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ABSTRACT: Background:Observational studies show that glucocorticoid therapy and the endogenous hypercortisolism of Cushing's syndrome (CS) are associated with increased rates of cardiovascular morbidity and mortality. However, the causes of these findings remain largely unknown.Objective:To determine whether CS patients have increased coronary atherosclerosis.Design:A prospective case-control study was performed.Setting:Subjects were evaulated in a clinical research center.Subjects:Fifteen consecutive patients with ACTH-dependent CS, 14 due to an ectopic source and 1 due to pituitary Cushing's disease were recruited. Eleven patients were studied when hypercortisolemic; 4 patients were eucortisolemic due to medication (3) or cyclic hypercortisolism (1). Fifteen control subjects with at least one risk factor for cardiac disease were matched 1:1 for age, sex, and body mass index.Primary outcome variables:Agatston score a measure of calcified plaque and non-calcified coronary plaque volume were quantified using a multidetector CT (MDCT) coronary angiogram scan. Additional variables included fasting lipids, blood pressure, history of hypertension or diabetes, and 24-hour urine free cortisol excretion.Results:CS patients had significantly greater noncalcified plaque volume and Agatston score (noncalcified plaque volume [mm(3)] median [interquartile ranges]: CS 49.5 [31.4, 102.5], controls 17.9 [2.6, 25.3], P < .001; Agatston score: CS 70.6 [0, 253.1], controls 0 [0, 7.6]; P < .05). CS patients had higher systolic and diastolic blood pressures than controls (systolic: CS 143 mm Hg [135, 173]; controls, 134 [123, 136], P < .02; diastolic CS: 86 [80, 99], controls, 76 [72, 84], P < .05).Conclusions:Increased coronary calcifications and noncalcified coronary plaque volumes are present in patients with active or previous hypercortisolism. Increased atherosclerosis may contribute to the increased rates of cardiovascular morbidity and mortality in patients with glucocorticoid excess.
The Journal of clinical endocrinology and metabolism 04/2013; · 6.50 Impact Factor
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Maya Lodish,
Urania Dagalakis, Ninet Sinaii,
Ethan Bornstein,
Aerang Kim,
Kelsey Brooke Lokie,
Andrea M Baldwin,
James C Reynolds,
Eva Dombi,
Constantine A Stratakis,
Brigitte C Widemann
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ABSTRACT: Concern for impaired bone health in children with Neurofibromatosis type 1 (NF-1) has led to increased interest in bone densitometry in this population. Our study assessed bone mineral apparent density (BMAD) and whole body bone mineral content (BMC)/height in pediatric patients with NF-1 with a high plexiform neurofibroma burden. Sixty-nine patients with NF-1 (age range 5.2-24.8; mean 13.7 ± 4.8 yrs) were studied. Hologic dual energy x-ray absorptiometry scans (DXA) (Hologic Inc, Bedford, MA) were performed on all patients. BMD was normalized to derive a reference volume by correcting for height through the use of the BMAD, as well as the BMC. BMAD of the lumbar spine (LS 2-4), femoral neck (FN), and total body BMC/height were measured and Z-scores were calculated. Impaired bone mineral density was defined as a Z-score ≤-2. Forty-seven percent of patients exhibited impaired bone mineral density at any bone site; with 36% at the LS, 18% at the FN and 20% total BMC/height. BMAD Z-scores of the LS (-1.60 ± 1.26) were more impaired compared both to the FN (-0.54 ± 1.58; p = 0.0003) and the whole body BMC/height Z-scores (-1.16 ± 0.90; p = 0.036). Plexiform neurofibroma (PN) burden was negatively correlated with LS BMAD (rs = -0.36, p = 0.01). In pediatric and young adult patients with NF1, LS BMAD was more severely affected than the FN BMAD or whole body BMC/height.
Endocrine Related Cancer 10/2012; · 4.36 Impact Factor
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ABSTRACT: 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.
