Primary hypophysitis: Experience of a Single Tertiary Center.

PURPOSE: The authors review the clinical outcomes of patients with primary hypophysitis (PH). METHODS: Patients with PH who were followed up between 2007 and 2018 at our clinic were evaluated. Clinical, endocrinologic, pathologic, radiologic findings and treatment modalities were assessed. RESULTS: Seventeen patients with PH were assessed. The median follow-up was 24 (range, 6-84) months. Histologic confirmation was available in 8 patients (6 lymphocytic hypophysitis, 1 lymphocytic-granulomatous hypophysitis, 1 xanthomatous hypophysitis). None of the cases were diagnosed after pregnancy. Two patients had an autoimmune disease. The most commonly seen symptom was headache. The most common anterior pituitary deficiencies were hypocortisolemia and hypothyroidism. The radiologic findings of the patients at the time of diagnosis revealed various results including space-occupying lesion (41.2%), loss of posterior hypophysis bright spot (47.1%), pituitary stalk thickening (41.2%), uniform contrast enhancement (17.6%), partially empty sella (11.8%), optic chiasm compression (11.8%). The most frequent initial treatment modality was observation. Ten patients who were followed up conservatively had no endocrinologic deterioration; additional treatment was not needed in 8 of these 10 patients. The second most frequent initial treatment modality was pituitary surgery. Five patients received steroid treatment. We found serious adverse effects during steroid treatment in 3 of 5 (60%) patients; unilateral avascular necrosis of the femoral head (n=2), diabetes mellitus(n=1). CONCLUSION: Correctly diagnosing PH and giving appropriate treatment is challenging. It is unclear whether active treatment with steroids improves clinical outcomes. The serious adverse effects of steroids are also taken into account. Observation, surgery and/or radiotherapy can be appropriate treatment modalities for selected patients.

Does treatment with sodium-glucose co-transporter-2 inhibitors have an effect on sleep quality, quality of life, and anxiety levels in people with Type 2 diabetes mellitus?

Background/aim: To evaluate the impact of treatment with sodium-glucose co-transporter-2 (SGLT2) Inhibitors on quality of life (QoL), sleep quality (SQ), and anxiety levels in patients with Type 2 diabetes mellitus (T2DM). Materials and methods: Ninety-seven patients with type 2 diabetes admitted to tertiary care hospital diabetes clinic were included. Fifty patients were randomized to receive SGLT2 inhibitors in addition to baseline treatment (Group A), 47 subjects continued with their baseline treatment or were added other medications as needed (Group B). Thirty healthy controls (HC) were recruited (Group C). All groups were subjected to the Turkish version of Short Form-36 (SF-36), Pittsburgh Sleep Quality (PSQ), and Beck Anxiety Inventory (BAI) scales both at baseline and final visit. Results: Physical function, emotional role limitation, vitality, mental health, pain, general health perception scores of SF-36 were significantly improved in Group A, at the end of the follow-up period. There was no significant change in terms of PSQ, BAI scores, and hypoglycaemia documented in all groups. The intervention-related change in HbA1c level, body weight, and body mass index were significantly higher in Group A. Conclusion: The QoL was improved in people with diabetes who were taking SGLT2 inhibitors. This may be explained by weight loss observed in participants.

Static and dynamic balances of patients with acromegaly and impact of exercise on balance.

