Beyond symptomatology: A comparative analysis of unilateral and bilateral macronodular mild autonomous cortisol secretion.

OBJECTIVE: To investigate the clinical, laboratory findings and signal intensity index (SII) on magnetic resonance imaging (MRI) of patients with bilateral and unilateral macronodular mild autonomous cortisol secretion (MACS). PATIENTS AND MEASUREMENTS: Clinical and laboratory findings of 81 patients with MACS were examined from retrospective records. SII of adenomas and internodular areas were evaluated by MRI. The unilateral group included patients with an adrenal macronodule (≥1 cm) in a single adrenal gland, while the bilateral group included patients with at least one macronodule in both adrenal glands. RESULTS: In total, 46 patients were in the unilateral (57%), while 35 (43%) patients were in the bilateral groups. The dehydroepiandrosterone sulphate (DHEA-S) level was lower in the unilateral than in the bilateral group (p < .001). The presence of type 2 diabetes mellitus (T2DM), glycosylated haemoglobin (HbA1c) and low-density lipoprotein (LDL) concentrations were higher in the bilateral group (p < .05). However, no significant difference was detected in terms of adrenocorticotropic hormone (ACTH) and overnight 1 mg dexamethasone suppression test (DST) between the two groups (p > .05). There was no difference in SII between adenomas within the same patient, as well as between the unilateral and bilateral groups (p > .05). Logistic regression analysis based on the differentiation between unilateral and bilateral macronodular MACS demonstrated that DHEA-S, HbA1c and LDL concentrations were associated factors. CONCLUSION: DHEA-S levels may not be as suppressed in patients with bilateral macronodular MACS as compared to those with unilateral adenoma. T2DM and hypercholesterolaemia have a higher frequency in bilateral patients. However, ACTH, overnight 1 mg DST and SII may not provide additional information for differentiation of bilaterality and unilaterality.

Cognitive functions and the brain-derived neurotrophic factor in patients with mild autonomous cortisol secretion.

CONTEXT: The impact of abnormal cortisol secretion on cognitive functions in patients with mild autonomous cortisol secretion (MACS) remains uncertain. OBJECTIVE: To assess cognitive functions, determine serum brain-derived neurotrophic factor (BDNF) concentration in patients with MACS, and investigate the association between cognitive subdomains and BDNF. METHODS: We prospectively recruited 84 participants-28 patients with MACS, 28 patients with nonfunctional adrenal adenoma (NFAA), and 28 control subjects matched for age, gender, body mass index (BMI), visceral adiposity, and educational level. The serum BDNF concentration of participants was measured. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-focused interviews and Montreal Cognitive Assessments (MoCA) were carried out by an experienced psychiatrist. RESULTS: Patients with MACS had a higher serum BDNF concentration than the NFAA (P = .001), while that of patients with NFAA was lower than the controls (P = .044). Linear regression analysis revealed BMI and morning cortisol after overnight 1 mg dexamethasone (DST) were mostly associated with BDNF (P < .05). No significant difference was found in MoCA scores between MACS and NFAA groups (P = .967), whereas those were lower than the control group (P = .004). When the cognitive subdomains were examined separately, MACS group performed higher memory score than NFAA (P = .045), but lower language scores than both the NFAA (P = .024) and control groups (P < .001). In the whole group, BDNF concentration was positively correlated with memory score (r = 0.337, P = .002), whereas DST was negatively correlated with language score (r = -0.355, P = .008). CONCLUSION: Low-grade hypercortisolism is associated with elevated BDNF concentrations, which may be a protective factor for memory function in patients with MACS relative to those with NFAA.

Alteration in gut microbial characteristics of patients with acromegaly.