The Journal of clinical endocrinology and metabolism 09/2012; · 6.50 Impact Factor
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ABSTRACT: Slow or insufficient enrollment in clinical research and a high demand for research participants raises questions about the need for and use of incentives to participate, including payment. Much of the available literature on payment to research participants focuses on ethical concerns, and rarely addresses guidelines, benchmarks, or formulas to assist investigators to assign or evaluate appropriate payment for individuals who take part in clinical research trials and procedures. Using four years of data collected about the inconvenience units assigned by intramural investigators to selected clinical research procedures conducted at the National Institutes of Health (NIH) Clinical Center, this study provides payment benchmarks for commonly performed procedures. Results were obtained from data collected on 36,273 incidents of payment made for procedures to research participants from August 2004 to August 2008. Analysis of the inconvenience units value assigned to specific procedures suggests that despite a wide distribution and frequent outliers, a convergence in practice around the center of distribution for most procedures does exist. As one of the first published studies reporting data reflecting payment amount for specific clinical research procedures, these data can guide investigators and institutional review boards as they establish and review an appropriate amount of payment to offer research participants. Our data may be useful in promoting payment standards for procedures, thereby complementing proposals or guidelines that advise payment calculations according to time and procedures.
Contemporary clinical trials 05/2012; 33(5):860-8. · 1.51 Impact Factor
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ABSTRACT: Recovery of the hypothalamic-pituitary-adrenal axis (HPAA) after transsphenoidal surgery (TSS) for Cushing's disease (CD) in children has not been adequately studied.
Our objective was to assess time to recovery of the HPAA after TSS in children with CD.
This was a case series at the National Institutes of Health Clinical Center.
Fifty-seven patients with CD (6-18 yr, mean 13.0 ± 3.1 yr) given a standard regimen of glucocorticoid tapering after TSS were studied out of a total of 73 recruited.
ACTH (250 μg) stimulation tests were administered at approximately 6-month intervals for up to 36 months. Age, sex, pubertal status, body mass index, length of disease, midnight cortisol, and urinary free cortisol at diagnosis were analyzed for effects on recovery.
The main outcome measure was complete recovery of the HPAA as defined by a cortisol level of at least 18 μg/dl in response to 250 μg ACTH.
Full recovery was reached by 43 (75.4%) of 57 patients, with 29 of the 43 (67.4%) and 41 of the 43 (95.3%) recovering by 12 and 18 months, respectively. The overall mean time to recovery was 12.6 ± 3.3 months. Kaplan-Meier survivor function estimated a 50% chance of recovering by 12 months after TSS and 75% chance of recovering within 14 months. By receiver operating characteristic curve assessment, the cutoff of at least 10-11 μg/dl of cortisol as the peak of ACTH stimulation testing at 6 months after TSS yielded the highest sensitivity (70-80%) and specificity (64-73%) to predict full recovery of the HPAA at 12 months. Two of the four patients that recovered fully within 6 months had recurrent CD.
Although this is not a randomized study, we present our standardized tapering regimen for glucocorticoid replacement after TSS that led to recovery of the HPAA in most patients within the first postoperative year. Multiple factors may affect this process, but an early recovery may indicate disease recurrence.
The Journal of clinical endocrinology and metabolism 03/2012; 97(5):1483-91. · 6.50 Impact Factor
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ABSTRACT: Decreased bone mineral density (BMD) has been documented in adults with Cushing disease (CD), and allelic variants of the vitamin D receptor (VDR) gene have been associated with osteopenia. Genetic factors play an important role in bone accrual and its response to various diseases; among them, the most studied are the allelic variants of the VDR gene. There is debate as to whether described variants in the VDR gene have an effect on BMD. In the current study, we sought to analyze whether BMD differences in patients with CD were associated with the Taq1 and Apal VDR allelotypes. The data showed lack of association between BMD and these widely studied VDR polymorphisms, suggesting that the effect of endogenous hypercortisolism on bone in the context of CD does not depend on VDR genotypes.
Journal of pediatric endocrinology & metabolism: JPEM 01/2012; 25(1-2):221-3. · 0.88 Impact Factor
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ABSTRACT: To understand whether and to what extent U.S. IVF clinics inform egg donors that resultant embryos initially intended to be implanted for reproductive purposes may in fact be used for research instead.
Four hundred seventy U.S. IVF clinics were asked to respond to a questionnaire and provide a copy of the egg donor consent form(s) used at the clinic.
