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Background Patients with rare diseases face health disparities and are often challenged to find accurate information about their condition. We aimed to use the best available evidence and community partnerships to produce patient education materials for congenital hypogonadotropic hypogonadism (CHH) and the olfacto-genital (Kallmann) syndrome (i.e., CHH and defective sense of smell), and to evaluate end-user acceptability. Expert clinicians, researchers and patients co-created the materials in a multi-step process. Six validated algorithms were used to assess reading level of the final product. Comprehensibility and actionability were measured using the Patient Education Materials Assessment Tool via web-based data collection. Descriptive statistics were employed to summarize data and thematic analysis for analyzing open-ended responses. Subsequently, translation and cultural adaption were conducted by clinicians and patients who are native speakers. Results Co-created patient education materials reached the target 6th grade reading level according to 2/6 (33%) algorithms (range: grade 5.9–9.7). The online survey received 164 hits in 2 months and 63/159 (40%) of eligible patients completed the evaluation. Patients ranged in age from 18 to 66 years (median 36, mean 39 ± 11) and 52/63 (83%), had adequate health literacy. Patients scored understandability at 94.2% and actionability at 90.5%. The patient education materials were culturally adapted and translated into 20 languages (available in Additional file 1). Conclusions Partnering with patients enabled us to create patient education materials that met patient- identified needs as evidenced by high end-user acceptability, understandability and actionability. The web-based evaluation was effective for reaching dispersed rare disease patients. Combining dissemination via traditional healthcare professional platforms as well as patient-centric sites can facilitate broad uptake of culturally adapted translations. This process may serve as a roadmap for creating patient education materials for other rare diseases. Electronic supplementary material The online version of this article (doi:10.1186/s13023-017-0608-2) contains supplementary material, which is available to authorized users.

Aim: Excess release of catecholamines is a characteristic for pheochromocytomas. The rate of catecholamine synthesis is determined by tyrosine hydroxylase (TH) enzyme. Usually, TH is detected by immunohistochemistry. In our study, we evaluated this enzyme in plasma from pheochromocytoma subjects establishing correlations with some metabolites. Subjects and Methods:10 subjects (9 women /1man aged 40-72 years ) clinically suspected of pheochromocytoma, were biochemically investigated for free plasma normetanephrines (NMNp)/ metanephrines (MNp), plasma chromogranin A (CgA), plasma TH and IGF-1.Comparison of tumoral metabolites values was done with our lab normal range. Statistical analysis used multiple regression to evaluate relationship between TH and all 3 parameters: NMNp/MNp/CgA. Results: All subjects showed excessive plasma NMNp (median: 1434 pg/mL); in 7 cases we observed an over-secretion of MNp (median: 441pg/mL) and CgA was higher in 9 cases (median: 668 ng/mL). TH was identified in all plasma samples with a median of: 2.08 ng/mL. Higher values of TH were detected in cases with an over-excess of metabolites. Good correlations were established between NMNp/TH (0.51), MNp/TH(0.81) and NMNp/CgA (0.71). Conclusion: Metabolites in excess are well correlated with TH values proving a great rate of catecholamine synthesis in some cases. We could affirm TH could be used as an index of functionality in pheochromocytoma diagnosis.

Background: Partial adrenalectomy has been widely performed in the last decades in order to diminish the number of patients who would become lifetime dependent of hormonal replacement. Method: between 2016 and 2018 seven patients were submitted to minimally invasive partial adrenalectomy in Ponderas Academic Hospital. Results: the median age at the time of surgery was 56 years (range 42-67 years) while the indications for partial adrenalectomy (PA) were represented by Conn's syndrome in four cases, bilateral pheochromocytoma in one cases and nonfunctional adrenal tumors in two cases. Preoperatively successful adrenal vein sampling was performed in one case. The indocyanine green test (ICG) as well as intraoperative ultrasound were used each in three cases. The transperitoneal approach was used for PA in all patients, laparoscopic in five and robotic assisted in two patients. No conversion to open surgery or to total suprarenalectomy was encountered. Conclusions: minimally invasive surgery seems to be a safe and effective method to perform partial adrenalectomy. Moreover, development of novel technologies such as adrenal vein sampling, indocyanine green test or intraoperative ultrasound seem to increase the feasibility of the method as well as the number of cases who could benefit from the type of approach. Use of new technology?

Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone with thrombogenic potential in high doses and long-term administration. Taurine, a widely distributed amino-sulfonic acid, is known for its beneficial effects in hypercoagulable states. In order to assess the impact of chronic administration of high doses of AAS and taurine upon haemostasis process in rats, 40 male Wistar rats were divided into four equal groups: control group (group C) - no treatment; androgen group (group A) - received 10 mg/kg per week of nandrolone decanoate (DECA); taurine (group T) - received oral supplementation of 2% taurine in drinking water; androgen and taurine group (group AT) - concomitant administration of DECA and taurine. After 12 weeks, blood samples were collected and haemostasis parameters were assessed with the thrombelastographic (TEG) analysis system: reaction time, clot kinetics (K, α), final clot strength, coagulation index and the clot lysis (Ly30). Nandrolone significantly decreased reaction time in group A compared with control (P0.001), whereas taurine significantly increase reaction time (P=0.01), and this effect was maintained in group AT compared with group A (P=0.009). Similar differences between groups have been recorded for the clot kinetics parameters K, α. The final clot strength and coagulation index were significantly increased in group A versus group C (P=0.04, respectively P0.001), but not in group AT versus group C (P0.05). There were no differences in clot lysis, as shown by Ly30. Nandrolone produces an accelerated clot development and an increased clot firmness in Wistar rats. Taurine association ensures a protective effect against this hypercoagulable state, partially restoring the altered parameters of the coagulation profile.

Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P

Background: Simultaneously determined plasma chromogranin A (CgA) and free metanephrines can substantially enrich laboratory diagnosis of pheochromocytoma (PHEO). CgA-like immunoreactivity was discovered in saliva. Salivary CgA (CgA-LIS) could precise PHEO diagnosis in a non-aggressive manner for the patient using saliva instead of plasma samples. Subjects and methods: A group of 10 PHEO patients: 7 women (22 to 72 years ) and 3 men (42 to 59 years) and a control group of 10 subjects were included in this retrospective study. Plasma free metanephrines and CgA were assayed by Elisa kits. Salivary CgA was assayed by an EIA kit. Both analytical and diagnosis performance of the CgA-LIS vs. CgA were compared using Passing& Bablok

Background. Advances in imaging techniques have led to increasing discovery of adrenal and pituitary “incidentalomas”, tumors with normal endocrine function and no compression mass effects. We evaluated the age at diagnosis (AD) in patients with benign non-functioning adrenal incidentalomas, as compared to pituitary non-functioning tumors, in a series of patients from a national center of endocrinology. Methods. From 2,123 consecutive patients with adrenal and pituitary tumors hospitalized between 1977 - 2009, 2,069 patients were analysed. The study groups included: group A - 137 patients with adrenal incidentalomas (AI), group B - 534 patients with pituitary incidentalomas (PI). Control groups included 1,398 patients: group C1 147 patients with adrenal carcinomas or benign hormone-secreting adrenal tumors, and group C2, 1,251 patients with pituitary secreting adenomas or large non-functioning pituitary macroadenomas (NFA). Imaging was done by computed tomography and/or magnetic resonance after 1981 and by skull X-ray or pneumoencephalography before 1981. Results. Mean age AD is more advanced in patients with AI (53 ± 11.9 years, range 21 - 78 yr) than in patients with PI (36.8 ± 13.1 years, range 10 - 81 yr), p < 0.01. AD was higher in AI than in patients with secreting adrenal tumors, but similar in patients with adrenal malignancy. There is an age-related increase in the proportion of AI among patients with adrenal tumors, and of NFA, but not of PI, among patients with pituitary tumors. In patients aged over 65 years, 74% of patients with adrenal tumors have AI, while only 18% of patients with pituitary tumors have PI and 42% have NFA. AD in NFA (49.3 ± 13.1 yr, range 12 - 79 yr) was more advanced than in PI (p < 0.01). AD does not correlate with tumor size. Tumor growth occurred in 24% of AI (follow-up 3.0 ± 2.8 yr) and only in 0.7% of PI, p

