Late-Night Salivary Cortisol for the Diagnosis of Cushing Syndrome: a Meta-Analysis

ObjectiveTo report a meta-analysis of late-night salivary cortisol testing for the diagnosis of Cushing syndrome.MethodsMEDLINE and EMBASE computer databases were searched to identify relevant articles published between January 1950 and December 2007. The search strategy used the following medical subject headings and keywords: cortisol, Cushing or Cushing’s, saliva, salivary, late-night, nocturnal, and nighttime. The results were limited to studies in humans older than 18 years. Titles and abstracts of all articles, as well as full text of relevant articles, were reviewed. Sensitivity, specificity, likelihood ratio positive, likelihood ratio negative, and diagnostic odds ratio were extracted by 2 authors. Discrepancies were resolved by mediation and discussion with a third author.ResultsSeven articles contained sufficient information to be included in the analysis. A total of 947 patients (339 with Cushing syndrome) were identified. Pooled data from the 7 studies revealed a sensitivity of 92% (95% confidence interval [CI], 88%-94%), specificity of 96% (95% CI, 94%-97%), and diagnostic odds ratio of 311 (95% CI, 92-1059). Likelihood ratio positive was 21 (95% CI, 1043), with a likelihood ratio negative of 0.08 (95% CI, 0.02-0.32). Inconsistencies for each of these results measured by the I² statistic ranged from moderate to high.ConclusionThis analysis demonstrates that latenight salivary cortisol has excellent diagnostic characteristics and as such, is a robust, convenient test for screening and diagnosis of Cushing syndrome. (Endocr Pract. 2009;15:335-342)     

Diagnosing the Unrecognized Systemic Absorption of Intra-Articular and Epidural Steroid Injections

ObjectiveTo present a case series of patients who were misdiagnosed with endocrine disorders because of failure to recognize the systemic absorption of intra-articular and epidural steroids and to discuss the utility of performing a urine screen to detect synthetic glucocorticoids.MethodsIn this case series, we describe the clinical, laboratory, and imaging findings of 3 patients referred to our clinic, each with a presumed endocrine disorder.ResultsPatient 1 was a 54-year-old woman with weakness, loss of appetite, and a hormonal profile suggestive of hypopituitarism. Patient 2 was a 49-year-old woman with chronic fatigue and history of physical abuse, whose history and test results were compatible with growth hormone deficiency secondary to head trauma. Patient 3 was a 46-year-old woman who was diagnosed with endogenous Cushing syndrome despite normal 24-hour urinary cortisol excretion. In each case, we subsequently elicited a history of intra-articular or epidural glucocorticoid injections, and a urine screen documented the presence of synthetic glucocorticoids. Systemic absorption of the injected steroids was thus determined to be the cause of the symptoms and abnormal laboratory findings in each case.ConclusionsThe potential for harm from intra-articular and epidural glucocorticoid administration is underrecognized by physicians, leading to expensive investigation, false diagnoses, and unnecessary treatment. A urine screen for synthetic glucocorticoids is a valuable adjunct towards appropriate diagnosis. (Endocr Pract. 2009;15:225-228)     

Successful Long-Term Treatment of Cushing Disease with Mifepristone (RU486)

ObjectiveWe describe a girl with Cushing disease for whom surgery and radiation treatments failed and the sub- sequent clinical course with mifepristone therapy.MethodsWe present the patient’s clinical, biochemi- cal, and imaging findings.ResultsA 16-year-old girl presented with classic Cushing disease. After transsphenoidal surgery, Cyberknife radiosurgery, ketoconazole, and metyrapone did not control her disease, and she was prescribed mifepristone, which was titrated to a maximal dosage of 1200 mg daily with subsequent symptom improvement. Mifepristone (RU486) is a high-affinity, nonselective antagonist of the glucocor- ticoid receptor. There is limited literature on its use as an off-label medication to treat refractory Cushing disease. Over her 8-year treatment with mifepristone, her therapy was complicated by hypertension and hypokalemia requir- ing spironolactone and potassium chloride. She received a 2-month drug holiday every 4 to 6 months to allow for withdrawal menstrual bleeding with medroxyprogester- one acetate. Urinary cortisol, serum cortisol, and cortico- tropin levels remained elevated during mifepristone drug holidays. While on mifepristone, her signs and symptoms of Cushing disease resolved. Repeated magnetic resonance imaging demonstrated stable appearance of the residual pituitary mass. Bilateral adrenalectomy was performed, and mifepristone was discontinued after 95 months of medical therapy.ConclusionsWe describe the longest duration of mifepristone therapy thus reported for the treatment of refractory Cushing disease. Mifepristone effectively controlled all signs and symptoms of hypercortisolism. Menstruating women who take the drug on a long-term basis should receive periodic drug holidays to allow for menses. The lack of reliable serum biomarkers to monitor the success of mifepristone therapy requires careful clini- cal judgment and may make its use difficult in Cushing disease. (Endocr Pract. 2012;18:e114-e120)     

