Background: Lithium augmentation is a first-line strategy for depressed patients resistant to antidepressive therapy, but little is known about patients’ subsequent long-term course or outcome predictors. We investigated long-term outcomes of unipolar depressed patients who had participated in a study on the effects of lithium augmentation on the hypothalamic-pituitary-adrenocortical system using the combined dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test. Methods: Twelve to 28 months (mean 18.6 ± 4.6 months) after lithium augmentation, 23 patients were assessed with a standardized interview, of which 18 patients had complete DEX/CRH test results. Relapse was diagnosed by DSM-IV criteria (Structured Clinical Interview for DSM-IV; SCID I). Results: Only 11 patients (48%) had a favorable follow-up, defined as absence of major depressive episodes during the observation period. Patients with a favorable and an unfavorable course did not differ in clinical or sociodemographic parameters, endocrinological results or continuation of lithium. However, fewer previous depressive episodes tended to correlate (p = 0.09) with a favorable course. Conclusion: Results from studies using the DEX/CRH test to predict relapse in depressed patients treated with antidepressants were not replicated for lithium augmentation. Our finding could reflect the elevation of DEX/CRH results by lithium, independent of clinical course. Limitations of the study are its small sample size, the heterogeneous clinical baseline conditions and the lack of lithium serum levels. The fact that lithium continuation did not predict the course might be related to the difference between the efficacy of lithium in controlled studies and its effectiveness in naturalistic settings. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Title: Acipimox during Short-Term Exercise Exerts A Negative Feedback of Growth Hormone on Ghrelin Secretion in Patients with Bulimia Nervosa and in Healthy Women: The Role of Lipolysis Objective: Eating disorders, such as bulimia nervosa (BN) and anorexia nervosa (AN), are characterized by abnormal eating behavior. The main features of BN are binge-eating and inappropriate compensatory methods to prevent weight gain. The appetite-modulating peptide ghrelin is secreted by the stomach and shows a strong release of growth hormone (GH). A potential GH-ghrelin feedback loop between stomach and the pituitary has been recently reported. Acipimox (Aci), an analogue of nicotinic acid, inhibits lipolysis in adipose tissue (AT) and reduces plasma glycerol and free fatty acids (FFA) levels. Exercise and Aci are stimulators of GH secretion. We suppose that a negative feedback from increased GH levels during exercise may play a role in reducing plasma ghrelin levels. We surmised that altered baseline activity and exercise-induced activation of the sympathetic nervous system (SNS) results in excessive stimulation of lipolysis associated with negative energy balance and may lead to abnormal AT metabolism in patients with BN. Disruption of the gut-brain-AT axis might be involved in the pathogenesis of BN. The...

The pathogenesis of insulin resistance is a complex and still intensively studied issue. Endocrine and paracrine activity of the adipose tissue together with mi- tochondrial dysfunction are the most discussed potential factors included in the development of insulin resistance. In the first part of our study we examined the involvement of the adipose tissue and its secretory products in the etiopathogenesis of insulin resistance in patients with Cushing's syndrome, acromegaly and simple obesity. We focused on three important regulators of metabolic homeostasis - fibroblast growth factors 21 and 19 (FGF-21 and FGF-19) and adipocyte fatty acid binding protein (FABP-4). We found significantly elevated circulating levels of FGF-21 and FABP-4 ac- companying insulin resistance in both patients with simple obesity and patients with obesity connected to Cushing's syndrome, as compared to healthy controls. The concentrations of both substances were comparable between hypercortisolic and obese patients. This finding together with the absence of correlation be- tween the levels of FGF-21 resp. FABP-4 and cortisol suggest that the reason for elevation of their concentrations is obesity and its metabolic consequences themselves rather then the effect of hypercortisolism on FGF-21 and FABP-4 production. We found no...

Trade-off between reproduction and longevity is a widely accepted fact, yet proximate mechanisms are scarcely understood. In this work I tested differences in lifespan between diapause and non-diapause males of a model insect, the linden bug Pyrrhocoris apterus. Also the role of juvenile hormone in regulation of longevity and immunity (measured by relative phenoloxidase activity) was assessed. In addition to that, I examined if juvenile hormone is the mediator of reduction in longevity induced by mating.