PURPOSE: Patients with acromegaly may have balance abnormalities due to changes in body composition. We aim to compare static and dynamic balances in patients with acromegaly and healthy volunteers, and to evaluate the effects of exercise on balance in patients with acromegaly. METHODS: This prospective study included 25 patients with acromegaly followed at endocrinology clinic of Cerrahpasa Medical Faculty and 13 healthy volunteers. The acromegalic patients were divided into 2 groups. Group A (n = 11) attended an exercise program 3 days/week for 3 months, whereas group B (n = 14) and healthy volunteers (Group C) were exercise-free. Bipedal and unipedal stance static and dynamic balance tests were performed using a Prokin 252N device. RESULTS: The ages, demographic characteristics, and body compositions were similar. In acromegalic patients, the static balance parameters of displacement of center-of-pressure in anterior-posterior direction (C.o.P.Y) while eyes open (p = 0.002) and on left leg (p = 0.001), in left-right direction (C.o.P.X) on right leg (p = 0.03), eyes-closed average medio-lateral velocity (AMLV) (p = 0.001) and the dynamic parameter of forward/backward front/right standard deviation (FBFRSD) (p = 0.02) were significantly different from healthy controls. When the exercise effect on balance was evaluated between group A and B, there were significant improvements in most parameters of dynamic balance measurements of both forward-backward and medial-lateral sway (FBFRSD, FBDME, and RLBLSD) (p = 0.02, p = 0.02, and p = 0.004, respectively) after exercise in group A. CONCLUSIONS: Patients with acromegaly had impairments at various static and dynamic balance parameters, especially in posterior direction. After a 3-month exercise program, the dynamic balance profoundly improved, but static balance was relatively preserved in patients with acromegaly.

The effects of pre-operative somatostatin analogue therapy on treatment cost and remission in acromegaly.

PURPOSE: To investigate the effects of preoperative somatostatin analogue (SSA) treatment on the annual cost of all acromegaly treatment modalities and on remission rates. METHODS: The medical records of 135 patients with acromegaly who were followed at endocrinology clinic of Cerrahpasa Medical Faculty for at least 2 years after surgery between 2009 and 2016 were reviewed. RESULTS: The mean follow-up time was 50.9 ± 25.7 months. Early remission was defined according to 3rd month values in patients who didn't achieve remission, and 6th month values in patients who achieved remission at the 3rd month after surgery. The early and late remission rates of the entire study population were 40% and 80.7%, respectively. The early remission of the preoperative SSA-treated group (61.5%) was significantly higher than SSA-untreated group (31.2%) (p = 0.002). The early remission of the preoperative SSA-treated patients with macroadenomas (52.2%) was also significantly higher than the SSA-untreated group (23.5%) (p = 0.02). In the subgroup analysis; this difference was much more pronounced in invasive macroadenomas (p = 0.002). There were no differences between the groups in terms of late remission.The median annual cost of all acromegaly treatment modalities in study population was €3788.4; the cost for macroadenomas was significantly higher than for microadenomas (€4125.0 vs. €3226.5, respectively; p = 0.03). Preoperative SSA use in both microadenomas and macroadenomas didn't alter the cost of treatment. The increase in the duration of preoperative medical treatment had no effect on early or late remissions (p = 0.09; p = 0.8). CONCLUSIONS: Preoperative medical treatment had no effect on the costs of acromegaly treatment. There was a benefical effect of pre-operative SSA use on early remission in patients with macroadenomas; however, this effect didn't persist long term.

The Role of Different Molecular Markers in Papillary Thyroid Cancer Patients with Acromegaly.

PURPOSE: Prevalence of papillary thyroid cancer (PTC) is increased in patients with acromegaly. We aimed to determine the protein expression of BRAF, RAS, RET, insulin like growth factor 1(IGF1), Galectine 3, CD56 in patients with PTC related acromegaly and to compare the extensity of these expressions with normal PTC patients and benign thyroid nodules. METHODS: We studied 313 patients with acromegaly followed in Cerrahpasa Medical Faculty, Endocrinology and Metabolism Clinic between 1998 and 2015. On the basis of availability of pathological specimen of thyroid tissues, thyroid samples of 13 patients from 19 with acromegaly related PTC (APTC), 20 normal PTC and 20 patients with multinodulary goiter (MNG) were histopathologically evaluated. Protein expressions were determined via immunohistochemical staining in ex-vivo tumor samples and benign nodules. RESULTS: The incidence of PTC in acromegaly patients were 6% (n=19). Among patients with PTC, APTC and MNG, all the immunohistochemical protein expressions we have studied were higher in papillary thyroid cancer groups (p<0.01, for all). Between PTC group without acromegaly and APTC, galectin 3 and IGF1 expression was significantly higher in acromegalic patients (p<0.01 for all) while RAS was predominantly higher in PTC patients without acromegaly (p<0.01). CONCLUSION: BRAF expression was not higher in PTC with acromegaly patients compared to PTC patients without acromegaly. Galectine 3 and IGF1 were expressed more intensively in APTC. These positive protein expressions may have more influence on determining malign nodules among acromegaly patients.