Unusual Cause of Ectopic Secretion of Adrenocorticotropic Hormone: Cushing Syndrome Attributable to Small Cell Prostate Cancer

ObjectiveTo report a rare cause of ectopic adrenocorticotropic hormone (ACTH) secretion leading to severe Cushing syndrome.MethodsWe describe the clinical presentation and management of a case of Cushing syndrome attributable to ectopic ACTH secretion from small cell cancer of the prostate.ResultsIn a 70-year-old man with hypertension and diabetes, congestive heart failure developed. He was found to have severe hypokalemia (serum potassium, 1.7 mEq/L) and a huge pelvic mass on a computed tomographic scan performed because of a complaint of urinary retention. Transurethral biopsy of the prostate showed features of small cell prostate cancer. Hormonal evaluation revealed a high urine free cortisol excretion of 6,214.5 μg/d (reference range, 36 to 137), confirming the diagnosis of Cushing syndrome. A serum ACTH level was elevated at 316 ng/dL (reference range, 10 to 52). An overnight highdose (8 mg orally) dexamethasone suppression test was positive (serum cortisol levels were 43.2 and 41 μg/dL before and after suppression, respectively), and magnetic resonance imaging of the pituitary gland disclosed no abnormalities. A prostate biopsy specimen showed small cell prostate cancer with positive staining for ACTH. The tumor was found to be unresectable, and the poor condition of the patient did not allow for bilateral adrenalectomy. He was treated with ketoconazole and metyrapone, which yielded good temporary control of his Cushing syndrome (24-hour urine free cortisol decreased to 55.2 μg/d). He received 1 cycle of chemotherapy (etoposide and cisplatin), but he died 6 months later as a result of sepsis.ConclusionSmall cell prostate cancer is a rare subtype that can be associated with ectopic secretion of ACTH and severe Cushing syndrome. With this subtype of prostate cancer, Cushing syndrome should be considered and appropriately managed. (Endocr Pract. 2010;16:249-254)     

Efficacy of Cabergoline in Uncured (Persistent Or Recurrent) Cushing Disease after Pituitary Surgical Treatment with Or Without Radiotherapy

ObjectiveTo evaluate the efficacy of cabergoline therapy in patients with Cushing disease who remained uncured (had persistent or recurrent disease) after a pituitary surgical procedure with or without radiotherapy.MethodsWe undertook a prospective, open-label, single-arm study, with short-term (5 months) and longterm (1 year) evaluations. In 20 patients with uncured Cushing disease, treatment was initiated with cabergoline at a dosage of 1 mg/wk, with a monthly increment of 1 mg, until midnight serum cortisol (MNSC) or low-dose dexamethasone suppression serum cortisol (LDSC) (or both) normalized or a maximal dosage of 5 mg/wk was reached.ResultsOverall, 5 of 18 patients (28%) responded in terms of LDSC or MNSC (or both) at a mean dosage of 3.6 mg/wk (range, 2 to 5). When the response was defined with use of either LDSC or MNSC level as an isolated criterion, it was achieved in 4 of 16 patients (25%) and 3 of 18 patients (17%), respectively. Four patients were treated for 1 year, and the response was persistent in 2 and 3 patients on the basis of MNSC and LDSC levels, respectively. Lower baseline serum cortisol (basal, MNSC, and LDSC) values were predictive of a therapeutic response.ConclusionCabergoline was an effective therapy in 28%, 25%, and 17% of patients with uncured Cushing disease in terms of LDSC or MNSC (or both), LDSC alone, and MNSC alone, respectively. Further studies are needed to address the persistence of the drug response and the effects on the dynamics of the hypothalamic-pituitary-adrenal axis. (Endocr Pract. 2010;16:968-976)     