Background: Lithium augmentation is a first-line strategy for depressed patients resistant to antidepressive therapy, but little is known about patients’ subsequent long-term course or outcome predictors. We investigated long-term outcomes of unipolar depressed patients who had participated in a study on the effects of lithium augmentation on the hypothalamic-pituitary-adrenocortical system using the combined dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test. Methods: Twelve to 28 months (mean 18.6 ± 4.6 months) after lithium augmentation, 23 patients were assessed with a standardized interview, of which 18 patients had complete DEX/CRH test results. Relapse was diagnosed by DSM-IV criteria (Structured Clinical Interview for DSM-IV; SCID I). Results: Only 11 patients (48%) had a favorable follow-up, defined as absence of major depressive episodes during the observation period. Patients with a favorable and an unfavorable course did not differ in clinical or sociodemographic parameters, endocrinological results or continuation of lithium. However, fewer previous depressive episodes tended to correlate (p = 0.09) with a favorable course. Conclusion: Results from studies using the DEX/CRH test to predict relapse in depressed patients treated with antidepressants were not replicated for lithium augmentation. Our finding could reflect the elevation of DEX/CRH results by lithium, independent of clinical course. Limitations of the study are its small sample size, the heterogeneous clinical baseline conditions and the lack of lithium serum levels. The fact that lithium continuation did not predict the course might be related to the difference between the efficacy of lithium in controlled studies and its effectiveness in naturalistic settings. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

We present the case of a 7-month-old baby with Cushing’s disease due to an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma combined with cells producing thyreotropin-secreting hormone (TSH). In MRI scans, a contrast-enhancing lesion was seen inside the pituitary fossa, and it extended into the suprasellar region. On the assumption of a pituitary adenoma, surgery was performed. Corresponding with biochemical findings, histopathological evaluation revealed an ACTH- and TSH-producing tumor. Genetic analysis did not demonstrate an alteration at codon 201 (Arg) and 227 (Glu). To our knowledge, this is the first case described in a child of this age. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The pathogenesis of insulin resistance is a complex and still intensively studied issue. Endocrine and paracrine activity of the adipose tissue together with mi- tochondrial dysfunction are the most discussed potential factors included in the development of insulin resistance. In the first part of our study we examined the involvement of the adipose tissue and its secretory products in the etiopathogenesis of insulin resistance in patients with Cushing's syndrome, acromegaly and simple obesity. We focused on three important regulators of metabolic homeostasis - fibroblast growth factors 21 and 19 (FGF-21 and FGF-19) and adipocyte fatty acid binding protein (FABP-4). We found significantly elevated circulating levels of FGF-21 and FABP-4 ac- companying insulin resistance in both patients with simple obesity and patients with obesity connected to Cushing's syndrome, as compared to healthy controls. The concentrations of both substances were comparable between hypercortisolic and obese patients. This finding together with the absence of correlation be- tween the levels of FGF-21 resp. FABP-4 and cortisol suggest that the reason for elevation of their concentrations is obesity and its metabolic consequences themselves rather then the effect of hypercortisolism on FGF-21 and FABP-4 production. We found no...

Title: Acipimox during Short-Term Exercise Exerts A Negative Feedback of Growth Hormone on Ghrelin Secretion in Patients with Bulimia Nervosa and in Healthy Women: The Role of Lipolysis Objective: Eating disorders, such as bulimia nervosa (BN) and anorexia nervosa (AN), are characterized by abnormal eating behavior. The main features of BN are binge-eating and inappropriate compensatory methods to prevent weight gain. The appetite-modulating peptide ghrelin is secreted by the stomach and shows a strong release of growth hormone (GH). A potential GH-ghrelin feedback loop between stomach and the pituitary has been recently reported. Acipimox (Aci), an analogue of nicotinic acid, inhibits lipolysis in adipose tissue (AT) and reduces plasma glycerol and free fatty acids (FFA) levels. Exercise and Aci are stimulators of GH secretion. We suppose that a negative feedback from increased GH levels during exercise may play a role in reducing plasma ghrelin levels. We surmised that altered baseline activity and exercise-induced activation of the sympathetic nervous system (SNS) results in excessive stimulation of lipolysis associated with negative energy balance and may lead to abnormal AT metabolism in patients with BN. Disruption of the gut-brain-AT axis might be involved in the pathogenesis of BN. The...

