Cutaneous findings in patients with acromegaly and its relationship with concomitant endocrinopathies.

OBJECTIVES: Skin changes in acromegaly are often the first sign of the disease. The aim of this study was to describe the cutaneous findings in patients with acromegaly. In addition, a secondary aim was to investigate the possible association of these findings with remission status and concomitant endocrinopathies. DESIGN, PATIENTS, AND MEASUREMENTS: In this prospective multicenter study, 278 patients over the age of 18 years with acromegaly who were followed up in 14 different tertiary healthcare institutions were included. These patients, who were followed up by the Endocrinology Department, were then referred to a dermatologist for dermatological examination. The frequency of skin lesions was investigated by detailed dermatologic examination. Dermatological diagnosis is reached by clinical, dermatological and/or dermoscopic examination, and rarely skin punch biopsy examinations in suspicious cases. The possible association of the skin findings between remitted and nonremitted patients and with concomitant endocrinopathies were evaluated. RESULTS: The most common skin findings in patients with acromegaly in our study were skin tags (52.5%), cherry angiomas (47.4%), seborrhoea (37%), varicose veins (33%), acneiform lesions (28.8%), hyperhidrosis (26.9%) and hypertrichosis (18.3%). Hypertrichosis was significantly more prevalent in patients nonremitted (p: .001), while xerosis cutis was significantly more prevalent in patients remitted (p: .001). The frequency of diabetes mellitus and hypothyroidism was significantly higher in patients with varicose veins and seborrhoeic keratosis than those without. Additionally, the coexistence of hypothyroidism, hyperthyroidism and galactorrhea was significantly higher in patients with Cherry angioma than in those without Cherry angioma (p-values: .024, .034 and .027, respectively). The frequency of hypogonadism in those with xerosis cutis was significantly higher than in those without (p: .035). CONCLUSIONS: Cutaneous androgenization findings such as skin tag, seborrhoea, acne and acanthosis nigricans are common in patients with acromegaly. Clinicians should be aware that skin findings associated with insulin resistance may develop in these patients. It can be said that the remission state in acromegaly has no curative effect on cutaneous findings. Only patients in remission were less likely to have hypertrichosis. This may allow earlier review of the follow-up and treatment of acromegaly patients presenting with complaints of hypertrichosis. Additionally, it can be said that patients with skin findings such as cherry angioma may be predisposed to a second endocrinopathy, especially hypothyroidism. Including dermatology in a multidisciplinary perspective in acromegaly patient management would be beneficial to detect cutaneous findings earlier.

Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study.

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5-10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients.

Vitamin D Receptor Level in Biopsy Specimen of Patients with Ulcerative Colitis: Results from a Center in Western Anatolia.

BACKGROUND: Ulcerative colitis (UC) is a chronic, inflammatory bowel diseases characterized by uncontrolled inflammatory condition of the colon and rectal mucosa marked by recurrent periods of remission and exacerbation. Vitamin D receptor (VDR) is a member of the steroid receptor family that mediates the effects of vitamin D by regulating transcription of multiple cellular genes. We aimed to evaluate vitamin d receptor level in biopsy specimen of patients with UC in this study. METHODS: VDR levels were retrospectively studied in colon biopsy specimens of UC patients. The Spearman's rho correlation analysis, The Kolmogorov-Smirnov, Mann Whitney U, and chi-square tests were used for statistical analysis. The p values below 0.05 were considered statistically significant. RESULTS: Study included 112 UC patients (65 male and 47 female) and 30 controls (19 female and 11 male) who had normal results in biopsy examinations carried out due to various reasons. VDR levels of UC patients were statistically lower than control subjects, and was not associated with duration of the disease and place of involvement. CONCLUSIONS: VDR is an important receptor in the pathogenesis of UC, and optimizing vitamin D levels could have a therapeutic role in UC.

The association between clinically suspect arthralgia and adipokines in obese patients.

