24-h Urinary Free Cortisol Research Articles

Clinical utility of routine laboratory testing to identify possible secondary causes in older men with osteoporosis: the Osteoporotic Fractures in Men (MrOS) Study.

We investigated the value of routine laboratory testing for identifying underlying causes in older men diagnosed with osteoporosis. Most osteoporotic and nonosteoporotic men had ≥1 laboratory abnormality. Few individual laboratory abnormalities were more common in osteoporotic men. The benefit of routine laboratory testing in older osteoporotic men may be low. To evaluate the utility of recommended laboratory testing to identify secondary causes in older men with osteoporosis, we examined prevalence of laboratory abnormalities in older men with and without osteoporosis. One thousand five hundred seventy-two men aged ≥65 years in the Osteoporotic Fractures in Men study completed bone mineral density (BMD) testing and a battery of laboratory measures, including serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), 25-OH vitamin D, total testosterone, spot urine calcium/creatinine ratio, spot urine albumin/creatinine ratio, creatinine-derived estimated glomerular filtration rate, 24-h urine calcium, and 24-h urine free cortisol. Using cross-sectional analyses, we calculated prevalence ratios (PRs) and 95 % confidence intervals (CI) for the association of any and specific laboratory abnormalities with osteoporosis and the number of men with osteoporosis needed to test to identify one additional laboratory abnormality compared to testing men without osteoporosis. Approximately 60 % of men had ≥1 laboratory abnormality in both men with and without osteoporosis. Among individual tests, only vitamin D insufficiency (PR, 1.13; 95 % CI, 1.05-1.22) and high alkaline phosphatase (PR, 3.05; 95 % CI, 1.52-6.11) were more likely in men with osteoporosis. Hypercortisolism and hyperthyroidism were uncommon and not significantly more frequent in men with osteoporosis. No osteoporotic men had hypercalciuria. Though most of these older men had ≥1 laboratory abnormality, few routinely recommended individual tests were more common in men with osteoporosis than in those without osteoporosis. Possibly excepting vitamin D and alkaline phosphatase, benefit of routine laboratory testing to identify possible secondary causes in older osteoporotic men appears low. Results may not be generalizable to younger men or to older men in whom history and exam findings raise clinical suspicion for a secondary cause of osteoporosis.

Dexamethasone-suppressed corticotropin-releasing hormone stimulation test in morbid obese adults

In order to differentiate between Cushing's syndrome (CS) and Pseudo-Cushing's syndrome, it is customary to use a test that is conducted by cortisol suppression with low-dose dexamethasone, followed by the administration of corticotropin releasing hormone (Dex-CRH test). In children with severe obesity, Dex-CRH test has shown a specificity of 55%. The aim of current study was to evaluate the specificity of Dex-CRH test in morbid obese adults. The study included a total of 19 subjects with a body mass index (BMI) equal or higher than 40kg/m(2). In all subjects Dex-CRH test was performed, and 24h urinary free cortisol was collected prior the test and during the second day of dexamethasone administration (2nd-day-UFC). BMI was 45.1±4.6kg/m(2) and 45.7±3.3kg/m(2) in women and men, respectively. 14 subjects underwent bariatric surgery. No subject had surgical or perioperative complications and surgically treated subjects had mean body weight loss of 46.5±16.6kg. All except for 2 subjects had normal Dex-CRH test, as 15-min cortisol falling below 1.4μg/dl. During follow-up, no subject gained additional weight, neither developed signs of CS. 15-min-cortisol concentration of 1.4μg/dl revealed a specificity of 89% and 2nd-day-UFC of 16μg/24h showed a specificity of 100%. Morbid obesity in adults seems not to comprise a significant confounder in Dex-CRH test, and 15-min-cortisol concentration of 1.4μg/dl had a higher specificity than previously reported in obese children.

Management of Cushing's disease: a single-center experience.