Four hundred seventy U.S. IVF clinics listed in a Centers for Disease Control and Prevention database; only forms from clinics that both accepted donor eggs and provided excess embryos for research were analyzed for content.
Not applicable.
Not applicable.
Responses to the questionnaire, demographic data from a Centers for Disease Control and Prevention database, and the content of egg donor consent forms.
Of 222 U.S. IVF clinics that responded to our query, 100 clinics both accepted donor eggs and provided some excess embryos for research. We received 66 consent forms from these 100 clinics, which showed that although most egg donor consent forms inform donors that they will not have control over embryos resulting from their eggs, 30% inform them that some embryos may be used for research, and even fewer mention stem cell research.
Egg donors in the United States, including some who may have a moral objection to research and stem cell research, are not being informed that embryos created with their donated eggs may in fact be used for these purposes. This can be corrected with the inclusion of succinct, nontechnical language in egg donor consent forms.
Fertility and sterility 12/2011; 97(2):427-33. · 3.97 Impact Factor
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Maya Lodish,
Urania Dagalakis,
Clara C Chen, Ninet Sinaii,
Patricia Whitcomb,
Alberta Aikin,
Eva Dombi,
Leigh Marcus,
Brigitte Widemann,
Elizabeth Fox,
Meredith Chuk,
Frank Balis,
Samuel Wells,
Constantine A Stratakis
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ABSTRACT: Most medullary thyroid cancers (MTC) express somatostatin receptors; therefore, (111)In-octreotide somatostatin receptor scintigraphy (SRS) may be useful in detecting sites of metastases in children with MTC.
The aim of the study was to evaluate tumor metastases in children and adolescents with MTC using SRS in comparison to conventional imaging.
A case series was conducted as part of baseline evaluation for cancer treatment protocol at the National Institutes of Health Clinical Center.
Eleven patients with a median age of 15 (range, 9-17) yr participated in the study, 10 with histologically proven, metastatic MTC due to the M918T mutation of the RET protooncogene, and one with a known RET polymorphism.
After receiving 0.086 mCi/kg (111)Indium-pentreotide, patients were examined with a single photon emission computed tomography scan 4 and 24 h after injection. Baseline conventional imaging, including computed tomography (neck, chest, abdomen, ± pelvis, adrenals), magnetic resonance imaging (neck), and bone scan, was performed on all patients.
SRS results were compared with conventional imaging.
Five of the 11 patients had abnormal findings on SRS. Of the 53 total target lesions present in the patients, only 24.5% were accurately identified through SRS.
SRS appears to be less sensitive than conventional imaging at detecting the full extent of metastatic disease in children and adolescents with hereditary MTC. SRS incompletely identified sites of tumor and failed to visualize small sites of tumor or liver and lung metastases, and it has a limited role in the evaluation of metastatic disease in pediatric MTC patients.
The Journal of clinical endocrinology and metabolism 12/2011; 97(2):E207-12. · 6.50 Impact Factor
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ABSTRACT: Multidrug-resistant Acinetobacter baumannii (MDRAB) is difficult to treat and eradicate. Several reports describe isolation and environmental cleaning strategies that controlled hospital MDRAB outbreaks. Such interventions were insufficient to interrupt MDRAB transmission in 2 intensive care unit-based outbreaks in our hospital. We describe strategies that were associated with termination of MDRAB outbreaks at the National Institutes of Health Clinical Center.
In response to MDRAB outbreaks in 2007 and 2009, we implemented multiple interventions, including stakeholder meetings, enhanced isolation precautions, active microbial surveillance, cohorting, and extensive environmental cleaning. We conducted a case-control study to analyze risk factors for acquiring MDRAB. In each outbreak, infection control adherence monitors were placed in MDRAB cohort areas to observe and correct staff infection control behavior.