OBJECTIVE: Obesity is a moderate low-grade chronic inflammatory condition. The cause of low-grade inflammation in obese patients who have clinically suspect arthralgia (CSA) may be the subject of debate in clinical practice. Our aim is to determine whether inflammation is associated with obesity or rheumatic disease, and the association between leptin, chemerin, visfatin and inflammatory markers in obese patients with/without musculoskeletal symptoms. METHODS: Seventy-four obese patients who admitted to our rheumatology clinic with CSA were enrolled. The control group consisted of 40 obese patients who have no rheumatic symptoms. Body mass index (BMI) was calculated in kg/m2 with body weight ratio to height squared, and obesity was defined as BMI 30 or above. Age, gender, BMI, waist and hip circumferences, waist-to-hip ratio (WHR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), leptin, chemerin, and visfatin were evaluated. The relationship between all parameters was assessed by Spearman correlation, Wilcoxon Signed-rank, and paired t-tests. RESULTS: There were no significant differences for age, gender, ESR and CRP between obese patients with CSA and control group. The mean TNF-α, IL-1ß, IL-6 concentrations were 60.8 pg/mL, 39.9 pg/ml, and 26.2% in obese patients with CSA, respectively. ESR, CRP, TNF-α, IL-6, and IL-1ß concentrations were higher in these patients compared to obese patients without any rheumatic symptoms. The mean WHR and waist circumference were 0.8±0.1 and 107.1±13.4 cm, respectively in patients with CSA. IL-6 correlated with WHR and waist circumference, positively. There were significant differences for adipokines such as chemerin, visfatin, but not for leptin between both group. Moreover, a significant correlation was found between pro-inflammatory cytokines and visfatin, chemerin. CONCLUSION: Visfatin and chemerin correlated with inflammation and may be useful indicators of undifferentiated inflammatory arthritis in obese patients with CSA.

Screening Fabry's disease in chronic kidney disease patients not on dialysis: a multicenter study.

OBJECTIVES: Fabry's disease is an X-linked inherited, rare, progressive, lysosomal storage disorder, affecting multiple organs due to the deficient activity of α-galactosidase A (α-Gal A) enzyme. The prevalence has been reported to be 0.15-1% in hemodialysis patients; however, the information on the prevalence in chronic kidney disease not on dialysis is lacking. This study aimed to determine the prevalence of Fabry's disease in chronic kidney disease. METHODS: The patients older than 18 years, enclosing KDIGO 2012 chronic kidney disease definitions, not on dialysis, were enrolled. Dried blood spots on Guthrie papers were used to analyze α-Gal A enzyme and genetic analysis was performed in individuals with enzyme activity ≤1.2 µmol/L/h. RESULTS: A total of 1453 chronic kidney disease patients not on dialysis from seven clinics in Turkey were screened. The mean age of the study population was 59.3 ± 15.9 years. 45.6% of patients were female. The creatinine clearance of 77.3% of patients was below 60 mL/min/1.73 m2, 8.4% had proteinuria, and 2.5% had isolated microscopic hematuria. The mean value of patients' α-Gal A enzyme was detected as 2.93 ± 1.92 µmol/L/h. 152 patients had low levels of α-Gal A enzyme activity (≤1.2 µmol/L/h). In mutation analysis, A143T and D313Y variants were disclosed in three male patients. The prevalence of Fabry's disease in chronic kidney disease not on dialysis was found to be 0.2% (0.4% in male, 0.0% in female). CONCLUSION: Fabry's disease should be considered in the differential diagnosis of chronic kidney disease with unknown etiology even in the absence of symptoms and signs suggestive of Fabry's disease.

Clinical Features of 294 Turkish Patients with Chronic Myeloproliferative Neoplasms.