Although multiple forms of testosterone replacement therapy are available to treat hypogonadism, none is ideal. This article reports on the pharmacokinetics of an innovative nasal formulation of testosterone in hypogonadal men. The first study was undertaken in eight men with a baseline total testosterone (TT) of 130.8 +/- 87.4 ng/dL and examined the pharmacokinetics of nasal testosterone given in a single dose of 7.6 mg, 15.2 mg or 22.8 mg, respectively. The second study examined the pharmacokinetics of nasal testosterone (7.6 mg) given either twice or three times a day in 21 severely hypogonadal men (baseline TT in 20 patients50 ng/dL, in one patient 152 ng/dL) for 14 days. The steady-state concentration of testosterone was within the normal range in all treatment groups, but only in the 3-times-a-day group was the 95% confidence interval completely within the physiological range. The average DHT level did not exceed the upper range of normal. The clinical global visual analogue scale improved in the whole group receiving testosterone (p0.001). All adverse events in both studies were of mild to moderate intensity and were evaluated as unlikely or not related to the administered study drug. No patients dropped out during treatment. Comparison with the normal circadian rhythm by computer modelling suggests that nasal testosterone can be used to mimic the normal diurnal pattern in eugonadal men. Thus, nasal testosterone can be administered safely to humans in doses that approximate serum concentrations in the normal physiological range.

Introduction. Multiple Endocrine Neoplasia type 2A (MEN 2A) is a rare genetic autosomal dominant disease caused by mutations of RET gene (Chr 10q11.21). Clinical features include medullary thyroid carcinoma (MTC) with 90-95% penetrance, pheochromocytoma (50% penetrance) and primary hyperparathyroidism (20-30%). Screening for RET gene mutation allows early identification of asymptomatic carriers who may benefit from prophylactic thyroidectomy, thus preventing morbidity and death. Aim. Implementation of RET mutation detection as screening procedure for Romanian MEN 2A families. Subjects and methods. We studied a three-generation MEN 2A Romanian family with one affected male (age 75) in the first generation, his affected descendants (one male-45y, one female-42y old) in the second generation and four asymptomatic subjects at risk (three males aged 15, 19 and 22y and one 18y old female) in the third generation. Mutation detection was performed by automated DNA sequencing of PCR-amplified exons 10 and 11 of RET gene. Results. A Cys634Arg (TGC/CGC) heterozygous mutation of RET gene was detected in affected individuals as well as in 3 asymptomatic male subjects, but was absent in one asymptomatic female. Sequencing results were confirmed by digestion of PCR products with HhaI restriction enzyme. Total thyroidectomy was proposed to all asymptomatic carriers, although this decision was postponed and patients continued biochemical screening. Conclusion. Despite success in implementation of mutation detection in clinical laboratory, this study illustrates the difficulty in acceptance of prophylactic thyroidectomy

At least one fifth of pituitary adenomas exhibit plurihormonality when using immunohistochemistry for anterior pituitary hormones. However, the correlation with clinical features is weak, without an agreement upon pathological predictors of tumor behavior. The aim was to determine the immunoreactivity for anterior pituitary hormones and alpha subunit in 276 consecutive pituitary adenomas patients, aged 22-79 years (44.3 ± 8), 154 F/ 122 M: 83 acromegalics (ACM), 173 nonfunctioning adenomas (NFA) and 20 prolactinomas (PRM) submitted to surgery via transfrontal (81) or transsphenoidal (195) along 10 years (1995-2005). In addition, clinical data, hormonal secretion and tumour size were evaluated before pituitary surgery. Local ethical committee approved the study design. The immunoreactivity performed by the avidin-biotin-complex method was evaluated for beta FSH, LH, TSH, alpha subunit, PRL and GH, using a semiquantitative scale of stained cells: strong (>20%), positive (10-20%), weak (5-10%) and negative ( 10% of stained cells) was between 1-2 cm in 6 ACM, 21 NFA and 2 PRM, while positive bigger tumors (2-4 cm) were in 7 ACM, 24 NFA and 2 PRM. Giant, over 4 cm tumors were positive in 3 ACM, 8 NFA and no PRM. A similar trend of the tumor size distribution was observed in the monohormonal or null cell adenomas. In conclusion, tumor size and gonadotrophin plurihormonality are independent factors in the management of pituitary adenomas.

Pituitary adenomas are fully characterized only by immunohistochemistry. The technical limitations, gaps and peculiarities influence the pathology diagnosis. More and more data shows that clinically nonfunctioning pituitary adenomas could synthesize or secrete hormones or their subunits. The tumor pathology is monomorphous or polymorphous, difficult to differentiate from normal adjacent tissue. Light microscopy (LM) qualitative analysis using basic or special stains can differentiate between tumor and normal tissue and allows elimination of artifacts. Electron microscopy (EM) completes the diagnosis in selected cases. Pituitary adenomas immunohistochemistry was done by LM in 120 cases (84 – clinically nonfunctioning adenomas – NFA and 36 acromegalics with or without PRL secreting adenomas - ACM) using the avidine-biotin complex method. In 26 cases we determined by EM the immunoreactive cells (17 NFA and 9 ACM) using the immunogold method. We observed high tumor immunoreactivity (mono or plurihormonal) in 43/84 (51%) NFA, 13/36 (36%) ACM respectively. Serum excess hormones and tissue immunoreactivity were significantly concordant for prolactin in NFA cases and for GH, in ACM cases (p

