Normal Cortisol Response on Low-Dose Synacthen (1 μg) Test in Children with Prader Willi Syndrome

Introduction: It has been postulated that central adrenal insufficiency (CAI), resulting from hypothalamic dysfunction, may contribute to the increased unexplained death rates in Prader Willi syndrome (PWS). A study using the overnight metyrapone test reported a 60% prevalence of CAI in children with PWS. We used a low-dose Synacthen test to screen for CAI in children with PWS. Methods: We studied 41 children with genetic diagnosis of PWS [20 males; mean age, 7.68 (±5.23) yr] in five pediatric endocrinology centers in Australasia. All participants were randomly selected, and none had a history of Addisonian crisis. Ten of the cohort were receiving sex hormone therapy, 19 were receiving GH, and four were receiving T4. Their mean body mass index z-score was +1.48 (±1.68). Baseline morning ACTH and cortisol levels were measured, followed by iv administration of 1 μg Synacthen. Post-Synacthen cortisol levels were measured at 30 min, and a cortisol level above 500 nmol/liter was considered normal. Results: The mean baseline ACTH and cortisol were 15 (±14) ng/liter and 223 (±116) nmol/liter, respectively. The mean 30-min plasma cortisol was 690 (±114) nmol/liter, and the average increase from baseline was 201%. Conclusions: Our result suggests that CAI is rare in children with PWS.

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Antidepressants Augmented with Aripiprazole in the Treatment of Major Depressive Disorder

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1977 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S141-S141

Author(s):

S. Bise ◽

G. Sulejmanpasic ◽

D. Begic ◽

M. Ahmic

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Low Dose ◽

Adjunctive Treatment ◽

Major Depressive ◽

The Us ◽

Minimal Improvement ◽

History Of ◽

The Mean ◽

Ad Therapy

IntroductionMajor depressive disorder (MDD) does not consistently respond to any single antidepressant (AD) therapy. Adjunctive therapy with atypical antipsychotics (AA) showed higher response rates compared with AD monotherapy. Aripiprazole, an oral quinolinone, is the first AA agent to be approved in the US as adjunctive treatment in adult patients with MDD.Aim The aim was to evaluate the efficacy and safety of adjunctive low-dose aripiprazole combined with AD versus AD monotherapy in patients with MDD with minimal improvement after 4 weeks of prior AD monotherapy.MethodsTen patients with MDD and a history of minimal improvement to 4 weeks of AD monotherapy (escitalopram 10–15 mg/day, sertralin 50–100 mg/day) were included in this study. The patients were randomly assigned to 2 groups: one (n = 5) with AD plus aripiprazole 5–7.5 mg/day and the other (n = 5) with AD alone. After baseline assessment, the subjects were followed up at weeks 2, and 4. The primary efficacy was the mean change in (HAM-D17) and CGI-I.ResultsThe aripiprazole group exhibited significantly better efficacy than the AD group in mean total score changes of HAM-D17 and CGI from the baseline to weeks 2, and 4. The item “work and social activities” of HAM-D 17 showed significant improvement at week 4, and the item “somatic symptoms (GI)” showed significant improvement at week 2.ConclusionsAdjunctive aripiprazole therapy significantly improved depressive symptoms in MDD who didn’t respond to AD monotherapy. Aripiprazole augmentation is an efficacious, well-tolerated and safe treatment for patients with MDD.

