Se Hee Park

No differences in metabolic outcomes between nadir GH 0.4 and 1.0 ng/mL during OGTT in surgically cured acromegalic patients (observational study).

AbstractMetabolic impairment is the common cause for mortality in acromegalic patients. In this study, long-term improvements of metabolic parameters were evaluated according to 2 different remission criteria.This was an observational cohort study before and up to 1 year after transsphenoidal adenomectomy (TSA). Participants were 187 patients with acromegaly. At 6 months after TSA, remitted patients with age- and sex-matched normalized IGF-1 were divided into 2 groups: remission 1 (R1), nadir growth hormone (GH) below 0.4 ng/mL; and remission 2 (R2), nadir GH between 0.4 and 1.0 ng/mL in oral glucose tolerance test (OGTT). Metabolic parameters during serial OGTTs were evaluated for 12 months. Remission was achieved in 157 (R1–136; R2–21) patients. Immediate postoperative metabolic parameters including body weight, body mass index, glucose, insulin, and free fatty acid in OGTT were all significantly improved in R1 and R2. HOMA-%&bgr; and HOMA-IR scores also improved in both R1 and R2. These improvements persisted for duration (12 months) of this study. However, no difference was present in metabolic parameters between R1 and R2. Although the patients with preoperative adrenal insufficiency presented significantly increased HOMA scores before TSA, there was no difference between classifications of deficient pituitary axes and changes of metabolic parameters after TSA. Remitted patients exhibited rapid restoration of metabolic parameters immediate postoperative period. Long-term improvements in metabolic parameters were not different between the 2 different nadir GH cut-offs, 0.4 and 1.0 ng/mL.

Comparative assessment of Graves’ disease and main extrathyroidal manifestation, Graves’ ophthalmopathy, by non-targeted metabolite profiling of blood and orbital tissue

Graves’ disease (GD) is an autoimmune disorder that causes the overproduction of thyroid hormones and consequent cascade of systemic metabolism dysfunction. Moreover, Graves’ ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves’ disease (GD). The goal of the study was to identify metabolic signatures in association with diagnostic biomarkers of GD without GO and GO, respectively. Ninety metabolites were profiled and analyzed based on a non-targeted primary metabolite profiling from plasma samples of 21 GD patients without GO, 26 subjects with GO, and 32 healthy subjects. Multivariate statistics showed a clear discrimination between healthy controls and disease group (R2Y = 0.518, Q2 = 0.478) and suggested a biomarker panel consisting of 10 metabolites. Among them, most of metabolites showed the positive association with the levels of thyrotropin receptor antibodies. With combination of proline and 1,5-anhydroglucitol, which were identified as GO-specific modulators, the re-constructed biomarker model greatly improved the statistical power and also facilitated simultaneous discrimination among healthy control, GO, and GD without GO groups (AUC = 0.845–0.935). Finally, the comparative analysis of tissue metabolite profiles from GO patients proposed putative metabolic linkage between orbital adipose/connective tissues and the biofluidic consequences, in which fumarate, proline, phenylalanine, and glycerol were coordinately altered with the blood metabolites.

Olfactory Receptor OR51E1 Mediates GLP-1 Secretion in Human and Rodent Enteroendocrine L Cells

Abstract Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), produced by intestinal enteroendocrine L cells, are important gut hormones that coordinate gastrointestinal physiology, metabolism, and appetite. We aimed to investigate the role of olfactory receptor (OR) OR51E1 in GLP-1 and PYY secretion. We analyzed the expression of olfactory marker protein (OMP), an indicator of OR-mediated events in nonolfactory systems, in human intestinal L cells. Furthermore, we analyzed OMP and OR51E1 expression in the L cell line NCI-H716. To investigate whether odorant-activated OR signaling stimulates GLP-1 and PYY secretion, we used nonanoic acid, a known OR51E1 ligand. Treatment with 100 μM nonanoic acid increased GLP-1 secretion by 2.32 ± 0.41-fold and PYY secretion by 1.44 ± 0.10-fold; however, this effect was attenuated on small interfering RNA-mediated OR51E1 knockdown. Oral administration of nonanoic acid to rats resulted in a 2.89 ± 0.53-fold increase in GLP-1 levels and reductions in blood glucose levels compared with the control group. Nonanoic acid stimulates GLP-1 and PYY secretion via OR51E1 signaling in L cells, thereby indicating a potential role of OR-mediated events in GLP-1 and PYY secretion; this could be translated into a therapeutic approach in treating diabetes.

Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAFV600E mutation

Diffuse lymphocytic infiltration (DLI) is frequently found with papillary thyroid cancer (PTC), so there has been long interest in how it affects the characteristics of PTC. This purpose of this study was to define the association between DLI and PTC aggressiveness according to thyroperoxidase antibody (TPOAb) and B‐type Raf (BRAF)V600E mutation positivity.

Lipidomic differentiation of Graves’ ophthalmopathy in plasma and urine from Graves’ disease patients

AbstractApproximately 50% of patients with Graves’ disease (GD) develop retracted eyelids with bulging eyes, known as Graves’ ophthalmopathy (GO). However, no simple diagnostic blood marker for distinguishing GO from GD has been developed yet. The objective of this study was to conduct comprehensive profiling of lipids using plasma and urine samples from patients with GD and GO undergoing antithyroid therapy using nanoflow ultrahigh performance liquid chromatography electrospray ionization tandem mass spectrometry. Plasma (n = 86) and urine (n = 75) samples were collected from 23 patients with GD without GO, 31 patients with GO, and 32 healthy controls. Among 389 plasma and 273 urinary lipids that were structurally identified, 281 plasma and 191 urinary lipids were quantified in selected reaction monitoring mode. High-abundance lipids were significantly altered, indicating that the development of GD is evidently related to altered lipid metabolism in both plasma and urine. Several urinary lysophosphatidylcholine species were found to be increased (3- to 10-fold) in both GD and GO. While the overall lipid profiles between GD and GO were similar, significant changes (area under receiver operating curve > 0.8) in GO vs. GD were observed in a few lipid profiles: 58:7-TG and (16:1,18:0)-DG from plasma, 16:1-PC and 50:1-TG from urine, and d18:1-S1P from both plasma and urine samples. An altered metabolism of lipids associated with the additional development of ophthalmopathy was confirmed with the discovery of several candidate markers. These can be suggested as candidate markers for differentiating the state of GO and GD patients based on plasma or urinary lipidomic analysis. Graphical abstract

Age- and Sex-Specific Differences as Predictors of Surgical Remission Among Patients With Acromegaly

Context Sex and age are factors conferring resistance to medical treatment in patients with acromegaly. However, their impact on outcomes of transsphenoidal-selective adenomectomy (TSA) has not been evaluated. Objective To analyze age- and sex-related differences concerning surgical outcomes of growth hormone (GH)-secreting pituitary adenomas. Design Retrospective. Setting Single-center tertiary hospital. Participants Patients with acromegaly (n = 463) who underwent TSA between January 2000 and July 2014. Intervention TSA. Main Outcome Measurements Tumor characteristics and surgical outcomes. Results Sex differences existed in the baseline insulinlike growth factor-1 levels and the mean tumor size. Overall, surgical remission rates were 89.7% and 76.5% in male and female patients, respectively (P < 0.001). Total tumor tissue resection was performed in 92.6% and 85.8% of male and female participants, respectively (P = 0.021). Premenopausal women had a higher proportion of pituitary adenoma with cavernous sinus invasion than did men aged <50 years (35.3% vs 21.7%, P = 0.007). In immediate postoperative, 75-g oral glucose tolerance tests, fewer premenopausal women reached <1 ng/dL nadir GH levels than did men aged <50 years (59.9% vs 87.7%, P < 0.001). Surgical results were similar in both sexes among older patients (≥50 years). However, premenopausal women had significantly lower long-term remission rates than did men aged <50 years (69.3% vs 88.0%, P < 0.001). Conclusion Premenopausal women with acromegaly tend to have larger tumors, more aggressive tumor types, and lower remission rates than do men. However, further studies on the clinical implications are needed.