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 MACS.

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 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. DSM-5-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 = 0.001), while that of patients with NFAA was lower than the controls (p = 0.044). Linear regression analysis revealed BMI and morning cortisol after overnight 1 mg dexamethasone (DST) were mostly associated with BDNF (p < 0.05). No significant difference was found in MoCA scores between MACS and NFAA groups (p = 0.967), whereas those were lower than the control group (p = 0.004). When the cognitive subdomains were examined seperately, MACS group performed higher memory score than NFAA (p = 0.045), but lower language scores than both the NFAA (p = 0.024) and control groups (p < 0.001). In the whole group, BDNF concentration was positively correlated with memory score (r = 0.337, p = 0.002), whereas DST and language score were negatively correlated (r = -0.355, p = 0.008). 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.

Disease-free survival and the prognostic factors affecting disease-free survival in patients with medullary thyroid carcinoma: a multicenter cohort study.

PURPOSE: Despite several factors that may have been associated with poor disease-free survival (DFS) in patients with medullary thyroid carcinoma (MTC), only a few studies have evaluated the prognostic factors affecting DFS in MTC patients. Therefore, this study evaluated the prognostic factors affecting DFS, in a large number of patients with MTC. METHODS: Patients treated for MTC were retrospectively analyzed. Patients were stratified as having persistent/recurrent disease and no evidence of disease (NOD) at the last follow-up. The factors affecting DFS after the initial therapy and during the follow-up period were investigated. RESULTS: This study comprised 257 patients [females 160 (62.3%), hereditary disease 48 (18.7%), with a mean follow-up time of 66.8 ± 48.5 months]. Persistent/recurrent disease and NOD were observed in 131 (51%) and 126 (49%) patients, respectively. In multivariate analysis, age > 55 (HR: 1.65, p = 0.033), distant metastasis (HR: 2.41, p = 0.035), CTN doubling time (HR: 2.7, p = 0.031), and stage III vs. stage II disease (HR 3.02, p = 0.048) were independent predictors of persistent/recurrent disease. Although 9 (8%) patients with an excellent response after the initial therapy experienced a structural recurrence, the absence of an excellent response was the strongest predictor of persistent/recurrent disease (HR: 5.74, p < 0.001). CONCLUSIONS: The absence of an excellent response after initial therapy is the strongest predictor of a worse DFS. However, a significant proportion of patients who achieve an excellent response could experience a structural recurrence. Therefore, careful follow-up of patients, including those achieving an excellent response is essential.

Relationship between gut microbiome and bone deficits in primary hyperparathyroidism: A proof-of-concept pilot study.

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age-sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and 1 month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversities were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of Subdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium, and Clostridium sensu stricto_1 were significantly lower in PHPT than in controls (p < 0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, and Ruminococcus and Alloprevotella increased (p < 0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p < 0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto_1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy.

Clinical prediction model for primary aldosteronism subtyping and special focus on adrenal volumetric assessment.

PURPOSE: Our aim was to develop a prediction model based on a simple score with clinical, laboratory, and imaging findings for the subtype diagnosis of primary aldosteronism (PA). The contribution of adrenal volumetric assessment to PA subtyping was also investigated. METHODS: Thirty-five patients with adequate cannulation in adrenal venous sampling (AVS) were included. Laboratory data, the saline infusion test (SIT), and the AVS results of patients with PA were retrospectively evaluated. Volumetric assessment was performed using magnetic resonance imaging (MRI) and the ratio of adrenal volumes was calculated after adjusting for gender- and side-specific mean reference values of both adrenal glands. RESULTS: The AVS was consistent with unilateral PA in 49% and bilateral in 51% of the patients. Hypertension as a reason for work-up, the highest aldosterone/lowest potassium value higher than 12, the percentage of plasma aldosterone concentration (PAC) reduction after SIT by equal or less than 43.5%, the use of oral potassium replacement, unilateral disease at pre-AVS imaging, and a ratio of adjusted adrenal volumes equal to or below 1.7 were indicative of unilateral disease in univariate logistic regression analysis concerning the distinction of PA subtyping (p < 0.05). Multivariate logistic regression analysis also revealed that adrenal volumetric assessment has an impact on PA subtyping (p < 0.05). In the prediction model, when each of the six parameters that were significant in the univariate logistic regression analysis was assigned one point, < 4 predicted bilateral PA, whereas ≥ 4 predicted unilateral PA (AUC:0.92, p < 0.001). CONCLUSION: This prediction model before AVS may serve as a convenient and practical approach, while an adjusted adrenal volumetric assessment can make a positive contribution to PA subtyping.