Alterations in Body Uneasiness, Eating Attitudes, and Psychopathology Before and After Cross-Sex Hormonal Treatment in Patients with Female-to-Male Gender Dysphoria.

Body dissatisfaction plays an important role in the development of psychiatric problems such as eating disorders as well as gender dysphoria (GD). Cross-sex hormonal treatment (CHT) alleviates the dissatisfaction by making various changes in the body. We examined the alteration of body uneasiness, eating attitudes and behaviors, and psychological symptoms longitudinally in Turkish participants with female-to-male gender dysphoria (FtM GD) after CHT. Thirty-seven participants with FtM GD and 40 female controls were asked to complete the Body Uneasiness Test to explore different areas of body-related psychopathology, the Eating Attitudes Test to assess eating disturbances, and the Symptom Checklist-90 Revised to measure psychological state, both before CHT and after 6 months of CHT administration. The baseline mean body weight, BMI scores, body uneasiness scores, and general psychopathological symptoms of participants with FtM GD were significantly higher than female controls, whereas baseline eating attitudes and behaviors were not significantly different. Over time, FtM GD participants' mean body weight and BMI scores increased, body uneasiness and general psychopathological symptoms decreased, and eating attitudes and behaviors had not changed at 24th weeks following CHT administration compared to baseline. CHT may have a positive impact on body uneasiness and general psychopathological symptoms in participants with FtM GD. However, CHT does not have an impact on eating attitudes and behaviors.

Seasonal vitamin D status and endothelial function in healthcare workers.

BACKGROUND/AIM: Healthcare workers have long working hours indoors and are at risk of vitamin D deficiency. The aim of this study was to determine seasonal vitamin D status and its relationship with early atherosclerotic markers, endothelial function, and carotid intima-media thickness (CIMT) in healthcare workers of Marmara University Hospital, Istanbul. MATERIALS AND METHODS: One hundred and ninety healthy volunteer healthcare workers and 66 nonmedical volunteers of Marmara University Hospital were included in the study and 25-hydroxyvitamin D (25(OH)D), calcium, intact parathyroid hormone (PTH), endothelial function, and CIMT were measured twice during winter and summer seasons. RESULTS: Mean vitamin D levels were 20 ng/mL in summer and 16.4 ng/mL in winter. Out of the healthcare workers, 48.9% were vitamin D deficient at the end of summer and 71.5% in winter. Flow-mediated dilation (FMD) values were similar in both groups in both seasons; however, FMD values of 64 healthcare workers in summer were significantly higher than in winter. Serum 25(OH)D was positively associated with FMD (r = 0.1797, P = 0.0441) and negatively correlated with serum PTH (r = -0.2459, P < 0.0001). A negative correlation between FMD and serum PTH (r = -0.1757, P = 0.0473) was observed. CONCLUSION: Vitamin D levels of healthcare workers are very low, even in summer time. Healthcare workers must be considered a group at major risk for vitamin D deficiency.

Vitamin D level is associated with mortality predictors in ventilator-associated pneumonia caused by Acinetobacter baumannii.

INTRODUCTION: Vitamin D plays a role in host defense and is known to be associated with mortality in patients in the intensive care unit (ICU). We aimed to evaluate the relationships between vitamin D levels and predictors of mortality in patients with ventilator-associated pneumonia (VAP) caused by extensively drug-resistant Acinetobacter baumanii (XDR A. baumanii). METHODOLOGY: A retrospective single-center study was conducted in an 18-bed adult ICU of a teaching hospital, including all patients with VAP due to XDR A. baumanii. Levels of 25(OH)D, procalcitonin (PCT), C-reactive protein (CRP), n-terminal pro-BNP (NT-proBNP), as well as clinical scores (Sequential Organ Failure Assessment [SOFA], Acute Physiology And Chronic Health Evaluation [APACHE II], Clinical Pulmonary Infection Score [CPIS) were recorded. RESULTS: Forty-for patients were studied over six months. All patients had vitamin D deficiency. The 28-day mortality in patients with 25(OH)D levels ≤ 10 ng/mL was higher than in patients with 25(OH)D > 10ng/mL (p = 0.001). The fourth- and seventh-day SOFA scores (p= 0.04 and p= 0.001) and first- and fourth-day procalcitonin levels (p = 0.03 and p = 0.004) were higher in patients with 25(OH)D levels ≤ 10 ng/mL. The clinical scores (SOFA, CPIS, and CEPPIS) and biomarkers (NT-proBNP, PCT) were negatively correlated with 25(OH)D levels in all study groups. CONCLUSIONS: Severe vitamin D deficiency was associated with adverse outcome in VAP due to XDR A. baumanii. Vitamin D levels may be a prognostic predictor of VAP. It is also important to evaluate the effect of rapid vitamin D replacement on mortality.