The purpose of this study was to review therapeutic outcomes and comorbidities of patients with Cushing's disease (CD) in a single center. We conducted a retrospective study of 33 patients with CD undergoing transsphenoidal surgery from January 2007 to February 2014 (27 females and 6 males, median age 38 years, range 18-71 years). The diagnosis of Cushing's syndrome was established on the basis of the patient's history, characteristic clinical features, and laboratory data including an elevated 24-h urinary free cortisol level, lack of serum cortisol suppression after dexamethasone suppression tests and an elevated midnight cortisol level. In 28/33 patients, the tumor was visualized on MR of the sellar region, while in 5 it was diagnosed using an inferior petrosal sinus sampling. Out of the 33 patients, 10 had macroadenoma and the remaining 23 had microadenoma. Twenty-one patients (63.6%) had hypertension, 17 (51.5%) dyslipidemia, and 7 (21.2%) had type 2 diabetes or impaired glucose tolerance. The median follow-up period was 28 months. Remission after transsphenoidal surgery was achieved in 78.8% of patients, while 7 patients failed to achieve disease remission. Those patients were treated with second-line treatment modalities (second operation, radiotherapy, bilateral adrenalectomy, and/or ketoconazole). One patient rejected all the treatment modalities after surgery. Cumulative remission after all the treatment modalities was achieved in 87.9% patients. Patients with Cushing's disease should be managed in centers with much experience due to high patient load. In our Center, the remission of the disease has been achieved in 78.8% of the patients following transsphenoidal surgery. Multimodal treatment which included radiotherapy and medical treatment led to biochemical remission of the disease in 87.9% of patients.

Crooke's Changes In Cushing's Syndrome Depends on Degree of Hypercortisolism and Individual Susceptibility.

Although Crooke's changes in the pituitary corticotrophs were initially described in 1935, the prevalence in which the changes occur in patients with Cushing's syndrome (CS) has not been established. This study aimed to determine the prevalence and assess clinical features associated with the presence or absence of Crooke's changes in a large set of patients with CS. Information from a prospective computer database and retrospective chart review was analyzed. The setting was an academic medical center. Consecutive patients (N = 213) who received surgery with a preoperative diagnosis of Cushing's disease are included. The patients received pituitary surgery and specimens obtained underwent pathological analysis. The presence or absence of Crooke's changes was determined by histopathological analysis of the normal pituitary tissue included with the specimen obtained at surgery. Cortisol production was measured by 24-hour urine cortisol production. Crooke's changes occurred in 144 of 177 patients (81%) with a histologically demonstrated ACTH-staining tumor and in 74% of 213 patients diagnosed with CS who had pituitary surgery. The presence of Crooke's changes correlated with the finding of an ACTH-staining tumor removed at surgery and with the degree of hypercortisolism. Among patients with histologically established ACTH-staining tumors the prevalence of Crooke's changes was particularly high in patients with a 24-h urinary free cortisol (UFC) of at least 4-fold the upper limit of normal, in which 91% of patients had Crooke's changes, compared with 74% of patients whose maximum UFC was less than 4-fold the upper limit of normal (P = .008). Crooke's changes occur in 75-80% of patients with CS, and depend on the degree of hypercortisolism and individual variability. Almost all patients with UFC at least 4-fold the upper limit of normal have them, whereas with less severe hypercortisolism the expression of Crooke's changes varies from person to person.

Relationship between pituitary stalk (PS) visibility and the severity of hormone deficiencies: PS interruption syndrome revisited.

Pituitary stalk interruption syndrome (PSIS) is a rare cause of combined pituitary hormone deficiency characterized by a triad shown in pituitary imaging, yet it has never been evaluated due to the visibility of pituitary stalk (PS) in imaging findings. The major objective of the study was to systematically describe the disease including clinical presentations, imaging findings and to estimate the severity of anterior pituitary hormone deficiency based on the visibility of the PS. This was a retrospective study including 74 adult patients with PSIS in Shanghai Clinical Center for Endocrine and Metabolic Diseases between January 2010 and June 2014. Sixty had invisible PS according to the findings on MRI, while the rest had a thin or intersected PS. Basic characteristics and hormonal status were compared. Of the 74 patients with PSIS, age at diagnosis was 25 (22-28) years. Absent pubertal development (97·3%) was the most common presenting symptom, followed by short stature. Insulin tolerance test (ITT) and gonadotrophin-releasing hormone (GnRH) stimulation test were used to evaluate the function of anterior pituitary. The prevalence of isolated deficiency in growth hormone (GH), gonadotrophins, corticotrophin and thyrotrophin were 100%, 97·2%, 88·2% and 70·3%, respectively. Although the ratio of each deficiency did not vary between patients with invisible PS and with visible PS, panhypopituitarism occurred significantly more frequent in patients with invisible PS. Patients with invisible PS had significantly lower levels of luteinizing hormone (LH), follicle stimulation hormone (FSH) and hormones from targeted glands including morning cortisol, 24-h urine free cortisol, free triiodothyronine (FT3), free thyroxine (FT4) and testosterone (T) in male than patients with visible PS. Moreover, patients with invisible PS had lower peak LH and FSH in GnRH stimulation test, and higher peak cortisol in ITT while peak GH remained unchanged between two groups. The prevalence of multiple anterior pituitary hormone deficiency was high in adult patients with PSIS. And more importantly, we found the visibility of PS shown on MRI might be an indication of the severity of PSIS.

