[Neuroendorine paraneoplastic syndromes]. / Neuroendokrine paraneoplastische Syndrome.

Skin is commonly affected by neuroendorine paraneoplastic syndromes (PNS). This is due to the expression of receptors in the skin by which abnormally secreted neuroendocrine hormones and mediators elicit directly, and indirectly, cutaneous key signs and thus facilitate early diagnosis of these diseases. In acromegaly, induction of the growth hormone-insulin-like growth factor­1 axis results in trophic changes of the acral portions of the skin and mucosal membranes including cutis verticis gyrata. The skin signs of non-iatrogenic Cushing syndrome are identical with those of exogenous prolonged intake of glucocorticoids: centripetal accumulation of adipose tissue, plethora and striae distensae. Episodic flushing of the face and trunk (together with explosive diarrhea) is a key feature of carcinoid tumors. Fibrotic remodeling of the heart and retroperitoneal space, and less commonly of the skin, are important complications mediated by abnormally secreted 5­hydroxytryptamine (serotonin, 5­HT), the latter eliciting profibrotic responses on HT2B-receptor-expressing fibroblasts. Androgen-secreting tumors lead to well-established receptor-mediated cutaneous signs of peripheral hyperandrogenisms: seborrhea, acne, hirsutism, and androgenetic alopecia. In contrast, the pathogenesis of necrolytic migratory erythema as a key feature of glucagonoma remains incompletely understood and is thought to be related to hypoaminoacidemia. This review summarizes the clinical features of neuroendocrine PNS with skin involvement, elucidates its underlying pathophysiology, lists differential diagnoses, and explains key diagnostic steps and principal therapeutic options. An interdisciplinary approach is essential to provide the best care of all patients with neuroendocrine PNS.

Caloric restriction improves memory in elderly humans.

Animal studies suggest that diets low in calories and rich in unsaturated fatty acids (UFA) are beneficial for cognitive function in age. Here, we tested in a prospective interventional design whether the same effects can be induced in humans. Fifty healthy, normal- to overweight elderly subjects (29 females, mean age 60.5 years, mean body mass index 28 kg/m(2)) were stratified into 3 groups: (i) caloric restriction (30% reduction), (ii) relative increased intake of UFAs (20% increase, unchanged total fat), and (iii) control. Before and after 3 months of intervention, memory performance was assessed under standardized conditions. We found a significant increase in verbal memory scores after caloric restriction (mean increase 20%; P < 0.001), which was correlated with decreases in fasting plasma levels of insulin and high sensitive C-reactive protein, most pronounced in subjects with best adherence to the diet (all r values < -0.8; all P values <0.05). Levels of brain-derived neurotrophic factor remained unchanged. No significant memory changes were observed in the other 2 groups. This interventional trial demonstrates beneficial effects of caloric restriction on memory performance in healthy elderly subjects. Mechanisms underlying this improvement might include higher synaptic plasticity and stimulation of neurofacilitatory pathways in the brain because of improved insulin sensitivity and reduced inflammatory activity. Our study may help to generate novel prevention strategies to maintain cognitive functions into old age.

[Epidemiology of obesity]. / Epidemiologie der Adipositas.

Decades of obesity research have yielded no generally accepted strategy for safe and lasting weight loss. In spite of the importance given to it, obesity seems to be spreading like a virus. Is there really an epidemic of obesity? This survey looks at studies of the last 10 years from Germany, Europe, and worldwide and compares them with older data.Currently 32.9% of US adults and 13% of US children are obese; in Europe 15.7% of adults are obese and 4% of children and adolescents; in Germany 22.9% of adults are obese, while the figure is 6.3% for children and adolescents. Obviously there are characteristic differences in the worldwide distribution: obesity is more prevalent among women and also in lower social classes or among migrants. Every seventh non-Hispanic black woman in the US has a body mass index of over 40 kg/m(2) (morbid obesity). Obesity is increasing worldwide, especially among children. Morbid obesity is growing twice as fast as diabetes mellitus prevalence and will overtake it.In summary, obesity has developed from a secondary issue to a major national and international epidemic. In the near future, costs of prevention and treatment of obesity and its complications can no longer be covered by the health system. This explains why obesity is politically not recognized as a chronic illness.

CRH test prior to discontinuation of long-term low-dose glucocorticoid therapy.

