Ninet Sinaii

Estimating population prevalence of posttraumatic stress disorder: An example using the PTSD checklist†

The PTSD Checklist (PCL) is among the most widely used self-report instruments for assessing PTSD. To determine PCLs performance on a population level, the authors combined data from published studies that compared the PCL with structured diagnostic interviews. Weighted average sensitivities and specificities were calculated for cutoff categories most often reported in the literature. Weighted average sensitivity decreased from .85 to .39 and specificity increased from .73 to .97 for cutoffs ranging from 30 to 60. The PCLs ability to accurately estimate PTSD prevalence varied as a function of cutoff and true PTSD prevalence. In populations with a true PTSD prevalence of 15% or less, cutoff values below 44 will substantially overestimate PTSD prevalence. Uncalibrated use of the PCL for prevalence estimation may lead to large errors.

Clinical characteristics of a cohort of 244 patients with congenital adrenal hyperplasia.

CONTEXT Patients with congenital adrenal hyperplasia (CAH) often suffer from long-term complications secondary to chronic glucocorticoid therapy and suboptimal treatment regimens. OBJECTIVE The aim of the study was to describe clinical characteristics of a large cohort of pediatric and adult CAH patients. DESIGN AND SETTING We conducted a cross-sectional study of 244 CAH patients [183 classic, 61 nonclassic (NC)] included in a Natural History Study at the National Institutes of Health. MAIN OUTCOME MEASURE(S) Outcome variables of interest were height sd score, obesity, hypertensive blood pressure (BP), insulin resistance, metabolic syndrome, bone mineral density, hirsutism (females), and testicular adrenal rest (TART). RESULTS The majority had elevated or suppressed androgens, with varied treatment regimens. Mean adult height SD score was -1.0 ± 1.1 for classic vs. -0.4 ± 0.9 for NC patients (P = 0.015). Obesity was present in approximately one third of patients, across phenotypes. Elevated BP was more common in classic than NC patients (P ≤ 0.01); pediatric hypertensive BP was associated with suppressed plasma renin activity (P = 0.001). Insulin resistance was common in classic children (27%) and adults (38% classic, 20% NC); 18% of adults had metabolic syndrome. The majority (61%) had low vitamin D; 37% of adults had low bone mineral density. Hirsutism was common (32% classic; 59% NC women). TART was found in classic males (33% boys; 44% men). CONCLUSIONS Poor hormonal control and adverse outcomes are common in CAH, necessitating new treatments. Routine monitoring of classic children should include measuring BP and plasma renin activity. Osteoporosis prophylaxis and TART screening should begin during childhood. A longitudinal study is under way.

Long-Term Treatment of 12 Children with Chronic Hypoparathyroidism: A Randomized Trial Comparing Synthetic Human Parathyroid Hormone 1-34 versus Calcitriol and Calcium

CONTEXT Hypoparathyroidism is among the few hormonal insufficiency states not treated with replacement of the missing hormone. This is the first randomized controlled study in children comparing treatment with synthetic human PTH 1-34 and calcitriol. OBJECTIVE The primary objective was to assess the efficacy and safety of long-term PTH 1-34 vs. calcitriol treatment in the maintenance of normal serum calcium values and renal calcium excretion in children with hypoparathyroidism. SETTING The study was conducted at a clinical research center. SUBJECTS Subjects included 12 children aged 5-14 yr with chronic hypoparathyroidism and without severe renal or hepatic insufficiency. STUDY DESIGN The study was a 3-yr randomized parallel trial comparing twice-daily calcitriol (plus calcium and cholecalciferol in four daily doses) vs. s.c. PTH 1-34 treatment, with weekly or biweekly monitoring of serum and urine calcium. RESULTS Mean predose serum calcium levels were maintained at, or just below, the normal range, and urine calcium levels remained in the normal range throughout the 3-yr study, with no significant differences between treatment groups. Creatinine clearance, corrected for body surface area, did not differ between groups and remained normal throughout the study. Markers of bone turnover were mildly elevated during PTH 1-34 therapy and remained within the normal range during calcitriol therapy. Mean bone mineral density Z-scores at the anterior-posterior lumbar spine, femoral neck, distal radius, and whole body remained within the normal range and did not differ between groups throughout the study. Similarly, height and weight percentiles did not differ between treatment groups and remained normal throughout the 3-yr follow-up. CONCLUSION We conclude that PTH 1-34 therapy is safe and effective in maintaining stable calcium homeostasis in children with hypoparathyroidism. Additionally, PTH 1-34 treatment allowed normal skeletal development because there were no differences in bone mineral accrual, linear growth, or weight gain between the two treatment arms over the 3-yr study period.