Chrousos syndrome: from molecular pathogenesis to therapeutic management.

Primary Generalized Glucocorticoid Resistance or Chrousos syndrome is a rare genetic condition characterized by end-organ insensitivity to glucocorticoids owing to inactivating mutations of the NR3C1 gene. We conducted a systematic review of the published, peer-reviewed medical literature using MEDLINE (1975 through November 2014) to identify original articles and reviews on this topic. The search terms included 'primary generalized glucocorticoid resistance', 'Chrousos syndrome', 'glucocorticoid receptor gene' and 'glucocorticoid receptor mutations'. Only a few cases of Chrousos syndrome have been described to date, ranging from asymptomatic to severe forms of mineralocorticoid and/or androgen excess. All reported cases have been associated with point mutations or deletions in the NR3C1 gene. The tremendous progress of molecular biology has enabled us to apply standard methods to investigate the molecular mechanisms of action of the mutant glucocorticoid receptors (GRs). We and others have identified and functionally characterized novel mutations causing Chrousos syndrome, while structural biology has enabled us to have a better understanding of how conformational changes of the receptor cause glucocorticoid resistance. In this review, we also present our results of the functional characterization of two recently described mutations, and we discuss the diagnostic approaches and therapeutic management of patients with Chrousos syndrome. Although Chrousos syndrome is a rare condition, many clinical cases remain unrecognized for a long time. We recommend determination of the 24-h urinary free cortisol excretion and sequencing of the NR3C1 gene in patients with hyperandrogenism and/or hypertension of unknown origin.

Ectopic Cushing's syndrome secondary to lung and mediastinal tumours -- report from a tertiary care centre in Iran.

Ectopic Cushing`s syndrome (ECS) secondary to neuroendocrine tumours (NETs) of the lung and mediastinum are rarely encountered. In this study, we present our experience in Iran on 15 patients with ECS secondary to lung and mediastinal tumours over a period of 27 years. Since 1985, 15 patients with ECS secondary to lung and mediastinal tumours have been diagnosed and prospectively followed by the endocrinology team of Taleghani Hospital, Tehran, Iran. The clinical signs and symptoms, laboratory findings, radiological features, immunohistochemical characteristics, management strategies and outcome data are here presented. There were six women and nine men, aged 26-70 years, all presenting with typical features of Cushing's syndrome. Based on histopathologic evaluations, four patients had small cell lung cancer (SCLC) and seven patients had pulmonary NETs, one patient had a thymic NET, and one case was diagnosed as a lung tumourlet. The mean ± SD serum cortisol, 24h urine free cortisol and plasma ACTH were 47.2 ± 20.5 μg/dL, 2,702 ± 5,439 μg/day, and 220 ± 147 pg/mL, respectively. Pulmonary lesions ranged in diameter from 1.1 to 4 cm (mean 1.9 ± 1.1 cm). One patient had a 10 cm mediastinal mass. The duration of follow up in these cases was between one month and seven years (mean 29.9 ± 27.5 months). The four patients with SCLC died within three months of diagnosis. Our data demonstrates the protean clinical and laboratory manifestations of ECS secondary to lung and mediastinal tumours, the problems encountered in diagnosis, and the need for a multidisciplinary approach. This study confirms other series from Western Europe and North America that, unlike the SCLC patients who show a poor outlook, ECS secondary to lung carcinoids has a more favourable prognosis.

