[Thyroid and pregnancy]. / Schilddrüse und Schwangerschaft.

During pregnancy thyroid hormones have profound effects on embryonal/fetal development and maternal health. Therefore, thyroid gland disorders should be immediately diagnosed and adequately treated. Pregnancy-specific physiological alterations during pregnancy cause changes in the reference interval for thyroid-stimulating hormone levels and trimester-specific thresholds must be taken into account. This article summarizes the most important diagnostic and therapeutic aspects before, during and after pregnancy. With reference to the period prior to pregnancy, the article discusses iodide supplementation, preconceptional examination of thyroid gland metabolism and the importance of thyroid gland functional disorders for fertility and fulfilling the desire to have children. With a view to the period during pregnancy, the effect of hypothyroxinemia, hypothyroidism, and hyperthyroidism as well as the effects of their treatment on the development of the child are explained. Finally, a description is given of what must be paid attention to in the breast-feeding period and in postpartum thyroiditis.

[Prevention and treatment of cachexia : Exercise and nutritional therapy]. / Prävention und Behandlung der Kachexie : Bewegungs- und Ernährungstherapie.

BACKGROUND: Cachexia is a multifactorial and complex syndrome characterized by progressive functional impairment and ongoing loss in quality of life, which lead to a deterioration of the prognosis for affected patients. The prevalence of cachexia can be very high and is up to 80 % in patients with malignant tumors. OBJECTIVE: The aim of the study was to assess the relevance of exercise and nutrition in the prevention and therapy of cachexia. METHODS: An evaluation of the current literature on exercise and nutritional therapy in patients with cachexia or with advanced stage diseases where a high prevalence of cachexia is probable, was carried out. RESULTS: There is a lack of scientific evidence for the benefits of exercise in cachexia. A major problem of relevant studies was that cachexia was frequently not defined according to valid criteria; however, data indicate a benefit of exercise training in patients with advanced diseases associated with a high prevalence of cachexia. A solely nutritional intervention and dietary counselling seem to be of minimal benefit. The administration of omega 3 fatty acids is controversially discussed. CONCLUSION: Although there is a lack of data on the effects of exercise and nutritional therapy in cachexia, there is evidence for the benefits. The present data indicate the necessity for the use of a multimodal treatment including exercise, nutritional and pharmacological therapy in cachexia. There is a great necessity for prospective studies.

[Epidemiological study on the dimension of vitamin D deficiency in North Germany]. / Epidemiologische Untersuchung zur Häufigkeit eines Vitamin-D-Mangels in Norddeutschland.

BACKGROUND AND PURPOSE: In North Germany, the recommended exposure to sunlight of 30 minutes per day to produce sufficient vitamin D is hardly achieved, in particular due to weather conditions. Moreover, lifestyle and working habits also contribute to this problem. The aim of our study was therefore to investigate the prevalence of the vitamin D deficiency in North Germany. METHODS: For this purpose, 25-hydroxy vitamin D levels of over 98,000 people from North Germany during the time period 2008-2011 were retrospectively analysed based on age, gender and season. 25-vitamin D status was divided into sufficient (> 75 nmol/l) and insufficient (50 to 75 nmol/l) supply as well as vitamin D deficiency (< 50 to 25 nmol/l) and severe vitamin D deficiency (< 25 nmol/l). RESULTS: An undersupply of vitamin D was evident in all age groups analysed both in women and men in North Germany. Overall, vitamin D deficiency was particularly present during the months with less sunlight: more than 30 % of the people analysed showed a severe vitamin D deficiency in the months January to April. The study also showed that 25-vitamin D tests were almost evenly distributed over the individual months of the whole year and that this analysis was requested more frequently in elderly than in younger people. However, a severe vitamin D deficiency could also be detected in 25 % of the people analysed in the adolescent and young adult age group. CONCLUSION: Based on these results, it can be recommended to test 25-vitamin D levels once a year during the months January to April to detect a severe deficiency and to early initiate preventive supplementation.

[Thyroid disorders and pregnancy]. / Schilddrüsenerkrankungen und Schwangerschaft.

