinologically investigated. Eighteen of them (66.6%) had endocrinological disorders. Thyroid diseases were present in 10 cases (37%): 4 cases with endemic goiter, 2 cases with nodular goiter and 4 cases with hypothyroidism (1 case with autoimmune thyroiditis, 1 case with nodular goiter, 1 case with cystic goiter and 1 case with hypothyroidism post thyroidectomy for thyroidal lymphoma). Twelve cases (44.4%) were found with tetania. The incidence of thyroid diseases in alopecia areata is higher then in general population (2%), as well as the incidence of tetania. These evidences suggest that it is necessary to make a screening of endocrinological disorders in patients with alopecia areata.

[The etiopathogenetic hypotheses in polycystic ovary]. / Ipoteze etiopatogenice în ovarul polichistic.

First described in 1935, polycystic ovary syndrome (PCOS) is a frequent endocrine disease (6% in female population). However its pathogenicity is not yet completely understood. The possible etio-pathogenic mechanisms include: neuroendocrine disorders (hypothalamic, as a result of congenital androgenism or of disorders of neurotransmitters or pituitary, with excess of LH), ovarian disorders (enhanced sensibility at LH, local growth factors, hyperactivity of Cit P450cl7 alpha enzymes), adrenal disorders, insulin resistance, genetic determinism, puberty onset. The authors discuss in detail this hypothesis and these possible importance.

[Contribution of ultrasonography in the evaluation of subacute thyroiditis]. / Contributia ecografiei în evaluarea tiroiditei subacute.

Ultrasonography is a useful tool in diagnosing and monitoring thyroid pathology. The aim of this study was to evaluate the value of thyroid ultrasonography in the follow-up of subacute thyroiditis (SAT). The study group included 48 subjects with clinical and biological diagnosis of subacute thyroiditis. All patients were evaluated by ultrasonography and followed-up for a mean period of 12 months. The evaluation protocol included biological data (TSH, T4, erythrocyte sedimentation rate--ESR) and ultrasonography, performed at 1, 2, 3, 6, and 12 months. Initially, all patients had an enlarged thyroid volume (median = 30.5 ml, range 23-90) and a low echogenicity, with an inhomogeneous aspect in 54.1% cases. After a mean period of 3 months thyroid volume had a significant reduction (median volume = 20.2 ml, range 7-36, p < 0.0001). Echogenicity was also significantly improved, with a decrement, on a semi-quantitative scale of 4 degrees (1 = normal, 4 = intense hypoechogenicity), from 3.25 to 2.48 (p < 0.0001). Almost half of the patients (45.8%) presented persistent (although slighter) hypoechoic/inhomogeneous pattern. Ultrasonographic abnormalities were not correlated with the intensity of the inflammatory syndrome and/or the thyroid status. Recurrence appeared in 10 (20.8%) patients. All patients presented a new thyroid enlargement (from a median = 16.1 ml to 31.5 ml, p = 0.056) and an extension of hypoechoic regions. The risk of recurrence could not be correlated with thyroid function, inflammatory syndrome or ultrasonographic aspect. There were not significant differences between the subgroups of patients with and without recurrence concerning the initial thyroid volume (p = 0.889), echogenicity (p = 0.735), TSH (p = 0.321) or ESR (p = 0.1332). Thyroid ultrasonography is useful not only for the initial diagnosis but also for the follow-up of patients with subacute thyroiditis. Remission and recurrence can be appreciated and monitored by the ultrasonographic pattern of the thyroid.

[Therapy with large doses of methylprednisolone in Basedow's ophthalmopathy]. / Terapia cu doze mari de metilprednisolon în oftalmopatia basedowiana.

Up to now there is no satisfactory therapeutical method in Graves' ophthalmopathy (GO). Recently, several authors have published the results of the so-called "pulse" method of corticotherapy, using intravenous methylprednisolone (MP) 1 g dissolved in 200 ml isotonic NaCl solution. We have treated with this method 4 patients (3 women and 1 man, aged between 35-62 years) with severe GO (III-V class after AMT Classification). Although the number of perfusions varied between 1 (2 patients) and 8, the results are encouraging: 3 improvements, 1 stationary evolution (after a single "pulse"). We have not noticed important side-effects. In conclusion we consider that the "pulse" method have proved its efficiency, recommendable in severe GO.

[Fertility in prolactinomas--considerations concerning some clinical cases]. / Fertilitatea în prolactinom--consideratii asupra unor cazuri clinice.

Prolactinoma is a frequent endocrine cause of infertility in both man and women. The aim of this study was to evaluate female fertility in association with hyperprolactinemia. The study is a retrospective one, based on the cases monitored in the Endocrinology Department of Iasi. From the 113 cases of prolactinoma in women we have selected 83 women aged between 18-45 years (fertile age). The diagnosis was suspected on clinical bases: endocrine (amenorrhea-galactorrhea, associated or isolated, spaniomenorrhea, infertility), and tumoral (headache, visual disturbances) syndromes and confirmed by biological (PRL dosage) and morphological (pituitary CT) tests. We classified the found associations between prolactinoma and fertility in: no correlation (previous pregnancies with no desire for another child--76 patients = 75.2%); prolactinoma diagnosed immediately after a pregnancy by persistency of galactorrhea, lack of menses reapparition, headache (16 cases = 15.8%); prolactinoma diagnosed before pregnancy, which was obtained thanks to the hyperprolactinemia treatment (9 patients = 8.9%). All 9 patients of the last group were in remission at the moment of pregnancy apparition and had a normal pregnancy, giving birth to normal children. Infertility associated with prolactinoma is reversible with treatment. Lowering of prolactin levels to normal is often necessary to permit ovulation. Bromocriptine used by pregnant women appears to be safe for the developing fetus, at least in our study where the treatment was interrupted in most cases in the first trimester of pregnancy.

