The relations of circulating agouti-related peptide and leptin with altered sleep architecture in patients with active Cushing's disease: a pilot study.

AIM: To evaluate sleep architecture of patients with Cushing's disease (CD) and to explore whether agouti-related peptide (AgRP) and/or leptin play a permissive role in sleep alterations in patients with active CD. METHODS: We performed polysomnography on 26 patients with active CD and age 26 age- and sex-matched control subjects. Blood samples were obtained from all participants for the analyzes of AgRP and leptin. The laboratory and sleep-related parameters were compared. RESULTS: The groups were similar in age, gender, and body mass index. The CD group had reduced sleep efficiency (71.6 ± 12.1% vs. 78.8 ± 12.6%, p = 0.042) and increased wake after sleep onset (WASO%) (24.7 ± 13.1% vs. 17.4 ± 11.6%, p = 0.040) as compared to control group. Seventeen patients with CD (65.4%) and 18 control subjects (69.2%) had obstructive sleep apnea. Serum AgRP (13.2 ± 7.4 pg/ml vs. 9 ± 3.1, p = 0.029), leptin (59.5 mcg/l, [IQR] 32.6-94.6 vs. 25.3 mcg/l, [IQR] 12.9-57.5, p = 0.007) were higher in CD group. AgRP and leptin correlated negatively with total sleep time, sleep efficiency, stage N2 sleep (%), and positively with WASO%. In multiple regression analyses, serum cortisol (ß = - 0.359, p = 0.042) and AgRP (ß = - 0.481, p = 0.01) were significant predictor of sleep efficiency. AgRP was also significant predictor of WASO% (ß = 0.452 and p < 0.05). CONCLUSIONS: Active CD carries an increased risk of impaired sleep efficiency and continuity which may worsen health-related quality of life. Elevated circulating AgRP and, to a lesser extent, leptin may be associated with decreased sleep efficiency and continuity in patients with CD. Patients with CD who have subjective sleep symptoms should be screened with polysomnography.

Improvement in clinical features of hypercortisolism during osilodrostat treatment: findings from the Phase III LINC 3 trial in Cushing's disease.

PURPOSE: Cushing's disease is associated with substantial morbidity and impaired quality of life (QoL) resulting from excess cortisol exposure. The current study explored improvements in clinical signs and additional specific manifestations of hypercortisolism during osilodrostat (potent oral 11ß-hydroxylase inhibitor) therapy by degree of control of mean urinary free cortisol (mUFC). METHODS: LINC 3 (NCT02180217) was a prospective, open-label, 48-week study of osilodrostat (starting dose: 2 mg bid; maximum: 30 mg bid) that enrolled 137 adults with Cushing's disease and mUFC > 1.5 times the upper limit of normal (ULN). mUFC (normal range 11‒138 nmol/24 h), cardiometabolic parameters (blood pressure, weight, waist circumference, body mass index, total cholesterol, fasting plasma glucose, glycated haemoglobin), physical manifestations of hypercortisolism (facial rubor, striae, fat distribution, bruising, hirsutism [females], muscle atrophy) and QoL were evaluated. mUFC was defined as controlled if ≤ ULN, partially controlled if > ULN but ≥ 50% reduction from baseline, and uncontrolled if > ULN and < 50% reduction from baseline. Concomitant medications were permitted throughout the study. RESULTS: At weeks 24 and 48, respectively, mUFC was controlled in 93 (67.9%) and 91 (66.4%) patients, partially controlled in 20 (14.6%) and 13 (9.5%), and uncontrolled in 24 (17.5%) and 33 (24.1%). Overall, mean improvements from baseline in cardiometabolic at week 24 were greater in patients with controlled or partially controlled versus uncontrolled mUFC; at week 48, improvements occurred irrespective of mUFC control. Generally, physical manifestations and QoL progressively improved from baseline irrespective of mUFC control. CONCLUSIONS: Improvements in clinical signs and additional specific manifestations of hypercortisolism associated with Cushing's disease occurred alongside decreases in mUFC. Trial registration NCT02180217 (first posted July 2014).

The relationship between temporal muscle thickness and disease activity in Cushing's disease.

