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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

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