Return of Chronic Pelvic Pain From Endometriosis After Raloxifene Treatment: A Randomized Controlled Trial

OBJECTIVE: To evaluate whether 6 months of raloxifene was effective in treatment of chronic pelvic pain in women with endometriosis. METHODS: Women with chronic pelvic pain and no endometriosis treatment for 6 months underwent laparoscopy for excision of all lesions. Those with biopsy-proven endometriosis were randomly allocated to raloxifene (180 mg) or placebo daily. A second laparoscopy was performed at 2 years, or earlier, if pain returned. Return of pain was defined as 2 months of pain equal to or more severe than that at study entry. Menstrual cycles and adverse events were recorded. The log rank test was used to compare the time to return of pain by drug group. Analyses were done as intent-to-treat. RESULTS: A total of 127 of 158 women underwent surgery. Of these, 93 had biopsy-confirmed endometriosis and were randomly assigned to study treatment. Menstrual cycle length, pelvic pain severity, quality of life, bone mineral density, and adverse events did not differ between treatment groups. The Data Safety Monitoring Committee terminated the study early when the raloxifene group experienced pain (P=.03) and had second surgery (P=.016) significantly sooner than the placebo group. Interestingly, biopsy-proven endometriosis was not associated with return of pain (P=.6). CONCLUSION: Raloxifene significantly shortened the time to return of chronic pelvic pain. Because recurrence of endometriosis lesions did not correlate with return of pain, other factors are implicated in pelvic pain. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.cliicaltrials.gov, NCT00001848 LEVEL OF EVIDENCE: I

Cortisol, obesity, and the metabolic syndrome: A cross-sectional study of obese subjects and review of the literature†‡

Circulating cortisol and psychosocial stress may contribute to the pathogenesis of obesity and metabolic syndrome (MS). To evaluate these relationships, a cross‐sectional study of 369 overweight and obese subjects and 60 healthy volunteers was performed and reviewed the previous literature.

Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis

OBJECTIVE To determine whether first physician seen and symptoms beginning in adolescence have an impact on the diagnostic experience of endometriosis. DESIGN Cross-sectional study of self-reported survey data. SETTING Academic research. PATIENT(S) Four thousand three hundred thirty-four Endometriosis Association Survey respondents reporting surgical diagnosis of endometriosis. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Specialty of first physician seen, timing of onset of symptoms, time to seeking medical care and to diagnosis, number of physicians seen, and satisfaction with care. RESULT(S) Almost all respondents reported pelvic pain. Fifty percent first saw a gynecologist and 45% saw a generalist for symptoms related to endometriosis. Two thirds reported symptoms beginning during adolescence; they waited longer to seek medical care than adults did. Those seeing a generalist first took longest to get diagnosed; those seeing a gynecologist first saw fewer physicians. Sometime before diagnosis, 63% were told nothing was wrong with them. CONCLUSION(S) Women and girls who reported seeing a gynecologist first for symptoms related to endometriosis were more likely to have a shorter time to diagnosis, to see fewer physicians, and to report a better experience overall with their physicians. The majority reported symptoms beginning during adolescence, also reporting a longer time and worse experience while obtaining a diagnosis.

Effects of Once Versus Twice-Daily Parathyroid Hormone 1–34 Therapy in Children with Hypoparathyroidism

CONTEXT Hypoparathyroidism is among the few hormonal insufficiency states not treated with replacement of the missing hormone. Long-term conventional therapy with vitamin D and analogs may lead to nephrocalcinosis and renal insufficiency. OBJECTIVE Our objective was to compare the response of once-daily vs. twice-daily PTH 1-34 treatment in children with hypoparathyroidism. SETTING The study was conducted at a clinical research center. SUBJECTS Fourteen children ages 4-17 yr with chronic hypoparathyroidism were studied. STUDY DESIGN This was a randomized cross-over trial, lasting 28 wk, which compared two dose regimens, once-daily vs. twice-daily PTH1-34. Each 14-wk study arm was divided into a 2-wk inpatient dose-adjustment phase and a 12-wk outpatient phase. RESULTS Mean predose serum calcium was maintained at levels just below the normal range. Repeated serum measures over a 24-h period showed that twice-daily PTH 1-34 increased serum calcium and magnesium levels more effectively than a once-daily dose. This was especially evident during the second half of the day (12-24 h). PTH 1-34 normalized mean 24-h urine calcium excretion on both treatment schedules. This was achieved with half the PTH 1-34 dose during the twice-daily regimen compared with the once-daily regimen (twice-daily, 25 +/-15 microg/d vs. once-daily, 58 +/- 28 microg/d; P < 0.001). CONCLUSIONS We conclude that a twice-daily PTH 1-34 regimen provides a more effective treatment of hypoparathyroidism compared with once-daily treatment because it reduces the variation in serum calcium levels and accomplishes this at a lower total daily PTH 1-34 dose. The results showed, as in the previous study of adult patients with hypoparathyroidism, that a twice-daily regimen produced significantly improved metabolic control compared with once-daily PTH 1-34.