OBJECTIVE: This study aimed to investigate the relationship between hypercortisolism and temporal muscle thickness (TMT) in Cushing's disease (CD). METHODS: A retrospective review of medical records was conducted for patients with CD who presented to our clinic between 2012 and 2022. Biochemical data and TMT measurements from sella imaging were evaluated during diagnosis and the first postoperative year. RESULTS: A total of 44 patients were included in the study, with an average age of 43.9 years, of which 38 were female. The mean TMT at the time of diagnosis was 19.07 ± 1.71 mm, with no significant difference between males and females (p = 0.097), and no correlation between the TMT and age at diagnosis (p = 0.497). There was an inverse relationship between TMT and serum cortisol levels, 24-h UFC, and midnight salivary cortisol at the time of diagnosis of CD (p < 0.05, for all). One year after surgery, TMT significantly increased in all patients compared to baseline (p < 0.001). Furthermore, patients who achieved postoperative remission had significantly higher TMT values compared to those who did not achieve remission (p = 0.043). Among the patients who achieved remission, those who achieved remission through surgery had significantly higher TMT compared to those who could not reach remission with surgery and patients who started medical treatment and achieved biochemical remission (p = 0.01). Patients with severe myopathy and sarcopenia had significantly lower TMT values than the others (p < 0.001). CONCLUSION: Temporal muscle thickness was found to be associated with disease activity and disease control in Cushing's disease.

Evaluation of sex hormone profile and semen parameters in acromegalic male patients.

OBJECTIVE: To investigate the changes in semen quality and bioavailable testosterone concentrations in acromegalic male patients according to their disease activity and compare them with patients with non-functional pituitary adenoma (NFA) and healthy controls (HC). METHODS: Twenty-four acromegalic patients with active disease, 22 acromegalic patients in remission, 10 HCs, and 10 patients with NFA were included. RESULTS: Total and calculated bioavailable testosterone concentrations were lower in patients with pituitary disease. Patients with acromegaly had more severely impaired total testosterone levels and semen parameters in comparison to HCs and patients with NFA. The degree of impairment was more prominent in acromegalic patients with active disease than acromegalic patients in remission. Acromegalic patients in remission had residual impairments in both semen quality and testosterone concentrations. Patients with NFA had the lowest concentrations of calculated bioavailable testosterone, followed by acromegalic patients with active disease and acromegalic patients in remission. Increasing growth hormone (GH) levels were found to be associated with both more severely impaired semen quality and androgen concentrations. CONCLUSION: Growth hormone hypersecretion can disturb reproductive biology and thereof semen quality. The reduction in semen quality and androgen levels may not fully recover upon disease control. Clinicians should be aware of the increased risk of impaired semen parameters and reduced total/bioavailable levels in acromegalic patients, especially in the setting of active disease.

Technological and textural properties of spent chicken breast, drumstick and thigh meats as affected by marinating with pineapple fruit juice.

1. This study was conducted to determine the effects of pineapple fruit juice at different marination times (0, 40, 80, 120 and 160 min) on pH, water holding capacity (WHC), cooking loss (CL) and colour (L*, a*, b*, hue angle and chroma) properties of breast, drumstick and thigh meats from spent hens. Textural properties (razor shear force and shear energy) and sensory analyses of the samples were tested. 2. With increasing marination time, there was a decrease in pH and WHC values, and an increase in CL values. However, marination treatment with pineapple fruit juice significantly affected the textural measurement of all the meat muscles compared with the control group. 3. Razor shear force and shear energy were lower when marination was performed for 160 min. Colour analyses showed that marination for 80 min resulted in significantly increased L*, a* and b* values. The samples marinated for longer times were most preferable, according to the tenderness scores assigned by the panellists.

RELIABILITY OF THE CORTICOTROPIN RELEASING HORMONE STIMULATION TEST FOR DIFFERENTIATING BETWEEN ACTH DEPENDENT AND INDEPENDENT CUSHING SYNDROME.

