Publications by authors named "Bina Shah"

43 Publications

Multiparametric ultrasound versus multiparametric MRI to diagnose prostate cancer (CADMUS): a prospective, multicentre, paired-cohort, confirmatory study.

Lancet Oncol 2022 03;23(3):428-438

Division of Surgical and Interventional Sciences, University College London, London, UK; Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK.

Background: Multiparametric MRI of the prostate followed by targeted biopsy is recommended for patients at risk of prostate cancer. However, multiparametric ultrasound is more readily available than multiparametric MRI. Data from paired-cohort validation studies and randomised, controlled trials support the use of multiparametric MRI, whereas the evidence for individual ultrasound methods and multiparametric ultrasound is only derived from case series. We aimed to establish the overall agreement between multiparametric ultrasound and multiparametric MRI to diagnose clinically significant prostate cancer.

Methods: We conducted a prospective, multicentre, paired-cohort, confirmatory study in seven hospitals in the UK. Patients at risk of prostate cancer, aged 18 years or older, with an elevated prostate-specific antigen concentration or abnormal findings on digital rectal examination underwent both multiparametric ultrasound and multiparametric MRI. Multiparametric ultrasound consisted of B-mode, colour Doppler, real-time elastography, and contrast-enhanced ultrasound. Multiparametric MRI included high-resolution T2-weighted images, diffusion-weighted imaging (dedicated high B 1400 s/mm or 2000 s/mm and apparent diffusion coefficient map), and dynamic contrast-enhanced axial T1-weighted images. Patients with positive findings on multiparametric ultrasound or multiparametric MRI underwent targeted biopsies but were masked to their test results. If both tests yielded positive findings, the order of targeting at biopsy was randomly assigned (1:1) using stratified (according to centre only) block randomisation with randomly varying block sizes. The co-primary endpoints were the proportion of positive lesions on, and agreement between, multiparametric MRI and multiparametric ultrasound in identifying suspicious lesions (Likert score of ≥3), and detection of clinically significant cancer (defined as a Gleason score of ≥4 + 3 in any area or a maximum cancer core length of ≥6 mm of any grade [PROMIS definition 1]) in those patients who underwent a biopsy. Adverse events were defined according to Good Clinical Practice and trial regulatory guidelines. The trial is registered on ISRCTN, 38541912, and ClinicalTrials.gov, NCT02712684, with recruitment and follow-up completed.

Findings: Between March 15, 2016, and Nov 7, 2019, 370 eligible patients were enrolled; 306 patients completed both multiparametric ultrasound and multiparametric MRI and 257 underwent a prostate biopsy. Multiparametric ultrasound was positive in 272 (89% [95% CI 85-92]) of 306 patients and multiparametric MRI was positive in 238 patients (78% [73-82]; difference 11·1% [95% CI 5·1-17·1]). Positive test agreement was 73·2% (95% CI 67·9-78·1; κ=0·06 [95% CI -0·56 to 0·17]). Any cancer was detected in 133 (52% [95% CI 45·5-58]) of 257 patients, with 83 (32% [26-38]) of 257 being clinically significant by PROMIS definition 1. Each test alone would result in multiparametric ultrasound detecting PROMIS definition 1 cancer in 66 (26% [95% CI 21-32]) of 257 patients who had biopsies and multiparametric MRI detecting it in 77 (30% [24-36]; difference -4·3% [95% CI -8·3% to -0·3]). Combining both tests detected 83 (32% [95% CI 27-38]) of 257 clinically significant cancers as per PROMIS definition 1; of these 83 cancers, six (7% [95% CI 3-15]) were detected exclusively with multiparametric ultrasound, and 17 (20% [12-31]) were exclusively detected by multiparametric MRI (agreement 91·1% [95% CI 86·9-94·2]; κ=0·78 [95% CI 0·69-0·86]). No serious adverse events were related to trial activity.

Interpretation: Multiparametric ultrasound detected 4·3% fewer clinically significant prostate cancers than multiparametric MRI, but it would lead to 11·1% more patients being referred for a biopsy. Multiparametric ultrasound could be an alternative to multiparametric MRI as a first test for patients at risk of prostate cancer, particularly if multiparametric MRI cannot be carried out. Both imaging tests missed clinically significant cancers detected by the other, so the use of both would increase the detection of clinically significant prostate cancers compared with using each test alone.

Funding: The Jon Moulton Charity Trust, Prostate Cancer UK, and UCLH Charity and Barts Charity.
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http://dx.doi.org/10.1016/S1470-2045(22)00016-XDOI Listing
March 2022

Protocol for a prospective double-blind, randomised, placebo-controlled feasibility trial of octreotide infusion during liver transplantation.

BMJ Open 2021 12 2;11(12):e055864. Epub 2021 Dec 2.