Iatrogenic Cushing Syndrome in Patients Receiving Inhaled Budesonide and Itraconazole or Ritonavir: Two Cases and Literature Review

ObjectiveTo present two cases of iatrogenic Cushing syndrome caused by the interaction of budesonide, an inhaled glucocorticoid, with ritonavir and itraconazole.MethodsWe present the clinical and biochemical data of two patients in whom diagnosis of Cushing syndrome was caused by this interaction. We also reviewed the pertinent literature and management options.ResultsA 71-year-old man was treated with inhaled budesonide for a chronic obstructive pulmonary disease and itraconazole for a pulmonary aspergillosis. The patient rapidly developed a typical Cushing syndrome complicated by bilateral avascular necrosis of the femoral heads. Serum 8:00 AM cortisol concentrations were suppressed at 0.76 and 0.83 µg/dL on two occasions. The patient died 4 days later of a massive myocardial infarction. The second case is a 46-year-old woman who was treated for several years with inhaled budesonide for asthma. She was put on ritonavir, a retroviral protease inhibitor, for the treatment of human immunodeficiency virus (HIV). In the following months, she developed typical signs of Cushing syndrome. Her morning serum cortisol concentration was 1.92 µg/dL. A cosyntropin stimulation test showed values of serum cortisol of <1.10, 2.65, and 5.36 µg/dL at 0, 30, and 60 minutes, respectively, confirming an adrenal insufficiency. Because the patient was unable to stop budesonide, she was advised to reduce the frequency of its administration and eventually taper the dose until cessation.ConclusionClinicians should be aware of the potential occurrence of iatrogenic Cushing syndrome and secondary adrenal insufficiency due to the association of inhaled corticosteroids with itraconazole or ritonavir. (Endocr. Pract. 2013;19:e138-e141)     

Relationship between urinary heavy metals with metabolic syndrome and its components in population from Hoveyzeh cohort study: A case-control study in Iran

BackgroundThe incidence of Metabolic Syndrome (MetS) has been growing rapidly and is rising to pandemic proportions. Although obesity is a primary risk factor for the enhancement of these conditions, not all obese individuals develop metabolic syndrome, indicating that the risk for developing MetS is impacted by other genetic and/or environmental factors such as heavy metals. Therefore, the present study focused on the association between exposures to heavy metal and MetS.MethodsUrine samples were collected from 150 participants (75 patients with MetS and 75 healthy participants), which were used from Hoveyzeh Cohort center. To make a quantitative comparison between the two groups, Man-Whitney nonparametric test was used. The logistic regression was performed adjusted for age, demographic, lifestyle factor, physical activity, occupational history and urine creatinine.ResultsThe results of logistic regression showed that OR and 95 % CI for Cd, Pb, Sr, As and Fe concentration were still significant after adjusting for urine creatinine. Moreover, there was a relationship between Cd and Pb levels and waist circumstance (WC). After adjusting for urine creatinine, age, sex, occupation, smoking status, education and place of residence, only Pb concentration was showed a significant association with systolic blood pressure (SBP). The subjects with high urine level of Cd had the high odds (OR: 6.273; 95 % Cl: 1.783–22.070) of MetS and low high-density lipoprotein (HDL-C). The relationship between As concentration and high fasting blood sugars confirmed the previous evidence suggesting that high As level can cause diabetes.ConclusionThese results indicated that outbreak of MetS and its component are associated with heavy metal concentrations in urine.     

Multidisciplinary Approach including Receptor Radionuclide Therapy with 90Y-DOTATOC ([90Y-DOTA0,Tyr3]-OCTREOTIDE) and 177Lu-DOTATATE ([177Lu-DOTA0,Tyr3]-OCTREOTATE) in Ectopic Cushing Syndrome from Ametastatic Gastrinoma: A Promising Proposal

