[Unexplained weight gain in a 41-year-old woman]. / Unklare Gewichtszunahme bei einer 41-jährigen Frau.

A 41-year-old female was admitted to our clinic due to weight gain and facial edema. The patient also reported hair loss, amenorrhea and the formation of striae. The laboratory diagnostics ensured the diagnosis of Cushing's syndrome. Unfortunately, the patient was among the 5-10% of patients in whom neither laboratory testing nor imaging revealed the source of the cortisol excess. Due to the dramatic decrease of her general condition, and the appearance of hypertension and diabetes mellitus we chose to refer the patient to bilateral minimally invasive adrenalectomy. The advantage of this therapeutic approach is, that it is a definitive treatment that provides immediate control of hypercortisolism. As disadvantage, the resultant permanent hypoadrenalism requires a lifelong glucocorticoid and mineralocorticoid replacement therapy. Furthermore, given that the problem was caused by occult pituitary microadenoma, Nelson's syndrome has to be considered. As only one adrenal could be excised due to technical reasons, the underlying pathology is thus not solved. In spite of this, the patient's general condition improved dramatically without need for replacement therapy. As the mortality of patients with persistent moderate hypercortisolism is increased 3,8- to 5 fold, mainly due to cardiovascular reasons, thorough surveillance for signs of recurrence is mandatory to be ready for quick intervention.

[38 year-old patient with suspected congenital hormonal dysfunction]. / 38-jähriger Patient mit Verdacht auf eine angeborene hormonelle Störung.

We present the case of a patient with suspected congenital hypopituitarism first diagnosed at the age of 38 years. Despite partial insufficiency of all pituitary-regulated hormonal axes, the patient never suffered from severe health problems. However, the patient was disfigured, and his intellectual and physical capacities were clearly impaired. The initiation of a hormone replacement therapy with hydrocortisone and thyroid hormones is essential in such a patient, but the substitution of sex hormones can create ethical problems.

[33-year-old male patient with recurrent syncopes and orthostatic hypotension]. / 33-jähriger Patient mit rezidivierenden Synkopen und orthostatischer Hypotension.

We describe the case of a 33 year old male patient with severe orthostatic hypotension, which was at times even in upright (sitting) position not tolerated, thus leading to complete immobilisation. The diagnostic measurements pointed to the group of primary autonomic degenerative disorders, the so-called "synucleinopathies". The clinical presentation und laboratory values confirmed the diagnosis of "pure autonomic failure". Finally, we describe the differential diagnosis of autonomic dysfunction.

COVID-19 - more than respiratory disease: a gastroenterologist's perspective.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2) outbreak is the most dramatic event since World War II. Originating as a cluster of unexplained cases of pneumonia, it turned out that this viral disease termed COVID-19 is not only a respiratory infection, but a systemic disease associated with a number of extrapulmonary complications. One of the medical disciplines that is strongly affected by this viral infection is gastroenterology. COVID-19 causes in some patients typical symptoms of enteritis such as diarrhea or abdominal pain. There is also evidence that this infection may lead to liver and pancreatic injury. Since the SARS-CoV2 virus was detected in stool, a fecal-oral route of transmission is possible. Moreover, viral receptor angiotensin converting enzyme 2 (ACE2) is highly expressed in the gastrointestinal tract and enables the invasion of the gastrointestinal epithelium as demonstrated in vitro and in vivo. COVID-19 pandemic has an impact on the daily practice and the workflows in endoscopy leading to a dramatic decrease of screening and surveillance procedures. COVID-19 impacts the therapy of patients with inflammatory bowel disease (IBD), particularly those using high doses of corticosteroids, immunosuppressive agents and biologics. Patients with preexisting liver disease, especially metabolic associated liver fatty disease (MALFD) with fibrosis or liver cirrhosis, are at high risk for severe COVID-19. As long as no active vaccine against SARS-CoV2 is available, gastroenterologists have to be aware of these problems that affect their daily routine practice.