The role of an acute pasireotide suppression test in predicting response to treatment in patients with Cushing's disease: findings from a pilot study.

Pasireotide is a multireceptor-targeted somatostatin analog effective in the treatment of Cushing's disease (CD). We evaluate the value of an acute pasireotide suppression test (PST) in predicting response to medium/long-term treatment in CD. Nineteen patients with active CD were prospectively investigated at two referral centers from May 2013 to August 2014. Follow-up data (median 6 months; range 1-9 months) were available for sixteen patients. All patients received at 09:00 h a single subcutaneous (sc) injection of 600 μg pasireotide. Serum cortisol and plasma ACTH were assessed before, and every 2 h for 8 h after, drug administration. Late-night salivary cortisol (LNSC) was assessed before and after pasireotide administration. After acute PST, all patients were continued on pasireotide 600 μg sc twice a day. During PST, cortisol and ACTH levels quickly decreased in all patients except one with a mean percentage fall, respectively, of 48.9 ± 24.3 and 48.1 ± 25.4 % compared to baseline. LNSC decreased in about 82 % of patients (14/17) achieving a normalization in five of them. Pasireotide treatment was associated with a normalization of 24-h urinary-free cortisol at last follow-up in about 68 % of patients. A fall >27 % of LNSC during PST calculated by ROC curve was the best parameter in predicting a positive response to treatment with pasireotide (sensitivity 91 %; specificity 100 %; positive predictive value 100 %; negative predictive value 75 %). Acute PST may be useful to identify CD patients who will benefit from pasireotide treatment. A LNSC fall >27 % as well as a LNSC normalization during PST is associated with a probability of 100 % of achieving a favorable response to pasireotide treatment in the medium/long term.

The accuracy of 24-h urinary free cortisol as a screening test in the diagnosis of Cushing's syndrome in children

The accuracy of 24-h urinary free cortisol as a screening test in the diagnosis of Cushing's syndrome in children

24-h urinary free cortisol from mid-pregnancy to 3-months postpartum: gender and parity differences and effects.

Pregnancy and postpartum have been associated to several physiological changes; however, empirical evidence was almost exclusively obtained in primiparous women and few studies focus on hormonal changes in men and second-time parents. The main aim of this study is to examine 24-h urinary free cortisol from mid-pregnancy to 3-months postpartum, comparing women/men and first/second-time parents. Twenty-six women and 22 men (N=48) were recruited from an antenatal obstetric unit in Porto, Portugal. 24-h urinary free cortisol was measured at the 2nd and 3rd trimester and at 3-months postpartum. Repeated measures analyses of variance were conducted, in order to analyze 24-h urinary free cortisol patterns of change over this period. Gender and parity were included in the analyses as potential modifiers, in order to compare women and men, and first- and second-time parents. An increase from the 2nd to the 3rd trimester (p=.006) and a decrease from the 3rd trimester to 3-months postpartum (p=.005) were reported in all parents' 24-h urinary free cortisol. The interaction effects for Time*Gender (p=.03) and Time*Parity (p=.02) were found. Women and first-time parents revealed higher levels, while men and second-time parents showed lower 24-h urinary free cortisol levels at the 2nd trimester than at 3-months postpartum. Findings appear to clarify the direction, as well as, the timing, gender and parity extension of 24-h urinary free cortisol changes from mid-pregnancy to 3-months postpartum. The same pattern of change in all parents' 24-h urinary free cortisol from mid-pregnancy to 3-months postpartum is consistent with the proposed role of hormones in preparation to parenting. Gender and parity differences and effects on 24-h urinary free cortisol are also consistent with cortisol as a stress biomarker for higher challenges associated to pregnancy and childbirth in women and first-time parents versus higher demands related to after childbirth parenting in men and second-time parents.

Effects of adverse life events on heart rate variability, cortisol, and C-reactive protein.