ObjectiveTo present a case of a young woman with Cushing syndrome caused by ectopic production of adrenocorticotropic hormone from a metastatic pancreatic gastrin-secreting endocrine carcinoma, who had a good response to combination peptide receptor radionuclide therapy.MethodsWe review the history, physical examination, laboratory investigations, and radiographic findings in this unusual patient. Moreover, the multimodal interventions are described and discussed.ResultsIn a 38-year-old woman with typical signs of cortisol excess, laboratory studies revealed diabetes mellitus, hypokalemia, and high levels of adrenocorticotropic hormone, plasma cortisol, and urinary cortisol. Abdominal computed tomography showed a 4-cm pancreatic mass and multiple metastatic lesions in the liver, and ectopic Cushing syndrome was diagnosed. Treatment consisted of surgical debulking of the tumor, ketoconazole, somatostatin analogues, chemoembolization of the liver metastatic lesions, and peptide receptor radionuclide therapy with the radiolabeled somatostatin analogues ⁹⁰Y-DOTATOC ([⁹⁰Y-DOTA⁰,Tyr³]-octreotide) and ¹⁷⁷Lu-DOTATATE ([¹⁷⁷Lu-DOTA⁰,Tyr³]-octreotate). The 5¹/2-year follow-up showed positive results, which included complete regression of all clinical and hormonal evidence of the tumor and substantial decrease in the size and number of hepatic metastatic lesions. The patient achieved and still maintains an optimal quality of life.ConclusionTo the best of our knowledge, this is the first report of a multidisciplinary approach including peptide receptor radionuclide therapy with ⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE, which proved to be effective in improving clinical outcome in a case of metastatic endocrine carcinoma of the pancreas in conjunction with ectopic Cushing syndrome. In this unusual case, the patient has one of the longest durations of survival in this setting described in the literature. (Endocr Pract. 2008; 14:213-218)     

Cushing’s Disease and Pregnancy: Case Report and Literature Review

ObjectiveTo describe a patient with untreated Cushing’s disease who had 2 spontaneous pregnancies that resulted in healthy babies on both occasions.MethodsWe present a case report with clinical, laboratory, and imaging data and discuss the literature pertaining to pregnancy in patients with Cushing’s syndrome.ResultsA 28-year-old woman came to our endocrinology clinic with a 1-year history of symptoms and signs of Cushing’s syndrome. An elevated 24-hour urinary cortisol excretion and an unsuppressed 1-mg overnight dexamethasone test confirmed the diagnosis. On her next visit, she reported a confirmed pregnancy, which ultimately resulted in the birth of a normal child. Further work-up subsequently showed 2 elevated 24-hour urinary cortisol values, loss of diurnal variation, and an elevated corticotropin level. There was lack of suppression on low-dose and high-dose overnight dexamethasone suppression tests. Magnetic resonance imaging of the pituitary showed normal findings. Inferior petrosal sinus sampling was recommended, but she declined the procedure. The patient returned 3 years later for reevaluation, at which time she reported the birth of another healthy child by cesarean delivery 10 months previously. There were no reported maternal or fetal complications. Examination at this visit revealed buccal pigmentation and proximal myopathy. Investigations showed increased 24-hour urinary cortisol excretion and serum corticotropin levels. Repeated magnetic resonance imaging disclosed a microadenoma on the right side of the pituitary. Unstimulated inferior petrosal sinus sampling showed a gradient to the right; thus, the presence of pituitary-dependent Cushing’s disease was confirmed.ConclusionOur case demonstrates that patients with pituitary-dependent Cushing’s disease are more likely to have spontaneous pregnancies with favorable outcomes than are patients with Cushing’s syndrome due to other causes. Our patient, despite having Cushing’s disease for more than 7 years, had 2 uneventful pregnancies that produced normal healthy children, without exacerbation of her disease during pregnancy. (Endocr Pract. 2007;13: 296-299)     

Cushing's Syndrome Due to Ectopic Adrenocorticotrophic Hormone Production by Olfactory Neuroblastoma