General health status and intelligence scores of children of mothers with acromegaly do not differ from those of healthy mothers.

PURPOSE: To determine the physical status and intelligence scores of children of acromegalic mothers and to compare them with those of children from mothers without acromegaly. METHODS: Six women with acromegaly who became pregnant under follow-up between 2010 and 2014 and their 16 children (group A) were assessed and compared with 16 children of healthy women (group B) and 15 children of women with prolactinoma (group C). The physical examinations of children were performed by the department of pediatric endocrinology and intelligence quotient (IQ) testing was undertaken by adult and pediatric psychiatry departments, using appropriate scales for their ages. RESULTS: Six of the 16 children (girls/boys: 7/9) were born after the diagnosis of acromegaly. Five of the 6 pregnancies occured when the patients were taking somatostatin analogs, none continued taking the drugs during pregnancy. The mean IQ of groups A, B, and C were 106.4 ± 12.5, 105.3 ± 12.5, and 103.2 ± 16.1 respectively (p > 0.05). The mean ages, birth percentiles, recent weight and height standard deviation scores were similar between groups (p > 0.05). Two siblings from group A and 1 child from group B were large for gestational age at birth. At recent follow-up, two children from group A were found tall for their age and one from group C was short for his age and was placed under the care of pediatric endocrinology clinic. CONCLUSIONS: Pregnancies in acromegaly seems to be uneventful and the general health status and IQ scores of children from women with and without acromegaly were found similar.

Multidisciplinary Approach for Acromegaly: A Single Tertiary Center's Experience.

BACKGROUND: Acromegaly is a multisystemic disease that requires a multidisciplinary approach. The aim of this study was to determine early and late remissions of patients who underwent surgery at our center and to evaluate relations between pathologic and radiologic properties of adenoma and medical and radiosurgical treatments with remissions. METHODS: The medical records of 103 patients with acromegaly who underwent endoscopic endonasal transsphenoidal surgery in Cerrahpasa Medical Faculty, Istanbul University, between 2007 and 2014 were reviewed. Clinical, biochemical, radiologic, and pathologic properties were determined. RESULTS: The total median follow-up time was 38 months [interquartile range: 24-53.5 months]. Thirty-two percent of the adenomas were microadenomas and 68% were macroadenomas The early remission rate was 51.5% and late remission was 75.2%. The sellar floor invasion was significantly lower in patients with early and late remissions (P = 0.01 and P = 0.009, respectively). The initial growth hormone (GH; P < 0.001), first-day GH (P = 0.03), 3-month GH (P = 0.001), insulin-like growth factor-1 (P = 0.004), and 6-month insulin-like growth factor-1 (P = 0.02) levels were significantly greater in patients with sellar floor invasion. The late remission rates (P = 0.004) were greter and reoperation needs (P = 0.05) were lower in patients with Ki-67 <3% than in patients with ≥3%. Seventy (68.6%) patients needed medical therapy during follow-up. CONCLUSIONS: Late remission was achieved using a multidiciplinary approach in 75.2% of 103 patients with acromegaly, and young age, male sex, high Ki-67 and mitosis indices, and cavernous sinus and sellar-floor invasion had negative effects on clinical and biochemical control of the disease.

Locally produced estrogen through aromatization might enhance tissue expression of pituitary tumor transforming gene and fibroblast growth factor 2 in growth hormone-secreting adenomas.

