The Importance of DHEA-S Levels in Cushing's Syndrome; Is There a Cut-off Value in the Differential Diagnosis?

The purpose of this study was to determine possible cut-off levels of basal DHEA-S percentile rank in the differential diagnosis of patients with Cushing's syndrome (CS) with ACTH levels in the gray zone and normal DHEA-S levels. In this retrospective study including 623 pathologically confirmed CS, the DHEA-S percentile rank was calculated in 389 patients with DHEA-S levels within reference interval. The patients were classified as group 1 (n=265 Cushing's disease; CD), group 2 (n=104 adrenal CS) and group 3 (n=20 ectopic ACTH syndrome).ROC-curve analyses were used to calculate the optimal cut-off level of DHEA-S percentile rank in the reference interval in the differential diagnosis of CS, and the effectiveness of this cut-off level in the identification of the accurate etiology of CS was assessed in patients who were in gray zone according to their ACTH levels. The DHEA-S percentile rank in the reference interval were significantly lower in group 2 compared to the other two groups (p<0.001), while group 1 and group 3 had similar levels. The optimal cut-off level of DHEA-S percentile rank in the reference interval providing differential diagnosis between group 1 and group 2 was calculated as 19.5th percentile (80.8% sensitivity, 81.5% specificity) and the level demonstrated the accurate etiology in 100% of CD and 76% of adrenal CS patients who were in the gray zone. This study showed that the cut-off value of DHEA-S level less than 20% of the reference interval could be used for differential diagnosis of CD and adrenal CS with high sensitivity and specificity, and it should be taken into the initial evaluation.

Thyroid involvement in ankylosing spondylitis and relationship of thyroid dysfunction with anti-TNF α treatment.

Association between rheumatological and autoimmune thyroid disorders has been demonstrated by many studies. However, a few data exist indicating the association between thyroid disorders and ankylosing spondylitis (AS). In this study, the frequency of thyroid disorders in patients with AS and the impact of anti-TNF α therapy on this were investigated. Data of 108 patients (female/male (F/M) 27/81) were analyzed. Data on free T3, free T4, thyroid-stimulating hormone, anti-thyroid peroxidase antibodies (TPO), anti-thyroglobulin antibodies, and thyroid ultrasound were assessed retrospectively. 44 (F/M 15/29) patients were receiving anti-TNF α, while 64 (F/M 12/52) were receiving other drugs [(sulfasalazine, anti-inflammatory drug (NSAIDs)]. Among those not receiving anti-TNF α therapy, TPO level was high in 23 patients (mean TPO value 86.69 ± 65.28 U/ml), while it was high only in nine receiving anti-TNF α (mean TPO 36.61 ± 14.02 U/ml) (p < 0.05). Investigating the data regarding gender in both populations, autoimmune thyroid disease frequency was found to be lower in the patient group receiving anti-TNF α treatment. Subclinical hyperthyroidism was discovered in three patients (one female two male), and subclinical hypothyroidism in two (two male). Thyroid nodule was detected in 29 patients. It was concluded that the frequency of thyroid autoimmune disease was higher in our study than that reported in the literature, and the frequency of thyroid disorder in patients with AS was lower in those receiving anti-TNF α compared to those not. This may arise from the role of TNF α on pathogenesis of thyroid disorders.

Dopamine Agonist-Induced Impulse Control Disorders in Patients With Prolactinoma: A Cross-Sectional Multicenter Study.

CONTEXT: Dopamine agonist (DA)-induced impulse control disorder (ICD) in patients with prolactinomas is not sufficiently known. OBJECTIVE: To evaluate the prevalence of DA-induced ICDs and possible risk factors related to these disorders in patients with prolactinoma. DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional multicenter study involving 308 patients with prolactinoma followed up in tertiary referral centers who received at least three months of DA therapy. DA-induced ICDs (pathological gambling, hypersexuality, compulsive shopping, and compulsive eating) and impulsivity were assessed using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson Disease and the Barratt Impulsiveness Scale-11, respectively. Patients were evaluated in terms of parameters related to ICD development. RESULTS: Any ICD prevalence was 17% (n = 51). Hypersexuality was most common (6.5%). Although any ICD and hypersexuality were more common in male patients (P = 0.009, P < 0.001, respectively), compulsive eating was more common in female patients (P = 0.046). Current smoking, alcohol use, and gambling history were more frequent (P = 0.033, P = 0.002, P = 0.008, respectively) in patients with any ICD. In Barratt Impulsiveness Scale-11 total, attentional, motor, and nonplanning scores were higher in patients with any ICD (P < 0.001). Current smoking and alcohol use were more frequent (P = 0.007, P = 0.003, respectively) and percentage increase of testosterone levels at last visit was higher (P = 0.021) in male patients with prolactinomas with hypersexuality. CONCLUSION: Any ICD may be seen in one of six patients with prolactinoma who are receiving DA therapy. Endocrinology specialists should be aware of this side effect, particularly in male patients with a history of gambling, smoking, or alcohol use.