Severe hypokalemia is a life threatening event, which triggers a number of therapeutic and diagnostic attitudes. In this paper we present a case of 63 years old man, who presented with progressive lassitude, edema, weight loss. The mild hypertension and hyperglycaemia were treated with spironolactone and diet. Initial evaluation showed severe hypokalemia (1.7 mmol/l), hepatomegalia, hyperplasic/nodular adrenal masses; in addition, he has developed a right middle lobe pneumonia which improved with antibiotics. Referred for the suspicion of hyperaldosteronism, aldosterone values were normal (9.3-9.5 µg/dl), but ACTH was high (725 pg/ml) and did not suppress (710.8 pg/ml) to high dose DXM, as well as cortisol: basal values 27.78 ug/dl, high dose DXM 35.06 ug/dl, showing an ACTH dependent Cushing syndrome despite lack of suggestive clinical signs. Tumor markers suggested a neuroendocrine neoplasia: carcinoembryonic antigen=101 ng/ml (normal values=0.52-6.3 ng/ml), CA 19-9= 155 ng/ml (N < 33 ng/ml). Further radiological evaluation showed a 3 cm right lobe lung tumour. Despite high potassium supplements and spironolactone, the hypokalemia remained around 3.2 mmol/l, characteristic for an apparent mineralocorticoid excess. Because of aggressive evolution of the lung tumour, he died three months after the initial admission into the hospital. Pathology report showed a lung carcinoma. ACTH immunostaining of the lung tumour was positive and revealed a paraneoplastic secretion.

Vertebrate nonapeptide neurohormones constitute an evolutionarily conserved family, involved in vital functions, such as hydro-osmotic balance regulation, reproduction and social behaviour. Two human members of this family are known, vasopressin (AVP) and oxytocin (OXT), with their highly homologous genes closely located on Chr 20p13. Presence of vasotocin (AVT) in man has been suggested, but remains controversial, and genetic evidence is lacking. AVT activity could be explained by the presence of a third distinct gene for AVT or an RNA-processing mechanism involving products of AVP and/or OXT genes. To test the first hypothesis, we developed bioinformatics and experimental approaches using genomic DNA and fetal tissues mRNAs. Family-specific primers for AVT and neurophysin were designed based on CODEHOP strategy and used in our experiments. Results of bioinformatics and genomic DNA experiments (family-specific and Alu step-out PCR) suggest there is no evidence for an AVT gene in the genome. RNA-based techniques 3’-RACE and Family-Specific Domain Restriction Fragment RTPCR provided evidence for new transcript species that could code for AVT. Further experiments will be needed to characterize them. We discuss potential mechanisms of AVT mRNA generation based on AVP and OXT mRNAs, by alternative splicing, heterologous transsplicing or RNA-editing. While all methods we developed proved feasible, current results suggest there is no AVT gene in the genome, but specific mRNAs could be present in fetal tissues. Their full characterization may potentially allow identification of vasotocin mRNA and shed light on

Objectif Afin de comprendre le role de l’homeostasie du zinc dans le SOPK (syndrome des ovaires polykystiques), nous avons explore plusieurs genes candidats par gene-SNPing. Patients et methodes Un nombre de 1299 SNPs (single nucleotide polymorphism) de 28 genes priorises ont ete genotypes par la puce MEDISCOPE (Affymetrix) chez 508 femmes avec SOPK et 425 controles (collection MEDIGENE). Dans le SOPK avec obesite, le syndrome metabolique (SMet) et la resistance a l’insuline ont ete retrouves a des prevalences de 48 % et 83 %, respectivement. Resultats L’association genetique a montre le role influent des 15 genes dans le SOPK, bien que seulement le SLC39A8 soit reste associe apres la correction de Bonferroni. Les SNPs rs13137350 et rs10002107 du gene SLC30A9 ont ete associes a l’hyperandrogenie (OR : 1,66, 95 % CI [1,3–2,0] et OR : 1,65, 95 % CI [1,3–2,0], Bonferroni p Discussion Notre etude a montre que de nombreux genes de l’homeostasie du zinc sont impliques dans le SOPK, dont quelques communs au SMet et ses composants et d’autres plus specifiques soit au SOPK, soit au SMet.