Credibility of ChatGPT in the assessment of obesity in type 2 diabetes according to the guidelines.

BACKGROUND: The Chat Generative Pre-trained Transformer (ChatGPT) allows students, researchers, and patients in the medical field to access information easily and has gained attention nowadays. We aimed to evaluate the credibility of ChatGPT according to the guidelines for the assessment of obesity in type 2 diabetes (T2D), which is one of the major concerns of this century. MATERIALS AND METHOD: In this cross-sectional non-human subject study, experienced endocrinologists posed 20 questions to ChatGPT in subsections, which were assessments and different treatment options for obesity according to the American Diabetes Association and American Association of Clinical Endocrinology guidelines. The responses of ChatGPT were classified into four categories: compatible, compatible but insufficient, partially incompatible and incompatible with the guidelines. RESULTS: ChatGPT demonstrated a systematic approach to answering questions and recommended consulting a healthcare provider to receive personalized advice based on the specific health needs and circumstances of patients. The compatibility of ChatGPT with the guidelines was 100% in the assessment of obesity in type 2 diabetes; however, it was lower in the therapy sections, which included nutritional, medical, and surgical approaches to weight loss. Furthermore, ChatGPT required additional prompts for responses that were evaluated as "compatible but insufficient" to provide all the information in the guidelines. CONCLUSION: The assessment and management of obesity in T2D are highly individualized. Despite ChatGPT's comprehensive and understandable responses, it should not be used as a substitute for healthcare professionals' patient-centered approach.

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.

A case of pseudogout attack after zoledronic acid treatment in primary hyperparathyroidism.

Pseudogout (PG) is an inflammatory arthropathy that develops due to the accumulation of calcium pyrophosphate dihydrate crystals in synovial structures. Herein, we present a 59-year-old male patient with PG developed as a result of zoledronic acid (ZA) infusion, which was administered due to primary hyperparathyroidism. The patient with parathyroid adenoma was given ZA since the calcium level did not decrease despite intravenous saline and loop diuretic. One day after ZA administration, the patient had severe pain, fever, and swelling in joints. The radiograph showed chondrocalcinosis. Calcium pyrophosphate deposition were observed in the arthrocentesis fluid under polarized light. The patient's symptoms regressed after anakinra and colchicine treatment. To the best of our knowledge, this is the first case report of a PG attack after ZA treatment for primary hyperparathyroidism. Additionally, there have been few cases of PG after bisphosphonate treatment for osteoporosis in the literature, signifying that more care should be taken when administering bisphosphonate therapy in patients with risk factors.

Time-restricted eating (16/8) and energy-restricted diet: effects on diet quality, body composition and biochemical parameters in healthy overweight females.