CONTEXT: It is a challenge to determine the origin of Cushing syndrome (CS), especially in patients with low-normal adrenocorticotropic hormone (ACTH) concentrations. OBJECTIVE: To evaluate the reliability of the corticotropin-releasing hormone (CRH) stimulation test in patients with CS whose origin of disease was not clearly identified using ACTH values, the high-dose dexamethasone suppression test (HDDST), and imaging in a single tertiary referral center. DESIGN AND METHODS: Twenty-one patients with CS who were admitted to the endocrinology-metabolism clinic between 2004 and 2016 whose ACTH concentrations were 5-20 pg/mL and needed CRH stimulation test were retrospectively assessed. RESULTS: Nine out of 21 patients were diagnosed as having Cushing's disease (CD) and 12/21 had adrenal CS. The CRH stimulation test had a sensitivity and specificity of 100% and 8%, and positive and negative predictive values of 100% and 45% according to the current diagnostic criteria, respectively. An increase in ACTH ≥115% at 15 minutes and cortisol ≥86% at 60 minutes after CRH were associated with the highest likelihood ratio. The sensitivity and specificity of ACTH was 67% and 83% (AUC=0.75±0.12, 95% CI: [0.5-0.9]; p=0.03), and for cortisol it was 75% and 78% (AUC=0.71±0.15, 95% CI: [0.5-0.9]; p=0.03). Cortisol suppression of more than 64% from basal level in the HDDST suggested CD with the highest likelihood ratio. When these cut-off values were used together, both tests were negative in the patients with CD. CONCLUSION: The CRH stimulation test has low specificity to localize CS in patients with ACTH concentrations of 5-20 pg/mL according to the current diagnostic criteria. Different diagnostic criteria may be used in the CRH stimulation test and also in the HDDST in this group of patients.

How does pregnancy affect the patients with pituitary adenomas: a study on 113 pregnancies from Turkey.

OBJECTIVE: Data regarding pregnancies in relation to pituitary tumors are limited. The effects of pregnancy on pituitary adenomas and the effects of adenoma itself (hormonal activity, mass effects and pituitary insufficiency) and/or treatment on the ongoing gestation and developing fetus were evaluated. METHODS: The study was a retrospective study. A questionnaire involving questions regarding medical history before index gestation, history of related pregnancy, result of index gestation and postpartum follow-up of the patients was filled by the investigator in one of the eight Referral Endocrinology Centers from Turkey. RESULTS: One hundred and thirteen (83 prolactinoma, 21 acromegaly, 8 NFPA and 1 plurihormonal pituitary adenoma) pregnancies of 87 (60 prolactinoma, 19 acromegaly, 7 NFPA and 1 plurihormonal pituitary adenoma) patients were reviewed. The clinically important pregnancy-related tumor growth of pituitary adenomas was found to be low in previously treated adenomas. Prolactinomas were more likely to increase in size during pregnancy especially if effective prior treatment was lacking. The risk of hypopituitarism is also minimal due to pituitary adenomas during pregnancy. The results of pregnancies did not differ in patients who were on medical treatment or not for prolactinomas and acromegaly during gestation. Neural tube defect and microcephaly associated with maternal cabergoline use; Down syndrome and corpus callosum agenesis associated with maternal bromocriptine use; unilateral congenital cataract, craniosynostosis and microcephaly associated with maternal acromegaly were detected for the first time. CONCLUSION: Medical treatment can be safely done stopped in patients with prolactinoma and acromegaly when pregnancy is confirmed and reinstituted when necessary. Prospective studies may help to determine the effects of medical treatment during gestation on the mother and fetus.

Daily life reflections of acromegaly guidelines.

PURPOSE: To determine the differences in acromegaly diagnosis, treatment, and follow-up among Turkish endocrinologists, and to investigate how the published guidelines are applied in clinical practice. METHODS: The questionnaire was formatted as an electronic survey, conducted between November and December 2015, and sent weekly for 6 weeks via e-mail to 528 endocrinologists in Turkey. RESULTS: The questionnaire was answered by 37.4 % of endocrinologists. Insulin-like growth factor-1 and nadir growth hormone level after 75 g oral glucose tolerance test (nadir GH-OGTT) were the most commonly preferred methods for the initial diagnosis. A total of 49.5 % of the participants reported using preoperative medical therapy (MT) either routinely or on a case-to-case basis. Somatostatin analogs were the most commonly used drugs, both in pre- and postoperative MT. Disease activity following surgery was assessed in the 3rd postoperative month using IGF-1 levels. Similarly, IGF-1 monitoring was preferred in the follow-up period. Monitoring nadir GH-OGTT levels was the most commonly used method in the assessment of discordant test results. The dose titration was done at month 3 after the start of MT. Resistance to SRLs was considered after using the maximal dose for at least 6 months. Pegvisomant was generally used in second- and third-line therapy. Similarly, cabergoline was not preferred in monotherapy by the majority of participants. Radiotherapy was considered in patients with incomplete response to surgery and medical treatments. CONCLUSIONS: Although there were subtle differences, clinical practice guidelines were usually followed among Turkish endocrinologists.

