Charlotte Steffensen

Epidemiology of Cushing's syndrome.

Overt Cushing’s syndrome is a rare disorder with an annual incidence of 2–3/million of which benign adrenal adenomas account for 0.6/million. The female:male ratio is 3:1. Preliminary data indicate a high proportion of subclinical Cushing’s syndrome in certain risk populations such as patients with type 2 diabetes or osteoporosis. The clinical implications of these observations are presently unclear. Surgery remains first line treatment for overt disease and initial cure or remission is obtained in 65–85% of patients with Cushing’s disease. Late recurrences, however, occur in up to 20% and the risk does not seem to plateau even after 20 years of follow-up. A 2- to 3-fold increase in mortality is observed in most studies, and this excess mortality seems confined to patients in whom initial cure was not obtained. Cushing’s syndrome continues to pose diagnostic and therapeutic challenges and life-long follow-up is mandatory.

Laccase‐catalyzed polymerization of tyrosine‐containing peptides

Laccase‐catalyzed polymerization of tyrosine and tyrosine‐containing peptides was studied in the presence and absence of ferulic acid (FA). Advanced spectroscopic methods such as MALDI‐TOF MS, EPR, FTIR microscopy and HPLC‐fluorescence, as well as more conventional analytical tools: oxygen consumption measurements and SDS/PAGE were used in the reaction mechanism studies. Laccase was found to oxidize tyrosine and tyrosine‐containing peptides, with consequent polymerization of the compounds. The covalent linkage connecting the compounds was found to be an ether bond. Only small amounts of dityrosine bonds were detected in the polymers. When FA was added to the reaction mixtures, it was found to be incorporated into the polymer structure. Thus, in addition to homopolymers, different heteropolymers containing two or four FA residues were formed in the reactions.

Cross-Linking Proteins by Laccase-Catalyzed Oxidation: Importance Relative to Other Modifications

Laccase-catalyzed oxidation was able to induce intermolecular cross-links in beta-lactoglobulin, and ferulic acid-mediated laccase-catalyzed oxidation was able to induce intermolecular cross-links in alpha-casein, whereas transglutaminase cross-linked only alpha-casein. In addition, different patterns of laccase-induced oxidative modifications were detected, including dityrosine formation, formation of fluorescent tryptophan oxidation products, and carbonyls derived from histidine, tryptophan, and methionine. Laccase-catalyzed oxidation as well as transglutaminase induced only minor changes in surface tension of the proteins, and the changes could not be correlated to protein cross-linking. The presence of ferulic acid was found to influence the effect of laccase, allowing laccase to form irreducible intermolecular cross-links in beta-lactoglobulin and resulting in proteins exercising higher surface tensions due to cross-linking as well as other oxidative modifications. The outcome of using ferulic acid-mediated laccase-catalyzed oxidation to modify the functional properties of proteinaceous food components or other biosystems is expected to be highly dependent on the protein composition, resulting in different changes of the functional properties.

Heart valve disease among patients with hyperprolactinemia: a nationwide population-based cohort study.

BACKGROUND Increased risk of heart valve disease during treatment with certain dopamine agonists, such as cabergoline, has been observed in patients with Parkinsons disease. The same compound is used to treat hyperprolactinemia, but it is unknown whether this also associates with heart valve disease. OBJECTIVES The objective of the study was to assess the incidence of diagnosed heart valve disease and cardiac valve surgery among patients with hyperprolactinemia, compared with a general population cohort in Denmark. DESIGN This was a nationwide, population-based, cohort study based on a nationwide hospital registry. METHODS We identified 2381 hyperprolactinemia patients with a first-time diagnosis recorded from 1994 through 2010 in the registry, with no previous hospital diagnosis of heart valve disease. Each patient was compared with 10 age- and gender-matched comparison cohort members from the general population. The association between hyperprolactinemia and heart valve disease was analyzed with Coxs proportional hazards regression, controlling for potential confounding factors. To assess the risk of cardiac valve surgery and avoid ascertainment bias, a subanalysis was made in a cohort of 2,387 hyperprolactinemia patients with no previous cardiac valve surgery and 23,870 comparison cohort members. RESULTS Nineteen hyperprolactinemic patients (0.80%) were diagnosed with heart valve disease during a total of 17,759.8 yr of follow-up, compared with 75 persons (0.31%) in the comparison cohort during 179,940.6 yr of follow-up [adjusted hazard ratio 2.27 (95% confidence interval 1.35-3.82)]. Seven of the 10 patients treated with cabergoline and diagnosed with heart valve disease were asymptomatic and diagnosed on the basis of an echocardiography performed as a safety measure. However, only two patients with hyperprolactinemia (0.08%) underwent surgery, compared with 28 persons in the general population cohort (0.12%) [adjusted hazard ratio 0.55 (95% confidence interval 0.13-2.42)]. CONCLUSIONS Data from the present register-based study do not support that hyperprolactinemia or its treatment is associated with an increased risk of clinically significant heart valve disease.

DIAGNOSIS OF ENDOCRINE DISEASE: Prevalence of hypercortisolism in type 2 diabetes patients: a systematic review and meta-analysis

OBJECTIVE Type 2 diabetes (T2D) and Cushings syndrome (CS) share clinical characteristics, and several small studies have recorded a high prevalence of hypercortisolism in T2D, which could have therapeutic implications. We aimed to assess the prevalence of endogenous hypercortisolism in T2D patients. DESIGN Systematic review and meta-analysis of the literature. METHODS A search was performed in SCOPUS, MEDLINE, and EMBASE for original articles assessing the prevalence of endogenous hypercortisolism and CS in T2D. Data were pooled in a random-effect logistic regression model and reported with 95% confidence intervals (95% CI). RESULTS Fourteen articles were included, with a total of 2827 T2D patients. The pooled prevalence of hypercortisolism and CS was 3.4% (95% CI: 1.5-5.9) and 1.4% (95 CI: 0.4-2.9) respectively. The prevalence did not differ between studies of unselected patients and patients selected based on the presence of metabolic features such as obesity or poor glycemic control (P = 0.41 from meta-regression). Imaging in patients with hypercortisolism (n = 102) revealed adrenal tumors and pituitary tumors in 52 and 14% respectively. CONCLUSIONS Endogenous hypercortisolism is a relatively frequent finding in T2D, which may have therapeutic implications.

Modifications of amino acids during ferulic acid-mediated, laccase-catalysed cross-linking of peptides

Abstract Mass spectral analysis demonstrated oligomerization of peptides that had been subjected to oxidation catalysed by Trametes (Coriolus) versicolor laccase. Peptide oligomerization occurred only when cysteines or tyrosines were present in the peptides. MS/MS confirmed the cross-linking in tyrosine-containing peptides to be located between tyrosine residues. Ferulic acid mediated oligomerization of cysteine-containing peptides, but prevented cross-linking of tyrosines when used in the same concentration as the peptides. This suggests an antioxidative effect of ferulic acid in relation to tyrosine oxidation, although incorporation of ferulic acid into peptide oligomers was found in some of the tyrosine-containing peptides. No other modifications to amino acid residues by laccase-catalysed oxidation were observed by mass spectroscopy. Thus, it is suggested that oxidative modifications of other amino acids observed in proteins oxidized by laccase are not major reaction products of laccase-catalysed oxidation.