Our objective was to assess whether self-reported adverse life events during childhood or over the lifespan are associated with altered activity of the autonomic nervous system (ANS), the hypothalamic-pituitary-adrenal axis (HPA axis), and the immune system. This study was performed in a population-based cohort of 1094 adults aged 33-79years, 46.3% male, average age 53 (SD 11.4). Two waves of data were collected at a 2-year interval, enabling replication of the analyses. Cumulative exposure to adverse life events was assessed by means of the List of Threatening Experiences. ANS function was assessed by spectral analysis of heart rate variability in the high-frequency band (HRV-HF). HPA axis function was assessed by 24-h urinary free cortisol (24-h UFC) excretion. Inflammation was assessed by high-sensitive C-reactive protein (hsCRP). Multiple linear regression analyses did not reveal any significant associations, with the exception of one significant negative association between the lifetime score of adverse life events and HRV-HF β=-0.028; P=0.037 at baseline, but not at follow up 2years later. In a large population-based cohort, adverse life events were not consistently associated with HRV-HF, 24-h UFC or (hsCRP).

Multiple endocrine neoplasia type 1 associated with breast cancer: A case report and review of the literature.

Multiple endocrine neoplasia type 1 (MEN1) is a cancer predisposition syndrome that includes a combination of endocrine and non-endocrine tumors. The present study reports a rare case of MEN1 associated with breast cancer with the MEN1 gene mutation. A 45-year-old female was diagnosed with breast cancer subsequent to presenting with a right breast mass. Pre-operative radiological studies indicated right breast cancer with a suspicious metastatic nodule of the lung. Further studies demonstrated bilateral thyroid nodules, a neuroendocrine tumor of the pancreas, paraganglioma, a left adrenal adenoma, gallstones, uterine subserosal myoma and pituitary macroadenoma. Laboratory examinations revealed hypercalcemia, hypophosphatemia and an increased intact parathyroid hormone level. The workup for the suspected MEN syndrome revealed an increased basal plasma level of insulin-like growth factor-1, prolactin and calcitonin, and an increased 24-h urinary free cortisol level. The patient underwent surgical removal of the breast cancer and the tumors of the pancreas, adrenal gland, thyroid and parathyroid glands, uterus, anterior mediastinum and lung. The pathological diagnosis of the resected breast was of invasive ductal carcinoma. Otherwise the pathological diagnosis was of calcitonin-producing pancreatic endocrine carcinoma, adrenal cortical adenoma, bilateral papillary thyroid carcinomas, parathyroid adenomas, uterine leiomyoma with adenomyosis, a thymic carcinoid tumor and lung hamatoma. Gene analysis was performed to determine the association between gene mutations and the development of tumors in this patient, and a germ-line MEN1 gene mutation was consequently detected. It could be assumed that MEN1 syndrome may have possibly predisposed the present patient to breast cancer. However, additional observations and further studies are required to demonstrate this association.

24 h urinary free cortisol in large-scale epidemiological studies: short-term and long-term stability and sources of variability.

Function of the hypothalamus-pituitary-adrenal (HPA) axis has been associated with several somatic and psychiatric health problems. The amount of free cortisol excreted in the urine during 24h (24-h UFC) has often been used as a proxy for HPA-axis function. Reference values for 24-h UFC and their stability in the short and long term, as well as sources of variability, are largely lacking. This study was performed in a general population cohort. Participants collected 24-h UFC on two consecutive days (T1), and repeated this collection approximately 2 years later (T2). Cortisol in urine was measured using LC-MS/MS. Height and weight were measured at the research facilities; glomerular filtration rate was estimated using creatinine clearance. Psychological distress (General Health Questionnaire), smoking, alcohol use and exercise were measured by means of questionnaires. 24-h UFC stability on a day-to-day basis was 0.69 (T1, N=1192) and 0.72 (T2, N=963) (both p<0.001). Long-term stability as indicated by correlation between 2-day averages of T1 and T2 was 0.60 (N=972, p<0.001). Multivariable linear regression analysis revealed that 24-h UFC was predicted by urine volume (standardized beta 0.282 (T1, N=1556) and 0.276 (T2, N=1244); both p<0.001) and glomerular filtration rate (standardized beta 0.137 (T1) and 0.179 (T2); both p<0.001), while also sex explained a small part (standardized beta for female sex -0.057 (T1) and -0.080 (T2); both p<0.05). 24-h UFC is moderately stable both in the short and the long term. The effects of urine volume and glomerular filtration rate on 24-h UFC are much stronger than those of sex.