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Evaluating the Low-Dose ACTH Stimulation Test in Children: Ideal Times for Cortisol Measurement

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00295 ◽

2019 ◽

Vol 104 (10) ◽

pp. 4587-4593 ◽

Cited By ~ 4

Author(s):

Harpreet Gill ◽

Nick Barrowman ◽

Richard Webster ◽

Alexandra Ahmet

Keyword(s):

False Positive ◽

Low Dose ◽

Retrospective Chart Review ◽

Stimulation Test ◽

Acth Stimulation Test ◽

Acth Stimulation ◽

Incremental Value ◽

Z Scores ◽

The Mean ◽

Cortisol Levels

Abstract Context Central adrenal insufficiency (AI) can be diagnosed with the low-dose ACTH stimulation test (LDST). Protocols determining timing of cortisol sampling vary, with 30 minutes after stimulation being most common. Objectives To determine optimal times to draw cortisol levels and factors predicting timing of peak cortisol levels in children undergoing LDST. Design Retrospective chart review of LDSTs between February 2014 and September 2017. Setting The Children’s Hospital of Eastern Ontario. Patients Patients 3 months to 20 years who underwent LDSTs. Intervention LDSTs were performed with cortisol levels at 0, 15, 30, and 60 minutes after 1 μg cosyntropin. Cortisol values <18 μg/dL (500 nmol/L) determined AI. Main Outcome Measures The incremental value of testing cortisol at 15 or 60 minutes, in addition to the standard 30-minute sample, was estimated. Results A total of 221 patients met inclusion criteria. The mean age was 9.7 years, and 32% were female. Peak cortisol levels were 19%, 67%, and 14% at 15, 30, and 60 minutes, respectively. One false positive LDST result would be prevented for every 24 (95% CI, 13 to 46) or 55 (95% CI, 22 to 141) patients tested at 15 or 60 minutes in addition to the standard 30-minute test. Of the 122 patients who passed the LDST, discontinuing the 15- and 60-minute samples would have misdiagnosed 12 patients (9.8%). Glucocorticoid exposure, age, and body mass index z scores were independent predictors of peak cortisol timing. Conclusion Although the majority of patients peak 30 minutes after cosyntropin administration, testing cortisol levels at 15 and 60 minutes reduces the risk of false positive LDSTs.

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555 Role of X-Ray Soft Tissue Neck in Children with Obstructive Sleep Apnea with a Previous History of Adenotonsillectomy

SLEEP ◽

10.1093/sleep/zsab072.553 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A219-A220

Author(s):

Quang Nguyen ◽

Karim El-Kersh ◽

Bakeerathan Gunaratnam ◽

Egambaram Senthilvel

Keyword(s):

Obstructive Sleep Apnea ◽

Soft Tissue ◽

Previous History ◽

Z Score ◽

X Ray ◽

Soft Tissue Neck ◽

Obstructive Sleep ◽

History Of ◽

The Mean

Abstract Introduction Adenoid recurrence in children after adenotonsillectomy can be an etiology for obstructive sleep apnea (OSA). The aim of this study was to assess the role of x-ray soft tissue neck (XR-STN) in evaluating adenoid recurrence from a sleep physician perspective and to assess the polysomnographic findings of pre and post revision adenoidectomy. Methods This was a single center retrospective study that included children <18 years old with a history of adenotonsillectomy who underwent sleep study that confirmed the diagnosis of OSA and had XR- STN to evaluate for adenoidal tissue recurrence at the University of Louisville/Norton Pediatric Sleep Disorders clinic from July 2012 to September 2020. XR-STN level of adenoidal obliteration, baseline and post revision adenoidectomy PSG data were analyzed. Results A total of 160 subjects were included in the study with a mean age of 9.71±3.5 years, 59.4% were male, 54.4% were Caucasians, and the mean z-score was 1.77±1.15. XR-STN was normal in 39.4% of the subjects and it showed mild, moderate, and complete adenoidal obliteration in 20.6%, 32.5% and 7.5% of the subjects, respectively. Multiple regression analysis showed that the total AHI, the mean for the moderate and complete adenoidal obliteration are significantly higher than children with no obstruction (p-value=000). However, mild obliteration, Z score, age, gender, and race were not significantly associated with an increased total AHI. Pre- and post- adenoid revision PSGs were available in 20 subjects and they showed significant improvement in AHI (10.4±12.9 vs. 21.1±23.9, p=0.04), arousal index (15.4 ±10.6 vs. 21.1± 14.9, p=0.04), and nadir SaO2 (86.7%±8.1 vs. 76.58% ±18.44, p=0.04). Conclusion Soft tissue neck x-ray was useful in assessing adenoid recurrence in our study. Revision adenoidectomy resulted in an overall improvement in several PSGs parameters of OSA. Pediatric sleep physicians may consider XR-STN in the evaluation of children with OSA with a previous history of adenotonsillectomy. Support (if any) None

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Bone Mineral Density in Transfusion Independent Thalassemia Patients.