Disorders of the thyroid in women are common during the reproductive years. Incorrect or delayed treatment during pregnancy can adversely affect the health of mother and child. Knowledge of the physiological changes during this time is essential. Thyroid disorders, in particular hypothyroidism, may compromise fertility. Autoimmune thyroiditis is associated with a higher risk of fetal loss. In women on thyroid hormone replacement therapy, the thyroxine dose has to be adjusted to meet the enhanced requirement during pregnancy. Thyroid hormone is vital to fetal brain development. During pregnancy and lactation, iodine supplementation is also recommended due to alterations in iodine metabolism. Hyperthyroidism during pregnancy can adversely affect pregnancy outcome and has to be treated accordingly. Propylthiouracil should be given using the least effective dose to keep free thyroxine levels at the upper limit of normal or slightly above. Hyperthyroidism in the fetus and the neonate can be induced by thyroid stimulating antibodies capable of passing the placenta.

[Clinical pathways in endocrinology and diabetology]. / Behandlungspfade in der Endokrinologie und Diabetologie.

Endocrinology and diabetology are disciplines with an interdisciplinary approach. Patients with diabetes or endocrine disorders are diagnosed and treated by multiple disciplines both in an outpatient or in-hospital setting. Additional diabetes-specific professions also participate in the care of diabetic patients. The development of clinical pathways and case-management in institutionalized "Diabetes Centers" and "Endocrinology Centers" as platforms of cooperation is one way to improve patient care and to pool resources. In such centers an interdisciplinary decision support within the diagnostic and therapeutic process is important. E. g., interdisciplinary case conferences expediate and intensify the necessary flow of information. This guarantees the implementation of a rational and concerted treatment according to guidelines and finally optimize the clinical pathways in a continuous process improvement.

Antibiotic therapy for diabetic foot infections: comparison of cephalosporines with chinolones.

Diabetic foot complications are the most common cause of non-traumatic lower extremity amputations and uncontrolled infections represent a major risk factor. This open prospective, multicenter trial compared the efficacy of two antibiotic regimens for treatment of foot infections Wagner stage II or III in diabetic adults. Three hundred diabetic patients with severe, limb-threatening foot infection were consecutively enrolled in a prospective, observational, matched pairs controlled study to test two different antibiotic regimes (ceftriaxone vs chinolones) in addition to standard treatment of foot infection. After matching, 90 patients--each receiving ceftriaxone or chinolones--were analyzed. Our study demonstrated that treatment with a third generation cephalosporine is as effective as a treatment with chinolones. Response (reaching Wagner I or 0) was achieved in 58.0% in the ceftriaxone group and in 51.1% in the chinolone group (NS.). Fourteen days after initiation of treatment, the number of patients with microbiological isolates decreased in both groups (52 to 5 in the ceftriaxone group and 60 to 12 in the chinolone group). At hospital discharge, 66.0% of ceftriaxone and 64.4 of chinolone-treated diabetic ulcers were cured or improved. In summary, both substances proved to be effective in the primary antibiotic treatment of the diabetic foot; an early broad spectrum antibiotic treatment, that covers both gram-positive and gram negative bacteria as well as anerobes is undisputedly an imperative therapeutic intervention for the treatment of diabetic foot infection.

Diabetes and cardiovascular risk evaluation and management in primary care: progress and unresolved issues - rationale for a nationwide primary care project in Germany.

This review highlights established and more recently recognized risk factors for coronary heart disease (CHD) relevant for patients seen in primary care, emphasizing the key role of diabetes mellitus type 2. Recent trends in risk factor research as well as current methods of risk stratification, and new systemic markers are discussed. Beyond the need for more forceful public health strategies to improve early recognition and intervention, the necessity of an integrated comprehensive investigation of the overall characteristics of cardiovascular disease, especially in primary care patients as a prerequisite for future concerted actions is pointed out. Based on this, a large-scale epidemiological investigation focusing on CHD and diabetes in the primary care sector is suggested.

Leptin resistance - or why leptin fails to work in obesity.

In experimental models of obesity high serum concentrations of leptin without subsequent inhibition of food intake indicate a resistance to the physiological effects of leptin. Similar to the animal model leptin concentrations in most of the obese patients are higher compared to normal-weight persons. The postulated leptin resistance is one major target in the search for a better understanding of obesity and the development of pharmacological tools to treat this spreading disease.

Effects of corticotropin-releasing hormone on locus coeruleus neurons in vivo: a microdialysis study using a novel bilateral approach.