Between May 2007 and December 2009, 63 patients acquired nosocomial MDRAB; 57 (90%) acquired 1 or more of 4 outbreak strains. Of 347 environmental cultures, only 2 grew outbreak strains of MDRAB from areas other than MDRAB patient rooms. Adherence monitors recorded 1,330 isolation room entries in 2007, of which 8% required interventions. In 2009, around-the-clock monitors recorded 4,892 staff observations, including 127 (2.6%) instances of nonadherence with precautions, requiring 68 interventions (1.4%). Physicians were responsible for more violations than other staff (58% of hand hygiene violations and 37% of violations relating to gown and glove use). Each outbreak terminated in temporal association with initiation of adherence monitoring.
Although labor intensive, adherence monitoring may be useful as part of a multifaceted strategy to limit nosocomial transmission of MDRAB.
Infection Control and Hospital Epidemiology 12/2011; 32(12):1166-72. · 3.67 Impact Factor
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ABSTRACT: Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation syndrome due to mutations of the 7-dehydrocholesterol reductase gene (DHCR7), which leads to a deficiency of cholesterol synthesis and an accumulation of 7-dehydrocholesterol. The SLOS clinical spectrum ranges from multiple major malformations to a mild phenotype with minor anomalies and intellectual disability. Several children with SLOS and adrenal insufficiency have been described. We performed ovine corticotropin (oCRH) testing in 35 SLOS patients and 16 age- and gender-matched controls. We reviewed prior adrenocorticotropin (ACTH) stimulation tests of our SLOS patients (19 of 35 available) and reviewed results of ACTH stimulation tests from 10 additional SLOS patients. Results from oCRH testing showed that patients with SLOS had significantly higher ACTH baseline values than healthy controls (24.8 ± 15.3 pg/ml vs. 17.8 ± 7.5 pg/ml, P = 0.034). However, no statistically significant differences were noted for peak ACTH values (74.4 ± 35.0 pg/ml vs. 64.0 ± 24.9 pg/ml, P = 0.303) and for baseline (14.2 ± 7.8 mcg/dl vs. 14.2 ± 6.3 mcg/dl, P = 0.992) and peak cortisol values (28.2 ± 7.9 mcg/dl vs. 24.8 ± 8.1 mcg/dl, P = 0.156). The area-under-the-curve (AUC) was not significantly different in SLOS patients compared to controls for both ACTH (250.1 ± 118.7 pg/ml vs. 195.3 ± 96.6 pg/ml, P = 0.121) as well as cortisol secretion (83.1 ± 26.1 mcg/dl vs. 77.8 ± 25.9 mcg/dl, P = 0.499). ACTH stimulation test results were normal in 28 of 29 tests. The individual with the abnormal test results had subsequent normal oCRH tests. The slightly increased baseline ACTH level seen during oCRH testing may be due to compensated adrenocortical insufficiency. However, we were able to show that our patients with SLOS had an adequate glucocorticoid response, and thus, in mild to moderate cases of SLOS stress steroid coverage may not be warranted.
American Journal of Medical Genetics Part A 11/2011; 155A(11):2732-8. · 2.39 Impact Factor
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ABSTRACT: To study whether pain location is related to lesion location in women with chronic pelvic pain and biopsy-proven endometriosis.
A secondary analysis was performed to compare self-reported pain location with recorded laparoscopy findings for location and characteristics of all visible lesions. All lesions were excised. Endometriosis was diagnosed using histopathology criteria. The pelvic area was divided into three anterior and two posterior regions. Lesion depth, number of lesions or endometriomas, and disease burden (defined as sum of lesion sizes, or single compared with multiple lesions) were determined for each region. Data were analyzed using t tests, Fisher exact tests, and logistic regression modeling, with P values corrected for multiple comparisons using the step-down Bonferroni method.
Women with endometriosis (n = 96) had lower body mass indexes, were more likely to be white, had more previous surgeries, and had more frequent menstrual pain and incapacitation than did chronic pain patients without endometriosis (n = 37). Overall, few patients had deeply infiltrating lesions (n = 38). Dysuria was associated with superficial bladder peritoneal lesions. Other lesions or endometriomas were not associated with pain in the same anatomic locations. Lesion depth, disease burden, and number of lesions or endometriomas were not associated with pain.
In this group of women with biopsy-proven endometriosis, few had deeply infiltrating lesions or endometriomas. Dysuria and midline anterior pain were the only symptoms associated with the location of superficial endometriosis lesions. The lack of relationship between pain and superficial lesion location raises questions about how these lesions relate to pain.
