ACTA ENDOCRINOLOGICA (BUC)

Context. Neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) are recent prognostic markers associated with inflammation in many diseases such as chronic kidney disease (CKD), malignancies, myocardial infarction. Objective. In this study, we investigated the relationship between NLR-PLR and parathyroid hormone (PTH) and vitamin D in patients with high PTH levels. Design. The patients with high PTH levels in Nephrology and Endocrinolgy Outpatient clinics were evaluated retrospectively. Subjects and methods. The medical records of the patients were examined and clinical data, including demographic details, clinical and laboratory findings, treatment and follow-up data were obtained. NLR and PLR were calculated. Serum creatinine, calcium, phosphorus, magnesium, lipid levels, calcium phosphorus product, PTH and vitamin D values were investigated. The relationship between NLR-PLR and laboratory parameters, GFR (MDRD-GFR), PTH and vitamin D were investigated. Results. 48 male and 253 female patients were enrolled in this study. The mean age was 57.57±13.28. NLR correlated negatively with albumin, hemoglobin, vitamin D, calcium and cholesterol and it positively correlated with creatinine and PTH. Multiple regression analysis showed that main determinants of NLR were PTH, albumin, LDLcholesterol, hemoglobin and gender. Conclusions. In this study NLR and PLR correlated negatively with hemoglobin and cholesterol. Positive correlation between NLR and creatinine could be explained by increased degrees of inflammation associated with more pronounced degrees of renal dysfunction. The impact of PTH on NLR was independent of GFR. In multiple regression model this suggests that PTH could be a pro-inflammatory parameter independent of the degree of renal dysfunction.

The RET proto-oncogene is the most well-known gene involved in medullary thyroid cancer (MTC). The associations between specific RET mutations and the age of onset and aggressiveness of MTC and the presence or absence of other endocrine neoplasms such as pheochromocytoma or hyperparathyroidism have been well documented. When a new mutation is identified in the RET gene, defining that mutation’s codon-specific risk level is important in the management of patients with MTC. Case Report. Here, we present the first report of a patient with a germline variant of Ala641Thr, in the transmembrane domain of the RET gene. A 37-year-old female presented with an anterior neck mass, which was confirmed to be MTC by biochemical tests and pathologic findings. The patient had no identifiable family history of MTC or multiple endocrine neoplasia syndromes. Histology revealed a single unilateral MTC lesion (21 mm × 16 mm) in the right thyroid lobe without cervical lymph node metastasis. Genetic testing revealed a germline Ala641Thr missense mutation in the RET gene. The RET gene variant was inherited by one of her children. Conclusion. Although this novel variant has unknown clinical significance at present, the causative role of this genetic variant in MTC pathogenesis could be clarified by further molecular structure-function studies and additional clinical cases showing a genotype-phenotype relationship.

Background. Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder caused by congenital deficiency of enzymes involved in cortisol biosynthesis from cholesterol in the adrenal cortex. In this article, we aimed to present a 29-year-old female patient with I2 splice point mutation detected in one allele and P453S mutation on the other allele of CYP21A2 gene associated with 21-hydroxylase deficiency. Her further investigation revealed that her mother had P453S mutation and her father had I2 splice mutation. Case report. A 29-year-old woman with CAH was admitted to our clinic with the request of pregnancy. Her physical examination revealed a height of 151 cm, weight 59 kg, body mass index 25.8 kg/m2. According to Tanner staging, she had Stage 3 breast development and pubic hair. Her laboratory test results were as follows: Glucose: 79 mg/dL (70-100 mg/dL), Creatinine: 0.6 (0.5-0.95 mg/ dL), Sodium: 138 mEq/L (135-145 mEq/L), Potassium: 4.4 mEq/L (3.5-5.1 mEq/L), Cortisol: 0.05 μg/dL, ACTH: <5.00 pg/mL (5-46 pg/mL), 17-OH progesterone: 7.67 ng/mL (0-3 ng/mL). Chromosome analysis revealed a 46, XX karyotype. CYP21A2 gene mutation analysis was performed for the patient whose clinical history and laboratory results were compatible with congenital adrenal hyperplasia. During the reverse dot blot analysis, I2 splice mutation in one allele and P453S mutation in the other allele were detected. Conclusion. Although the I2 splice mutation detected in our case was mostly associated with a saltwasting form of CAH, it was thought that the other P453S mutation detected may explain the relatively good clinical course in our case.

