TY - JOUR AB - PURPOSE: Hypertension is the most frequent co-morbidity in active Cushing's syndrome (CS) and regarded as a major cardio-vascular risk factor. It is unknown whether blood pressure and related parameters, such as kidney function, recover in the long-term following remission of CS. METHODS: Blood pressure and related co-morbidities were analyzed in a cohort of 81 patients with CS (Cushing's disease: 52, ectopic CS: 8, adrenal CS: 21) from a single tertiary care center. Patients were longitudinally evaluated at baseline, at 7.1 years (6.3-7.4) and at 14 years (13.5-14.4) after biochemical remission. Data were compared to a control group matched for BMI, age and sex (n = 243) from the "Cooperative Health Research in the Region of Augsburg" study (KORA) in a 1:3 fashion. RESULTS: Patients with CS showed a higher median blood pressure and lower median glomerular filtration rate (GFR) compared to the matched controls, at baseline, 7 and 14 years after biochemical remission. Although the prevalence of hypertension and chronic kidney disease increased over time in the KORA cohort, patients treated for CS had a significantly higher prevalence of both comorbidities. Notably, the number of patients on antihypertensive medication declined in the Cushing's cohort, resulting in significantly higher rates of uncontrolled hypertension at follow-up. CONCLUSION: The prevalence of hypertension and impaired kidney function remained elevated in patients with CS years after biochemical remission, potentially contributing to an unfavorable long-term clinical outcome. This highlights the critical need for increased monitoring and treatment of co-morbidities in patients with CS following surgical remission. AU - Ritzel, K.* AU - Fedtke, V.* AU - Then, C.* AU - Nowak, E.* AU - Vogel, F.* AU - Braun, L.* AU - Zopp, S.* AU - Zimmermann, P.* AU - Peters, A. AU - Heier, M. AU - Linkohr, B. AU - Roden, M.* AU - Bidlingmaier, M.* AU - Beuschlein, F.* AU - Reincke, M.* AU - Rubinstein, G.* C1 - 75255 C2 - 57892 CY - One New York Plaza, Suite 4600, New York, Ny, United States TI - Hypertension and kidney dysfunction despite long-term remission of Cushing's syndrome. JO - J. Endocrinol. Invest. PB - Springer PY - 2025 SN - 0391-4097 ER - TY - JOUR AB - Background Recently, five branched-chain and aromatic amino acids were shown to be associated with the risk of developing type 2 diabetes (T2D). Aim We set out to examine whether amino acids are also associated with the development of hypertriglyceridemia. Materials and methods We determined the serum amino acids concentrations of 1,125 individuals of the KORA S4 baseline study, for which follow-up data were available also at the KORA F4 7 years later. After exclusion for hypertriglyceridemia (defined as having a fasting triglyceride level above 1.70 mmol/L) and diabetes at baseline, 755 subjects remained for analyses. Results Increased levels of leucine, arginine, valine, proline, phenylalanine, isoleucine and lysine were significantly associated with an increased risk of hypertriglyceridemia. These associations remained significant when restricting to those individuals who did not develop T2D in the 7-year follow-up. The increase per standard deviation of amino acid level was between 26 and 40 %. Conclusions Seven amino acids were associated with an increased risk of developing hypertriglyceridemia after 7 years. Further studies are necessary to elucidate the complex role of these amino acids in the pathogenesis of metabolic disorders. AU - Mook-Kanamori, D.O.* AU - Römisch-Margl, W. AU - Kastenmüller, G. AU - Prehn, C. AU - Petersen, A.K. AU - Illig, T.* AU - Gieger, C. AU - Wang-Sattler, R. AU - Meisinger, C. AU - Peters, A. AU - Adamski, J. AU - Suhre, K. C1 - 30947 C2 - 34029 CY - New York SP - 369-374 TI - Increased amino acids levels and the risk of developing hypertriglyceridemia in a 7-year follow-up. JO - J. Endocrinol. Invest. VL - 37 IS - 4 PB - Springer PY - 2014 SN - 0391-4097 ER - TY - JOUR AB - BACKGROUND: Ghrelin is a gastrointestinal peptide that promotes a positive energy balance. The enzyme ghrelin O-acyltransferase (GOAT) esterifies an n-octanoic acid to the peptide, thereby enabling ghrelin to bind and activate the ghrelin receptor. Although ghrelin has previously been implicated in the control and maintenance of body core temperature (BCT), the role that this acylation may play in thermoregulation has not been examined. AIM: We aimed to investigate the endogenous role of ghrelin acylation in thermoregulation. METHODS: In this study, we exposed mice lacking the enzyme GOAT as well as wild type (WT) control mice to cold temperatures under ad libitum and fasting conditions. Additionally, we investigated the role of GOAT in metabolic adaptation to cold temperatures by analyzing BCT and energy metabolism in mice with and without GOAT that were progressively exposed to low ambient temperatures (31-7°C). RESULTS: We find that regardless of nutritional status, mice lacking GOAT maintain a similar BCT as their WT counterparts during an 8 h cold exposure. Furthermore, mice lacking GOAT maintain a similar BCT and metabolic adaptation as WT controls during acclimatization to low ambient temperatures. CONCLUSIONS: We conclude that the absence of the enzyme GOAT does not play a significant role in maintenance of BCT or metabolic adaptation during exposure to low external temperatures. AU - Heppner, K.M.* AU - Müller, T.D.* AU - Kirchner, H.* AU - Perez-Tilve, D.* AU - Pfluger, P.T.* AU - Tschöp, M.H. AU - Hofmann, S.M. C1 - 11131 C2 - 30512 SP - 180-184 TI - The role of ghrelin-octanoyl-acyl-transferase in thermoregulation. JO - J. Endocrinol. Invest. VL - 36 IS - 3 PB - Editrice Kurtis SRL PY - 2013 SN - 0391-4097 ER - TY - JOUR AB - Multiple endocrine neoplasias (MEN) are autosomal dominant disorders characterized by the occurrence of tumors in at least two endocrine glands. Until recently two MEN syndromes were known, i.e. the MEN type 1 (MEN1) and type 2 (MEN2), which are caused by germline mutations in the MEN1 and RET genes, respectively. These two syndromes are characterized by a different tumor spectrum. A few years ago we described a variant of the MEN syndromes, which spontaneously developed in a rat colony and was named MENX. Affected animals consistently develop multiple endocrine tumors, with a spectrum that shares features with both MEN1 and MEN2 human syndromes. Genetic studies identified a germline mutation in the Cdkn1b gene, encoding the p27 cell cycle inhibitor, as the causative mutation for MENX. Capitalizing on these findings, germline mutations in the human homologue, CDKN1B, were searched for and identified in patients with multiple endocrine tumors. As a consequence of this discovery, a novel human MEN syndrome, named MEN4, was recognized, which is caused by heterozygous mutations in p27. These studies identified Cdkn1b/CDKN1B as a novel tumor susceptibility gene for multiple endocrine tumors in both rats and humans. Here we review the characteristics of the MENX and MEN4 syndromes and we briefly address the main function of p27 and how it is affected by MENX- or MEN4-associated mutations. AU - Lee, M. AU - Pellegata, N.S. C1 - 27968 C2 - 32882 CY - New York SP - 781-787 TI - Multiple endocrine neoplasia syndromes associated with mutation of p27. JO - J. Endocrinol. Invest. VL - 36 IS - 9 PB - Editrice Kurtis PY - 2013 SN - 0391-4097 ER -