ObjectiveTo review a case of olfactory neuroblastoma (ON) with Cushing’s syndrome (CS) due to ectopic production of adrenocorticotrophic hormone (ACTH) and compare the histopathologic diagnosis, treatment modality, and prognostic factors with the literature.MethodsWe report the clinical presentation, biochemistry, imaging, histopathology, treatment, and outcome of a patient with ON. We conducted an English language literature review of CS due to ectopic ACTH production and ON.ResultsCS due to ectopic ACTH production is uncommon, and CS due to ON is extremely rare. A 19-year-old Hispanic man presented with right nasal obstruction, involuntary weight gain, and intensely pruritic skin rash. Examination revealed large, wide purple striae on both arms and the abdomen. Head magnetic resonance imaging (MRI) revealed a right ethmoid sinus enhancing mass extending into the orbit, nasal cavity, and maxillary and sphenoid sinuses. Laboratory results showed a pm cortisol level of 26 mcg/dL, a 24-hour urinary free cortisol level of 7,507 mcg, an ACTH level of 83 pg/mL, and nonsuppression of cortisol with an overnight dexamethasone suppression test (1 and 8 mg). A biopsy revealed ON, and immunohistochemistry (IHC) was positive for ACTH. He underwent chemotherapy followed by surgical debulking and adjuvant radiation therapy, with no disease recurrence through the last follow-up in February 2012. Plasma and urinary cortisol levels normalized following surgery.ConclusionThis is the first case reported of a Hispanic male with an uncommon tumor (ON) and an even more uncommon presentation, ectopic ACTH production causing CS. The extremely high ACTH levels and plasma and urine cortisol levels dramatically dropped following multimodality management. So far, he has had 2.5 years of disease-free survival. (Endocr Pract. 2014;20:e47-e52)     

Spontaneous pasteurellosis in captive Rocky Mountain bighorn sheep (Ovis canadensis canadensis): clinical, laboratory, and epizootiological observations.

We observed clinical signs, compared adrenal responses, and performed diagnostic tests on 12 captive Rocky Mountain bighorn sheep (Ovis canadensis canadensis) during a spontaneous outbreak of pasteurellosis. Cortisol in urine and feces was measured for bighorns sampled three times between 20 October and 1 November 1986. By 6 November, four of these had developed pneumonia, four showed only mild rhinitis, and four remained clinically normal. Bighorns that ultimately developed pneumonia showed elevated mean urinary (P = 0.003) and fecal (P = 0.046) cortisol excretion over the 12-day sampling period. Twenty-four hour mean urine cortisol: creatinine ratios ranged from 10 to 57 ng/mg dry matter for affected and 5 to 22 ng/mg for healthy individuals; 24 hr mean fecal cortisol concentrations ranged from 7.2 to 20 ng/g dry matter for affected and 3.6 to 9.1 ng/g dry matter for healthy individuals. Elevated cortisol excretion preceded clinical pneumonia in affected bighorns by less than or equal to 16 days. Beta-hemolytic Pasteurella haemolytica biotype T, serotype 3 or 4, was isolated from nasal and pharyngeal swabs from all eight bighorns with pneumonia or mild rhinitis. We detected no evidence of parainfluenza 3, bovine respiratory syncytial virus, or Chlamydia psittaci using fluorescent antibody and/or serologic tests. Although elevated cortisol excretion was associated with pneumonia, we also believe age, reproductive physiology, and/or prior recovery from clinical pasteurellosis may have influenced individual susceptibility to pneumonia during this epizootic.     

Corticotropin-Independent Macronodular Adrenal Hyperplasia Associated With Insulinoma

ObjectiveTo report a case of corticotropin-independent macronodular adrenal hyperplasia (AIMAH) associated with an insulinoma.MethodsWe describe the clinical, radiographic, laboratory, and histopathologic findings of the study patient; review the current protocols for management of AIMAH; and discuss the disease etiology.ResultsA 64-year-old woman with multiple intradermal facial nevi experienced intermittent light-headedness, tremor, and confusion and was found to have a venous plasma glucose concentration of 52 mg/dL. Hypoglycemia and hyperinsulinemia after 18 hours of fasting suggested the presence of an insulinoma. Hepatic venous sampling for insulin after selective arterial calcium injection localized the insulinoma to the pancreatic head. The insulinoma was excised, and there was no recurrence over the 5 years the patient was in our care. During the workup for insulinoma, bilateral adrenal masses were incidentally discovered on computed tomography. Twenty-hour urinary free cortisol excretion was elevated and serum corticotropin was suppressed. Overt signs of Cushing syndrome were not present, and subsequent urinary cortisol measurements were within the reference range for several years. After 4 years, Cushing syndrome developed and bilateral adrenalectomy was performed. AIMAH was diagnosed on the basis of histopathologic findings.ConclusionsThis appears to be the first reported case of AIMAH associated with an insulinoma. In the absence of other stigmata of multiple endocrine neoplasm type 1 and in the presence of multiple nevi, it may represent a novel endocrine syndrome. (Endocr Pract. 2011;17:e43-e47)     