LONGER CECUM INSERTION TIME AND MORE INADEQUATE COLONIC PREPARATION IN PATIENTS WITH ACROMEGALY: IS A DIFFERENT COLONOSCOPY PREPARATION NEEDED?

PURPOSE: To investigate whether there is a difference between acromegalic and non-acromegalic cases in terms of bowel preparation and colonoscopic intervention. METHODS: Patients with controlled and uncontrolled acromegaly and as a control group (CG) patients without acromegaly between January 2010 and March 2014 were included. Groups were compared regarding adequacy of bowel preparation, cecal insertion time (CIT) and colonoscopy results. RESULTS: Fifty-nine patients with acromegaly (controlled n=30, uncontrolled n=29) and 73 age and gender matched volunteers without acromegaly were evaluated. CIT in cases with controlled, uncontrolled acromegaly cases and in CG was 5.33 [4.00-6.00], 7.00 [4.91-11.31], and 3.10 [2.35-4.65] minutes, respectively (p<0.001). Cases in CG had shorter CIT compared to controlled and uncontrolled acromegaly cases ( p=0.014 and p<0.001, respectively). There was no significant difference regarding CIT between controlled and uncontrolled acromegaly cases (p=0.247). Six (20%) of controlled acromegaly patients, 10 (35%) of uncontrolled acromegaly patients and three (4%) of CG had inadequate bowel cleansing (p<0.001). Although statistically insignificant, cases with inadequate bowel cleansing had tendency towards having prolonged CIT in comparison to cases with adequate bowel cleansing (6.00 [3.87-9.00] and 4.16 [2.95-5.70] minutes, respectively, p=0.07). CONCLUSION: Inadequate bowel cleansing is one of the main problems encountered during colonoscopic investigation/surveillance in acromegalic patients. Therefore, a different protocol for colonoscopy preparation may be needed for these cases.

Familial partial lipodystrophy linked to a novel peroxisome proliferator activator receptor -γ (PPARG) mutation, H449L: a comparison of people with this mutation and those with classic codon 482 Lamin A/C (LMNA) mutations.

AIMS: To describe the phenotype associated with a novel heterozygous missense PPARG mutation discovered in a Turkish family and to compare the fat distribution and metabolic characteristics of subjects with the peroxisome proliferator activator receptor -γ (PPARG) mutation with those of a cluster of patients with familial partial lipodystrophy with classic codon 482 Lamin A/C (LMNA) mutations. METHODS: The study involved four subjects with familial partial lipodystrophy who had a novel PPARG mutation (H449L) and six subjects with classic codon 482 LMNA mutations (R482W). RESULTS: Compared with subjects with LMNA R482W mutation, fat loss was generally less prominent in subjects with the PPARG H449L mutation. Partial fat loss was limited to the extremities, whilst truncal fat mass was preserved. The PPARG H449L mutation was associated with insulin resistance, hypertriglyceridaemia and non-alcoholic fatty liver disease in all affected subjects, but the severity was variable. Three out of four mutation carriers had overt diabetes or impaired glucose tolerance. Pioglitazone therapy in these three individuals resulted in a modest improvement in their metabolic control, and regular menstrual cycles in the two female subjects. CONCLUSIONS: We suggest that relatively modest fat loss in patients with PPARG mutations may render the recognition of the syndrome more difficult in routine clinical practice. The PPARG H449L mutation is associated with insulin resistance and metabolic complications, but their severity is variable among the affected subjects.

The problem of unrecognized acromegaly: surgeries patients undergo prior to diagnosis of acromegaly.