Reduced frequency of peripheral dendritic cells in type 2 diabetes.

OBJECTIVE: It is a common clinical experience that type 2 diabetic patients are susceptible to opportunistic infections. The underlying reasons for this immune deficiency are not yet understood. Dendritic cells (DC) play a key role in initiating innate and adapted immune responses. DESIGN: In order to investigate changes in the DC compartment in the peripheral blood in type 2 diabetes, we analyzed blood from patients under poor and good metabolic control and compared them to healthy controls. PATIENTS: 5 mls of blood were collected from 15 healthy controls, 15 diabetic patients with an HbA1c <7.0 and 15 patients with an HbA1c >9.5%. Age range was 44-80 years. Patients were age-matched with the control group. MEASUREMENT: Blood DC were enumerated by flow cytometry after staining with antibodies against the blood dendritic cells antigens 1-3 (BDCA 1-3). This allows quantification of the DC subtypes: myeloid dendritic cells type 1 (mDC1, mDC2) and plasmacytoid dendritic cells (pDC). RESULTS: The relative and absolute frequency for both mDC1 and pDC was clearly diminished in patients with poor metabolic control as compared to healthy controls. In patients with good metabolic control the reduction of DC was less pronounced but still significant, particularly for mDC1. CONCLUSION: Hyperglycemic metabolism does affect the pool of peripheral DCs and leads to a reduction of both, mDC1 and pDC. Even patients considered to be under good metabolic control appear to have a reduced peripheral pool of DC.

Hypoglycemic side effects of sulfonylureas and repaglinide in ageing patients - knowledge and self-management.

Insulinotropic oral antidiabetics (OAD) such as sulfonylureas and (SU) glinides are among the frequently prescribed OAD. Side effects are the potential to induce hypoglycemias and weight gain. The aim was to assess the self-managing skills in case of a hypoglycemic event in an elderly type 2 diabetic patient population. In a 2-year period, 160 hospitalized patients (mean age 77.4 years) under insulinotrophic OAD were interviewed using a standardized questionnaire. Additionally, possible dementia was evaluated by using the Mini-Mental State Examination (MMSE) and the Clock-Drawing Test (CDT). The mean HbA1c was 7.6%. MMSE and CDT did intraindividually correlate well and 23.8% of the patients had moderate dementia (10 - 20 points MMSE), 13.1% had severe dementia (0 - 10 points MMSE) at the time of the survey. When under treatment with a sulfonylurea, only 16.0% of patients were aware of the potential hypoglycemia-inducing side effect. Moreover, only 11.8% of patients treated with a combination of a sulfonylurea and insulin knew this side effect of the OAD. The awareness of the side effects of repaglinide was 21.6% (without insulin therapy) versus 21.4% in the insulin-comedicated group. Only 42.6% of patients treated with sulfonylureas or repaglinide knew how to act in the case of hypoglycemia. Even under comedication with insulin, only in 41.2% of the respondents in the comedicated group knew how to take action if they were to experience hypoglycemia. Our findings raise concerns and demonstrate, that the self-managing skills in an elderly patient group are not good, which may become an increasing problem in an ageing population. The prescription or the re-prescription of insulinotropic OAD needs to be adapted to the current cognitive situation and re-evaluated regularly.

Serum resistin increases in a postprandial state during liquid meal challenge test in healthy human subjects.

The role of resistin in humans is controversial although resistin has been linked to atherosclerotic and inflammatory processes. In rodents, resistin expression is suppressed after food restriction while central administration of resistin promotes short-term satiety. However, the nature of postprandial responses in circulating resistin in humans is unknown. Therefore, we investigated postprandial resistin concentrations in a pilot study in 19 healthy subjects and 19 controls matched for age and body mass index (BMI). Serum resistin, insulin and non-esterified fatty acids (NEFA) concentrations as well as plasma glucose and triglycerides were repeatedly assessed before and after ingestion of an isocaloric standardized liquid meal during a 300 min period.After consumption of liquid meal, serum resistin levels increased compared to fasting control (p=0.037). Postprandial plasma glucose and serum insulin increased (p<0.001) with lower glucose responses in females (p=0.001) and lower insulin responses in males (p=0.012). Plasma triglycerides increased and serum NEFA decreased with similar gender responses (p=0.025 and p<0.001, respectively). Serum resistin was not correlated to glucose, insulin, triglyceride, and NEFA responses to liquid meal challenge tests. The present data suggest that serum resistin increases postprandially in healthy humans. Additional studies are needed to elucidate normal 24-h daytime profiles in humans and differential response of serum resistin to macronutrient composition of meals.