Impact of Obesity on the Metabolic Control of Type 2 Diabetes: Results of the Turkish Nationwide Survey of Glycemic and Other Metabolic Parameters of Patients with Diabetes Mellitus (TEMD Obesity Study).

BACKGROUND: Obesity is the main obstacle for metabolic control in patients with type 2 diabetes. Turkey has the highest prevalence of obesity and type 2 diabetes in Europe. The effect of obesity on the metabolic control, and the macro- and microvascular complications of patients are not apparent. OBJECTIVES: This nationwide survey aimed to investigate the prevalence of overweight and obesity among patients with type 2 diabetes and to search for the impact of obesity on the metabolic control of these patients. We also investigated the independent associates of obesity in patients with type 2 diabetes. METHODS: We consecutively enrolled patients who were under follow-up for at least 1 year in 69 tertiary healthcare units in 37 cities. The demographic, anthropometric, and clinical data including medications were recorded. Patients were excluded if they were pregnant, younger than 18 years, had decompensated liver disease, psychiatric disorders interfering with cognition or compliance, had bariatric surgery, or were undergoing renal replacement therapy. RESULTS: Only 10% of patients with type 2 diabetes (n = 4,648) had normal body mass indexes (BMI), while the others were affected by overweight (31%) or obesity (59%). Women had a significantly higher prevalence of obesity (53.4 vs. 40%) and severe obesity (16.6 vs. 3.3%). Significant associations were present between high BMI levels and lower education levels, intake of insulin, antihypertensives and statins, poor metabolic control, or the presence of microvascular complications. Age, gender, level of education, smoking, and physical inactivity were the independent associates of obesity in patients with type 2 diabetes. CONCLUSION: The TEMD Obesity Study shows that obesity is a major determinant of the poor metabolic control in patients with type 2 diabetes. These results underline the importance of prevention and management of obesity to improve health care in patients with type 2 diabetes. Also, the results point out the independent sociodemographic and clinical associates of obesity, which should be the prior targets to overcome, in the national fight with obesity.

Effect of clozapine on serum leptin, insulin levels, and body weight and composition in patients with schizophrenia.

OBJECTIVE: Weight gain frequently occurs during treatment with clozapine. However, the pathophysiology of clozapine-induced weight gain remains unclear. The aim of this study was to investigate the influence of clozapine on hormones leptin and insulin in relation to body weight and composition measures to determine their contribution to clozapine-induced weight gain. METHOD: Data are reported on 19 patients with schizophrenia (11 women and 8 men) who completed 10 weeks of treatment with clozapine. Insulin levels, weight measurements, body mass index (BMI), and body composition measurements were evaluated at baseline and at the end of treatment. Leptin levels were assessed at baseline and after 4 and 10 weeks of treatment. Analysis of variance with repeated measures was used to evaluate changes in weight, body composition measures, leptin, and insulin. The Pearson correlations were used to assess the relationships between changes in hormone levels and weight along with body composition measurements. The correlations of change in Positive and Negative Syndrome Scale (PANSS) score with changes in hormone levels, weight gain and body composition measures were evaluated with Pearson correlations. RESULTS: Leptin and insulin levels did not show any significant alterations across time. The use of clozapine was associated with significant increases in BMI (F=19.8, P<.001), lean muscle mass (F=8.2, P=.01), and fat mass (F=15.4, P=.001), while total body fluid percentage (F=4.1, P=.05) significantly decreased. Improvement in PANSS scores was not correlated to change in leptin, insulin, weight, BMI, or body composition measurements. The change in leptin levels was correlated to change in body fat mass. CONCLUSION: The role of leptin in weight gain induced by clozapine might be a regulatory mechanism rather than being etiologic.

Plasma levels of free tissue factor pathway inhibitor in patients with various thyroid disorders.

Various coagulation abnormalities occur in thyroid disorders and its range may vary from subclinical laboratory abnormalities to clinically significant disorders of coagulation. Tissue factor pathway inhibitor (TFPI), which inhibits the initial reaction of tissue factor mediated coagulation pathway, is reported to be increased in patients with Graves disease (GD) in one study. Hyperthyroid (n=10), hypothyroid (n=10) and subclinical hypothyroid (n=10) patients and control cases (n=16) were evaluated for free and total tissue factor pathway inhibitor (tTFPI), plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) levels in disease and euthyroid states. Free TFPI levels were significantly higher in hyperthyroid patients compared with the control group and subclinic hypothyroid patients (p<0.001), but not with hypothyroid patients (p>0.05). After the euthyroid state was obtained in the hyperthyroid group, the levels of total TFPI (p<0.05), free TFPI (fTFPI) (p<0.005), t-PA (p<0.005) and PAI-1 (p<0.02) decreased significantly. In hyperthyroid patients, there was a strong correlation between thyroid functions and free TFPI levels. In conclusion, we hypothesize that coagulation abnormalities seen in thyroid disorders cannot be explained directly with the impaired fibrinolytic activity but also with the elevated fTFPI levels. Both increased plasma fTFPI and PAI-1 levels could be markers of the peripheral activity of thyroid hormones.

Coexistence of gastrointestinal stromal tumors (GISTs) and pheochromocytoma in three cases of neurofibromatosis type 1 (NF1) with a review of the literature.