PURPOSE: Studies on intestinal microbiota in acromegaly are scant. This study aimed to characterize the gut microbiome in patients with acromegaly. METHOD: Stool samples were collected from 11 patients newly diagnosed with acromegaly and 12 healthy controls matched for body mass index (BMI) and age after three days on a standard diet. Clinical and gut microbial composition assessments were performed for the two participant groups using 16S rRNA gene amplicon sequencing. RESULTS: There was no difference in the alpha diversity of the microbiota between the samples from patients with acromegaly and those from the healthy controls. Based on beta diversity measurements, differences in microbial community structures were found to be significant only when compared using the Jaccard similarity index. The corresponding Firmicutes/Bacteroidota ratio tended to be higher in individuals with acromegaly than in healthy controls. The mean relative abundance of Actinobacteriota was 2.3 times higher in the acromegaly patient group than in the control group. Eggerthellaceae, Christensenellaceae, and Bacteroidaceae were among the significantly abundant bacterial families in the samples from the acromegaly patient group, while Butyricicoccaceae and Tannerellaceae were decreased. At the level of the genus, the most discriminative features were the abundance of Prevotella 7, Bacteroides, Senegalimassilia, Enterohabdus, the Family XIII AD3011 group, Howardella, and Hungatella in the samples from the acromegaly patient group. In contrast, the Butyrivibrio and the Eubacterium eligens group were the most discriminative genera for the healthy controls and were significantly less abundant in patients with acromegaly. While there were no significantly differentiated taxa between the diabetic and non-diabetic subgroups, Prevotella_7 was significantly enriched in the osteoarthritis (OA) subgroup. No significant association was found between individual genera and growth hormone (GH) levels and insulin-like growth factor-1 (IGF-1) levels as well as the upper limit of normal (ULN). CONCLUSION: Although alpha and beta diversity were mainly similar between the two groups, significant differences were observed between the acromegaly group and the control group at the family and genus levels. These results suggest that the differences between the microbial communities in patients with acromegaly and those in healthy individuals consist primarily of compositional differences independent of abundance. Prospective studies are needed to further explore the clinical implications of gut microbiome dysbiosis in patients with acromegaly.

Detecting the interferences in adrenocorticotropic hormone measurement - three cases reinforcing the efficiency of the complementary clinical and laboratory audit.

Accurate measurement of adrenocorticotropic hormone (ACTH) is crucial in the evaluation of pituitary and adrenal disorders. Although great progress has been achieved in ACTH measurement with immunometric assays, interference may occur and adversely affect the clinical management. The report contributes to compiling the evidence on the clinical challenges with the management of the interferences in the ACTH measurement by presenting three cases: two with clinically overt hypercortisolism and discrepant ACTH concentrations within the reference interval; the third case describes the falsely elevated ACTH in a patient with secondary adrenal insufficiency. In all patients, the results obtained with the two immunometric platforms, chemiluminescence (CLIA) immunoassay (Siemens, Immulite) and electrochemiluminescence (ECLIA) immunoassay (Roche, Cobas), were discordant. Serial dilution of plasma samples revealed nonlinearity. After polyethylene glycol (PEG) precipitation recoveries were less than 22%, 26%, and 3%, respectively, supporting interference. Moreover, a decrease in ACTH concentration after incubation in a heterophile antibody-blocking tube was observed in the second case. In the first case, misinterpretation of ACTH led to inferior petrosal sinus sampling (IPSS), whereas timely detection of assay interference prevented further investigations in other cases. Increasing awareness regarding ACTH interference and comprehensive approach in evaluation could allow timely detection, helping to prevent unnecessary testing and perplexing clinical outcomes.

Assessment of forearm muscles with ultrasound shear wave elastography in patients with acromegaly.

PURPOSE: The effects of acromegaly on soft tissues, bones and joints are well-documented, but information on its effects on muscle mass and quality remains limited. The primary goal of this study is to assess the sonoelastographic features of forearm muscles in patients with acromegaly. METHOD: Forty-five patients with acromegaly and 45 healthy controls similar in terms of gender, age, and body mass index (BMI) were included in a single-center, multidisciplinary, cross-sectional study. The body composition was analyzed using bioelectrical impedance analysis (BIA), and height-adjusted appendicular skeletal muscle index (hSMI) was calculated. The dominant hand's grip strength was also measured. Two radiologists specialized in the musculoskeletal system employed ultrasound shear wave elastography (SWE) to assess the thickness and stiffness of brachioradialis and biceps brachii muscles. RESULTS: The acromegaly group had significantly higher thickness of both the biceps brachii (p = 0.034) and brachioradialis muscle (p = 0.046) than the control group. However, the stiffness of the biceps brachii (p = 0.001) and brachioradialis muscle (p = 0.001) was lower in the acromegaly group than in the control group. Disease activity has not caused a significant difference in muscle thickness and stiffness in the acromegaly group (p > 0.05). The acromegaly group had a higher hSMI (p = 0.004) than the control group. The hand grip strength was similar between the acromegaly and control group (p = 0.594). CONCLUSION: The patients with acromegaly have an increased muscle thickness but decreased muscle stiffness in the forearm muscles responsible for elbow flexion. Acromegaly can lead to a permanent deterioration of the muscular structure regardless of the disease activity.