OBJECTIVE: Myeloproliferative neoplasms (MPNs) share common clonal stem cells but show significant differences in their clinical courses. The aim of this retrospective study was to evaluate thrombotic and hemorrhagic complications, JAK2 status, gastrointestinal and cardiac changes, treatment modalities, and survival in MPNs in Turkish patients. MATERIALS AND METHODS: Medical files of 294 patients [112 essential thrombocythemia (ET), 117 polycythemia vera (PV), 46 primary myelofibrosis, and 19 unclassified MPN cases] from 2 different universities in Turkey were examined. RESULTS: Older age, higher leukocyte count at diagnosis, and JAK2 mutation positivity were risk factors for thrombosis. Platelet count over 1000x109/L was a risk factor for hemorrhagic episodes. Hydroxyurea treatment was not related to leukemic transformation. Median follow-up time was 50 months (quartiles: 22.2-81.75) in these patients. Patients with primary myelofibrosis had the shortest survival of 137 months when compared with 179 months for ET and 231 months for PV. Leukemic transformation, thromboembolic events, age over 60 years, and anemia were found to be the factors affecting survival. CONCLUSION: Thromboembolic complications are the most important preventable risk factors for morbidity and mortality in MPNs. Drug management in MPNs is done according to hemoglobin and platelet counts. Based on the current study population our results support the idea that leukocytosis and JAK2 positivity are more important risk factors for thrombosis than hemoglobin and platelet values.

Minimally invasive parathyroidectomy without using intraoperative parathyroid hormone monitoring or gamma probe.

OBJECTIVE: Minimal invasive parathyroidectomy (MIP) is a common surgical technique for the treatment of primary hyperparathyroidism (PHPT) and is usually done in conjunction with positive imaging techniques. We aimed to assess the results of this technique, performed without the use of intraoperative tests, in cases with PHPT caused by a single parathyroid adenoma. MATERIAL AND METHODS: The data for patients who were diagnosed with PHPT were assessed retrospectively. Only those who had undergone a parathyroid adenoma localization study with ultrasonography (US) and parathyroid scintigraphy (PS) before the surgery, along with those patients for whom the MIP technique was routinely performed with frozen pathology, were included. RESULTS: The study group was made up of 65 patients who had undergone the MIP technique. The mean age of the patients was 56±14 (20-81), with most being females [M/F: 19 (29.2%)/46 (70.8%)]. The mean calcium values before the operation were 11.24±1.26 mg/dL (8-15.5) (normal range: 8.4-10.2), and the parathyroid hormone (PTH) values were 388 pg/mL (249-707.75). These same values, measured 24 hours after the operation, were determined as 9.04±1.04 mg/dL (6.8-13.9) and 27 pg/mL (6-86), respectively. The follow-up period for the patients was an average of 26.6±9.4 (3-76) months, and only 3 (4.6%) cases of persistent hyperparathyroidism were detected within this period. CONCLUSION: Our success rate with MIP in PHPT cases was determined to be 95.4%; therefore, this technique may be applied with a high success rate without any assistance from intraoperative tests, such as rapid serum PTH (rPTH) assays or gamma probes, in the presence of localization results of PS and US.

Relationship between glycemic control and histochemical myeloperoxidase activity in neutrophils in patients with type 2 diabetes.

BACKGROUND: Myeloperoxidase (MPO) is a lysosomal hemoprotein found in the azurophilic granules in neutrophils. Myeloperoxidase plays an important role in oxygen-dependent killing of bacteria, fungi, virus and malignant cells. Diabetes mellitus (DM) is listed among conditions that may lead to secondary MPO deficiency in neutrophils but inconsistent results concerning MPO activity in diabetic patients have been reported in the literature. In this study, we aimed to evaluate the relationship between glycemic control in patients with type 2 DM and MPO activity in neutrophils from a histochemical perspective. METHODS: The study included 40 patients with type 2 DM with poor glycemic control, 30 patients with type 2 DM with good glycemic control and 31 healthy controls. Peripheral blood smears were analyzed for each patient included in the study. Myeloperoxidase dye was used for staining. Myeloperoxidase ratios in neutrophil were evaluated for proportions of staining with MPO in 100 neutrophils in each smear. SPSS 16.0 version was used for statistical analyses. RESULTS: Myeloperoxidase ratios in neutrophils were 70 (58.5-80) in type 2 DM patients with poor glycemic control compared to 80 (73.75-90) in those with good glycemic control and 88 (78-92) in healthy controls. The DM group with poor glycemic control was statistically significantly different from the other groups (p < 0.001). CONCLUSIONS: Poor glycemic control in diabetic patients results in decreased MPO activity in neutrophils histochemically.