Relapse of Graves' disease following development of a pheochromocytoma.

Catecholamines stimulate thyroid hormone synthesis as well as release of thyroid hormone and cause immunologic disturbances that possibly contribute to the manifestations of Graves' disease. This has led to repeated speculations about the possible role of catecholamines in the initiation and maintenance of hyperthyroidism. We describe a patient with Graves' disease who was treated with antithyroid drugs for 2 years. After withdrawal of antithyroid drugs, the patient was in remission for 5 years. After the antithyroid drug treatment and the long remission, the probability of relapse of Graves' disease was very low. Nonetheless, a relapse did occur. Two years after subtotal thyroid resection, further investigation because of persistent hypertension revealed a pheochromocytoma. Retrospective anamnestic data suggest that this pheochromocytoma had been present 2 years before the patient's relapse of Graves' disease. This sequence of diseases has not been described previously. The low probability for a Graves' disease relapse in this patient and the association of this patient's relapse with the manifestation of a pheochromocytoma suggest a possible etiologic role of excess catecholamine production in the relapse of Graves' disease.

Pioglitazone, a Specific Ligand of the Peroxisome Proliferator-Activated Receptor Gamma Reduces Gastric Mucosal Injury Induced by Ischaemia/Reperfusion in Rat.

BACKGROUND: The peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent nuclear receptor that has been implicated in the control of metabolism and numerous cellular processes, including cell cycle control, carcinogenesis, and inflammation. The present study was designed to investigate the effect of the specific PPARγ ligand, pioglitazone, on the mucosal lesions induced by ischaemia and reperfusion (I/R) in rats. METHODS: I/R lesions were induced in Wistar rats by applying a small clamp to the coeliac artery for 30 min (ischaemic phase), followed by the removal of the clamp for 3 h (reperfusion phase). Vehicle (saline) or increasing doses of pioglitazone (2.5, 10, and 30 mg/kg i.g.) were given 30 min before exposure to I/R. The animals were killed immediately after the end of the reperfusion phase (time 0) and at 12 and 24 h after I/R. The area of gastric lesions was measured by planimetry, and the gastric blood flow was determined by the H[Formula: See Text] gas clearance method. The gastric mucosal gene expressions of PPARγ, interleukin-1beta (IL-1ß), tumour necrosis factor alpha (TNF-α), leptin, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were examined by RT-PCR. In addition, protein expression of COX-2 and leptin was assessed by Western blot. RESULTS: The pretreatment with pioglitazone reduced in a dose-dependent manner the mean lesion area induced by I/R, and this effect was accompanied by a significant increase in the gastric blood flow. The decrease in gastric ulcerations by pioglitazone was also observed 12 and 24 h after the I/R. The PPARγ mRNA was weakly expressed in the intact gastric mucosa, but significantly up-regulated after exposure to I/R at each time interval studied. The expression of IL-1ß was not changed significantly after pioglitazone applied i.g. at doses 2.5 and 10 mg/kg, but it was down-regulated at the dose 30 mg/kg. TNFα mRNA was strongly increased after the exposure to I/R, but it was down-regulated after pioglitazone pretreatment. In contrast, both leptin and COX-2 mRNA and protein expression were increased in the gastric mucosa after exposure to I/R. The pretreatment with pioglitazone caused a significant up-regulation of mRNA and protein expression of leptin, reaching its peak at the dose 30 mg/kg i.g. In contrast, COX-2 expression did not change significantly after the 2.5 and 10 mg/kg of pioglitazone, but it significantly decreased after pioglitazone at dose 30 mg/kg given to rats before exposure to I/R. CONCLUSIONS: Pioglitazone reduces the acute erosions and deeper gastric lesions induced by I/R. The beneficial effect of this PPARγ ligand on I/R-induced gastric damage may be due to its anti-inflammatory properties, especially to the reduction in TNF-α expression and to up-regulation of leptin mRNA in the gastric mucosa. The inhibition of COX-2 expression by pioglitazone may reflect the anti-inflammatory properties of this compound.