In einem Fütterungsversuch mit 15 weiblichen, genetisch identischen Zwillingspaaren wurde der anhaltende Effekt energetisch unterschiedlich konzentrierter Futterrationen auf Körper- und Blutmerkmale zwischen dem vierten und 21. Lebensmonat erfasst. Die gleichen Merkmale wurden an den Tieren auch während der Laktation erhoben, als die Tiere einheitlich gefüttert wurden. Zusätzlich wurde die Milchleistung untersucht. Während der Aufzucht wurden Körpergewicht, tägliche Gewichtszunahme, Rückenfettdicke und Widerristhöhe von der Fütterungsintensität signifikant beeinflusst. Körpergewicht und Rückenfettdicke zeigten vom siebenten bis 15. Lebensmonat die größten Unterschiede zwischen den Fütterungsgruppen. Im Gegensatz zum Körpergewicht, wurde der Fettansatz bis zum 21. Lebensmonat kaum gebremst. Für die Serumkonzentrationen von Insulin, Glukose und beta-Hydroybuttersäure und die Erythrozytenindizes MCV und MCH konnte ein signifikanter Fütterungseinfluss während der gesamten Aufzuchtphase nachgewiesen werden. Kortisol, Kreatinin, ASAT, GGT, GLDH, MCHC, Leukozytenzahl, Thrombozytenzahl reagierten auf den Fütterungsstimulus nur innerhalb bestimmter Altersabschnitte. Bis zum neunten Monat differierte der Insulinspiegel zwischen den Fütterungsgruppen kaum, ab dem 10. Lebensmonat aber sehr deutlich. Es kann daher ausgeschlossen werden, dass der Insulinspiegel im präpubertären Abschnitt die Entwicklung der späteren Milchleistung beeinflusste. Nach dem Abkalben war die intensiv gefütterte Gruppe stärkeren metabolischen Belastungen ausgesetzt und hatte eine geringere Milchleistung als die moderat gefütterte Gruppe. Offensichtlich wurde der Stoffwechsel durch die vorangegangene Fütterung geprägt, da der Fettansatz in der Intensivgruppe bei gleicher Fütterung früher einsetzte und auch intensiver erfolgte. Einige Kennwerte beim Jungtier korrelierten signifikant mit der späteren Milchleistung. Altersabhängige Veränderungen der Korrelationskoeffizienten weisen auf unterschiedlich sensible Phasen für die Prägung der späteren Milchleistung hin. / In a feeding trial with 15 pairs of genetically identical female twins, the effect of feeding intensity on body condition and blood parameters were investigated between the fourth and 21st month. The same traits were analysed on the cows during the first lactation when the animals were uniformly fed. In addition to these traits, the milk yield was investigated. During the rearing period; body weight, daily weight gain, back fat thickness, and withers height were significantly influenced by feeding. The largest differences between the feeding groups in body weight and back fat thickness were seen between the ages of seventh to 15th months. In contrast to body weight, back fat thickness hardly exceeded the 21st month between the groups. The serum concentrations of insulin, glucose, beta-Hydroxybutyric acid, and the erythrocyte indices MCV and MCH showed a significant feeding effect throughout the growing period. Cortisol, creatinine, Aspartate transaminase (AST), y-glutamyltransferase (GGT), Glutamate dehydrogenase (GDH), mean corpuscular hemoglobin concentration (MCHC), white blood cells (WBC) and platelet responded to the feeding stimulus only within certain ages. At age nine months, insulin levels were barely differed between the feeding groups but were distinct as from the 10th month. It can therefore be concluded that insulin levels at the pre-pubertal development affects the subsequent milk yield. After calving, the intensively fed group had more metabolic stress and had a lower milk yield than the moderately fed group. Obviously, the metabolism was programmed in the previous feeding period. There was an early onset and a more intensive fat deposition in the intensive group though; they had the same feeding level. Some traits in young animals were significantly correlated with subsequent milk yield. Age-dependent changes in the correlation coefficients suggest the fact that differences in sensible juvenile phases in traits could contribute to milk yield later.