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00001848.
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Obstetrics and Gynecology 08/2011; 118(2 Pt 1):223-30. · 4.73 Impact Factor
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ABSTRACT: To examine the prevalence of migraine in women with chronic pelvic pain with and without endometriosis.
Prospective study of headache, pelvic pain, and quality of life before laparoscopic surgery for pelvic pain. Endometriosis was diagnosed pathologically. Headaches were classified as migraine or non-migraine using International Headache Society criteria.
Clinical research hospital.
108 women in a clinical trial for chronic pelvic pain (NCT00001848).
Laparoscopy to diagnose endometriosis, assessment by neurologist to assess headaches.
Prevalence of migraine and other headaches in women with chronic pelvic pain with or without endometriosis. Headache frequency, severity and relationship to pelvic pain and endometriosis.
Lifetime prevalence of definite or possible migraine was 67% of women with chronic pelvic pain. An additional 8% met criteria for possible migraine. Migraine was no more likely in women with endometriosis than those without. Women with the most severe headaches had a lower quality of life compared with those with pelvic pain alone.
Migraine headache is common in women with chronic pelvic pain, regardless of endometriosis, and contributes to disability in those with both conditions. The strong association suggests a common pathophysiology.
Fertility and sterility 03/2011; 95(3):895-9. · 3.97 Impact Factor
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ABSTRACT: To comprehensively phenotype parents identified with nonclassic congenital adrenal hyperplasia (NCCAH) by family genetic studies, termed here as cryptic NCCAH and to define the incidence of cryptic NCCAH in the parents of a large cohort of patients with 21-hydroxylase deficiency.
Genotyping was performed on 249 parents of 145 unrelated congenital adrenal hyperplasia (CAH) patients. Parents with two CYP21A2 mutations underwent extensive evaluation.
Of the 249 parents, ten (4%; seven females and three males) were identified as having cryptic NCCAH. The majority was of ethnicities previously reported to have a higher incidence of NCCAH. Cosyntropin stimulation performed in eight parents provided biochemical confirmation (17-hydroxyprogesterone range 56-364 nmol/l) and cortisol response was ≤500 nmol/l in three parents (38%). Of the seven women (27-54 years) with cryptic NCCAH, four had prior infertility, two reported irregular menses, two had treatment for hirsutism, one had androgenic alopecia. Men were asymptomatic. All cryptic NCCAH parents reported normal puberty and had normal height. Adrenal hypertrophy and a small adrenal myelolipoma were observed in two parents; testicular adrenal rest tissue was not found.
Parents diagnosed with NCCAH by genetic testing are mostly asymptomatic. Temporary female infertility and suboptimal cortisol response were commonly observed. Ongoing glucocorticoid therapy is not indicated in adults with CAH identified by family genotype studies unless symptomatic, but glucocorticoid stress coverage should be considered in select cases. Parents of a child with CAH have a 1:25 risk of having NCCAH; if the mother of a child with CAH has infertility, evaluation for NCCAH is indicated.
European Journal of Endocrinology 03/2011; 164(6):977-84. · 3.42 Impact Factor
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ABSTRACT: Very little is known about the mental health status in children with genetic causes of hyperandrogenism. This study sought to characterize psychiatric morbidity in this group.
Children (8-18 years) with the diagnosis of classic congenital adrenal hyperplasia (CAH) or familial male precocious puberty (FMPP) underwent a semi-structured psychiatric interview, the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version. According to sex and the literature, incidence of identified psychopathology was compared between the two endocrinological groups. We evaluated 72 patients: 54 CAH (21 females) and 18 FMPP.
Twenty-four (44.4%) CAH patients and 10 (55.6%) FMPP patients met the criteria for at least one lifetime psychiatric diagnosis. Attention-deficit hyperactivity disorder (ADHD) was present in 18.2% of CAH males, 44.4% of FMPP males, and one case (4.8%) in CAH females. A high rate of anxiety disorders was also found in all the three groups (17-21%). Relative to females with CAH, the FMPP patients exhibited higher rates of ADHD. Age at diagnosis and the treatment modalities were not associated with psychopathology. Rates of psychiatric disorder, specifically ADHD and anxiety disorders, were higher than in the general population.