Often long-term low-dosage glucocorticoid therapy cannot be terminated. This is due to the fact that even low doses which are within the physiological replacement range can cause a detectable, though clinically insignificant suppression of the adrenal gland function, resulting in "corticosteroid withdrawal syndrome". Another reason is the fact that it is necessary to be able to suppress undesirable inflammatory reactions caused by the underlying disease. ACTH testing of the adrenal capacity is widespread, but repeated testing may lead to undesirable side effects, such as allergic reactions. This study investigates the usefulness of testing the function of the pituitary-adrenal axis in predicting withdrawal problems. In 21 patients with chronic inflammatory disease who were treated with glucocorticoid doses of 5 to 10 mg prednisolone equivalent daily for a period of 2 to 131 months, stimulation with 100 microg hCRH (human corticotrophin-releasing hormone) was performed prior to the gradual withdrawal of medication. Blood samples were taken at baseline and after 45 minutes to measure ACTH and cortisol levels. Four weeks after steroid withdrawal the patients were reevaluated for signs of a relapse of the underlying disease in order to establish the necessity of reintroducing steroid therapy. This reevalution comprised clinical criteria, laboratory tests and the patients' own assessment of his/her well-being. In sixteen patients who later successfully withdrew from glucocorticoid therapy, a significant increase in cortisal levels was noticed after stimulation with CRH (p < 0.05). In five patients, with whom steroid withdrawal was not successful, baseline levels of cortisol were significantly lower than in the others (p < 0.05) and no sufficient increase was achieved after stimulation with CRH. These results show that successful withdrawal of a long-term low-dosage glucocorticoid therapy depends on the integrity of the pituitary-adrenal axis. Therefore CRH testing for evaluation of the pituitary-adrenal axis can be helpful in identifying patients in whom glucocorticoid withdrawal would be troublesome.

Standardized grey scale ultrasonography in Graves' disease: correlation to autoimmune activity.

OBJECTIVE: Graves' disease leads to thyroid enlargement and to reduction of tissue echogenicity. Our purpose was to correlate grey scale ultrasonography of the thyroid gland with clinical and laboratory findings in patients with Graves' disease. DESIGN: Fifty-three patients with Graves'disease were included in our study, 100 euthyroid volunteers served as control group. Free thyroxine (FT(4)), TSH and TRAb (TSH receptor antibodies) values were measured and correlated with sonographic echogenicity of the thyroid gland. METHODS: All patients and control persons underwent ultrasonographical histogram analyses under standardized conditions. Mean densities of the thyroid tissues were determined in grey scales (GWE). RESULTS: Compared with controls with homogeneous thyroid lobes of normal size (25.6 +/- 2.0GWE, mean +/- S.D.) echogenicity in patients with Graves' disease was significantly lower (21.3 +/- 3. 3GWE, mean +/- S.D., P < 0.0001). Among the patients with Graves' disease significant differences of thyroid echo levels were revealed for patients with suppressed (20.4 +/- 3.1 GWE, mean +/- S.D., n=34) and normalized TSH values (22.5 +/- 3.6GWE, mean +/- S.D., n=19, P < 0.02). Significantly lower echogenicities were also measured in cases of persistent elevated TRAb levels (19.9 +/- 2.9GWE, mean +/- S.D., n=31) in comparison with normal TRAb levels (22.9 +/- 3.5 GWE, mean +/- S.D., n=22, P < 0.0015). No correlation could be verified between echogenicity and either still elevated or already normalized FT(4) values or the thyroid volume. In coincidence of hyperthyroidism and Graves' ophthalmopathy (19.7 +/- 3.5GWE, mean +/- S.D., n=23) significantly lower echogenicity was measured than in the absence of ophthalmological symptoms (22.3 +/- 3.3GWE, mean +/- S.D., n=30, P < 0.016). Patients needing active antithyroid drug treatment revealed significantly lower thyroid echogenicity (20.3 +/- 3.1 GWE, mean +/- S.D., n=40) than patients in remission (23.7 +/- 3.4 GWE, mean +/- S.D., n=13, P < 0.001). Statistical evaluation was carried out using Student's t-test. CONCLUSIONS: Standardized grey scale histogram analysis allows for supplementary judgements of thyroid function and degree of autoimmune activity in Graves' disease. Whether these values help to estimate the risk of recurrence of hyperthyroidism after withdrawal of antithyroid medication should be evaluated in a prospective study.

Analysis of a protein kinase C-alpha mutation in human pituitary tumours.

It is generally accepted that protein kinase C-alpha (PKC-alpha) is an important enzyme in the cellular regulation of growth and differentiation by phosphorylating proteins. Recent studies have described a point mutation of PKC-alpha (position 908 of the genetic sequence, codon GAC becoming GGC) in invasive human pituitary tumours which leads to an exchange of amino acids in the protein. We investigated 11 human pituitary tumours to evaluate the data obtained previously. cDNA was subcloned and up to ten individual clones were sequenced from each tumour, resulting in 85 clones analyzed in total. All of the pituitary adenomas showed a normal wild-type sequence of PKC-alpha DNA. Even if the tumour was 'invasive' (infiltration of the dura mater) no mutation at position 908 of the sequence was found. Moreover, using Western blot analyses we did not observe any differences in PKC-alpha protein expression in invasive as compared with noninvasive pituitary adenomas. Until now we have been unable to confirm the data of other investigators, suggesting that mutated PKC-alpha is an inconsistent feature of invasive pituitary tumours.