Blood ◽

10.1182/blood.v108.11.3353.3353 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3353-3353

Author(s):

Zahra Pakbaz ◽

Zhe Zhang ◽

Ellen Fung ◽

Nancy Sweeters ◽

Sylvia Singer ◽

...

Keyword(s):

Bone Mineral Density ◽

Family History ◽

Bone Mineral ◽

Z Score ◽

Low Bone Mass ◽

Mineral Density ◽

Patients Âgés ◽

Z Scores ◽

History Of ◽

The Mean

Abstract Low bone mineral density (BMD) is commonly seen in regularly transfused thalassemia patients; however, there have been few reports for bone mineral density assessment in transfusion independent thalassemia patients. The present report includes the results of BMD assessments in patients with transfusion independent thalassemia who were referred to the bone density clinic through 2002–2006. BMD was evaluated by dual energy x-ray absorptiometry (DXA, Hologic Delphi A). A convenience sample of 24 patients (Females=15) with transfusion independent thalassemia were measured with a mean age of 22.1 ± 13.8 years. Subjects younger than 10 yrs old (n = 7) underwent scans for Lumbar spine (LS; L1-L4) and whole body (WB), patients ages 10–20 (n = 5) were assessed for LS, WB, and non-dominant hip, and for patients older than 20 (n = 12), LS and hip scans were completed. Z-scores specific for age and gender were generated using Zemel BS et al.(J. Bone Min Res 2004) database. Z-scores less than −2.0 were considered as low bone density. Calcium intake was assessed by a brief food frequency questionnaire. Past medical history, medications, history of fractures, and family history of osteoporosis were obtained by chart review and patient interview. Data is presented as Mean ± SD. T-test was used to assess differences in continuous variables. The mean LS Z-score (n = 24) was −1.5 ± 1.0 and the mean hip Z-score (n = 17) was −0.5 ± 1.1. Mean WB Z-score (n = 10) was −2.0 ± 1.2. There was a significant (p<0.001) difference between spine and hip Z-scores. Overall 46% had a Z-score less than −2.0. Thirty-three percent of patients have spine Z-scores of less than −2.0 and 25% spine Z-scores between −2.0 and −1.0. Average spine Z-score in patients younger than 10 years old (n=7) was −1.6 ± 0.5. In WB scans, 50% of the patients had WB Z-scores worse than −2.0. None of the young patients (5–9 yrs; n = 7) consumed inadequate intake of calcium (< 2/3 of RDA age specific) while 75% of patients ages 10–20 (n = 4) years old consumed inadequate intake of calcium (dietary + supplement). Neither spine nor hip Z-score was related to patients’ gender, age, and calcium intake. Two patients reported fractures in the past and two reported family history of osteoporosis. Six patients had delayed puberty and one has hypogonadism. Seven patients have short stature. This data suggests that low bone mass is not only a problem in transfused thalassemia patients, but is also observed in non-transfused patients. The significance and pathophysiology of low bone mass should be studied further in non-transfused patient population, especially in younger children.

