Cardivascular Risk Profile in Patients with Diabetes and Acromegaly or Cushing's Disease - Analysis from the DPV Database.

BACKGROUND: Although diabetes is a common complication of acromegaly or Cushing´s disease, there are only few detailed studies with a focus on cardiovascular risk, metabolic control or diabetes therapy. Here, we provide a comprehensive characterization from the longitudinal DPV (Diabetes Patienten Verlaufsdokumentation) registry. METHODS: Patients from the registry≥18 years of age with diabetes and acromegaly or Cushing´s disease were compared to patients with type 1 diabetes or type 2 diabetes using the statistical software SAS 9.4. RESULTS: Patients with diabetes and acromegaly (n=52) or Cushing's disease (n=15) were significantly younger at diabetes onset (median age 50.1 and 45.0 vs. 59.0 years in type 2 diabetes; both p<0.05). Dyslipidemia was common in both diseases (71.0% and 88.9% vs. 71.8% in type 2 diabetes; n.s.), while hypertension was most frequent in acromegaly (56.8% vs. 20.9% in type 1 diabetes, p<0.00001). 36.5% of patients with acromegaly and 46.7% with Cushing´s disease receive insulin, compared to 50.4% with type 2 diabetes. Oral antidiabetic drugs were used in 36.5% of patients with acromegaly and 40% with Cushing´s disease, with a predominance of biguanides and dipeptidyl peptidase-4 inhibitors. HbA1c was well controlled in both groups (median 7.0% and 6.5%; vs. 7.2% in type 2 diabetes). CONCLUSION: Patients with acromegaly are at a high risk for cardiovascular disease, reflected by dyslipidemia and hypertension. A high proportion of patients with diabetes in acromegaly or Cushing´s disease receives insulin. Based on a multicenter register, a sufficient number of patients with rare forms of diabetes can be analyzed.

The impact of hospitalization on the performance of capsule endoscopy (CE).

BACKGROUND: For proper evaluation of capsule endoscopy (CE), a complete examination is necessary. AIM: We evaluated risk factors of an incomplete CE with focus on patient hospitalization. METHODS: We retrospectively evaluated 161 consecutive patients who underwent CE between 01.07.2013 and 13.03.2016. Main indications were active bleeding, iron deficiency anemia (IDA), inflammatory bowel disease (IBD), abdominal pain, and familial adenomatous polyposis (FAP). RESULTS: We report the results of 103 in-patients and 56 out-patients. Eighty-two patients were male, average age was 58.9 years (range 18-90). Indications for CE were active bleeding (103 patients), IDA and IBD (16 patients), and FAP, abdominal pain and others (eight examinations each). All FAP patients were out-patients, but showed the longest small bowel transit time (SBTT) of 443.6min (p=0.0001). The shortest SBTT was found in out-patients without FAP (267.5min, p<0.05). In the in-patient group, nine endoscopies did not record the entire small bowel (8.7%) due to battery depletion, compared with only one incomplete examination in the out-patients (1.8%, p=0.036). We found pathologic lesions in the last 30min of the SBTT in 43 patients, and this indicates the necessity for complete examination. Thirteen of these 43 patients showed major lesions such as ulcers or angiodysplasia in this last region alone. CONCLUSION: In-patients might require special treatment to ensure complete examination, since a considerable amount of pathologies can only be found in the ileum.

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.

GLP-1 analogues as a new treatment option for hypothalamic obesity in adults: report of nine cases.

BACKGROUND: Patients with hypothalamic pathology often develop morbid obesity, causing severe metabolic alterations resulting in increased morbidity and mortality. Glucagon-like peptide-1 (GLP-1) analogues improve glycaemic control in type 2 diabetic patients and cause weight loss in obese patients by yet unknown mechanisms. Here we tested whether GLP-1 analogues were also effective in the treatment of obesity and associated metabolic alterations in patients with hypothalamic disease. METHODS: Nine patients (eight with type 2 diabetes mellitus) with moderate to severe hypothalamic obesity were treated with GLP-1 analogues for up to 51 months. Body weight, homeostasis model assessment - insulin resistance (HOMA-IR), HbA1c and lipids were assessed. RESULTS: Eight patients experienced substantial weight loss (-13.1±5.1 kg (range -9 to -22)). Insulin resistance (HOMA-IR -3.2±3.5 (range -9.1 to 0.8)) and HbA1c values (-1.3±1.4% (range -4.5 to 0.0)) improved under treatment (24.3±18.9 months (range 6 to 51)). Five patients reported increased satiation in response to the treatment. Two of the eight patients complained about nausea and vomiting and one of them abandoned therapy because of sustained gastrointestinal discomfort after 6 months. One patient suffered from intolerable nausea and vomiting and discontinued treatment within 2 weeks. CONCLUSION: GLP-1 analogues can cause substantial and sustained weight loss in obese patients with hypothalamic disease. This offers a new approach for medical treatment of moderate to severe hypothalamic obesity and associated metabolic alterations.

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.

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.