PURPOSE: To reveal the variety of symptoms experienced by patients before acromegaly diagnosis and to emphasize unneeded surgeries that patients undergo related to acromegaly prior to diagnosis of the disease. METHODS: In total, 490 consecutive adult patients with acromegaly who were treated at our institution between 1998 and 2014 were included in this cross-sectional study, of which 313 could be contacted. Participants were questioned about their complaints at initial consultation and at the time of diagnosis, the first medical professional who they consulted, interval between onset and diagnosis, and surgeries they had undergone. RESULTS: This study included 313 participants, of whom 181 were women. The mean age was 48.8 ± 12.0 years. Patients most frequently presented with acral growth of hands and feet (32.6%) and headache (26.2%). Internists were the medical specialists who were most frequently first consulted (29.4%) then neurosurgeons (11.8%). Acromegaly was generally diagnosed by endocrinologists (55%), followed by neurosurgeons (23%). The median elapsed period prior to diagnosis was 24 months, interquartile range 6.0-48.0 months. Some 45.7% had undergone surgery; 35.2% were related to acromegaly symptoms: head and throat surgery (12.8%), nose surgery (9.3%), thyroidectomy (6.4%), carpal tunnel surgery (4.8%). The delay period for patients who had an operation prior to acromegaly diagnosis was significantly longer than for those who had no operations (p < 0.001). CONCLUSIONS: Acromegaly patients mostly present to internal medicine professionals. Surgeries related to acromegaly complications and symptoms before diagnosis cause a long delay period before diagnosis. Medical staff must be more aware of the clinical aspects of acromegaly.

Quality of life in female patients with acromegaly.

AIM: The aim of the study was to assess the quality of life and depression status in female patients with acromegaly. PATIENTS AND METHODS: Fifty-seven female patients with acromegaly (21 inactive, 36 active) who were being followed-up at the Cerrahpasa Medical School, Endocrinology and Metabolism out-patient clinic, were included in the study. Depression status and quality of life of the patients were evaluated according to disease activity using the Beck Depression Inventory (BDI) and the Acromegaly Quality of Life (AcroQoL) Questionnaire. Prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-SO4), 17α-hydroxyprogesterone, androstenedione, free thyroxin (FT4), thyrotropin (TSH), cortisol, GH and IGF-I were studied in the groups. RESULTS: The AcroQoL total score in female patients with controlled acromegaly and uncontrolled acromegaly were 45.5 [Interquartile range (IQR)= 32.9-57.4], 47.7 [(IQR)= 38.6-63.3], respectively (p=0.53). There was no difference in BDI scores in acromegalic patients according to disease activity (p=0.41). In the correlation analysis, a strong negative correlation was found between AcroQoL total score and BDI score (r=-0.72, p<0.0001), OSAS (r=-0.32, p=0.01). CONCLUSION: This study showed that QoL was impaired in female patients with acromegaly even if they were in remission. Depressive mood and obstructive sleep apnea syndrome (OSAS) could affect QoL in female patients with acromegaly.

Procalcitonin can be used as a marker of premature atherosclerosis in acromegaly.

The objective of the study was to evaluate arterial morphologic changes of early atherosclerosis and changes in procalcitonin (PCT) levels in patients with acromegaly according to disease activity. Thirty-three active and 20 inactive acromegaly patients followed at Endocrinology-Metabolism out-patient clinic of Cerrahpasa Medical Faculty between 2004 and 2008 were included in the study. Twenty gender and age matched healthy subjects were included as the control group. Intima-media thickness (IMT) of the carotid arteries was measured by ultrasonography. Blood was drawn for biochemical tests and the serum concentrations of C-reactive protein (CRP) and PCT. Intergroup analysis revealed no significant differences between Growth hormone (GH), insulin like growth factor-1 (IGF-1), and IMT (P = 0.42, P = 0.47 respectively). No significant differences were found in the fibrinogen, CRP and PCT levels of the acromegaly patients and the subjects in the control group (P = 0.57, P = 0.84, P = 0.68 respectively). In the patients with IMT ≥ 1 mm, PCT (0.4 [IQR: 0.4-0.55]) levels were significantly different from the patients without atherosclerosis (0.06 [IQR: 0.05-0.12], P < 0.001). The correlation between IMT and PCT (P = 0.001, r = 0.47) was more significant than the correlation between IMT and CRP (P = 0.01, r = 0.28). There was a positive correlation between IMT and atherosclerotic risk factors such as age (P = 0.01, r = 0.27) and body mass index (BMI; P = 0.005, r = 0.32). Our results showed that PCT increases before CRP and it can be useful for the assessment of premature atherosclerosis in acromegaly as well.

Medical therapy of acromegaly in Turkey.

Acromegaly is associated with multiple co-morbidities and risk of premature mortality. Mortality rate of acromegalic patients is similar to that of the general population when normal GH levels are achieved. Surgery is the mainstay of acromegaly but when surgery fails to achieve disease control, or when surgery is impossible or contraindicated, patients are offered medical therapy and/or radiotherapy. Current medical therapy modalities were revised in this short review.