[Body composition in amenorrheic and eumenorrheic underweight patients]. / La composition corporelle des patientes sous-ponderales amenorrheiques et eumenorrheiques.

Relationship between weight and hypothalamic-pituitary-ovarian axis has been long time studied. Underweight female patients can have or not disturbances of gonadal system and the importance of the weight or body composition in the mechanisms of these abnormalities is not clear. In our study, we have investigated body composition in 15 underweight female patients. Five patients have had anorexia nervosa, with amenorrhea (group AN), and other 10 patients were eumenorrheic, but with low body weight (hypoanabolic syndrome--group HA). Bioelectrical impedance method was used to investigate body composition. Total body water (TBW), lean mass (LM), and fat mass (FM) were determined. Nutritional status was also assessed using body mass index (BMI). The mean body weight was significantly decreased (p = 0.05, 36.6 +/- 4.68 Kg versus 44.1 +/- 4.67 Kg) in group AN as compared to group HA. Fat mass was very low in group AN (9.45% of body weight versus 11.3% of body weight in group HA), but there was not significant difference. Lean mass was significantly decreased in group AN (33.24 +/- 2.37 Kg) in comparison with group HA (39.3 +/- 4.06 Kg). Correlations between anthropometric indices were studied. Positive significant correlations were obtained between body weight and lean mass, total body water and basal metabolism in both groups. In conclusion, our study reveals that body weight has a relative importance in ovarian axis dysfunction, and the most important of body compartments seems to be lean mass.

[The use of echography in the diagnosis of autoimmune thyropathies]. / Utilitatea ecografiei în diagnosticul tireopatiilor autoimune.

Ultrasonography is a first line method in thyroid imaging. The aim of this study was to evaluate the usefulness of thyroid ultrasonography in the diagnosis of thyroid autoimmune diseases (TAD): Graves' disease (GD) and autoimmune thyroiditis (AT)--Hashimoto's and atrophic thyroiditis. Ultrasonography was performed with a 7.5 MHz transducer in 1033 consecutive patients. The excluding criteria was nodular goiter, irrespective of its function. Thyroid volume was calculated using the formula of a rotating ellipsoid. Hypoechogenicity was appreciated using a qualitative scale: 1 = absent, 2 = mild, 3 = moderate, 4 = marked. In patients with TAD thyroid hypoechogenicity was significantly higher than in normal subjects (2.5 +/- 1 in GD and 2.7 +/- 1 in AT, vs. 1.2 +/- 0.6 in normal subjects, p < 0.0001). The specificity of the test in identifying TAD was 91.4%, the sensitivity was 68.6% for GD and 80.8% for AT, positive predictive value was 91.5%, and negative predictive value 91.5%. Ultrasonography is useful in identifying patients with probable autoimmune thyroid diseases, being useful in epidemiological studies and having an important contribution in confirmation of the diagnosis.

[Thyroxine therapy in benign thyroid nodules]. / Tratamentul cu tiroxina al nodulilor tiroidieni benigni.

Levothyroxine (LT4) treatment in benign thyroid nodules is a controversial management. The favorable response varies between 10-60%, being, in some studies, comparable between treated and untreated groups. The aim of this study was to evaluate the response of uninodular goiter at the LT4 treatment, in comparison with untreated patients. The study group (S) included 53 patients diagnosed with nodular goiter, treated with LT4 for 1 year. 26 patients with nodular goiter, age and sex-matched, untreated, constituted the control group (C). All patients were from a minor iodine deficient area. The including criteria were euthyroidism, single nodule, solid (ultrasonography), cold (Scintigraphy), and benign (FNAB). After 1 year mean nodular volume had a significant decrement in both groups, higher in group S (35%: from 7.8 to 5.2 mL, p = 0.0098) than in group C (25%: from 8.4 to 5.9 mL, p = 0.026). Linear regression showed a slight correlation between the nodular decrement and the initial volume (r = 0.23): the responders percentage was higher in nodules with a volume < 5 ml than in those with volume > 5 ml (51.5% vs o 19.6%, p < 0.0001). The evolution of treated nodules seamed to be better than of the untreated ones, but the differences were only slightly significant. We believe that the evolution of thyroid nodules under LT4 treatment can be influenced by the iodine supply, since in most of the studies from minor iodine deficiency regions (Europe, South America) the response is better than in regions with sufficient iodine supply (North America). Knowing the potential side effects of LT4 therapy, this kind of management of benign thyroid nodules should be reserved to selected cases.