Craniopharyngioma in Adults

Craniopharyngiomas are slow growing benign tumors of the sellar and parasellar region with an overall incidence rate of approximately 1.3 per million. During adulthood there is a peak incidence between 40 and 44 years. There are two histopathological types, the adamantinomatous and the papillary type. The later type occurs almost exclusively in adult patients. The presenting symptoms develop over years and display a wide spectrum comprising visual, endocrine, hypothalamic, neurological, and neuropsychological manifestations. Currently, the main treatment option consists in surgical excision followed by radiation therapy in case of residual tumor. Whether gross total or partial resection should be preferred has to be balanced on an individual basis considering the extent of the tumor (e.g., hypothalamic invasion). Although the overall long-term survival is good it is often associated with substantial morbidity. Preexisting disorders are often permanent or even exacerbated by treatment. Endocrine disturbances need careful replacement and metabolic sequelae should be effectively treated. Regular follow-up by a multidisciplinary team is a prerequisite for optimal outcome of these patients

Expression der Komponenten des Renin-Angiotensin-Systems entlang des Mausnephrons

Einleitung: Das Renin-Angiotensin-System (RAS) spielt die zentrale Rolle in der Elektrolyt- und Volumenhomöosthase sowie auch in der Blutdruckregulation bei Säugetieren. Hierbei wurde sowohl ein systemisches, als auch ein lokales RAS in verschiedenen Organsystemen beschrieben. In dieser Arbeit wurde die segmentspezifische Expression von RAS-Komponenten entlang des Nephrons in der Mausniere untersucht. Material und Methoden: Definierte Nephronsegmente von adulten C57BL/6 Mäusen wurden nach Kollagenaseverdau mikrodisseziert und die mRNA wurde isoliert. Anschließend wurde die Genexpression von Renin, Angiotensinogen (AGTN), AT1a-, AT1b- und AT2-Rezeptor sowie Angiotensin Converting Enzyme (ACE) mittels RT-PCR untersucht. Ergebnisse: Renin mRNA war in Glomeruli, proximalem Tubulus (PCT und PST), distalem Konvolut (DCT) und kortikalem Sammelrohr (CCD) nachweisbar. AGTN mRNA ließ sich in PCT, PST, im dünnen Teil des absteigenden und medullären Teil der aufsteigenden Henle Schleife (dTL und mTAL) detektieren. AT1a-, AT1b- und AT2-Rezeptor mRNA war in Glomeruli und proximalen Konvolut (PCT) nachweisbar. ACE mRNA war trotz positivem Signal in der Positivkontrolle in keinem Segment des Mausnephrons nachweisbar. Dies ist mit der bekannten Expression von ACE mRNA im renalen Gefäßsystem vereinbar. Diskussion: Zusammenfassend lässt sich eine segmentspezifische Verteilung der verschiedenen RAS-Komponenten feststellen. Hierbei zeigt sich, dass alle Komponenten, mit Ausnahme von ACE, im proximalen Konvolut vertreten sind. Dies untermauert die Hypothese eines lokal aktiven RAS und unterstreicht die Beteiligung des RAS an der Elektrolyt- und Volumenhomöosthase

Nephron-specific expression of components of the renin–angiotensin–aldosterone system in the mouse kidney

Introduction: The renin–angiotensin–aldosterone system (RAAS) plays an integral role in the regulation of blood pressure, electrolyte and fluid homeostasis in mammals. The capability of the different nephron segments to form components of the RAAS is only partially known. This study therefore aimed to characterize the nephron-specific expression of RAAS components within the mouse kidney. Materials and methods: Defined nephron segments of adult C57B/16 mice were microdissected after collagenase digestion. The gene expression of renin, angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin II receptors 1a (AT1a), 1b (AT1b), and 2 (AT2) was assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Results: Renin mRNA was present in glomeruli, in proximal tubules, in distal convoluted tubules (DCT) and cortical collecting ducts (CCD). AGT mRNA was found in proximal tubules, descending thin limb of Henle’s loop (dTL) and in the medullary part of the thick ascending limb (mTAL). ACE mRNA was not detectable in microdissected mouse nephron segments. AT1a, AT1b and AT2 mRNA was detected in glomeruli and proximal convoluted tubules. Conclusions: Our data demonstrate a nephron-specific distribution of RAAS components. All components of the local RAAS – except ACE – are present in proximal convoluted tubules, emphasizing their involvement in sodium and water handling

Intérêt du signal T2 des adénomes hypophysaires à GH traités par analogues de la somatostatine - premiers résultats de l'étude IRMA#2

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T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly.

GH-secreting pituitary adenomas can be hypo-, iso- or hyper-intense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the relationship between T2-weighted signal intensity on diagnostic MRI and hormonal and tumoral responses to somatostatin analogs (SSA) as primary monotherapy. Acromegaly patients receiving primary SSA for at least 3 months were included in the study. Hormonal, clinical and general MRI assessments were performed and assessed centrally. We included 120 patients with acromegaly. At diagnosis, 84, 17 and 19 tumors were T2-hypo-, iso- and hyper-intense, respectively. SSA treatment duration, cumulative and mean monthly doses were similar in the three groups. Patients with T2-hypo-intense adenomas had median SSA-induced decreases in GH and IGF-1 of 88% and 59% respectively, which were significantly greater than the decreases observed in the T2-iso- and hyper-intense groups (P < 0.001). Tumor shrinkage on SSA was also significantly greater in the T2-hypo-intense group (38%) compared with the T2-iso- and hyper-intense groups (8% and 3%, respectively; P < 0.0001). The response to SSA correlated with the calculated T2 intensity: the lower the T2-weighted intensity, the greater the decrease in random GH (P < 0.0001, r = 0.22), IGF-1 (P < 0.0001, r = 0.14) and adenoma volume (P < 0.0001, r = 0.33). The T2-weighted signal intensity of GH-secreting adenomas at diagnosis correlates with hormone reduction and tumor shrinkage in response to primary SSA treatment in acromegaly. This study supports its use as a generally available predictive tool at diagnosis that could help to guide subsequent treatment choices in acromegaly