In vivo efficacy of heated and non-heated humidifiers during nasal continuous positive airway pressure (nCPAP)-therapy for obstructive sleep apnoea.

Upper airway dryness is a frequent side-effect of nasal continuous positive airway pressure therapy (nCPAP) in obstructive sleep apnoea (OSA). In this situation, heated or non-heated passover humidifiers are often added to the nCPAP-therapy. The efficacy of these two modes in terms of increasing the absolute humidity of the inspired air in vivo has so far not been established. The present investigation was therefore designed to compare various heated and non-heated passover humidifiers in terms of the their ability to increase the absolute humidity in the inspired air during nCPAP. In six healthy test individuals, nCPAP-therapy at pressures of 5 mbar and 10 mbar was simulated, and the relative humidity and temperature of the air within the tube at the junction between CPAP tube and mask were measured. In each test person, measurements were carried out both with and without the two heated (HC 100, Fischer&Paykel Inc., New Zealand and HumidAire, ResMed Ltd., Australia) and two non-heated (Oasis and Humidifier, both from Respironics Inc., U.S.A.) passover humidifiers under steady-state conditions. The absolute humidity was calculated from the relative humidity and temperature measurements. The mean (SD) absolute humidity (gm(-3)) in the steady-state was significantly (P<0.05 higher with each of the humidifiers than that calculated when no humidifier was used. The relevant figures were as follows: no humidifier: 10(-2) (1.8) gm(-3) (at 5 mbar)/9.8 (1.8) gm(-3) (at 10 mbar); Humidifier: 16.4 (0.97)/15.6 (1.26); Oasis: 17.3 (0.97)/ 16.7 (0.93); HC100: 26.5 (1.40)/26.2 (1.23); HumidAire: 31.8 (2.50)/30.9 (2.64). The mean increase in absolute humidity (in gm(-3)) with the aid of the heated humidifiers was 16.3 (5 mbar) gm(-3)/16.4 (10 mbar) gm(-3) with HC100 and 21.6/21.1 with HumidAire, and in both cases was clearly and significantly (P=0.028) higher in comparison with the non-heated humidifiers--6.2/5.8 with Humidifier and 7.2/6.9 with Oasis. In terms of the absolute humidity achieved within the CPAP tube system, the heated humidifiers were clearly superior to the non-heated humidifiers. These results were, however, obtained under laboratory conditions, and therefore cannot be translated unreservedly to the situation represented by long-term CPAP-treatment. Furthermore, it is possible that the smaller humidification capacity of the non-heated humidifiers may still suffice to meet the requirements of clinical use in terms of effectively preventing dry airways under CPAP treatment. This point, however, needs further investigation on the basis of long-term clinical studies.

Ghrelin-a new gastroprotective factor in gastric mucosa.