Should We Use Prolactin Adjustment in Bilateral Inferior Petrosal Sinus Sampling to Diagnose Cushing Disease? A Joint Meta-Analysis of Head-to-Head Diagnostic Tests Accuracy Studies

ObjectivePrevious studies have shown inconsistent results regarding the usefulness of prolactin adjustment in bilateral inferior petrosal sinus sampling (BIPSS) in the differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome (CS). This meta-analysis compared the diagnostic accuracy of prolactin adjustment versus no adjustment in BIPSS.MethodsThis study searched the PubMed, Embase, Web of Science, Cochrane library, and WanFang databases for published data as of March 2022 on the use of prolactin adjustment in BIPSS to differentially diagnose ACTH-dependent CS. A Bayesian joint bivariate model was used in the head-to-head comparison of the diagnostic accuracy.ResultsThis meta-analysis included a total of 10 studies with 300 patients. The combined sensitivity and specificity for BIPSS without prolactin adjustment were 94.47% (95% CI, 88.67%-98.44%) and 91.14% (95% CI, 57.17%-99.80%), respectively. The combined sensitivity and specificity after prolactin adjustment were 99.97% (95% CI, 99.03%-100.00%) and 80.69% (95% CI, 50.27%-97.82%), respectively. After the prolactin adjustment, the sensitivity of BIPSS to diagnose Cushing disease was improved with a statistically significant difference (difference in sensitivity, 5.39%; 95% CI, 1.37%-11.26%), whereas the decrease in specificity was without a statistically significant difference (difference in specificity, −9.20%; 95% CI, −42.02% to 26.61%).ConclusionThis meta-analysis indicated that prolactin adjustment in BIPSS might help to recognize Cushing disease among patient with ACTH-dependent CS. However, prolactin adjustment may not help identify ectopic ACTH syndrome in BIPSS.     

Postnatal disappearance of the pregnancy-associated reduced sensitivity of plasma cortisol to feedback inhibition

We recently observed that the characteristic insensitivity of the pituitary-adrenal system in women to feedback inhibition during pregnancy persists for at least four days postnatally. We therefore examined women during the first five weeks after delivery to assess when the sensitivity of plasma cortisol to glucocorticoid inhibition returns to normal. Dexamethasone (DEXA, 1 mg) was ingested at 11 pm by normal healthy women, once between the 3rd and 27th postnatal days, and again on day 35. Blood plasma was collected at 4 pm on the following day for cortisol assay. Plasma cortisol levels (nmol/L, mean +/- sem [n]) after DEXA in the first two weeks (216 +/- 28, [47]) were higher (p less than 0.001) than in nonmedicated nonpregnant women (47.4 +/- 8.9 [12]) and were normal by the 35th day after delivery (41.7 +/- 4.8 [74]). A negative association was found between post-DEXA cortisol and time after delivery in the first 4 post-partum weeks (r = -0.46, p less than 0.001). The study confirms that insensitivity of plasma cortisol to feedback inhibition persists beyond normal pregnancy in a significant proportion of healthy women for two to three weeks, and is absent by the 5th postnatal week.     

Narrow-band ultraviolet B (NB UV-B) exposures improve mood in healthy individuals differently depending on chronotype

ABSTRACT

The evening chronotype is associated with psychological symptoms such as depressed mood, while skin exposure to ultraviolet radiation (UVR) may affect mood and behavior through neural and humoral routes. This pilot study aimed to investigate the impact of whole-body narrow-band (NB) UV-B exposure on current mood state and circulating 25-hydroxyvitamin D3 (25(OH)D₃), interleukin-6 (IL-6), cortisol and β-endorphin (β-END) levels in healthy participants. Here, eleven healthy women received full-body NB UV-B exposures on four afternoons, and the chronotype was assessed with a shortened version of Horne and Östberg’s Morningness-Eveningness Questionnaire (MEQ). Perceived mood was evaluated using the Visual Analogue Scale (VAS), and serum 25(OH)D₃, IL-6, cortisol and β-END concentrations were monitored daily. Decreasing VAS values showed mood to improve significantly over the five days after the four suberythematous NB UV-B exposures (p = .038), and the more the circadian preference was inclined toward eveningness, the greater the improvement in the mood dimension of wellbeing (p = .021). Baseline mood state was correlated with baseline 25(OH)D₃ (r = ?0.54, 95% CI: ?0.86 to ?0.09) and with baseline cortisol (r = ?0.57, 95% CI: ?0.87 to ?0.04). During the NB UV-B exposures, 25(OH)D₃ increased significantly, as expected, and IL-6 declined significantly by ?0.35 (95% CI: ?0.69 to ?0.07) pg/mL from the initial values of 1.12 ± 0.66 pg/mL (p = .025). In conclusion, in our pilot study, NB UV-B exposure improved mood, especially among those with evening preference for their daily activities, as well as circulating 25(OH)D₃ levels, whereas circulating IL-6 levels decreased.