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Evaluation of Risk Factors in Children with Hypospadias

Grand Journal of Urology ◽

10.5222/gju.2021.47956 ◽

2021 ◽

Author(s):

Eda Çelebi Bitkin ◽

Alper Bitkin ◽

Ender Cem Bulut ◽

Oğuz Tuncer

Keyword(s):

Risk Factors ◽

Environmental Factors ◽

Genetic Factors ◽

Congenital Defects ◽

Pediatric Endocrinology ◽

Fertility Status ◽

The Family ◽

History Of ◽

The Mean ◽

Maternal Bmi

Objective: Hypospadias is one of the most common congenital defects in boys. Multifactorial factors such as genetic predisposition and environmental factors play a role in the etiology of hypospadias. In this study, we investigated the risk factors of patients diagnosed with hypospadias. Materials and Methods: Thirty-six patients who applied to the pediatric endocrinology and urology outpatient clinics with the diagnosis of hypospadias were evaluated retrospectively. Risk factors were evaluated by recording the parental ages, exposure to environmental factors, the maternal BMI, history of pregnancy, drug use, and the father’s fertility status. Results: The mean age of the patients was 3.5 ± 2 years. The patients had anterior (n:27 : 75%), middle (midshaft) (n:8 ; 22.2%), and posterior (n:1 ; 2.8%) hypospadias. The mean body mass index (BMI) of the mothers was 24 ± 4.1 kg/m2. Eight (22.2%) mothers were overweight and six (16.6%) mothers were obese. There was a history of hypospadias in the family of 4 (11%) patients. Conclusion: Although combinations of environmental and genetic factors play a role in the etiology of hypospadias, many unexplained factors are responsible for this disease.

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Descriptive Study of a 488 Patients Cohort with Inherited Retinal Diseases and a Low Genetic Diagnosis Rate.

10.21203/rs.3.rs-78231/v1 ◽

2020 ◽

Author(s):

Rosa M. Coco-Martin ◽

Miguel Diego-Alonso ◽

W. Andres Orduz-Montaña ◽

M. Rosa Sanabria ◽

Hortensia Sanchez-Tocino

Keyword(s):

Genetic Study ◽

Genetic Diagnosis ◽

Retinal Diseases ◽

Significant Delay ◽

Delay In Diagnosis ◽

Mean Delay ◽

Castilla Y Leon ◽

Diagnosis Rate ◽

History Of ◽

The Mean

Abstract Backgorund: To analyze the distribution of inherited retinal diseases (IRDs), describe the clinical characteristics of patients, and determine the percentages of patients with genetic diagnoses in the Castilla and Leon region of Spain.Methods: All patients with an IRD seen in the two major referral units of Castilla y Leon during a 20-year period were included. The ages at symptom onset, diagnosis, and the last visit; sex; family history; history of consanguinity; type of inheritance; status of the fundus and electroretinogram; lens and macular status, visual acuity; and visual field data were recorded. Patients were divided into those with retinitis pigmentosa (RP) and all others. The genetic mutations were gathered.Results: Four hundred eighty-eight patients with IRDs were studied, 216 with RP (of which 15.74% had syndromic disease) and 272 with other conditions (59.19% of which were macular dystrophies). A genetic study had been performed in 27.31% of patients (29.31% of which were negative) among the patients with RP and in 26.1% of the rest of the IRDs (28.16% of which were negative). In the group without a genetic diagnosis, 70.6% of subjects had good remaining vision. The mean delay in diagnosis was 6-16.2 years.Conclusions: The percentage of patients with IRDs that are candidates for undergoing personalized treatments including gene therapy in our region is low and must be improved. Most patients with RP who did not undergo a genetic study have good remaining vision, so they would be candidates for receiving treatments aimed at maintaining vision. There is a significant delay in diagnosis.

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Molecular Characterization of a Patient Presumed to Have Prader-Willi Syndrome

Clinical Medicine Insights Case Reports ◽

10.4137/ccrep.s11510 ◽

2013 ◽

Vol 6 ◽

pp. CCRep.S11510 ◽

Cited By ~ 3

Author(s):

Marina Falaleeva ◽

Carlos R. Sulsona ◽

Horst R. Zielke ◽

Kathleen M. Currey ◽

Pierre de la Grange ◽

...