Leukocyte Telomere Length and Neuregulin-4 Levels in Female Patients with Acromegaly: The Relationship between Disease Activity and Body Fat Distribution.

The study aimed to examine leukocyte telomere length (LTL) and serum neuregulin-4 levels and their relationship with disease activity, co-morbidities and body fat distribution in female acromegaly patients. Forty female patients with acromegaly and thirty-nine age and body mass index (BMI) similar healthy female volunteers were included in the study. Patients were classified into two groups: active acromegaly (AA) and controlled acromegaly (CA). The quantitative polymerase chain reaction (PCR) method was used to study LTL, and T/S ratio < 1 was accepted as shortened telomere length. Neuregulin-4 was studied by ELISA. There was no difference in median LTL between acromegaly and the control group (p = 0.530). The percentage of T/S < 1 in patients with acromegaly (60.0%) was similar to that of the control group (43.6%) (p = 0.144). However, serum neuregulin-4 was significantly higher in patients with acromegaly than those in the control group (p = 0.037). There were no significant differences concerning LTL, percentage of T/S < 1 and neuregulin-4 levels between active and controlled acromegaly groups (p > 0.05). Neuregulin-4 correlated positively with fasting glucose, triglyceride (TG), triglyceride/glucose (TyG) index, and lean body mass in the acromegaly group. A negative correlation was observed between LTL and neuregulin-4 in the control group (p = 0.039). When the factors affecting neuregulin-4 were evaluated by multivariate linear regression analysis with an enter method, TG (ß: 0.316, p = 0.025) was independently and positively associated with neuregulin-4. Our findings indicate that acromegaly is associated with unchanged LTL and high neuregulin-4 levels in female patients. However, the relationship between acromegaly, the aging process, and neuregulin-4 involves complex mechanisms, and further studies are needed.

Evaluation of Lipohypertrophy in Patients With Type 1 Diabetes Mellitus on Multiple Daily Insulin Injections or Continuous Subcutaneous Insulin Infusion.

OBJECTIVE: To determine lipohypertrophy (LH) in patients with type 1 diabetes mellitus (T1DM) on multiple daily insulin injections (MDII) or continuous subcutaneous insulin infusion (CSII) and to reveal the factors associated with the development and severity of LH. METHODS: Sixty-six patients with T1DM treated with MDII (n = 35, 53%) or CSII (n = 31, 47%) for at least 1 year were included. LH localizations were detected with palpation and ultrasonography (USG). RESULTS: The LH detection rate with USG was significantly higher than that by palpation in the whole group (P < .001). The LH was detected with USG in 30 (85.7%) patients in the MDII group and 22 (71.0%) patients in the CSII group (P = .144). Advanced LH was detected in 13 (37.1%) of the patients treated with MDII and in 3 (9.7%) of the patients treated with CSII. LH was more severe in the MDII group than in the CSII group (P = .013). Diabetes duration and length of infusion set use were significantly longer and body mass index, hypoglycemia, and complication rates were higher in patients with LH than those in patients without LH (P < .05). A positive correlation was found between LH severity and HbA1C and insulin dose (P < .05, for both). MDII as insulin administration method, incorrect rotation, and a history of ketosis were found to be the most related factors with LH severity in a multiple linear regression analysis (P < .05). CONCLUSION: USG might be an effective approach for detecting and evaluating the severity of LH. MDII might cause more severe LH than CSII in patients with T1DM. In this study, LH was found to be associated mostly with incorrect rotation technique and a history of ketosis.