BACKGROUND: Time-restricted eating (TRE) is a current popular dietary strategy for noncommunicable diseases. However, studies demonstrated contradictory results for it and in all dietary strategies, diet quality is an the important part of the well-being. Our study aimed to investigate the effect of TRE and energy-restricted diet (ERD) on the nutritional status and diet quality of individuals. METHODS: This pilot study was completed 23 healthy overweight female. Anthropometric and body composition measurements of individuals were taken. The energy expenditure was measured using indirect calorimetry. Blood pressure and heart rate measurements were made. Biochemical parameters were evaluated and food consumption were taken. The quality of dietary intake was assessed using the Healthy Eating Index (HEI) -2015. The physical activity levels of the individuals were estimated using the physical activity record. The Statistical Package for the Social Sciences (version 22.0) software was used for all analyses. A p-value of less than 0.05 was considered to be statistically significant. RESULTS: After 8 weeks of intervention, while no change was observed in the diet quality of the individuals in the TRE group (p > 0.05), a significant increase was found in the diet quality score of the individuals in the ERD group (p < 0.05). There was a 3.2% and 5.5% decrease in body weight of individuals in the TRE and ERD groups, respectively (p < 0.05). While no significant change was observed in the body fat percentage of individuals in the TRE group (p > 0.05), a 7.1% decrease was observed in the ERD group (p < 0.05). A statistically significant decrease was found in the total cholesterol (3.7%) in the ERD group, and in the total cholesterol (6.7%) and low density lipoprotein cholesterol (LDL-C) (6.5%) in the TRE group. In addition, a statistically significant increase was found in adiponectin (77.3%) and total antioxidant status (TAS) (13.2%) in the ERD group. CONCLUSION: Energy-restricted diet yielded better results in weight loss and improvement of body composition and diet quality compared to TRE. Also, a decrease in total cholesterol level was found in the ERD group. However, more studies should be done with longer follow-ups and high sample sizes are very important in terms of creating public health-based recommendations.

Sleep quality in patients with non-functioning pituitary adenoma: impact of replacement therapies with an emphasis on the time of hydrocortisone.

PURPOSE: Sleep disturbances are widespread and associated with pituitary diseases, even those under long-term therapeutic management. The aim of this study was to investigate sleep quality in patients with non-functioning pituitary adenoma (NFPA) and determine the factors that might influence sleep quality, including the detailed features of replacement therapy. METHODS: Eighty-two patients with NFPA and 82 age- and gender-matched control subjects were included. Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS) and International Physical Activity Questionnaire (IPAQ) were used. RESULTS: In the NFPA group, 57.3% of patients had decreased sleep quality, compared to 35.4% in the control group (p=0.005). Although there was no relationship between the presence of hydrocortisone replacement and sleep quality (p>0.05), a strong positive correlation was observed between PSQI and morning hydrocortisone replacement time in patients with secondary adrenal insufficiency (r=0.834, p<0.001). Diabetes insipidus was found to be significantly higher in the group with decreased sleep quality (p=0.01). Moreover, there was a negative correlation between PSQI and IGF-1 in patients with NFPA (r=-0.259, p=0.01). A multivariate logistic regression model revealed that depression score and free T4 level in the upper half of the normal limit influence the sleep quality of patients with NFPA. CONCLUSION: Our study indicated the presence of depression, and a free T4 level in the upper half of the normal range have an impact on the sleep quality of patients with NFPA. The time of hydrocortisone replacement might be important factor for improved sleep quality in patients with secondary adrenal insufficiency.

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.

Relationships between serum and dietary magnesium, calcium, and metabolic parameters in women with type 2 diabetes mellitus.

BACKGROUND & AIMS: Magnesium and calcium are essential minerals in several enzymatic activities that modulate essential biological functions. Hypomagnesemia occurs in patients with type 2 diabetes mellitus (T2DM), especially those with poor metabolic control. Dietary magnesium and calcium intake play a protective role in the development of T2DM. This research aimed to investigate the association of dietary and serum magnesium and calcium with metabolic control parameters in diabetic women. METHODS: This case-control study was conducted on 80 women, including 40 patients diagnosed with T2DM and 40 healthy controls aged 35-60 years. Some anthropometric measurements of the individuals were taken, and their body mass index was calculated. In addition, some biochemical parameters, serum magnesium, and calcium were analyzed. A validated 96-item quantitative food frequency questionnaire was used to obtain dietary magnesium and calcium intake data. RESULTS: Serum magnesium levels were lower in subjects with diabetes than in controls, and there was a similar incidence of hypomagnesemia in T2DM patients and controls, but not statistically significant (p > 0.05). In T2DM patients, there was a statistically significant inverse association between HbA1c and serum magnesium (p < 0.05). Dietary magnesium intake was inversely associated with HOMA-IR scores (p < 0.05) but had a positive association with serum magnesium levels in patients with T2DM (p < 0.05). There were no significant differences in the calcium/magnesium ratio between T2DM patients and healthy controls (p > 0.05). In a multiple linear regression analysis, dietary magnesium intake and HbA1c were found to be significantly related to altered serum magnesium in T2DM patients. CONCLUSION: The present findings suggest that lower serum magnesium levels were associated with higher HbA1c levels in subjects with T2DM. Increased dietary magnesium intake in T2DM may enhance HOMA-IR scores and serum magnesium levels.