Symptoms of depression and diabetes-specific emotional distress are associated with a negative appraisal of insulin therapy in insulin-naïve patients with Type 2 diabetes mellitus. A study from the European Depression in Diabetes [EDID] Research Consortium.

AIMS: A meta-analysis concluded that depression is associated with poor glycaemic control in Type 2 diabetes (DM2). In DM2 patients with deteriorating glycaemic control, the initiation of insulin therapy is often postponed. The aim of the present study was to determine whether symptoms of depression and diabetes-specific emotional distress are associated with a more negative appraisal of insulin therapy. METHODS: We collected cross-sectional data in two outpatient university clinics in Istanbul, Turkey. The study sample consisted of 154 insulin-naïve patients with DM2. A self-report questionnaire was used to obtain demographic and clinical data. Main instruments were the Centre for Epidemiologic Studies Depression Scale, (CES-D), the Problem Areas In Diabetes scale (PAID) and the Insulin Treatment Appraisal Scale (ITAS). RESULTS: Analysis of variance revealed that patients with a higher depression score rated insulin therapy significantly more negative then patients with lower depression scores. Moreover, 47% of patients with a high depression score had a negative appraisal of insulin therapy on 7 or more of the 20 ITAS-items, compared to 25 to 29% of those with low-moderate depression scores. Multiple regression analyses showed that a negative appraisal of insulin therapy was significantly associated with higher depression and diabetes-distress scores and low education, but not with sex, age or duration of diabetes. CONCLUSIONS: Our results suggest that in insulin-naïve Type 2 diabetes patients, higher levels of depression and diabetes-distress tend to be associated with more negative beliefs about insulin. Whether these negative attitudes translate into postponing initiation of insulin therapy needs to be tested in longitudinal research.

Behçet's syndrome is not associated with vitiligo.

OBJECTIVE: Behçet's syndrome (BS) has many features that are different from autoimmune diseases, including a lack of association with Sjögren's syndrome. Vitiligo is frequently associated with various autoimmune disorders such as autoimmune thyroiditis, pernicious anemia and Addison's disease. Our informal observation was that vitiligo is also uncommon among BS patients. With this controlled and masked study we formally surveyed the presence of vitiligo among BS patients and suitable controls. METHODS: Patients with Behçet's syndrome, Graves' disease, and Hashimoto's thyroiditis being followed in the rheumatology and endocrinology departments of a university hospital and healthy controls were examined. Subjects with hypopigmented lesions were re-examined by a dermatologist in a masked protocol. Wood's lamp was used to confirm the diagnosis of vitiligo in suspected lesions. RESULTS: 253 consecutive BS patients, 34 Graves' disease patients, 32 Hashimoto's thyroiditis patients, and 439 healthy controls were surveyed. None of the BS patients had vitiligo, while 6/34 (17.6%) of Graves' disease patients, 6/32 (18.7%) of Hashimoto's thyroiditis patients, and 4/439 (0.9%) of healthy controls had vitiligo. All the subjects with vitiligo, except for one patient with associated Graves' disease, were women. CONCLUSION: In contrast to two autoimmune diseases, Hashimoto's thyroiditis and Graves' disease, the frequency of vitiligo was not increased among patients with BS. This constitutes further evidence that traditional autoimmune mechanisms may not be operative in BS.

Preoperative Somatostatin Analogue Treatment Might Trigger Apoptosis and Autophagy in Tumor Tissues of Patients with Acromegaly: A Pilot Study.