Keyword(s):

Molecular Characterization ◽

Genetic Diagnosis ◽

Chromosome 15 ◽

Rna Expression ◽

Prader Willi Syndrome ◽

Post Mortem ◽

Tissue Donors ◽

Human Phenotype ◽

History Of

Prader-Willi syndrome (PWS) is caused by the loss of RNA expression from an imprinted region on chromosome 15 that includes SNRPN, SNORD115, and SNORD116. Currently, there are no mouse models that faithfully reflect the human phenotype and investigations rely on human post-mortem material. During molecular characterization of tissue deposited in a public brain bank from a patient diagnosed with Prader-Willi syndrome, we found RNA expression from SNRPN, SNORD115, and SNORD116 which does not support a genetic diagnosis of Prader-Willi syndrome. The patient was a female, Caucasian nursing home resident with history of morbid obesity (BMI 56.3) and mental retardation. She died at age of 56 from pulmonary embolism. SNORD115 and SNORD116 are unexpectedly stable in post mortem tissue and can be used for post-mortem diagnosis. Molecular characterization of PWS tissue donors can confirm the diagnosis and identify those patients that have been misdiagnosed.

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Normal Cortisol Response to High-Dose Synacthen and Insulin Tolerance Test in Children and Adults with Prader-Willi Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-0782 ◽

2011 ◽

Vol 96 (1) ◽

pp. E173-E180 ◽

Cited By ~ 25

Author(s):

Stense Farholt ◽

Rasmus Sode-Carlsen ◽

Jens Sandahl Christiansen ◽

John R. Østergaard ◽

Charlotte Høybye

Keyword(s):

Hpa Axis ◽

Genetic Diagnosis ◽

Tolerance Test ◽

Insulin Tolerance Test ◽

High Dose ◽

Prader Willi Syndrome ◽

University Hospitals ◽

Insulin Tolerance ◽

Synacthen Test ◽

Clinically Significant

Context: Prader-Willi syndrome (PWS) is a genetic disease associated with hypogonadism and partial GH insufficiency, possibly explained in part by a hypothalamic dysfunction. Partial insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis has recently been suggested. Objective: The objective of the study was to further explore the HPA axis in PWS by use of routine tests. Design: Nonselected PWS patients were examined with a standard high-dose synacthen test or the insulin tolerance test (ITT). A random serum (s) cortisol was measured in case of acute illness. Setting: The study was conducted at university hospitals in Denmark and Sweden. Patients: Sixty-five PWS patients with a confirmed genetic diagnosis participated in the study. Main Outcome Measures: A s-cortisol value above 500 nmol/liter as well as an increase of 250 nmol/liter or greater was considered a normal response. Results: Fifty-seven PWS patients (median age 22 yr, total range 0.5–48 yr) were examined with the high-dose synacthen test. The median s-cortisol at the time of 30 min was 699 (474–1578) nmol/liter. Only one patient had a s-cortisol level below 500 nmol/liter but an increase of 359 nmol/liter. This patient subsequently showed a normal ITT response. Two patients had increases less than 250 nmol/liter but a time of 30-min s-cortisol values of 600 nmol/liter or greater. These three patients were interpreted as normal responders. Eight patients [aged 26 (16–36) yr] examined with the ITT had a median peak s-cortisol of 668 (502–822) nmol/liter. Four children admitted for acute illnesses had s-cortisol values ranging from 680 to 1372 nmol/liter. Conclusion: In this PWS cohort, the function of the HPA axis was normal, suggesting that clinically significant adrenal insufficiency in PWS is rare.