It is well known that neurofibromatosis type 1 (NF1) is uncommonly associated with pheochromocytoma development and also, to a larger extent, with gastrointestinal stromal tumors (GISTs). We herein document three cases with the rare condition of NF1 coexisting with GIST and pheochromocytoma, while one of them also has a composite tumor and another has papillary thyroid carcinoma.

Is every joint symptom related to acromegaly?

Acromegaly is a chronic endocrinopathy characterized by the hypersecretion of growth hormone and insulin-like growth factor-1. Musculoskeletal pain is a frequent problem encountered in acromegaly and is associated with a reduction in the quality of life. In this study, the presence of inflammatory and degenerative rheumatologic diseases in acromegaly has been retrospectively evaluated. Forty patients with acromegaly who were in remission according to laboratory findings, but still having joint and back pain problems, were referred to rheumatology outpatient clinic and all the patients were examined by clinical, radiological, and laboratory data. Mean age was 47.1 years (22-75). When the radiological data were evaluated, erosions of the left sacroiliac joint were found by means of magnetic resonance imaging in 1 patient and degenerative joint changes were observed in 24 patients by X-ray imaging. However, there was no pathology in the radiological data of 15 patients. Laboratory data revealed antinuclear antibody positivity (3 nucleolar and 1 homogeneous) in 4 patients, rheumatoid factor positivity in 4, and cyclic citrullinated peptide positivity only in 1 patient. The diagnosis of an inflammatory rheumatologic disease, including rheumatoid arthritis, ankylosing spondylitis, or undifferentiated connective tissue disease was made in 3 patients. Besides, the diagnosis of diffuse idiopathic skeletal hyperostosis was also established in 6 patients. While degenerative joint diseases were frequently observed in our group similar to the literature, inflammatory rheumatologic diseases were also found in three patients. Distinguishing these two diseases is important because response to medical treatment is dramatically better in inflammatory diseases than in degenerative pathologies. A multidisciplinary approach is imperative for appropriate management of these patients.

Multiglandular parathyroid carcinoma: case report and review of the literature.

OBJECTIVE: To report the fifth case of multiglandular parathyroid carcinoma and highlight the necessity of bilateral neck exploration in some circumstances. METHODS: We report a case of simultaneous bilateral and multiglandular parathyroid carcinoma in a 48-year-old woman presenting with primary hyperparathyroidism. Ultrasonography revealed a 24- by 24- by 34-mm nodule on the right lobe of the thyroid and a 20- by 20- by 32-mm parathyroid gland inferior to the left thyroid lobe. Technetium Tc 99m sestamibi scan revealed bilateral increased uptake consistent with the parathyroid glands. She was treated with bilateral neck exploration and parathyroidectomy with en bloc resection of the adjacent thyroid lobe in the right lower gland and parathyroidectomy with resection of surrounding soft tissue in the left lower gland. RESULTS: The presence of a thick fibrous capsule, invasion of surrounding tissues, trabecular and solid growth pattern without necrotic foci, and vascular invasion on pathology slides enabled the diagnosis of parathyroid carcinoma of both glands. Her calcium and parathyroid hormone levels were within normal limits during a follow-up period of 4 years. CONCLUSION: Since surgical resection offers the only curative treatment and initial operation may be the determinant of survival, a high index of suspicion for carcinoma both clinically and intraoperatively is vital. We aim to reemphasize that bilateral neck exploration in select cases of parathyroid carcinoma should be considered if there is concrete evidence of a second tumor, since parathyroid carcinoma can coexist with hyperplasia, adenoma, or even carcinoma of other parathyroid glands.

Adrenocortical oncocytic neoplasm presenting with Cushing's syndrome: a case report.

INTRODUCTION: Oncocytic neoplasms occur in several organs and are most commonly found in the thyroid, kidneys and salivary glands. Oncocytic neoplasms of the adrenal cortex are extremely rare and are usually non-functioning. CASE PRESENTATION: We report the case of an adrenocortical oncocytic neoplasm with uncertain malignant potential in a 31-year-old man with Cushing's syndrome. The patient had been operated on following diagnosis of a 7 cm adrenal mass. Following surgery, the Cushing's syndrome resolved. The patient is still alive with no metastases one year after the surgery. CONCLUSION: Adrenocortical oncocytic neoplasms must be considered in the differential diagnosis of both functioning and non-functioning adrenal masses.

Differential diagnosis of polyuria and polydipsia in a patient with spinal cord injury.

We report the case of a 35-yr-old tetraplegic man who experienced increased water intake, constant thirst, and a copious amount of urine excretion after his spinal cord injury and in whom an intermittent catheterization program was unmanageable. Laboratory evaluation revealed low serum and urine osmolality, which were suggestive of psychogenic polydipsia, and hypokalemia, which might lead to polyuria with a compensatory polydipsia. His water intake was reduced with antidepressant therapy and potassium supplementation and normalized on the third month of the treatment. Physicians should be aware of the differential diagnosis of polyuria and polydipsia, which interfere with neurogenic bladder management in patients with spinal cord injury.