ACTA ENDOCRINOLOGICA (BUC)

Background. Molecular defects in the SHOX gene including deletions, duplications or pathogenic point mutations are responsible for well-known pathologies involving short stature as a clinical manifestation: Léri–Weill dyschondrosteosis, Langer mesomelic dysplasia, Turner syndrome or idiopathic short stature. Duplications flanking the SHOX gene (upstream or downstream of the intact SHOX gene involving conserved non-coding cis-regulatory DNA elements - CNEs) have been described but their clinical involvement is still difficult to understand. Results. We describe two cases with short stature and normal GH-IGF1 status. Multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (arrayCGH) identified in both cases heterozygous duplications involving downstream regions of SHOX gene, within CNEs (CNE8, CNE9 and CNE4, CNE5, CNE6, ECR1, CNE8, CNE9 and surrounding areas, respectively). One of the cases showed a maternally inherited duplication. Although every case has several particularities, we consider that duplications in these non-coding regions of SHOX gene may explain the short stature phenotype. Conclusion. To our knowledge, these are the first Romanian-reported cases of ISS with a large duplication of downstream SHOX enhancers CNEs region. The spectrum of phenotypic consequences and the exact mechanism of the presumed clinical expression of these genetic alterations still needs to be evaluated and described.

Background: Simultaneously determined plasma chromogranin A (CgA) and free metanephrines can substantially enrich laboratory diagnosis of pheochromocytoma (PHEO). CgA-like\r\nimmunoreactivity was discovered in saliva. Salivary CgA (CgA-LIS) could precise PHEO diagnosis in a non-aggressive\r\nmanner for the patient using saliva instead of plasma samples.\r\nSubjects and methods: A group of 10 PHEO patients: 7 women (22 to 72 years ) and 3 men (42 to 59 years) and a control\r\ngroup of 10 subjects were included in this retrospective study. Plasma free metanephrines and CgA were assayed by\r\nElisa 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 regression and Receiver Operating Curves (ROC analysis).\r\nResults: In tumor group, mean values for all 4 assayed parameters were significantly increased in comparison with\r\nthe same parameters in normal group as expected: free plasma normetanephrines (NMNp) was: 2773 ? 704.57pg/mL versus 48.51 ? 9.87 pg/mL in controls; free plasma metanephrines (MNp) was: 864.4 ? 330.75 pg/mL versus 19.18 ? 3.69 pg/mL in normals; CgA was: 695.10?235.22 ng/mL versus 74.4?5.37 ng/mL in controls; CgALIS was: 17.62?6.79 pmol/L versus 0.94 ?\r\n0.20 pmol/L in normals. Passing & Bablok regression equation for CgA-LIS versus CgA was: Y=0.0181 + 0.0146X. Cusum test\r\nfor linearity revealed no significant deviation from linearity (P>0.10). A significant correlation between NMNp and CgA-LIS was established in all 20 subjects: r=0.82, P<0.0001. Pairwise comparison of ROC curves for both markers showed no significant difference between areas. Salivary CgA could be successfully used instead of plasma CgA in biochemical diagnosis of pheochromocytoma.\r\nConclusions: We can conclude that salivary CgA could be used as a nonstressfull marker for diagnosis purpose in pheochromocytoma.

Context. Hypothalamic-pituitary-adrenal (HPA) axis irregularities have been described both in bipolar disorder and suicidal behaviour, but few studies have examined the relationship between suicidal behaviours and cortisol levels in bipolar disorder. Objective. We compared HPA axis activity in bipolar I (BPD I) individuals with and without suicidal ideation and behaviour through multiple measurement of serum and salivary cortisol. Design. Cross-sectional, observational study. Subjects and Methods. 75 BPD I patients were assigned into 3 groups (no history of suicidal behaviour, history of suicidal ideation, history of suicide attempt), according to the C-SSRS. Socio-demographical and clinical data was obtained by using MINI 6.0 and a semi-structured questionnaire. Salivary samples were collected using Sarstedt Cortisol Salivette synthetic swab system for two consecutive days at 08:00, 16:00, 23:00 and salivary cortisol concentrations were determined by ELISA technique. A unique 1mg dose of dexamethasone was administered on the first day, at 23:00, after the collection of the saliva sample. Blood was collected on the first day at 8:00 AM and basal morning serum cortisol levels were determined by immunoassay with fluorescence detection. Results. Cortisol parameters in our BPD I sample did not vary significantly in respect to suicidal history. However, patients with a history of suicidal ideation have significantly higher total cortisol outputs than patients with no history of suicidal behaviour in the 18 to 40 age category compared with the above 40 age category. Conclusions. Total cortisol daily output varies significantly in an age-dependent manner in respect to suicidal thoughts in BPD I individuals.