Although anxiety disorders may occur at an increased rate in children with chronic illness, androgens may contribute to higher risk for psychopathology in pediatric patients with genetic cause of excess androgen. Early diagnosis and treatment of childhood hyperandrogenism is essential for optimal development. The results suggest that assessment for psychiatric disorders should be part of the routine evaluation of these patients.
European Journal of Endocrinology 11/2010; 163(5):801-10. · 3.42 Impact Factor
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ABSTRACT: To evaluate bone mineral density (BMD) in children with Cushing disease before and after transphenoidal surgery (TSS).
Hologic dual-energy x-ray absorptiometry (DXA) scans of 35 children with Cushing disease were analyzed retrospectively. Sixteen of the 35 patients had follow-up DXA scans performed 13 to 18 months after TSS. BMD and bone mineral apparent density (BMAD) for lumbar spine (LS) L1 to L4 and femoral neck (FN) were calculated.
Preoperatively, 38% and 23% of patients had osteopenia of the LS and FN, respectively. Both BMD and BMAD Z-scores of the LS were worse than those for the FN (-1.60 +/- 1.37 versus -1.04 +/- 1.19, P = .003), and (-1.90 +/- 1.49 versus -0.06 +/- 1.90, P < .001); postoperative improvement in BMD and BMAD were more pronounced in LS than in the FN (0.84 +/- 0.88 versus 0.15 +/- 0.62, P<.001; and 0.73 +/- 1.13 versus -0.26 +/- 1.21, P = .015). Pubertal stage, cortisol levels, and length of disease had no effect on BMD.
In children with Cushing disease, vertebral BMD was more severely affected than femoral BMD and this effect was independent of degree or duration of hypercortisolism. BMD for the LS improved significantly after TSS; osteopenia in this group may be reversible.
The Journal of pediatrics 06/2010; 156(6):1001-5. · 4.02 Impact Factor
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ABSTRACT: 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.
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.
The study was conducted at a clinical research center.
Subjects included 12 children aged 5-14 yr with chronic hypoparathyroidism and without severe renal or hepatic insufficiency.
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.
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.
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.
The Journal of clinical endocrinology and metabolism 06/2010; 95(6):2680-8. · 6.50 Impact Factor
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ABSTRACT: Context: Because ectopic ACTH-secreting (EAS) tumors are often occult, improved imaging is needed. Objective: Our objective was to evaluate the utility of [(111)In-DTPA-d-Phe]pentetreotide scintigraphy [octreotide (OCT)] imaging at 6 mCi [low OCT (LOCT)] and 18 mCi [high OCT (HOCT)], [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) and [(18)F]l-3,4-dihydroxyphenylalanine (F-DOPA)-PET scans, computed tomography (CT), and magnetic resonance imaging (MRI). Design and Setting: The study was a prospective evaluation at a clinical research center. Patients: Forty-one subjects participated, 30 (17 female) with resected EAS tumors and 11 (three female) with occult EAS, based on inferior petrosal sinus sampling results and imaging studies. Intervention: Intervention included CT and MRI of neck, chest, abdomen, LOCT (with or without HOCT) and FDG- or F-DOPA-PET without CT every 6-12 months. Main Outcome Measure: Tumor identification was the main outcome measure. Results: Most recent results were analyzed. Eighteen patients had tumor resected on the first visit; otherwise, surgery occurred 33 +/- 25 (9-99) months later. Tumor size was 1.9 +/- 1.7 (0.8-8.0) cm; 83% were intrathoracic. CT, MRI, LOCT, HOCT, FDG-PET, and F-DOPA-PET had sensitivities per patient of 93% [95% confidence interval (CI) = 79-98%], 90% (95% CI = 74-96%), 57% (95% CI = 39-73%), 50% (95% CI = 25-75%), 64% (95% CI = 35-85%), and 55% (95% CI = 28-79%) and positive predictive values (PPV) per lesion of 66, 74, 79, 89, 53, and 100%, respectively. LOCT and PET detected only lesions seen by CT/MRI; abnormal LOCT or F-DOPA-PET improved PPV of CT/MRI. By modality, the fraction of patients with one or more false-positive findings was 50% by CT, 31% by MRI, 18% by L/HOCT, and 18% by FDG-PET. Eight occult EAS patients had 64 +/- 58 (9-198) months follow-up; others had none. Conclusions: High sensitivity and PPV suggest thoracic CT/MRI plus LOCT scans for initial imaging, with lesion confirmation by two modalities.