Purpose. About 30% of patients with liver cirrhosis have diabetes. Postprandial hyperglycemia is more problematic than fasting hyperglycemia when managing diabetic patients with cirrhosis. Nateglinide decreases in the mealtime plasma glucose levels. The present study aims to determine\r\nwhether nateglinide is suitable for the management of diabetic patients with liver cirrhosis.\r\nMethods. This was a retrospective analysis of the cirrhotic patients who were treated at CNUH between Jan 2003 and Dec\r\n2009. A total of 81 Child-Pugh Class A or B patients who had been treated with insulin (I, n=27) or nateglinide (N, n=27) for at least 12 months were included in the study, while 27 cirrhotic patients without diabetes (C, n=27) were included as a control group. We compared the efficacy of treatment and the safety between the groups.\r\nResults. The basal mean HbA1c level was higher in the insulin treatment group than that in the nateglinide treatment group. The mean HbA1c was lowered in thepatients treated with insulin (9.36 ? 1.71% &#8594; 7.69?1.52%, p=0.026), but this was not changed in the patients treated with\r\nnateglinide (8.01?2.37 % &#8594; 7.78?2.11%, p=0.692) after 12 months treatment. There was no change in the Child-Pugh score in all the groups.\r\nConclusion. In case of mild hyperglycemia, nateglinide may be used for glycemic control in diabetic patients with\r\ncirrhosis as an insulin substitute without worsening the state of liver cirrhosis.

Background. Graves’ disease results in various clinical cardio-pulmonary manifestations such as tachycardia, atrial fibrillation, and pulmonary edema. Clinical Case. A 62-year-old woman presented with palpitations and dyspnea. Laboratory and radiologic examination revealed markedly elevated free T4 (4.79 ng/dL), T3 (4.42 ng/mL), lowered TSH (0.01 uIU/mL), atrial fibrillation and multifocal lung haziness. She was initially diagnosed with atrial fibrillation with pulmonary edema, which subsequently changed to pulmonary alveolar proteinosis by further evaluations such as computed tomography and bronchoscopic biopsy. Conclusion. Pulmonary alveolar proteinosis is a rare lung disease. Clinicians should carefully assess lung lesions in thyrotoxicosis patients as they can be easily mistaken for pulmonary edema in clinical practice.

Purpose. Short chain fatty acids (SCFAs) play a major regulatory role in adipocyte function and metabolism. The aim of this study was to investigate the effects of SCFAs on adiponectin and leptin expression in adipocytes, and also to determine whether the effects of SCFA treatment in visceral adipocytes obtained from healthy subjects are different relative to the effects in adipocytes from patients with type 2 diabetes. Materials and Methods. Human pericardiac preadipocytes and human pericardiac preadipocytes type 2 diabetes were differentiated into adipocytes for 21 days in 48-well plates. After differentiation, two kinds of mature adipocytes, human pericardiac adipocytes (HPAd) and human pericardiac adipocytes-type 2 diabetes (HPAd-T2D) were incubated with or without 1 mM of acetic acid (AA), butyrate acid (BA), and propionic acid (PA). After 48 hours of incubation, intracellular lipid accumulation was measured using oil red staining. In addition, mRNA levels of adiponectin, leptin and Peroxisome Proliferator-Activated Receptor γ (PPARγ) were determined by Real-Time PCR system. Results. In HPAd, SCFA supplementation did not inhibit lipid accumulation. By contrast, both AA (p<0.01) and PA (p<0.01) significantly inhibited lipid accumulation in HPAd-T2D. Regarding mRNA levels of adiponectin, no significant changes were found in HPAd, while all three types of SCFAs significantly increased (p<0.05) adiponectin expression in HPAd-T2D. Leptin mRNA expression levels were significantly increased by treatment with all three types of SCFAs in both HPAd (p<0.05) and HPAd-T2D (p<0.05). Conclusion. SCFAs inhibited lipid droplet accumulation and increased mRNA expression of adiponectin and leptin in T2D-derived adipocytes.