OBJECTIVE: Stress-induced release of noradrenaline (NA) from locus coeruleus (LC) neurons is mainly regulated by corticotropin-releasing hormone (CRH). Tyrosine is a precursor of NA and plays an intriguing role in the regulation of NA release. DESIGN: We studied the effects of injecting CRH into the LC using a novel bilateral approach which relies on the mainly ipsilateral projections of LC neurons allowing stimulation of one hemisphere while using the other as control. To analyze the modification of the CRH effect, tyrosine was given intraperitoneally. A combination of CRH and its antagonist d-Phe was administered for validation of the specificity of CRH effects. METHODS: Wistar rats were used in all experiments. Injections were made through fused silica capillaries implanted into both LCs and microdialysis samples were collected bilaterally from the prefrontal cortex (PFM) every 20 min for 1 h before and 3 h after injections. The effects of LC stimulation were investigated by determining 3-methoxy-4-hydroxyphenylglycol (MHPG) in the dialysates. RESULTS: Following CRH injection into one LC and contralateral infusion of artificial cerebrospinal fluid (aCSF), MHPG levels, which are indicative of NA release, increased only in the ipsilateral PFM. These effects were blocked by d-Phe. Simultaneous administration of tyrosine i.p. led to a significant prolongation of MHPG release. CONCLUSIONS: These data provide the first physiological evidence of unilateral LC projections with the bilateral stimulation design proving to be a very valuable tool for the study of LC firing rate, to decrease number of animals and time expenditure. Prolongation of MHPG release after tyrosine supplementation is most likely due to increased NA synthesis.

A double-blind trial of perindopril and nitrendipine in incipient diabetic nephropathy.

UNLABELLED: We conducted a randomised, double-blind multicentre trial to compare the efficacy of the inhibitor of the angiotensin-converting enzyme (ACE) perindopril (P) with nitrendipine (N) in incipient diabetic nephropathy. METHODS: Forty-six patients with insulin-treated diabetes mellitus and mild-to-moderate hypertension and stable microalbuminuria were examined. P 4 or 8 mg once daily was compared to N 20 or 40 mg once daily; an optional open combination treatment with indapamide 2.5 mg once daily was given when needed. Main outcome measures were urinary albumin excretion rate, creatinine clearance and isotopic clearance measurements after 12 months. RESULTS: Baseline characteristics (blood pressure, HbA1, renal function) were highly comparable between groups. No serious adverse events occurred during the study period. Blood pressure was controlled (<140/90 mmHg) in all patients except for one in each group who dropped out. At the end of the study, albumin excretion rate was stabilized in both groups (P: 72% of baseline, N: 108%, NS). There were no significant differences found in radiometric clearance measurements. Creatinine clearance rose in patients treated with P by 10.0 ml/min on average, while it decreased by 9.8 m/min under N treatment (group effect: p<0.05). CONCLUSIONS: In this head-to-head comparison, P and N were effective in stabilising most parameters of renal function in incipient diabetic nephropathy.

Octreotide scintigraphy and catecholamine response to an octreotide challenge in malignant phaeochromocytoma.

OBJECTIVE: Octreotide scintigraphy has been reported to visualize chromaffine tumours. This study in patients with malignant phaeochromocytoma was designed to assess octreotide in comparison with standard m-iodobenzylguanidine (MIBG) scintigraphy and to study functional activity of somatostatin receptors. Finally, two cases of octreotide treatment are reported. DESIGN: Open, prospective clinical trial. PATIENTS: In 12 patients with histologically proven malignant phaeochromocytoma, 111In-octreotide scintigraphy, 123I-MIBG scintigraphy and computed tomography were performed. In ten patients plasma catecholamine response to a single dose of octreotide (200 micrograms i.v.) was monitored up to 5 hours after injection. Two patients were treated with octreotide over several months. MEASUREMENTS: Plasma catecholamines were measured by high performance liquid chromatography (HPLC). Scintigraphy was performed using a large field gamma camera and SPECT technique where appropriate. RESULTS: At least one metastatic lesion was visualized by octreotide scintigraphy in eight patients while the remaining four patients had negative findings. In total, 43 out of 54 known metastases (79.6%) were detected by MIBG, 24 (44.4%) by octreotide. Nevertheless, octreotide scintigraphy detected six metastases that were negative by MIBG. There was no correlation between the results of octreotide scintigraphy and catecholamine suppression after i.v. octreotide. In two patients on octreotide treatment, symptomatic improvement, but not mass reduction, could be documented. CONCLUSIONS: Octreotide scintigraphy behaves in part complementary to MIBG, thus, increasing diagnostic sensitivity. Presence of somatostatin receptors, as demonstrated by octreotide scintigraphy, does not necessarily predict functional activity or therapeutic response.

Relationship between pituitary ACTH content and hypothalamic catecholamines in the rat.