A pharmacokinetic and pharmacodynamic study of delayed- and extended-release hydrocortisone (Chronocort) vs. conventional hydrocortisone (Cortef) in the treatment of congenital adrenal hyperplasia.

Objective  Existing glucocorticoid treatment for congenital adrenal hyperplasia (CAH) is suboptimal and nonphysiological. We compared hormonal profiles during therapy with a new modified‐release hydrocortisone (MR‐HC), Chronocort™, to conventional hydrocortisone (HC), Cortef™, in patients with CAH.

Macronodular Adrenal Hyperplasia due to Mutations in an Armadillo Repeat Containing 5 (ARMC5) Gene: A Clinical and Genetic Investigation

CONTEXT Inactivating germline mutations of the probable tumor suppressor gene, armadillo repeat containing 5 (ARMC5), have recently been identified as a genetic cause of macronodular adrenal hyperplasia (MAH). OBJECTIVE We searched for ARMC5 mutations in a large cohort of patients with MAH. The clinical phenotype of patients with and without ARMC5 mutations was compared. METHODS Blood DNA from 34 MAH patients was genotyped using Sanger sequencing. Diurnal serum cortisol measurements, plasma ACTH levels, urinary steroids, 6-day Liddles test, adrenal computed tomography, and weight of adrenal glands at adrenalectomy were assessed. RESULTS Germline ARMC5 mutations were found in 15 of 34 patients (44.1%). In silico analysis of the mutations indicated that seven (20.6%) predicted major implications for gene function. Late-night cortisol levels were higher in patients with ARMC5-damaging mutations compared with those without and/or with nonpathogenic mutations (14.5 ± 5.6 vs 6.7 ± 4.3, P < .001). All patients carrying a pathogenic ARMC5 mutation had clinical Cushings syndrome (seven of seven, 100%) compared with 14 of 27 (52%) of those without or with mutations that were predicted to be benign (P = .029). Repeated-measures analysis showed overall higher urinary 17-hydroxycorticosteroids and free cortisol values in the patients with ARMC5-damaging mutations during the 6-day Liddles test (P = .0002). CONCLUSIONS ARMC5 mutations are implicated in clinically severe Cushings syndrome associated with MAH. Knowledge of a patients ARMC5 status has important clinical implications for the diagnosis of Cushings syndrome and genetic counseling of patients and their families.

Specificity of Screening Tests for Cushing’s Syndrome in an Overweight and Obese Population

CONTEXT Recent reports suggest a higher prevalence (1-5%) of Cushings syndrome in certain patient populations with features of the disorder (e.g., diabetes), but the prevalence in the overweight and obese population is not known. OBJECTIVE The aim of the study was to evaluate the diagnostic performance of screening tests for Cushings syndrome in overweight and obese subjects with at least two other features of the disorder. DESIGN AND SETTING We conducted a cross-sectional prospective study. SUBJECTS AND METHODS A total of 369 subjects (73% female) completed two or three tests: a 24-h urine cortisol, and/or late-night salivary cortisol, and/or 1 mg dexamethasone suppression test (DST). If any result was abnormal [based on laboratory reference range or cortisol after DST > or = 1.8 microg/dl (50 nmol/liter)], tests were repeated and/or a dexamethasone-CRH test was performed. Subjects with abnormal DST results and a low dexamethasone level were asked to repeat the test with 2 mg of dexamethasone. RESULTS In addition to obesity, subjects had a mean of five to six features of Cushings syndrome. None was found to have Cushings syndrome. Test specificities to exclude Cushings syndrome for subjects who completed three tests were: urine cortisol, 96% [95% confidence interval (CI), 93-98%]; DST, 90% (95% CI, 87-93%); salivary cortisol, 84% by RIA (95% CI, 79-89%) and 92% by liquid chromatography-tandem mass spectrometry (95% CI, 88-95%). The combined specificity (both tests normal) for all combinations of two tests was 84 to 90%, with overlapping CIs. CONCLUSION These data do not support widespread screening of overweight and obese subjects for Cushings syndrome; test results for such patients may be falsely abnormal.