OBJECTIVE: To evaluate the effect of preoperative somatostatin analog (SRL) treatment on proteins associated with apoptosis and autophagy in patients with acromegaly and to determine factors correlating with these parameters. METHODS: Ex-vivo tumor samples of 11 SRL-treated and 9 SRL-untreated patients were retrospectively included in the study. Apoptotic and autophagic proteins were determined via immunohistochemical staining and apoptosis was evaluated via in situ DNA end labeling (TUNEL). RESULTS: TUNEL, caspase-3, and ATG-5 immunopositivity was significantly increased (p<0.01, p=0.01, p=0.01, respectively), survivin and beclin-1 immunopositivity was significantly decreased (p=0.03, p=0.02, respectively) in SRL-treated patients as compared with SRL-untreated controls. Ki-67 index was decreased significantly in the SRL-treated group (p=0.01). Significant positive correlations were detected between TUNEL and caspase-3 immunopositivity (r=0.577, p<0.01), and between survivin and beclin-1 immunopositivity (r=0.503, p=0.03). Age at diagnosis, preoperative GH, IGF-1 levels, tumor size, and invasion status were not found to affect TUNEL positivity nor did they correlate with caspase-3, survivin, beclin-1, ATG-5 immunopositivity (p>0.05 for all). Preoperative SRL treatment was the only factor that had a significant effect on TUNEL positivity (adjusted R2=0.39, p=0.02). Preoperative treatment duration was positively correlated with TUNEL and caspase-3 immunopositivity (r=0.526, p=0.02; r=0.475, p=0.04, respectively) and negatively correlated with survivin immunopositivity (r=-0.533, p=0.01). CONCLUSIONS: Somatostatin analog treatment might induce apoptosis, increase autophagy, and decrease cell proliferation in GH-secreting adenomas. Also, proteins related to cross-talk between autophagy and apoptosis are upregulated after SRL treatment.

An intronless homolog of human proto-oncogene hPTTG is expressed in pituitary tumors: evidence for hPTTG family.

A novel proto-oncogene, PTTG (Pituitary Tumor Transforming Gene), was isolated in our laboratory by virtue of its increased expression in rat pituitary tumor cell lines. Cells which overexpress human or rat PTTG form tumors in athymic mice. hPTTG is highly expressed in cancer cell lines, pituitary adenomas and in normal testis, suggesting that hPTTG protein has different tissue-specific interactions in normal cells and in cancer. Alternatively, different hPTTG gene family members may be functional in normal development and in tumorigenesis. While mapping the chromosomal location of hPTTG to 5q33, we discovered a second gene, hPTTG2, which is intronless and maps to chromosome 4p12. Using gene-specific oligonucleotide hybridization in a PCR-ELISA assay, we determined that hPTTG2 is expressed in both normal and tumorous pituitary. However, high levels of hPTTG mRNA in cancer cell lines are due to increased expression of hPTTG1. Thus, this family of proto-oncogenes appears to differentially participate in tumor-specific pathogenesis.

Plasmapheresis: an effective therapy for refractory hyperthyroidism in the elderly.

Hyperthyroidism in the elderly often presents diagnostic challenges. Elderly patients rarely present with classical signs and symptoms of hyperthyroidism. More commonly, their presentation is ayical which leads to a delay in making a diagnosis. Such delays can sometimes decrease the functional capacity of the affected patient and reduce their chance for recovery. Herein we report a 66-year-old woman whose diagnosis of hyperthyroidism was delayed. Standard therapies were ineffective. Plasmapheresis was performed to control the manifestations of the hyperthyroid state, resulting in improvement in the patient's condition.

Sexual dysfunction and depression in premenopausal women with mucocutaneous Behçet's disease.

AIM: The aim of this study was to investigate depression and sexual dysfunction in female patients with mucocutaneous Behçet's disease (BD). METHODS: Twenty-five consecutive, sexually active premenopausal female patients with mucocutaneous BD (mean age: 34.76 ± 4.61 SD years) followed at a rheumatology outpatient clinic were enrolled into the study. The control group consisted of 27 age-matched (mean age: 37.0 ± 4.6 SD years), sexually active, healthy volunteers. The Female Sexual Function Index (FSFI) and Beck Depression Inventory (BDI) were used for sexual and psychiatric assessment. RESULTS: Depression was found in four of 27 (14.8%) in the control group and eight of 25 (32%) in the BD group (P = 0.01). The median total FSFI score for patients with BD was 21.85 (interquartile range [IQR]: 18.25-27.9) and for healthy controls, 27 (IQR 21.5-29.3; P = 0.03). Female sexual dysfunction was diagnosed in 14 of 25 (56%) in the BD group and in 11 of 27 (41%) in the control group (P = 0.27). The pain domain was significantly higher in the BD group at 5.6 (4.4-6.0) than in the control group at 4.4 (3.2-5.5; P = 0.03). None of the other domains (desire, arousal, lubrication, orgasm and satisfaction) of the BD and control groups were different. There were no statistically significant differences between the FSFI, BDI scores and presence of genital ulceration in the BD patients. CONCLUSION: Depression and FSD were more common in the patients with BD than in the healthy subjects. This might have been a result of the depressive effect of chronic disease as well as BD and low androgen levels.