The ocular biometric differences of diabetic patients.

PURPOSE: To investigate the differences in ocular biometric and keratometric characteristics in comparison with biometric measurements using the noncontact optical low coherence reflectometer (OLCR) (Lenstar LS 900, Haag-Streit) on diabetic patients. METHODS: The eyes of 170 patients were included in this study, including 81 diabetic and 89 nondiabetic subjects. Optical biometric measurements of diabetic and nondiabetic patients (between the ages of 25 and 85 years) who applied to the ophthalmology clinic were noted from March to June 2013. Detailed ophthalmologic examinations were done for every subject. Biometric measurements were done using the noncontact OLCR device. RESULTS: Patient age ranged from 29 to 83 years. Subgroup analyses were done in diabetic patients according to their Hba1C levels. The minimum Hba1C value was 5.3, maximum was 12.4, and mean was 7.56 ± 1.48. The median duration of diabetes was 5 years (25th-75th percentile 3.00-11.75). Diabetic patients were found to have thicker lens and shallower anterior chamber in both eyes compared to nondiabetic control subjects. There were no statistical differences between the groups according to central corneal thickness, axial length, or keratometric values in both eyes. However, lens thicknesses were found to be thicker and anterior chamber depth values were found to be shallower in the diabetic group in both eyes. CONCLUSIONS: It may useful to determine eyeglasses prescription, refractive surgery calculation, lens selection, and previous cataract surgery according to biometric measurements after the regulation of blood glucose.

Esophageal Leiomyoma in Patients with Megaloblastic Anemia.

Esophageal leiomyoma is the most common benign intramural tumor of esophagus. Although its incidence is not exactly known, it is very rare (0.006%-0.1% in autopsy series). It is generally asymptomatic and detected incidentally. Here, we present a rare case report describing coexistence of megaloblastic anemia and esophageal leiomyoma. How to cite this article: Coskun A, Unubol M, Yukselen O, Yukselen V, Aydin A, Sen S, Karaoglu AO. Esophageal Leiomyoma in Patients with Megaloblastic Anemia. Euroasian J Hepato-Gastroenterol 2014;4(2):98-100.

Adrenal incidentaloma and the Janus Kinase 2 V617F mutation: A case-based review of the literature.

Adrenal incidentaloma was detected in an 81-year-old male patient and a 37-year-old female patient who had been diagnosed with essential thrombocytosis. Each patient's Janus Kinase 2 (JAK2) V617F mutation was positive, and they were evaluated as having non-functional adrenal incidentaloma. The JAK2 activates the signal transducers and activators of transcription (STAT) proteins which then activate the phosphoinositol-3 kinases, Ras, mitogen-activated protein (MAP) kinases, and transcription. Constitutive activation causes cell proliferation and dysregulation of apoptosis. It is thought that STAT3 activation-mediated JAK family kinases have a central role in the solid tumor cell series. Permanent activation of STAT3 and STAT5 causes tumor cell proliferation, survival, metastasis, and an increase in tumor-mediated inflammation in solid and hematologic tumors. According to our literature screening, irregular JAK signaling, seen at the pathogenesis of many solid and hematologic tumors, has not been previously evaluated with regard to adrenal tumors. As a result, our cases are the first coexistence of JAK V617F mutation with adrenal incidentaloma in the literature. Because of this, we think that JAK2 mutation must be evaluated to clarify the etiology of adrenal incidentalomas.

QT dispersion in patients with acromegaly.