The Journal of clinical endocrinology and metabolism 03/2010; 95(3):1207-19. · 6.50 Impact Factor
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ABSTRACT: To assess the prevalence of patient-reported, physician-diagnosed comorbid conditions in women with endometriosis.
Cross-sectional study of self-reported survey data.
Academic research.
Four thousand three hundred thirty-one Endometriosis Association (EA) members reporting surgically diagnosed endometriosis.
None.
Self-reported, physician-diagnosed infectious diseases, cancers, and endocrine diseases.
Nearly two-thirds of women reported one or more of the assessed conditions. Recurrent upper respiratory infections and recurrent vaginal infections were common and more likely in women responding to the EA survey. Melanoma was reported by 0.7% (n=29), breast cancer by 0.4% (n=16), and ovarian cancer by 0.2% (n=10). While ovarian cancer and melanoma were significantly more common than in the general population, breast cancer was surprisingly less common. Addison's disease and Cushing's syndrome were rare (0.2% and 0.1%, respectively).
Respondents reported a higher prevalence of recurrent upper respiratory or vaginal infections, melanoma, and ovarian cancer than the general population. These findings document other potential associations related to the immune system, which may help focus future research into this disease.
Fertility and sterility 11/2009; 94(5):1627-31. · 3.97 Impact Factor
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ABSTRACT: Recent reports suggest a higher prevalence (1-5%) of Cushing's 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.
The aim of the study was to evaluate the diagnostic performance of screening tests for Cushing's syndrome in overweight and obese subjects with at least two other features of the disorder.
We conducted a cross-sectional prospective study.
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.
In addition to obesity, subjects had a mean of five to six features of Cushing's syndrome. None was found to have Cushing's syndrome. Test specificities to exclude Cushing's 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.
These data do not support widespread screening of overweight and obese subjects for Cushing's syndrome; test results for such patients may be falsely abnormal.
The Journal of clinical endocrinology and metabolism 07/2009; 94(10):3857-64. · 6.50 Impact Factor
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ABSTRACT: While detection of pituitary tumours with magnetic resonance imaging (MRI) may reduce diagnostic costs and improve surgical outcomes for patients with Cushing's disease, the optimal T1-weighted spin-echo (SE) MRI protocol remains unknown. We hypothesized that specific MR scanning parameters influence detection of corticotropinomas.
Between December 1997 and November 2004, 21 of 84 consecutive patients with Cushing's disease had a falsely negative initial pituitary MRI study and a lesion identified subsequently at the National Institutes of Health Clinical Center. This study retrospectively reviewed and compared technical parameters used for the two pituitary T1-weighted SE MRIs in 18 patients with available scans.
Repetition time (TR)/echo times (TE), field of view (FOV), matrix size, magnetic field strength, slice thickness, use of gadolinium contrast and the time interval between studies were recorded.
The MRI interscan interval was 5.4 +/- 1.1 months. All scans used gadolinium, matrix sizes were similar and nearly all had 3-mm thick slices. Parameters that differed between the NIH- and externally performed scans were: TR (400 ms vs. 492 +/- 19 ms, P = 0.0002); TE (10.3 +/- 0.5 vs. 17.2 +/- 1.2 ms, P = 0.0003); FOV (12 x 12 cm vs.17 +/- 0.6 x 18 +/- 0.7 cm, P < 0.0001). Immunohistochemistry of tumours resected at transsphenoidal surgery confirmed all to be corticotropinomas.
Not all 'T1-weighted SE' scans are equally accurate. MRI technique, particularly FOV and TR/TE value, influences results. We recommend that endocrinologists consider pituitary MRI parameters when interpreting the results.
Clinical Endocrinology 06/2009; 72(4):502-6. · 3.17 Impact Factor