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Ageing in people with Prader–Willi syndrome: mortality in the UK population cohort and morbidity in an older sample of adults

Psychological Medicine ◽

10.1017/s0033291714001755 ◽

2014 ◽

Vol 45 (3) ◽

pp. 615-621 ◽

Cited By ~ 8

Author(s):

J. E. Whittington ◽

A. J. Holland ◽

T. Webb

Keyword(s):

Mortality Rate ◽

Uniparental Disomy ◽

Genetic Diagnosis ◽

Population Based ◽

Prader Willi Syndrome ◽

Maternal Uniparental Disomy ◽

Early Onset Dementia ◽

Premature Ageing ◽

History Of

BackgroundThe past two decades have seen a great improvement in the care of people with Prader–Willi syndrome (PWS), particularly with regard to control of diet and behaviour management. Has this affected mortality rates or thrown up new issues regarding premature ageing or dementia? We investigated two aspects of ageing in people with PWS: (1) an estimate of mortality over 9 years in a cohort of people with PWS, originally recruited in 1998–2000; and (2) premature ageing or dementia in people aged ⩾40 years.Method(1) A follow-up of the population-based 1998–2000 cohort to investigate the subsequent mortality rate; and (2) the recruitment and structured assessment of all members of the Prader–Willi Syndrome Association UK (PWSA-UK) aged ⩾40 years who agreed to participate.ResultsFollow-up of the population-based 1998–2000 cohort gave a mortality rate of at least 7/62 over 9 years (1.25% per annum; 20 untraced), age at death was between 13 and 59 years. Twenty-six members of the PWSA-UK aged ⩾40 years were recruited, 18 of whom had a genetic diagnosis (gd) of PWS. Twenty-two (14 gd) showed no evidence of dementia. Four, with possible symptoms, are described in more detail; all are female, of maternal uniparental disomy (mUPD) genetic subtype, or have a disomic region, and all have a long history of psychotic illness.ConclusionsThe mortality rate in people with PWS seems to be declining. The subgroup of people with PWS due to UPD or disomic region with female gender and a history of psychosis may be at risk of early onset dementia.

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LDCT Screening in Smokers in India—A Pilot, Proof-of-Concept Study

Indian Journal of Radiology and Imaging ◽

10.1055/s-0041-1734227 ◽

2021 ◽

Author(s):

Sanghavi Parang ◽

Jankharia Bhavin

Keyword(s):

Private Practice ◽

Low Dose ◽

Smoking History ◽

Western World ◽

Lung Nodules ◽

Proof Of Concept ◽

Endemic Country ◽

Concept Study ◽

History Of ◽

The Mean

Abstract Aim The aim of the study is to assess the effectiveness of low dose CT scan (LDCT) to pick up nodules and carcinomas in smokers in India. Methods A retrospective study of 350 smokers scanned with LDCT was performed in a private practice center in Mumbai, India. Their demographic profile, smoking history in pack-years, lung nodules, and associated findings/superimposed complications were recorded and analyzed. The nodules were assigned the appropriate Lung-RADS category and results of the patients undergoing biopsy were recorded. Results Of the 350 smokers, 15 (4%) were women . The mean age was 61 years (32–90 years) with a mean smoking history of 22 pack-years (1–160 pack-years). Lung nodules were found in 335 (93%) smokers, with Lung-RADS category 1 nodules seen in 117 (36%), category 2 in 133 (41%), category 3 in 29 (9%), and category 4 in 46 (14%) of positive scans. Seven of the category 4 patients who underwent biopsy showed carcinoma, with a mean smoking history of 30 pack years. Superimposed interstitial lung disease, airways diseases, and infections were also seen in the scans and recorded. Discussion It has been proven in the Western world that screening for lung cancer with LDCT saves lives with early pick-up of malignant nodules. This pilot study from India, shows that even in a tuberculosis endemic country, LDCT picks up malignant lung nodules early and saves lives. Conclusion Smokers with a more than 20 pack years history have a higher incidence of lung nodules, which may represent carcinoma, in a tuberculosis endemic country like India, as has been proven in other countries in the Western world. Larger studies and trials may be performed to elaborate further on this proof-of-concept study.

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