Hypothalamic concentrations of epinephrine and norepinephrine were determined in rats following 6-hydroxydopamine lesions of the locus coeruleus and subcoeruleus system and following sham-operation. These concentrations were correlated with pituitary ACTH content. While the lesion procedure did not have a major effect on hypothalamic monoamine levels, we were able to demonstrate a strong negative correlation between hypothalamic epinephrine and pituitary ACTH content independent of the experimental condition. Only a weak negative correlation was observed for hypothalamic norepinephrine and pituitary ACTH. Our recent and previous data suggest a tonic and phasic inhibition of ACTH release by hypothalamic monoamines.

Long-term effects of a complex behavioral treatment of essential hypertension.

A multidimensional behavioral program was developed for the treatment of essential hypertension. Over a course of 6 weeks, 108 patients of a rehabilitation center were treated with this program consisting of health education, self-monitoring of blood pressure, relaxation techniques, and a social skill training in addition to standard medical treatment alone. Blood pressure and other cardiovascular risk factors were monitored for a period of 12 months. Blood pressure levels became normotensive in both groups at the end of the 6-week training program. However, the blood pressure reduction in the behavioral treatment group was achieved with fewer patients taking antihypertensive medication than in the control group. The number of patients taking antihypertensive drugs in the treatment group was 60.2% prior to treatment and 44.4% after treatment; figures for the control group were 68% and 73.8%, respectively (p less than or equal to 0.01). Almost identical data were obtained at the 6- and 23-month follow-up examinations. No consistent changes were observed in weight, smoking, or blood lipids. These results demonstrate beneficial and long-lasting effects of a combined medical and psychologic treatment of essential hypertension as compared to medical treatment alone.

[Characteristics and mechanisms of tumor anorexia]. / Merkmale und Mechanismen der Tumoranorexie.

Tumor anorexia can be defined as a continuous reduction in dietary intake with a steadily increased cost of energy of the organism. A possible basis for this nutritional imbalance during the course of the illness is provided by metabolic dysfunction, changes in taste, neuroendocrine alterations and behavioral factors. At the present time no uniform explanation exists, thus only adjuvant therapeutic strategies can be deducted.

Dietary tyrosine suppresses the rise in plasma corticosterone following acute stress in rats.

Acute, uncontrollable stress increases norepinephrine (NE) turnover in the rat's brain (depleting NE) and diminishes the animal's subsequent tendency to explore a novel environment. Pre-treatment with tyrosine can reverse these adverse effects of stress, presumably by preventing the depletion of NE in the hypothalamus. Numerous studies suggest that NE inhibits the release of adrenocorticotropic hormone (ACTH) by suppressing corticotropic releasing factor (CRF) secretion in the hypothalamus. In the present study, we found that pre-treatment with supplemental tyrosine not only prevented the behavioral depression and hypothalamic NE depletion observed after an acute stress, but also suppressed the rise in plasma corticosterone. These results support a role for brain NE in stress-induced corticosterone secretion and demonstrate that supplemental tyrosine can protect against several adverse consequences of such stress.

Neurochemical and behavioral consequences of acute, uncontrollable stress: effects of dietary tyrosine.

Acute, uncontrollable stress increases norepinephrine (NE) turnover in the rat's brain (thereby depleting NE) and diminishes the animal's subsequent tendency to explore a novel environment. We determined whether supplemental dietary tyrosine could prevent some of these changes. Rats given a control diet or diets enriched with tyrosine or tyrosine plus valine were exposed to tail-shock stress or to no stress over a 60-min period. Exposure to the stress caused an increase in NE turnover, decreasing NE and increasing 3-methoxy-4-hydroxy-phenylethylene glycol sulfate (MHPG-SO4) concentrations within the locus coeruleus, hypothalamus and hippocampus. No changes were detected in serotonin (5-HT) levels or turnover. Behavioral deficits following the stress were observed using measures of locomotion and of exploration in a novel open-field environment: stressed animals displayed much less spontaneous motor activity, hole-poking or frequency of standing on their hind legs than control animals. Animals receiving the tyrosine-enriched diet displayed neither the stress-induced depletion of NE nor the behavioral depression. These preventive effects of tyrosine were abolished by co-administration of valine, a large neutral amino acid that competes with tyrosine for transport across the blood-brain barrier. Since tyrosine alone, in animals not subjected to stress, did not change NE turnover nor the behaviors studied, our observations affirm that catecholaminergic neurons respond to the precursor amino acid only when they are physiologically active. Supplementary tyrosine may be useful therapeutically in people exposed chronically to stress.