Screening for Cushing's syndrome in obese patients; is it really necessary?

to be more frequent among patients with metabolic syndrome. Previous studies have suggested to perform a routine screening for CS in obese patients; however, more recent reports only recommend a case-finding approach in patients with uncontrolled diabetes and hypertension, despite appropriate treatment. Objective: The aim of this study was to evaluate the prevalence of unsuspected CS in morbidly obese patients in an outpatient’s clinic. Patients and methods: Retrospective case-note study. We reviewed the medical records of morbidly obese patients referred to our clinic prior to bariatric surgery between january 2001 and december 2011. All patients had a complete medical history including physical examination, and 399 underwent screening for CS as part of our pre-surgical protocol. As screening for autonomous cortisol secretion, we performed an overnight 1 mg Dexamethasone Suppression Test (DST). Serum cortisol < 1.8 μg/dl was the cut-off point for normal suppression. Results: 399 patients (308 female; mean age 41.9 ± 10.5 years; mean BMI 51.5 ± 8.4 kg/m2). In the retrospective analysis, prediabetes and diabetes mellitus were observed in 10.3% and 27.8% respectively. In 21 of 399 patients, screening was considered to be abnormal. Eight of these 21 patients had subsequent normal 24h Urinary Free Cortisol (UFC) levels (150 μg/24h). In 13 of 20 patients, we repeated an overnight 1mg DST, on suspicion of failing to take the dexamethasone correctly. Three patients failed to suppress their cortisol levels, two of them were on carbamazepine, which was considered to be a false positive result. The other patient with abnormal UFC levels was diagnosed with CS (0.26%), whose cause was a pituitary microadenoma. Conclusion: A low proportion of patients with morbid obesity were found to have CS. Our findings suggest that morbidly obese patients should not be routinely screened for CS.

The diagnostic performance of urinary free cortisol is better than the cortisol:cortisone ratio in detecting de novo Cushing's syndrome: the use of a LC-MS/MS method in routine clinical practice.

The Endocrine Society Clinical Guidelines recommend measuring 24-h urinary free cortisol (UFF) levels using a highly accurate method as one of the first-line screening tests for the diagnosis of Cushing's Syndrome (CS). We evaluated the performance of UFF, urinary free cortisone (UFE), and the UFF:UFE ratio, measured using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The LC-MS/MS was used to analyze UFF and UFE levels in 43 surgically confirmed CS patients: 26 with Cushing's disease (CD, 16 de novo and ten recurrences), 11 with adrenal CS and six with ectopic CS; 22 CD patients in remission; 14 eu-cortisolemic CD patients receiving medical therapy; 60 non-CS patients; and 70 healthy controls. Sensitivity and specificity were determined in the combined groups of non-CS patients, healthy controls, and CD in remission. UFF>170 nmol/24 h showed 98.7% specificity and 100% sensitivity for de novo CS, while sensitivity was 80% for recurrent CD patients, who were characterized by lower UFF levels. The UFF:UFE and UFF+UFE showed lower sensitivity and specificity than UFF. Ectopic CS patients had the highest UFF and UFF:UFE levels, which were normal in the CD remission patients and in those receiving medical therapy. Our data suggest high diagnostic performance of UFF excretion measured using LC-MS/MS, in detecting de novo CS. UFF:UFE and UFF+UFE assessments are not useful in the first step of CS diagnosis, although high levels were found to be indicative of ectopic CS.