Ghrelin, a novel peptide expressed in the gastrointestinal tract, especially in the gastric mucosa, exerts several biological activities including the stimulation of appetite and food intake, the stimulation of intestinal motility and the release of growth hormone. The aim of this study was to examine the expression of ghrelin in gastric mucosa after its exposure to ethanol and its effects on gastric lesions induced by ethanol with and without pretreatment with indomethacin. Acute gastric lesions were induced by intragastric administration of 75% ethanol in rats pretreated with saline-vehicle or ghrelin injected intraperitoneally (i.p.) without or with i.p. pretreatment with indomethacin. At the end of experiments, the rats were anesthetized, the stomach was exposed to measure gastric blood flow (GBF), to determine the area of gastric lesions and to take biopsy samples from the oxyntic mucosa for determination of transcripts of ghrelin, tumor necrosis alpha (TNF-alpha) and transforming growth factor alpha (TGFalpha) using RT-PCR and to assess the generation of PGE(2) by RIA. Exposure of gastric mucosa to 75% ethanol resulted in numerous mucosal lesions of an area of about 115 mm(2) and in the increase of mucosal expression of TNF-alpha, PGE(2), TGFalpha and ghrelin with concomitant decrease in GBF. Exogenous ghrelin reduced dose-dependently acute gastric lesions with simultaneous attenuation of GBF and a decrease in the expression of TNF-alpha but not TGFalpha. Pretreatment with indometahcin, which suppressed the generation of PGE(2) by about 85%, augmented ethanol-induced gastric lesions and eliminated the ghrelin-induced protection of mucosa against ethanol. We conclude that ghrelin, whose mucosal expression is enhanced after exposure to ethanol, exhibits a strong gastroprotection, at least in part, due to its anti-inflammatory action mediated by prostaglandins.

[Isolated ACTH deficiency as a rare cause of recurrent syncope and hypoglycemia]. / Isolierter ACTH-Mangel als seltene Ursache rezidivierender Synkopen und Hypoglykämien.

HISTORY AND CLINICAL FINDINGS: A 63-year-old man was assigned into emergency room presenting with an acute syncope associated with hypoglycemia and hypotension. Clinical findings showed a pale, waxing-colored skin and a disorder of impulse. During the clinical stay the patient's behavior was slowed down and adynamic. INVESTIGATIONS: After exclusion of cardiovascular and neurologic disorders as reason for the repeated syncopes a detailed endocrine diagnostic screening was performed, which revealed a deficiency of cortisol with missing increase of cortisol in the ACTH stimulation test. The ACTH-GnRH-TRH test showed an isolated deficiency of corticotropic hormones. Stimulation with CRH revealed no increase of ACTH or cortisol. Insulin tolerance test revealed an isolated ACTH insufficiency with consecutive deficit of cortisol. A tumor of the adrenal gland was excluded by abdominal scan. Cerebral CT was inconspicuous. Cerebral NMR was suspicious of volume deficiency of the hypophysis. TREATMENT AND COURSE: Under therapy with hydrocortisone 20 mg and fludrocortisone 0.05 mg orally the clinical symptoms of the patient improved impressively. The patient became efficient and dynamic. Systolic blood pressure increased in mean over 120 mm Hg. There were no more hypoglycemic episodes. CONCLUSION: Secondary insufficiency of the adrenal gland should be considered as a rare cause of hypoglycemia if combined with hypotensive circulatory disturbance and missing pigmentation of the skin.

[Osteoporosis and multiple pregnancy--a case report with positive outcome]. / Osteoporose und Mehrlingsgravidität--ein Erfahrungsbericht mit positivem Ausgang.

BACKGROUND: Pregnancy-associated osteoporosis is a rare condition. Due to the rareness of pregnancy-associated osteoporosis, no guidelines concerning an adequate therapy exist. However, since many antiresorptive drugs are potentially teratogenous, the therapeutic approach is limited. CASE REPORT: In a 30-year-old patient, pubic fracture occurred during her first pregnancy. Osteodensitometry revealed a distinct osteoporosis. The bone density improved under therapy with sex hormones, alendronate, 1,000 mg calcium and 1,000 IU cholecalciferol daily, but still remained osteoporotic when the patient again became pregnant 3 years later. During her triplet pregnancy the patient was treated with 3,000 mg calcium and 1,500 IU cholecalciferol daily. After delivery the bone density remained at the same level as immediately before the second pregnancy. CONCLUSION: Regarding the nonoccurrence of the expected considerable bone loss with this treatment the efficacy of this therapeutic approach during pregnancy warrants further study.