Context. Suicide is a global public health issue. Bipolar disorder (BPD) has the highest suicide risk among individuals suffering from mental disorders. Serotoninergic dysfunctions have been linked to suicidal behaviour and platelet serotonin is recognised as a reliable index for the presynaptic serotonin activity. Objective. Our aim was to assess whether alterations occur in platelet serotonin concentrations in BPD type I in respect to suicide attempters compared with nonattempters. Design. This was a cross-sectional, observational study. Subjects and Methods. Plasma platelet serotonin concentrations were measured using ELISA technique in 71 BPD I patients. The participants were assigned into 3 groups (non-attempters, low lethality and high lethality suicide attempters), according to the Columbia-Suicide Severity Rating Scale. Socio-demographical and clinical data was obtained by using MINI 6.0 and a semi-structured questionnaire designed specifically for this research. Results. Our study showed significant lower levels of platelet serotonin in suicide attempters compared with non-attempters (p = 0.030) and in high-lethality attempters compared with low-lethality attempters (p = 0.015). The study recorded a higher number of total lifetime and lifetime depressive episodes for suicide attempters with BPD I. Conclusions. Our results subscribe to the importance of platelet serotonin as a reliable biomarker in suicide risk assessment.

Background. Malignant melanoma is the most aggressive form of skin cancer with a rapidly increasing incidence rate. In contrast to other tumors, the role of sex steroid hormones\r\nin the initiation and progression of melanoma remains unclear.\r\nObjective. To assess the interaction between the content and composition of gangliosides and sex steroid hormones 17&#946;-\r\nestradiol (E2) and testosterone (T) in malignant melanoma.\r\nPatients and methods. The analysis included 45 melanoma patients (age 28-86; 14 men, 15 non -pregnant women in mid\r\nfollicular phase and 16 postmenopausal women) and 46 healthy controls. Serum levels of gangliosides (GM1-3, GD1a,b,2,3, GT1b, GQ1b), estradiol, testosterone measured in serum by chromatographic and immunochemiluminescence methods were correlated with sex and age.\r\nResults. Steroid hormones levels showed no differences between groups (p>0.05), while total gangliosides in normal\r\nserum were significantly lower than total ganglioside concentrations determined in melanoma samples (18.63 ? 3.17 mg/dL versus 74.82 ? 34.56 mg/dL) (p<0.05). There were no differences related to sex or age within groups regarding total gangliosides levels. Gangliosides pattern in\r\nmelanoma patients compared to control showed lower GM3, higher GD3, lower GM3/GD3 ratio, increased GD2 levels, and\r\nno significant variation of GM1, GM2, GD1a, GT1b gangliosides. There is a positive correlation between estradiol levels and total gangliosides concentration both in non-pregnant premenopausal and postmenopausal melanoma patients. GM3 is negatively correlated with estradiol levels in melanoma group, GT1b and O-Acetyl GD3 concentrations are positively correlated with estradiol levels in women with melanoma. Testosterone levels showed no significant\r\ncorrelation with the content and pattern of gangliosides in melanoma patients.\r\nConclusions. The correlations between content and composition of gangliosides and estradiol in melanoma suggest a possible role of these molecules in melanoma behavior.

Background: Salivary monitoring of hormone levels has many advantages over the more conventional serum/plasma analysis. Salivary free metanephrines (MN) and normetanephrines (NMN) could precise biochemical diagnosis of pheochromocytoma (PHEO) as an alternative to plasma metabolites.\r\nSubjects and methods: The prospective case-control study included a group of 30 patients confirmed with PHEO an age-matched control group of 70 normotensive subjects. The PHEO diagnosis was suspected on clinical ground and confirmed by imaging studies and classical neuroendocrine markers. Free plasma and salivary NMN and MN were assayed using enzyme immunoassay for both metabolites.\r\nResults: In tumor cases all metabolites were increased. As expected, values for all 4 parameters (mean?SEM) differed significantly in tumor group vs. normal group: free plasma\r\nnormetanephrines (NMNp): 1514.16 ? 282.97 pg/mL vs 47.82?2.52 pg/mL; free salivary normetanephrines (NMNs):\r\n663.63?168.47 pg/mL vs 44.98? 2.47 pg/mL; free plasma metanephrines (MNp): 445.20 ? 99.92 pg/mL vs 18.87?1.03\r\npg/mL; free salivary metanephrines (MNs):206.60?91.48 pg/mL vs 14.47?0.72 pg/mL with significant correlations in all\r\n100 subjects. Passing & Bablok regression showed no significant deviation from linearity in Elisa assay of NMNs vs NMNp; a significant deviation from linearity existed\r\nin Elisa assay of MNs vs MNp. Cut-off values, sensitivity and specificity for all 4 parameters were calculated by ROC\r\nanalysis. Plasma and salivary normetanephrines proved similar sensitivity (100%) and specificity (100%). Pairwise\r\ncomparison of ROC curves areas showed no significant differences between NMNp vs NMNs and MNp vs MNs. Ten cases were investigated post-surgery. All 4 parameters\r\nshowed no significant differences vs. control group.\r\nConclusions: Salivary free normetanephrines could be used as a nonstressful marker for diagnosis purpose in pheochromocytoma proving similar sensitivity and specificity as plasma free normetanephrines.