Abbreviations: UVR: Ultraviolet radiation; NB UV-B: narrow-band UV-B; VAS: Visual Analogue Scales; β-END: β-endorphin; IL-6: Interleukin-6     

环境丰容对笼养川金丝猴日常行为以及粪便皮质醇水平的影响

在笼养条件下,由于有限的空间和单调的笼舍结构,川金丝猴行为和生理指标发生变化,包括出现刻板行为和产生较高的粪便内应激激素。本论文旨在研究环境丰容对笼养川金丝猴日常行为以及粪便皮质醇水平的影响。于2013年8月1日至11月1日对杭州动物园内7只川金丝猴进行环境丰容后的行为观察。采用瞬时扫描法记录上午08:30-10:30和下午14:00-16：00的动物行为,并统计15种行为的发生频率。比较丰容前后每种行为的发生频率,结果表明环境丰容降低了川金丝猴的不活跃行为（P=0.021）和刻板行为（P=0.034）,增加了其活跃行为频率（P=0.018）。环境丰容后,动物表现出更多的攀爬（P = 0.012）、探究（P = 0.014）和环顾行为（P = 0.010）。粪便皮质醇激素的结果表明,除1只雄性个体激素上升外,其余6只个体的粪便皮质醇含量显著下降（P=0.028）。以上结果提示环境丰容可改善川金丝猴的福利状况。     

Sex-specific difference in the interconversion of cortisol and cortisone in men and women

Objective: Our objective was to demonstrate that the smaller oxoreductase activity of 11β‐HSD1 in women would shift the interconversion of cortisol and cortisone toward cortisone, resulting in a larger amount of generated labeled cortisone in healthy women than in healthy men. Research Methods and Procedures: Using mass spectrometry, the amount of cortisone generated from a continuous infusion (8 am to 6 pm ) of stable‐labeled cortisol (1α,2α‐d‐cortisol) was determined in non‐obese and in obese (BMI >35 kg/m²) men and women during steady‐state conditions (from 2 pm to 6 pm ). In this setting, the amount of generated labeled cortisone (expressed as % of the achieved steady‐state concentrations of labeled cortisol) reflects the sum of the bi‐directional conversion of cortisol into cortisone (and vice versa) by 11β‐hydroxysteroid dehydrogenase. Results: The amount of generated labeled cortisone was higher in men than in women (p < 0.0001). This sex difference was higher in obese than in non‐obese patients (p = 0.0062). Conclusions: The interconversion of cortisol and cortisone during steady‐state conditions is shifted toward cortisol in men as compared with women. This suggests a higher overall oxoreductase activity of 11β‐hydroxysteroid dehydrogenase type 1 in men than in women. This sex‐specific difference is maintained in obesity.     

The role of urinary KIM-1, NGAL,CA19-9 and β2-microglobulin in the assessment of ureteropelvic junction obstruction in adults

Purpose: The objective of this study is to evaluate the diagnostic properties of urinary biomarkers in adults with ureteropelvic junction obstruction: KIM-1, NGAL, CA19-9, and β2-microglobulin. We also assessed urinary biomarker concentrations following pyeloplasty.

Material and methods: We prospectively studied adults from December 2013 to February 2015. We included 47 patients with a mean age of 38.6?±?12.7 years. Each patient provided four samples of voided urine for biomarker measurement, one at pre-operative consultation and the others at 1, 3, and 6 months of post-operative follow-up. The control group consisted of 40 healthy individuals with no hydronephrosis on ultrasound evaluation.