<p>Hormon rasta ima ključnu ulogu u mnogim fiziolo&scaron;kim procesima, anabolički efekti, stimulisanje rasta dugih kostiju, regulacija transkripcije gena u ciljnim ćelijama su uglavnom posredovani preko mitogenog polipeptida, insulinu sličan faktor rasta tip 1 (insulin like growth factor 1-IGF-1). Hormon rasta indukuje proizvodnju IGF-1 u jetri, koji reaguje sa receptorima ciljnih organa indukujući rast, odnosno IGF-1 posreduje svim stimulativnim dejstvima hormona rasta na kost, hrskavicu, rast mi&scaron;ić a i na metabolizam masti i ugljenih hidrata. U proceni redovnosti, bezbednosti i efikasnosti terapije hormonom rasta koristi se merenje koncentracije IGF-1 u serumu. Istraživanje je urađeno kao retrospektivno-prospektivna studija, a obuhvatilo je 80 pacijenata na terapiji hormonom rasta koja se kontroli&scaron;u i leče na Odeljenju za endokrinologiju, dijabetes i bolesti metabolizma Instituta za zdravstvenu za&scaron;titu dece i omladine Vojvodine u Novom Sadu. Istraživani uzorak je obuhvatio 80 pacijenata, od kojih 35 dece sa nedostatkom hormona rasta, 24 dece rođene male za gestacionu dob i 21 devojčicu sa Tarnerovim sindromom. Svi ispitanici su praćeni od početka primene hormona rasta i tokom prve dve godine terapije hormonom rasta. U ovom istraživanju su praćeni auksolo&scaron;ki i laboratorijski parametri u cilju ispitivanja odgovora na terapiju hormonom rasta. Praćene su bazalne vrednosti IGF-1 i promene nivoa IGF-1 u serumu tokom terapije hormonom rasta i kori&scaron;ćene da bi se ispitao odgovor na terapiju hormonom rasta, praćenjem brzine rasta, promena skora standardnih devijacija - SSD za telesnu visinu i ko&scaron;tanog sazrevanja. Ciljevi istraživanja su bili da se utvrdi povezanost vrednosti insulinu sličnog faktora rasta tip 1, brzine rasta i ko&scaron;tanog sazrevanja tokom terapije hormonom rasta. Takođe je poređena brzina rasta dece sa deficitom hormona rasta, devojčica sa T arnerovim sindromom i dece rođene male za gestaciono doba na terapiji hormonom rasta. U istraživanom uzorku, dvogodi&scaron;njim praćenjem terapije hormonom rasta je postignut dobar odgovor na terapiju, među decom sa nedostatkom hormona rasta je 71,5% postiglo normalnu telesnu visinu (&plusmn;2 SSDTV) posle dve godine terapije hormonom rasta, 79,2% dece rođene male za gestacionu dob i 42,9% devojčica sa Tarnerovim sindromom. Značajna zastupljenost dece prepubertetskog uzrasta na početku terapije hormonom rasta, među decom sa nedostatkom hormona rasta 77,2%, među decom rođenom malom za gestacionu dob 79,1% i među devojčicama sa Tarnerovim sindromom 90,5% &scaron;to je značajno uticalo na uspe&scaron;nost terapije. Tokom terapije hormonom rasta je utvrđeno povećanje brzine rasta i SSD TV kod sve tri grupe ispitanika. U sve tri grupe ispitanika je tokom terapije hormonom rasta utvrđen porast nivoa IGF-1 seruma i SSDIGF-1 i ubrzanje ko&scaron;tanog sazrevanja tokom terapije hormonom rasta. Za prvih &scaron;est meseci terapije nema statistički značajnih razlika među grupama u brzini rasta (p&gt;0,05), dok je za period prve i druge godine terapije hormonom rasta utvrđeno da postoji statistički značajna razlika među grupama (p&lt;0,05), da je brzina rasta kod devojčica za Tarnerovim sindromom statistički značajno manja i od brzine rasta kod dece sa nedostatkom hormona rasta (p &lt;0,05), i od brzine rasta kod dece rođene male za gestacionu dob (p&lt;0,05). Među decom sa nedostatkom hormona rasta i dece rođene male za gestacionu dob nema statistički značajne razlike u brzini rasta (p&gt;0,5). U ovom istraživanju je praćenjem auskolo&scaron;kih i laboratrijskih parametara tokom dvogodi&scaron;nje primene hormona rasta, konstruisano vi&scaron;e matematičkih modela za predviđanje odgovora na terapiju hormona rasta koji su statistički veoma značajani sa visokim koeficijentom vi&scaron;estruke linearne korelacije. U ovom istraživanju nije dobijena statistički značajna korelacija izmedju nivoa promene IGF-1 i brzine rasta za ceo uzorak, kao ni za decu sa nedostatkom hormona rasta, decu rođenu malu za gestacionu dob i devojčice za Tarnerovim sindromom. Nije dobijena statistički značajna korelacija izmedju nivoa promene IGF-1 i ubrzanja ko&scaron;tanog sazrevanja za ceo uzorak i za tri grupe pacijenata.