Relationships Between 24-Hour Urinary Free Cortisol Concentrations and Metabolic Syndrome in Obese Children

Clinical features of Metabolic Syndrome (MetS) and Cushing's Syndrome are similar, suggesting a pathogenetic role of hypothalamus-pituitary-adrenal axis in MetS. The aim of the study was to determine whether MetS diagnosis and specific clusters of MetS components (waist circumference, dyslipidemia, hypertension, and impaired glucose metabolism) are associated with serum cortisol (SC) or 24-h urinary free cortisol (UFC) levels. We conducted cross-sectional analyses of data from our obesity cohort. We studied 264 obese children (age, 11.0 ± 2.8 years; male, 48%; BMI, 28.2 ± 5.4 kg/m(2)). We examined UFC, SC, homeostasis model assessment (HOMA), and features of MetS (waist circumference, blood pressure, fasting lipids, and glucose). Slightly increased UFC concentrations were measured in 30.7% of the children. Obese children with MetS had significantly (P = .003) higher UFC levels compared with obese children without MetS. Girls demonstrated significantly higher UFC concentrations compared with boys independent of pubertal stage. UFC and SC levels were significantly related to features of MetS, but the associations were stronger for UFC. In multivariate analyses adjusted for age, sex, and body mass index, none of the features of MetS but HOMA index was correlated with UFC, whereas SC demonstrated no significant association to any parameter of MetS or HOMA. Our findings support the hypothesis that changes in the hypothalamus-pituitary-adrenal axis are related to MetS in obesity. UFC seems to be a suitable marker for this relationship. Norm values for UFC adapted to obese children may help to avoid unnecessary dexamethasone suppression tests.

LOW-TRAUMATIC FRACTURES IN PATIENTS WITH ENDOGENOUS HYPERCORTISOLISM. PREDICTORS AND RISK FACTORS, THE IMPACT ON QUALITY OF LIFE

The objective of this study was to investigate the prevalence of low traumatic fractures, the factors influencing fractures in endogenous Cushing’s syndrome (CS) of various etiologies and their contributions into functional abilities and quality of life in patients with CS. Materials and methods: the retrospective data of patients, who had received treatment due to endogenous CS, (2001-2011), was evaluated. All enrolled patients underwent standard spinal radiographs in lateral positions of the vertebrae Th4-L4. Recent low traumatic non-vertebral fractures were recorded in the medical cards. Bone mineral density (BMD) was measured by DXA GE Lunar Prodigy. Serum samples on octeocalcin (OC), carboxyterminal cross-linked telopeptide of type I collagen (CTx), latenight cortisol in serum were assayed by electrochemiluminescence (ECLIA). 24h urinary free cortisol (24hUFC) was measured by an immunochemiluminescence assay (extraction with diethyl ether). Functional assessment was performed using «chair rising», «up and go» and «tandem» tests. Universal pain assessment tool (verbal descriptor scale, Wong-Baker facial grimace scale, activity tolerance scale), EQ-5D and ECOS-16 questionnaires were given to patients and they self-reported their conditions. Results: Among 215 patients, 178 were females and 37 males, median age 35 (Q25-Q75 27-48); 88patients (40,9%) had low traumatic fractures, including vertebral fractures in 76 cases (in 60 cases multiple vertebral fractures) and non-vertebral fractures in 27 cases (17 patients had rib fractures, 3 -fractures of metatarsal bones, 2 fractures of radius, 2 fractures of tibia and fibula, 1 humerus, 1 breastbone; 1 hip fracture). Patients with fractures had higher 24hUFC, late-night cortisol in serum, lower OC, Total Hip BMD, but did not differ in age, BMI, CTx or etiology of CS. After applying the logistic regression analysis (adjusted for sex, age, BMI, BMD, OC), the main predictor of fractures was late-night serum cortisol level (p=0,001). Patients with late-night serum cortisol higher than 597 nmol/l were more likely to have low traumatic fractures (Odds ratio 2,86 (95%CI 1,55-5,28) p=0,001). Patients with fractures suffered from more pain and reported worse functional abilities. They had slightly worse results in «tandem» test, but did not differ in other functional tests, which assessed mainly muscle power. Conclusions: Patients with CS have very high risk of low traumatic fractures. The severity of hypercortisolemia is the best predictor of low traumatic fractures in patients with CS. Patients with fractures sufferedfrom more severe pain and because of this they restricted their daily activity even more than patients with CS without fractures. Consequently, patients with higher levels of late-night serum cortisol need earlier preventive treatment for osteoporosis.