Aromatase, a key enzyme in local estrogen synthesis, is expressed in different pituitary tumors including growth hormone (GH)-secreting adenomas. We aimed to evaluate aromatase, estrogen receptor α (ERα), estrogen receptor ß (ERß), pituitary tumor transforming gene (PTTG), and fibroblast growth factor 2 (FGF2) expressions in GH-secreting adenomas, and investigate their correlation with clinical, pathologic, and radiologic parameters. This cross-sectional study was conducted in a tertiary center in Turkey. Protein expressions were determined via immunohistochemical staining in ex vivo tumor samples of 62 patients with acromegaly and ten normal pituitary tissues. Concordantly increased aromatase, PTTG, and FGF2 expressions were detected in the tumor samples as compared with controls (p < 0.001 for all). None of the tumors expressed ERα while ERß was detected only in mixed somatotroph adenomas. Aromatase, ERß, PTTG expressions were not significantly different between patients with and without remission (p > 0.05 for all). FGF2 expression was significantly higher in patients without postoperative and late remission (p = 0.002 and p = 0.012, respectively), with sphenoid bone invasion, optic chiasm compression, and somatostatin analog resistance (p = 0.005, p = 0.033, and p = 0.013, respectively). Aromatase, PTTG and FGF2 expressions were positively correlated with each other (r = 0,311, p = 0.008 for aromatase, FGF2; r = 0.380, p = 0.001 for aromatase, PTTG; r = 0.400, p = 0.001 for FGF2, PTTG). PTTG-mediated FGF2 upregulation is associated with more aggressive tumor features in patients with acromegaly. Also, locally produced estrogen through aromatization might have a role in this phenomenon.

Vitamin D Levels in Takayasu's Arteritis and a Review of the Literature on Vasculitides.

OBJECTIVE: Takayasu's arteritis (TAK) is a chronic, large-vessel vasculitis. Vitamin D, as a steroidal hormone, has recently been shown to have immunoregulatory and immunosuppressive effects. Low vitamin D levels are demonstrated in various autoimmune disorders. The aim of this study is to investigate vitamin D levels in patients with TAK. A comprehensive review of vitamin D levels in systemic vasculitides (SVs) is also performed. METHODS: The study included 36 patients with TAK, 28 patients with Behçet's disease (BD) as disease control and 30 sex-matched healthy controls. Plasma 25-hydroxy vitamin D (25(OH) vit D) levels were measured with high-performance liquid chromatography. "Deficiency" was defined as 25(OH) vit D levels below 25 nmol/l and "insufficiency" as below 50 nmol/l. RESULTS: Plasma 25(OH) vit D levels were significantly lower in TAK patients (16.93 ± 10.62 nmol/l) than healthy controls (64.63 ± 21.82 nmol/l). Vitamin D level in BD patients (38.8 ± 20.9 nmol/l) is lower than healthy controls but higher than TAK patients. The frequency of vitamin D deficiency was 83.3% in patients with TAK compared to 3.3% in healthy controls. Plasma 25(OH) vit D levels were same between clinically active and inactive patients. In literature review, very few studies were found to investigate vitamin D in SVs. CONCLUSION: We observed a high prevalence of vitamin D deficiency in patients with TAK. As various immune effects of vitamin D on mononuclear cells and arterial endothelium is shown, vitamin D deficiency can be a predisposing factor for immune activation in SV. We therefore suggest monitorization and replacement of vitamin D status in all TAK and other SV patients.

Life-Threatening Hypercalcemia due to Graves' Disease and Concomitant Adrenal Failure: A Case Report and Review of the Literature.

A 47-year-old woman presented with the complaints of nausea, vomiting, and weight loss. She had a history of bilateral surrenalectomy due to Cushing's syndrome. On examination she had tachycardia and orthostatic hypotension. Laboratory examinations revealed hypercalcemia and suppressed parathyroid hormone levels. She also had thyrotoxicosis due to Graves' disease. The investigations to rule out a malignancy were negative. With steroid, zoledronic acid, and antithyroid drug treatment her symptoms were resolved and calcium level was normalized. This case highlights the importance of recognizing thyrotoxicosis and concomitant adrenal failure as a possible cause of severe hypercalcemia.