Fiberoptic Endoscopic Evaluation of Swallowing in Patients with Type 2 Diabetes Who Have Self-Reported Swallowing Difficulties.

INTRODUCTION: People with diabetes frequently have gastrointestinal problems and related deglutition disorders. OBJECTIVE: The aims of the present study are to determine the symptomatic swallowing complaints and to evaluate the functionality of oropharyngeal swallowing in patients with type 2 diabetes mellitus (T2DM) by using the Turkish Eating Assessment Tool-10 (T-EAT-10) and fiberoptic endoscopic evaluation of swallowing (FEES). METHODS: In this descriptive cross-sectional study, the T-EAT-10 questionnaire was completed by 121 patients with diabetes, and FEES was planned for each individual whose baseline score of the T-EAT-10 was ≥3. Before swallowing trials via samples of nectar-thick consistency, laryngeal sensation and severity of secretion in the hypopharynx were observed. While the swallowing safety was determined using the Penetration-Aspiration Scale (PAS), the Yale Pharyngeal Residue Severity Rating Scale was used to assess the swallowing efficiency. RESULTS: Of the total participants, 22.3% (n = 27) were found to have abnormal swallowing function (T-EAT-10 ≥3), 27.3% (n = 33) had concomitant neuropathy and 28.1% (n = 34) mentioned a reflux complaint. The results of the multivariate linear regression analysis exposed that the T-EAT-10 score was significantly associated with neuropathy (r = 3.763, p < 0.001) and reflux complaint (r = 2.254, p = 0.031). Of the total FEES-tested subjects (n = 20), 95% (n = 19) had a safe swallowing function (PAS = 1). However, diminished laryngeal sensation, increased secretion and presence of residue revealed that patients with T2DM who have self-reported swallowing difficulties have reduced swallowing efficiency. CONCLUSIONS: This study has demonstrated that almost 1 out of 4 T2DM patients reported to have swallowing-related problems, and the score of the T-EAT-10 was found to be independently associated with both neuropathy and reflux complaint. FEES results pointed out that swallowing efficiency was relatively reduced in the target population. However, further research is still necessary before obtaining a definitive answer to oropharyngeal swallowing problems in patients with T2DM.

Serum Total Sialic Acid Level is Elevated in Hypothyroid Patients as an Atherosclerotic Risk Factor.

BACKGROUND: Serum total sialic acid (TSA) concentration is regarded as an indicator of the risks of atherosclerosis and cardiovascular diseases. The association between SA levels and atherosclerosis risk factors has not been assessed in patients with thyroid diseases. METHODS: Sixty newly diagnosed treatment-naive hypothyroid patients, 35 with subclinical and 25 with overt hypothyroidism, and 30 euthyroid individuals were analyzed. SA was measured in fasting blood samples, as were routine biochemical parameters, some atherosclerosis markers and carotid artery intima media thickness (CIMT). RESULTS: Mean SA (38.1 ± 12.0 vs. 46.0 ±15.8; P = 0.019) and CIMT (0.57 ± 0.06 vs. 0.62 ± 0.12; P = 0.013) were found to be higher in the patient group compared with the control group. Mean sialic acid was higher in overt hypothyroidism patients compared with subclinical hypothyroidism patients and the control group. No difference was found between the subclinical hypothyroidism group and the control group. Sialic acid level and CIMT had a positive correlation in both the entire population and the hypothyroidism group. The linear regression model established for mean CIMT level in the entire population showed that risk factors of LDL (B ± SE = 0.454 ± 0.206; P = 0.030), uric acid (B ± SE = 1.902 ± 0.686; P = 0.007), hs-CRP (B ± SE = 1.003 ± 0.380; P =0.010), and SA (B ± SE = 2.419 ± 0.450; P < 0.001) were independent predictors of CIMT level. CONCLUSION: Sialic acid level is elevated in hypothyroid patients. However, this elevation is not related to thyroid hormone levels and autoantibodies. Correlations between SA and atherosclerosis indicators, such as CIMT, LDL, hs-CRP, and uric acid, in hypothyroid individuals suggest that SA may be an indicator of atherogenesis in these patients.