Acromegaly is a rare condition caused by a pituitary adenoma that secretes growth hormone. The mortality rate is 72 % higher in patients with acromegaly than in the general population according to meta-analyses. Mortality analysis has shown as many as 60 % of acromegalic patients die due to cardiovascular disease. Sudden cardiac death may occur in patients with acromegaly and malignant ventricular arrhythmia may play an important role in this fatal complication; however, the precise mechanism is not fully known. QT dispersion (dQT) is an electrophysiological factor known to be associated with a tendency for ventricular arrhythmia and sudden cardiac death. This study aimed to evaluate dQT as an early predictor of ventricular tachyarrhythmia, as sudden cardiac death commonly occurs in acromegalic patients. This cross-sectional case-control study enrolled 20 patients (10 female and 10 male) with acromegaly and 20 healthy controls (11 female and 9 male) after exclusion criteria were applied. Each participant underwent 12-lead electrocardiography, including ≥3 QRS complexes, at a speed of 25 mm/s after a 15-min rest. In each participant, the QT interval (beginning of the Q wave to the end of the T wave) was corrected (QTc) for heart rate using Bazett's formula [Formula: see text] QTc dispersion (dQTc) (QTc max - QTc min) was also calculated. There was no significant difference in median dQTc between the acromegalic patients (0.79 s) and the controls (0.45 s) (p > 0.05). Active acromegalic patients (n = 14) were estimated to have a median dQTc of 0.82 s, after excluding from the analysis six patients that were under full biochemical control, and that had randomly obtained growth hormone levels <0.4 ng/mL, GH <1 ng/mL based on oral glucose tolerance test, and normal IGF-I for age and gender. A significant difference was noted in median dQTc between the active acromegalic patients and the controls (p = 0.015). The dQT in active acromegalic patients was longer than that in the control group, which indicates that patients with active acromegaly might have an elevated risk for ventricular arrhythmia. We think that a non-invasive, simple and inexpensive marker-measurement of dQT-as part of cardiac monitoring could be valuable for screening complications in acromegalic patients.

Coexistence of Multiple Endocrine Neoplasia Type 2B and Chilaiditi Sign: A Case Report.

We present a 15-year-old female patient with medullary thyroid carcinoma, marfanoid habitus, and mucosal ganglioneuromatosis. Our case had a RET protooncogene mutation ser836 polymorphism in exon 14 and ser904 polymorphism in exon 15. Our patient is thought to be atypical MEN2B due to the absence of M918T or A883F mutations. Chilaiditi sign is an incidental radiographic finding of a usually asymptomatic condition in which a part of intestine is located between the liver and diaphragm; however, the term "Chilaiditi syndrome" is used for symptomatic hepatodiaphragmatic interposition. The patient had no symptoms as abdominal pain, constipation, diarrhea, or emesis. Incidentally, Chilaiditi sign was diagnosed with chest radiograph and thoracoabdominal CT. Our case is the first in the literature indicating the coexistence of Chilaiditi sign and MEN2B.

Imatinib-associated bilateral gynecomastia and unilateral testicular hydrocele in male patient with metastatic gastrointestinal stromal tumor: a literature review.

Imatinib mesylate is a drug that has been approved for treatment of advanced gastrointestinal stromal tumors (GISTs) and patients with leukemia such as chronic myeloid or Philadelphia chromosome-positive acute lymphoblastic. Although it has been described only in one patient with testicular hydrocele and gynecomastia in the literature, several cases of male gynecomastia have been reported with the use of imatinib mesylate in chronic myeloid leukemia (GML). Generally, male mastoplasia resolves after discontinuation of imatinib treatment. We report a 73-year-old male with metastatic GISTs who developed gynecomastia and unilateral testicular hydrocele while receiving imatinib mesylate. Nine months after commencing imatinib treatment, gynecomastia and testicular hydrocele were determined. Hormone analyses requested showed serum testosterone levels below and serum estrogen levels above normal limits. During the first month after discontinuing imatinib mesylate treatment, serum testosterone level was normal and there was a partial regression in gynecomastia and testicular hydrocele. To our knowledge, this is the second report of male gynecomastia following imatinib mesylate treatment of a patient with GIST. In conclusion, male patients who are to receive treatment with imatinib mesylate may be monitored for serum testosterone levels and for other reproductive hormone profiles before initiation of the treatment and their breasts may be examined during follow-up visits.