Background. Thyroid hormone resistance (RTH) is defined as a decrease in response to thyroid hormones in the target tissue. Most patients present with nonspecific findings. In this article, we aimed to represent a 22-yearold female patient who presented with palpitation, fatigue, and heat intolerance. She was thought to have thyroid hormone resistance and her genetic examination revealed NM_001128177.1 (THRβ): c.1034G > A (p.Gly345Asp) pathogenic variation in the THRβ gene. Case report. A 22-year-old female patient presented with complaints of fatigue, heat intolerance and palpitations. She was taking Propranolol twice daily at admission. Her family history revealed hypothyroidism in her grandmother. Her physical examination results were as follows: height 160 cm, weight 65 kg, body mass index 25.4kg/m2, body temperature 36.5˚C, respiratory rate 18/min, heart rate 86 beats/min, blood pressure 120/80 mmHg. Her palms were sweaty. The heart sounds were normal, and no heart murmur was auscultated. The laboratory results were TSH: 5.31uU/mL, fT3: 6.83 pg/mL, and fT4: 2.43 ng/dL. THRβ gene mutation analysis was requested for our patient whose clinical history and laboratory results were compatible with thyroid hormone resistance. The pathogenic variation NM_001128177.1(THRβ):c.1034G>A (p.Gly345Asp) was detected after analysis. Conclusion. A diagnosis of RTH requires high clinical suspicion and a genetic mutation analysis should be requested in the case of clinical suspicion. In this way, unnecessary anti-thyroid treatment can be prevented.

Context and Objective. The risk of needing lifelong thyroid hormone supplementation is an important factor affecting treatment decisions for both patients and clinicians ahead thyroid lobectomy. The purposes of this study were to assess the predictive factors of levothyroxine medication after thyroid lobectomy. Methods. We retrospectively reviewed 252 patients who had undergone lobectomy for benign thyroid nodules between April 2009 and April 2017. We conducted two independent analyses: patients who started taking levothyroxine after surgery were compared with those who did not, and patients who did not need levothyroxine at last follow-up were compared with those who required continued treatment. We investigated the correlations of patient clinicopathological characteristics and levothyroxine medication after lobectomy. Results. Ninety-eight patients started levothyroxine after surgery. Of these, 34 patients successfully ceased medication and 64 patients continued treatment as of their last follow-up. In multivariate analysis, older age and preoperative TSH ≥2.0mIU/L were associated with levothyroxine initiation after surgery. In terms of continuity of levothyroxine, both older age and TSH ≥ 3.0mIU/L showed a significant correlation with continuous medication. We created a risk-scoring system to predict likelihood of starting and maintaining levothyroxine using the two significant factors in each comparison. A risk score of 3 or more indicated an increased risk of starting levothyroxine (specificity = 81.8%; sensitivity = 48.0%). A risk score of 3 or more indicated increased risk of continuous medication, (specificity = 94.2%; sensitivity = 35.9%). Conclusions. Greater age and higher preoperative TSH levels correlated with initiation and continuity of levothyroxine medication after lobectomy.

Streptococcus pneumoniae generally causes pneumonia or meningitis. The psoas abscess and osteomyelitis is mainly caused by Staphylococcus aureus. We report here on a patient with type 2 diabetes mellitus who had a psoas abscess and foot ulcer caused by Streptococcus pneumoniae after acupuncture\r\nand moxibustion.

Background. The incidence of adrenal incidentaloma has been increasing proportional to the use of radiologic examination. Multiple endocrine neoplasia1 (MEN1) syndrome may present with various tumors. The present study reports a case of adrenal incidentaloma with unrecognised MEN1 syndrome associated with breast cancer. Clinical case. A 48-year-old woman presented with a 2.4cm left adrenal incidentaloma on abdominal computed tomography. Her history revealed primary amenorrhea, recurrent peptic ulcer and nephrolithiasis. Laboratory and radiologic examination revealed two pancreatic tail mass lesions with markedly elevated gastrin levels (1462 pg/mL), hypercalcemia with increased parathyroid hormone levels (72 pg/mL), a 1.5cm pituitary mass with hyperprolactinemia (234 ng/mL), a 1.0cm meningioma and a nonfunctional left adrenal mass. During this image work up, a 0.6cm nodule in the right breast was incidentally detected. Surgeries (laparoscopic distal pancreatectomy, parathyroidectomy and wide local excision of breast) and pathologic findings confirmed pancreatic neuroendocrine tumors, parathyroid gland hyperplasia, and breast cancer. Carbergoline treatment for 12 months decreased prolactin levels to 27 ng/mL. Genetic testing using peripheral blood revealed a pathogenic variant in MEN1 on chr11q13 (NM_000244.3:c.1365+1_1365+11 del, GTGAGGGACAG, heterozygous). Conclusion. Considering the increasing incidence of adrenal incidentaloma and 20% prevalence of adrenal tumors in patients with MEN1, it is important to rule out MEN1 association in patients with adrenal incidentaloma. Additionally, breast cancer was detected during MEN1 workup in this case. Female patients with MEN1 are at increased risk for breast cancer. Therefore, intensified breast cancer screening at a relatively young age should be considered in female MEN1 patients.