Results: KIM-1 had an area under the curve of 0.79 (95% CI 0.70–0.89), NGAL 0.71 (95% CI 0.61–0.83), CA19-9 0.70 (95% CI 0.60–0.81), and β2-microgloblin 0.61 (95% CI 0.50–0.73). KIM-1 was the most sensitive marker with a cut-off of 170.4?pg/mg creatinine (sensitivity 91.4%, specificity 59.1%), whereas CA19-9 was the most specific with a cut-off of 51.3?U/mg creatinine (sensitivity 48.9%, specificity 88.0%). Urinary concentrations of biomarkers decreased after pyeloplasty.

Conclusions: The evaluation of urinary biomarkers is useful in adults undergoing pyeloplasty. KIM-1, NGAL, and CA19-9 were elevated and significantly decreased after surgery.     

Atypical Clinical Presentation of Acth-Dependent Cushing's Syndrome in a Patient Treated with Retinoic Acid

ObjectiveThe leading signs and symptoms of Cushing’s syndrome (CS) in adolescents, which depend on the duration and the severity of hypercortisolemia, are: a decrease in growth velocity with an increase in body weight, redistribution of fat tissue (round face), and less commonly, acne due to hyperandrogenization. A widely used antiacne drug, retinoic acid, can change the clinical presentation of CS and delay the diagnosis.MethodsWe report an atypical presentation of adrenocorticotropic hormone (ACTH)-dependent CS in a patient treated with retinoic acid due to severe acne.ResultsThree months after the discontinuation of retinoic acid treatment (at a dose of 40 mg daily for 6 months, with a 4 month break and then for an additional 6 months), a 17.5-year-old male presented with short stature (− 3.0 SD), muscle weakness, difficulty concentrating, insomnia, and depressed mood. Body weight (body mass index, 22 kg/m²), fat tissue distribution, pubertal status (testicular volume equal to 20 mL, pubarche V, axillarche present), and blood pressure were normal, and the patient’s bone age was equal to his chronologic age. His bone mineral density was decreased (Z-score, − 3.5 SD). The morning serum cortisol level was normal (8:00 am, 171.9 ng/mL) and did not decrease in the evening (8:00 pm, 178.9 ng/mL) or after 1 mg of dexamethasone (100.4 ng/mL). The patient’s urinary free cortisol was elevated on 3 occasions (274.5, 217.3, and 253.7 μg/day). Increased ACTH levels in the morning (97.5 to 141.1 pg/mL) and postcorticoliberine (577.6 pg/mL) pointed to ACTH-dependent CS. A magnetic resonance imaging scan of the pituitary gland confirmed the presence of a microadenoma.ConclusionRetinoic acid treatment may alter the clinical presentation of ACTH-dependent CS and consequently delay the diagnosis. (Endocr Pract. 2014;20:e119-e122)     

Assessment of the Utility of the High-Dose Dexamethasone Suppression Test in Confirming the Diagnosis of Cushing Disease

ObjectiveTo determine the utility of high-dose dexamethasone suppression (HDDS) tests to confirm the diagnosis of Cushing disease (CD).MethodsIn this retrospective study, we reviewed medical records of patients who underwent either the overnight 8-mg HDDS test or the 2-day 2-mg HDDS test every 6 hours. The percentage suppression of morning serum cortisol and the percentage suppression of 24-hour urine free cortisol (UFC) were calculated.ResultsOf 141 patients with proven CD who underwent HDDS tests, 77 (55%) underwent the overnight 8-mg HDDS test and 64 (45%) underwent the 2-day 2-mg HDDS test every 6 hours. With the overnight 8-mg HDDS test, 73 of 77 patients (95%) had greater than 50% suppression and 48 of 77 patients (62%) had greater than 80% suppression of the morning serum cortisol in comparison with the baseline value. With the 2-day 2-mg HDDS test, only 41 of 64 patients (64%) had greater than 90% suppression of 24-hour UFC.ConclusionWe conclude that the overnight 8-mg HDDS test accurately confirmed the diagnosis of CD with a high sensitivity of 95% with use of a criterion of greater than 50% suppression; in contrast, the sensitivity was only 62% with use of a more precise cutoff of greater than 80% suppression. The 2-day 2-mg HDDS test with a criterion of greater than 90% suppression of 24-hour UFC had a sensitivity of 64%. These results confirm the limited precision of the HDDS tests. (Endocr Pract. 2012;18:152-157)