</p> / <p>Growth hormone plays a key role in many physiological processes. The anabolic effects, the stimulation of growth of the long bones and the regulation of gene transcription in the target cells are mediated mainly via mitogenic polypeptide and insulin-like growth factor type 1 (insulin like growth factor 1-IGF-1). Growth hormone induces the production of IGF-1 in the liver, which interacts with receptors of the target organs inducing growth, that is, IGF-1 mediates all the stimulating effects of growth hormone on bone, cartilage, muscle growth and the metabolism of fats and carbohydrates. In assessing the regularity, safety and efficacy of growth hormone therapy, measuring the concentration of IGF-1 in serum is used. The survey was conducted as a retrospective-prospective study and involved 80 patients treated with growth hormone, monitored and treated at the Department of Endocrinology, Diabetes and Metabolic Diseases, at the Institute for Health Protection of Children and Youth of Vojvodina in Novi Sad. Investigated sample included 80 patients, of whom 35 children have growth hormone deficiency, 24 children were born small for gestational age and 21 girls with Turner syndrome. All the patients were monitored from the beginning of the administration of growth hormone and during the first two years of growth hormone therapy. In this study, auxological and laboratory parameters were monitored for the purpose of examining the response to treatment of growth hormone. The basal values of IGF-1 and changes in IGF-1 levels in serum, along with monitoring the rate of growth velocity and recent changes in standard deviation - SSD for body height and bone maturation, were monitored during growth hormone therapy and used for the evaluation of the response to growth hormone therapy. The objectives of the study were to determine the correlation of insulin-like growth factor type 1 values, the growth velocity and maturation of bone during growth hormone therapy. Also, the growth velocity in children with growth hormone deficiency was compared with the growth velocity in girls with Turner syndrome and in children born small for gestational age while treated with growth hormone. Two-year monitoring of growth hormone therapy in the study sample has show n good response to therapy. 71.5% of children with growth hormone deficiency, 79.2% of children born small for gestational age, and 42.9% of girls with Turner syndrome achieved normal body height (&plusmn; 2 SSDTV) after two years of growth hormone therapy. There was a significant share of children at prepubertal age at the beginning of growth hormone therapy: 77.2% of children with growth hormone deficiency, 79.1% of children born small for gestational age and 90.5% of girls with Turner syndrome, which significantly influenced the success of the therapy. During the growth hormone therapy there was an increase of growth velocity and SSD TV in all three groups of children. An increase in levels of IGF-1 serum and SSDIGF-1 and acceleration of bone maturation were determined in all three groups of patients during growth hormone therapy. For the first six months of therapy there was no statistically significant difference between groups in growth velocity (p&gt; 0.05), while the period of the first and second year of growth hormone therapy showed a statistically significant difference between groups (p &lt;0.05). The growth velocity in girls with Turner syndrome was significantly lower than the growth velocity in children with growth hormone deficiency (p &lt;0.05) and in children born small for gestational age (p &lt;0.05). Between children with growth hormone deficiency and children born small for gestational age there was no statistically significant difference in growth velocity (p&gt; 0.5). By monitoring auxological and laboratory parameters during the two years of application of growth hormone, several highly statistically significant mathematical models for predicting the response to treatment of growth hormone were constructed in this study with a high coefficient of multiple linear correlation. In this study, there was no statistically significant correlation between the level of change in IGF-1 and growth velocity for the entire sample, as well as for children with growth hormone deficiency, children born small for gestational age and girls for Turner syndrome. There was no statistically significant correlation between the level of change in IGF-1 and acceleration of bone maturation for the entire sample and for the three groups of patients.</p>