Overlooked complication of Cushing's syndrome: Reactivation of hepatitis B.

OBJECTIVE: Individuals infected with hepatitis B virus (HBV) are at increased risk of reactivation when they receive immunosuppressive therapies. Although exogenous corticosteroid use as immunosuppressive therapy is elaborated in current guidelines on HBV reactivation, Cushing's syndrome (CS) with endogenous hypercortisolemia is not addressed. We aimed to investigate the prevalence of HBV infection and discuss the necessity of antiviral prophylaxis in patients with CS as in other immunosuppressed patients. DESIGN AND PATIENTS: We included 72 patients with CS (Adrenocorticotropic hormone (ACTH) dependent or independent) who were screened for HBV between 2016 and 2021. Patients were categorized into three groups: overt, mild autonomous cortisol secretion (MACS), and remission according to the cortisol burden. Changes in patients' HBV serology and clinical findings over time were analyzed retrospectively. RESULTS: Twenty-six patients had overt hypercortisolism, 18 had mild autonomous cortisol secretion and 28 patients were in remission. Nineteen (26.3%) patients were anti-HBc IgG positive, 4 of them were chronic HBV and 15 were isolated anti-HBc IgG positive. HBsAg was positive in four (5.5%) of the patients, who were all compatible with inactive chronic HBV. While two patients developed HBV reactivation, HBV flare was observed in one patient. CONCLUSION: Since it is not always possible to achieve rapid remission in CS and these patients have long-term hypercortisolemia, we suggest that consensus should be reached on HBV serological assessment, standardization of follow-up, and planning of HBV prophylaxis in required instances in patients with CS especially in regions with a high prevalence of HBV infection.

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.

A de novo heterozygous HOXA11 variant in a patient with mesomelic dysplasia with urogenital abnormalities.

Mesomelic dysplasias are a genetically and clinically heterogeneous group of diseases with more than 10 types defined. This article presents an 18-year-old female patient with normal intelligence and a multisystem phenotype including disproportionate short stature, scoliosis, mesomelic limb shortening, radial bowing, short fourth to fifth metacarpals and metatarsals, fusions in the carpal/tarsal bones, operated pes equinovarus, primary amenorrhea, uterine hypoplasia, vesicoureteral reflux, and chronic kidney disease. Whole-exome sequencing revealed a de novo heterozygous c.881T>G (p.Met294Arg) variant in HOXA11 (NM_005523.6) gene. The variant was located in the homeodomain of HOXA11 and predicted to alter DNA-binding ability of the protein. In silico analyses indicated that the variant could promote the alterations in the protein-protein interaction. The possible functional effect of the variant was supposed as dominant-negative. Hoxa11-mutant mice have been reported to exhibit homeotic transformations in the thoracic and sacral vertebrae, zeugopodal phenotype in forelimb and hindlimb, and urogenital abnormalities. Although mice models were reported as mesomelic dysplasia and urogenital abnormalities (MDUGA), this phenotype has not yet been reported in humans. This was the first case with MDUGA putatively related to a de novo variant in HOXA11.