Auto-CPAP therapy based on the forced oscillation technique.

Autoadjusting CPAP devices (APAP) are designed to continuously adjust the positive pressure to the required levels, and thus increase treatment quality and patient compliance. The results of APAP treatment strongly depend on the control mechanism of the respective APAP device. In agreement with other working groups, we have recently shown that the forced oscillation technique (FOT) is capable of detecting incipient upper airway obstruction prior to physiological reactions such as the onset of increasing esophageal pressure swings or microarousals. Therefore we studied efficacy and acceptance of a novel APAP device controlled exclusively by FOT. 100 consecutive patients with OSAS confirmed by polysomnography (mean AHI 47.9 +/- 22.6) and daytime sleepiness (Epworth sleepiness scale, ESS 12.6 +/- 3.9) were randomized to either APAP treatment (n = 50) or conventional CPAP treatment (n = 50). Polysomnographies were performed at the second treatment night and subjective sleepiness (modified ESS) was established in the morning. The respiratory disturbance was largely normalized in both treatment groups in the second treatment night (AHI 4.7 +/- 5.3 vs. 3.7 +/- 3.4; n.s.). Both groups showed largely improved sleep profiles and had markedly reduced ESS-scores (6.6 +/- 3.6 vs. 7.0 +/- 3.4; n.s.). The mean treatment pressure during APAP was significantly lower than during CPAP treatment (6.0 +/- 2.0 vs. 9.0 +/- 1.8 mbar; p < 0.001). There were no significant differences between APAP and CPAP treatment in any parameter of efficacy or acceptance. APAP treatment with this device controlled exclusively by FOT is well accepted by the patients and permits an adequate treatment of OSAS without the need for invidiual CPAP titration.

[New trends in therapy of diabetes. More freedom, fewer risks, comfortable insulin administration]. / Neue Trends in der Diabetestherapie. Mehr Freiheiten, weniger Risiken, komfortable Insulingabe.

The incidence of diabetes mellitus is increasing worldwide. Strict metabolic control can prevent late sequelae of this disease. For this purpose, not only more potent drugs with fewer side effects are needed, but also user-friendly techniques and devices for self-monitoring of blood glucose and the less painful application of insulin (jet application, inhalable insulin). More user-friendly insulins are the rapid- and short-acting human insulin analogues, which do away with the bothersome injection/meal interval, and improve the postprandial glycemic response. New long-acting insulins reduce the frequency of injections and the occurrence of nocturnal hypoglycemia. Type 2 diabetics will presumable benefit from the use of the rapid, short-acting glinides, for example, by enabling a greater measure of eating freedom during the course of the day. The thiazolidinediones, a group of agents that enhance the effects of insulin in target tissue, reduce insulin resistance and improve insulin sensitivity.

[Prevention and therapy of diabetic foot syndrome. Preventing complications]. / Prävention und Therapie des diabetischen Fusssyndroms. So vermeiden Sie Komplikationen.

Selective prevention and stage-orientated treatment of the diabetic foot syndrome helps to avoid late complications. A prerequisite is good blood sugar control, early use of ACE inhibitors, CSE inhibitors and--based on the vascular situation, with consideration given to indications--platelet aggregation inhibitors. Regular inspection of the feet must be taken seriously. Every diabetic should be taught the rules of behavior in young years. The primary physician is responsible for coordinating further treatment and early referral to specialized foot clinics. In the event of an infection, specific treatment of the usually polymicrobial infection should be initiated. Long-term antibiotic treatment is not to be recommended. Wherever necessary, the calculated antibiotic therapy must be corrected on the basis of the results of antibiotic sensitivity testing of swabs taken from deep tissue (better: exudate from the floor of the wound. In the case of superinfected ulcers, wound debridement by the specialist surgeon is considered a must. Also, late stages of diabetic foot can be successfully managed in specialized centers by "foot-relieving" measures, revascularization, arthrodesis, etc.