Familial SDHC mutation associated with prolactin/gh-secreting pituitary adenoma and paraganglioma

Introduction: SDH genes mutations are associated with hereditary phaeochromocytoma and paraganglioma syndromes. We describe the case of a patient with SDHC related familial paraganglioma and pituitary adenoma. Case: A 65-year old man consulted for an incidentally discovered 7 cm abdominal mass on CT-scan, lateral to the right kidney, invading inferior vena cava, associated to a retroperitoneal adenomegaly and a lesion on the body of L2 vertebra with spinal MRI aspect of metastasis. All these lesions showed hypermetabolism on 18F-FDG PET. Continuous blood pressure monitoring, plasma catecholamines and their methoxylated metabolites were normal. Chromogranine A was four times normal (Normal range<100 μg/l). Total right adrenalectomy, lumbo-aortic lymphadenectomy and nephrectomy were performed. Vertebral metastasis was treated by radiofrequency. Histopathology of the primary tumor confirmed the diagnosis of paraganglioma with 2% mitotic index. During follow-up, erectile dysfunction developed. Endocrine evaluation revealed partial hypogonadotropic hypogonadism (testosterone 214 ng/dl Normal: (280–820), LH 2.2 mUI/ml, FSH 2.5 mUI/ml) with hyperprolactinaemia (470 ng/ml, normal value <19 ng/ml) and elevated IGF1 level (214 ng/ml, normal: 41–196 ng/ml). OGTT confirmed GH hypersecretion. MRI showed a T2 hyperintense pituitary adenoma of 15×17 mm with left cavernous sinus extension without optic compression. We retained the diagnosis of PRL/GH-secreting pituitary adenoma and started dopamine agonist plus somatostatin analogue treatment. Genetic analysis revealed an new mutation on SDHC gene on exon 4 c239-242dupGTGC. The same mutation was found in his siblings (son, daughter and the grandson). His son had a non-secreting pituitary microadenoma, without pituitary abnormalities in the daughter. Work-up for paraganglioma was negative in siblings. Conclusion: This case suggests that SDHC gene mutations could be related to pituitary adenomas occurrence in association with paraganglioma syndromes, but more studies should be conducted to define the pathogenic pathways of this relationship

The Functional Anatomy of Sound Intensity Discrimination

The human neuroanatomical substrate of sound intensity discrimination was investigated by combining psychoacoustics and functional neuroimaging. Seven normal subjects were trained to detect deviant sounds presented with a slightly higher intensity than a standard harmonic sound, using a Go/No Go paradigm. Individual psychometric curves were carefully assessed using a three-step psychoacoustic procedure. Subjects were scanned while passively listening to the standard sound and while discriminating changes in sound intensity at four different performance levels (d′ = 1.5, 2.5, 3.5, and 4.5). Analysis of regional cerebral blood flow data outlined activation, during the discrimination conditions, of a right hemispheric frontoparietal network already reported in other studies of selective or sustained attention to sensory input, and in which activity appeared inversely proportional to intensity discriminability. [...

Pitfalls in the quest of neuroprotectants for the perinatal brain

Sick preterm and term newborns are highly vulnerable to neural injury, and thus there has been a major search for new, safe and efficacious neuroprotective interventions in recent decades. Preclinical studies are essential to select candidate drugs for clinical trials in humans. This article focuses on ‘negative’ preclinical studies, i.e. studies where significant differences cannot be detected. Such findings are critical to inform both clinical and preclinical investigators, but historically they have been difficult to publish. A significant amount of time and resources is lost when negative results or nonpromising therapeutics are replicated in separate laboratories because these negative results were not shared with the research community in an open and accessible format. In this article, we discuss approaches to strengthen conclusions from negative preclinical studies and, conversely, to reduce false-negative preclinical evaluations of potential therapeutic compounds. Without being exhaustive, we address three major issues in conducting and interpreting preclinical experiments, including: (a) the choice of animal models, (b) the experimental design, and (c) issues concerning statistical analyses of the experiments. This general introduction is followed by synopses of negative data obtained from studies of three potential therapeutics for perinatal brain injury: (1) the somatostatin analog octreotide, (2) an AMPA/kainate receptor antagonist, topiramate, and (3) a pyruvate derivative, ethyl pyruvate