Irregularity in Plantar Fascia, Muscle Edema and Tendon Thickness in Patients with High-Risk for Diabetic Foot.

AIM: To investigate the alterations in the plantar fascia (PF), intrinsic muscles, and tendons in the feet of patients at high risk for developing diabetic foot. METHODS: The healthy feet of 22 patients with type 2 diabetes, who had developed diabetic foot ulcers on a single foot without any pathology on the contralateral extremity, and those of 22 healthy volunteers were evaluated by magnetic resonance imaging. The volume of the Achilles tendon (AT), the surface area of the PF, the thickness of AT, flexor hallucis longus, flexor digitorum longus, tibialis posterior, and peroneus longus tendons, irregularity in the PF, and edema of intrinsic foot muscles were examined. RESULTS: Nineteen patients (86%) had irregularity in the PF, whereas none of the healthy controls had any (p<0.001). Intrinsic muscle edema was more common in the group with diabetes (p=0.006). The volume of AT and the surface area of PF were decreased in patients with peripheral arterial disease (PAD) (p<0.05). Patients with diabetes mellitus but without PAD had a larger surface area of PF than that of controls (p<0.05). There were no differences in the volume of AT, the surface area of the PF, and other tendon thickness between the groups. CONCLUSION: Irregularity in the PF and muscle edema may indicate a high risk for the diabetic foot. The presence of PAD may lead to regression in the structure of AT and PF.

Evaluation of common carotid artery in type 1 diabetes mellitus patients through speckle tracking carotid strain ultrasonography.

PURPOSE: We aimed to evaluate the effectiveness of speckle tracking carotid strain (STCS) technique, which enables measurement of arterial stiffness and strain parameters, in the detection of early atherosclerotic findings in type 1 diabetes mellitus (T1DM). METHODS: We prospectively enrolled 30 T1DM patients and 30 age- and sex-matched control participants with no history of cardiovascular disease. All study population underwent carotid ultrasonography. Radial and circumferential movement of the common carotid artery (CCA) in the transverse plane as the well as the radial movement of the CCA in the longitudinal plane were calculated automatically by using the STCS method. In addition, the strain (%), strain rate (per second), and peak circumferential and radial displacements (mm) were calculated. Arterial stiffness parameters, such as elastic modulus, distensibility, arterial compliance, and ß-stiffness index, were calculated using the radial measurements. The mean value of the carotid intima media thickness (CIMT) was calculated semi-automatically for each CCA, in the longitudinal plane. We also analyzed the patients' overall body composition. RESULTS: T1DM and control groups were compared in terms of strain and stiffness parameters and no statistically significant difference was found (p > 0.05). CIMT was higher in diabetic patients than in the control group (p = 0.039). In both groups, age was correlated with all arterial stiffness and strain parameters (p < 0.05). The duration of diabetes was also correlated with ß-stiffness index, distensibility, and elastic modulus in the longitudinal plane (p < 0.05). In the diabetic group, abdominal fat ratio, whole body fat ratio, and fat mass were correlated with radial and circumferential displacement and strain parameters in transverse plane, and radial displacement in longitudinal plane (p < 0.05, for each). Diabetic patients were divided into subgroups according to the presence of nephropathy and dyslipidemia. Although no significant difference was found between the groups in terms of CIMT, patients with nephropathy had higher values for transverse and longitudinal elastic modulus, pulse-wave velocity, and longitudinal ß-stiffness index, as well as lower values for longitudinal arterial compliance and distensibility, compared with patients without nephropathy (p < 0.05). Also, patients with dyslipidemia had higher longitudinal ß-stiffness and elastic modulus values compared with patients without dyslipidemia (p < 0.05). CONCLUSION: STCS ultrasonography is an effective, easy, and noninvasive method for evaluating the arterial elasticity. It may provide an early assessment of atherosclerosis in patients with T1DM, especially in the presence of nephropathy and dyslipidemia; thus, together with CIMT measurement, it may be used more frequently to detect subclinical damage and stratify atherosclerosis.