Desmopressin test in the diagnosis and follow-up of cyclical Cushing's disease

To assess the utility of the desmopressin (DDAVP) test in the diagnosis and follow-up of a cyclical Cushing's disease (CCS) case. Laboratory tests included morning and midnight serum cortisol levels, 24h urine free cortisol excretion, midnight salivary cortisol levels, serum cortisol levels after low (1 mg) and high (8 mg) dexamethasone, plasma ACTH and serum cortisol levels after DDAVP. Magnetic resonance imaging (MRI) was used to assess the presence of a pituitary adenoma. The resected tumor specimen was studied by histological, immunohistochemical and cell biology techniques. A patient was referred to our unit with a diagnosis of Cushing's syndrome (CS) for further evaluation and treatment. However, no biochemical evidence of hypercortisolism was observed in the follow-up evaluations. Furthermore, the typical features of CS fluctuated throughout this period. A consistent positive response to the DDAVP stimulation test was observed during the diagnostic work-up, even when overt clinical features of CS were not apparent, raising suspicion for CCS. After two years of follow-up a definitive diagnosis of hypercortisolism was established. An MRI scan revealed a pituitary adenoma, as the source of ACTH production. After transphenoidal surgery, clinical signs of CS resolved and the response to DDAVP became negative. DDAVP induced a significant increase in ACTH levels in cultured pituitary adenoma cells, consistent with the in vivo DDAVP test results. Our case illustrates the utility of the DDAVP test in the evaluation of patients with suspected CCS. The DDAVP test could facilitate the management of CCS by shortening the time of diagnosis.

Diagnostics of hypercortisolism — comparison between the clinical usefulness of salivary and serum cortisol measurements

The aim of this study was the comparison of 24h urine free cortisol (UFC), serum cortisol at 11pm (SCM) and late-nightsalivary cortisol (LSC) in patients suspected for hypercortisolism, and an assessment of the usefulness of these measurements in diagnosingovert Cushing's (OCS) syndrome, pseudo Cushing's state (PCS) and subclinical Cushing's syndrome (SCS). The study group consisted of 82 patients, of whom four patients had SCS, three OCS and eight PCS. For measurementsof LSC, the ELISA method was used, and for UFC and SCM determination, chemiluminescent microparticle immunoassay was used. The highest correlation coefficient characterised LSC and SCM (r = 0.72). Area under curve (AUC) for SCM and LSC in receiveroperating characteristic (ROC) for OCS was: 0.86 v. 0.74; for PCS: 0.83 v. 0.70; and for SCS: 0.74 v. 0.79. Our findings suggest that LSC is more useful compared to SCM in diagnosing subclinical Cushing's syndrome. Moreover,LSC seems to be a valuable diagnostic criterion to distinguish pseudo Cushing's state. However, to obtain reliable cut-offs for LSC values,a larger group of hypercortisolic patients is needed.

A case of cushing’s disease evaluated by Inferior petrosal sinus sampling – a novel Approach in bangladesh

A 16 years old boy presented to the Department of Endocrinology, Sir Salimullah Medical College &amp; Mitford Hospital with the complaints of occasional headache, vomiting and gradual weight gain for the last 5 years. He was overweight &amp; has moon face, lipomastia, striae over the abdomen. His random blood sugar was 15 mmol/l, serum potassium was low, no suppression of serum cortisol on low dose 1mg dexamethasone suppression test (297 nmol/l)(cut of &lt;140 nmol/l), loss of diurnal rhythm of serum cortisol (morning 430 nmol/l, midnight 992 nmol/l), 24h urinary free cortisol in the upper limit of normal (164mcg), modest elevation of serum adrenocorticotropic hormone (ACTH) (59.7 pg/ml), no significant gradient of serum ACTH level between internal jugular and femoral vein, normal adrenal glands on computed tomography (CT) abdomen, pituitary microadenoma on magnetic resonance imaging (MRI) of Sella. On above clinical examination and, investigation he was diagnosed as Cushing’s disease with diabetes mellitus. This patient was referred to department of neurosurgery for surgical management. The patient is now on medical treatment. Ketoconazole for hypercortisolism, lifestyle modification and metformin for diabetes mellitus. He is expected to have the neurosurgical treatment shortly. DOI: http://dx.doi.org/10.3329/jdmc.v22i1.15708 J Dhaka Medical College, Vol. 22, No. 1, April, 2013, Page 96-101