Division of Surgery & Interventional Science, University College London, London, UK.

Introduction: Liver transplantation is a complex operation that can provide significant improvements in quality of life and survival to the recipients. However, serious complications are common and include major haemorrhage, hypotension and renal failure. Blood transfusion and the development of acute kidney injury lead to both short-term and long-term poor patient outcomes, including an increased risk of death, graft failure, length of stay and reduced quality of life. Octreotide may reduce the incidence of renal dysfunction, perioperative haemorrhage and enhance intraoperative blood pressure. However, octreotide does have risks, including resistant bradycardia, hyperglycaemia and hypoglycaemia and QT prolongation. Hence, a randomised controlled trial of octreotide during liver transplantation is needed to determine the cost-efficacy and safety of its use; this study represents a feasibility study prior to this trial.

Methods And Analysis: We describe a multicentre, double-blind, randomised, placebo-controlled feasibility study of continuous infusion of octreotide during liver transplantation surgery. We will recruit 30 adult patients at two liver transplant centres. A blinded infusion during surgery will be administered in a 2:1 ratio of octreotide:placebo. The primary outcomes will determine the feasibility of this study design. These include the recruitment ratio, correct administration of blinded study intervention, adverse event rates, patient and clinician enrolment refusal and completion of data collection. Secondary outcome measures of efficacy and safety will help shape future trials by assessing potential primary outcome measures and monitoring safety end points. No formal statistical tests are planned. This manuscript represents study protocol number 1.3, dated 2 June 2021.

Ethics And Dissemination: This study has received Research Ethics Committee approval. The main study outcomes will be submitted to an open-access journal.

Trial Sponsor: The Joint Research Office, University College London, UK.Neither the sponsor nor the funder have any role in study design, collection, management, analysis and interpretation of data, writing of the study report or the decision to submit the report for publication.

Trial Registration: The study is registered with ClinicalTrials.gov (NCT04941911) with recruitment due to start in August 2021 with anticipated completion in July 2022.

Clinical Trials Unit: Surgical and Interventional Group, Division of Surgery & Interventional Science, University College London.
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http://dx.doi.org/10.1136/bmjopen-2021-055864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640665PMC
December 2021

Harnessing rare variants in neuropsychiatric and neurodevelopment disorders-a Keystone Symposia report.

Ann N Y Acad Sci 2021 12 2;1506(1):5-17. Epub 2021 Aug 2.

Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.

Neurodevelopmental neuropsychiatric disorders, such as autism spectrum disorder and schizophrenia, have strong genetic risk components, but the underlying mechanisms have proven difficult to decipher. Rare, high-risk variants may offer an opportunity to delineate the biological mechanisms responsible more clearly for more common idiopathic diseases. Indeed, different rare variants can cause the same behavioral phenotype, demonstrating genetic heterogeneity, while the same rare variant can cause different behavioral phenotypes, demonstrating variable expressivity. These observations suggest convergent underlying biological and neurological mechanisms; identification of these mechanisms may ultimately reveal new therapeutic targets. At the 2021 Keystone eSymposium "Neuropsychiatric and Neurodevelopmental Disorders: Harnessing Rare Variants" a panel of experts in the field described significant progress in genomic discovery and human phenotyping and raised several consistent issues, including the need for detailed natural history studies of rare disorders, the challenges in cohort recruitment, and the importance of viewing phenotypes as quantitative traits that are impacted by rare variants.
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http://dx.doi.org/10.1111/nyas.14658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688183PMC
December 2021

Auto-destruction of the thyroid gland and coexisting glutamic acid decarboxylase mediated neurological disease in an adolescent: an unusual presentation of autoimmunity.

J Pediatr Endocrinol Metab 2021 Oct 24;34(10):1329-1333. Epub 2021 Jun 24.

Pediatric Endocrinology, NYU Langone Medical Center, New York, USA.

Objectives: Hashimoto's thyroiditis (HT) is characterized by lymphocytic thyroid infiltration. Gradual thyroid failure can occur due to thyroid cell apoptosis. Rarely neurological autoimmunity due to glutamic acid decarboxylase (GAD) antigen can co exist with HT.

Case Presentation: A seven-year-old male presented with tiredness, weight loss, frequent falls, tachycardia, firm thyromegaly, and abnormal gait. Biochemical markers and thyroid ultrasound (TUS) showed autoimmune hyperthyroidism. Methimazole (MMI) was started and continued for 2.2 years. MRI brain was normal and neurological symptoms resolved. At nine years, he became hypothyroid and levothyroxine (LT4) was started. Serial TUS showed progressive thyroid atrophy. At 14.8 years, he developed epilepsy and fourth cranial nerve palsy, and diagnosed with GAD-65 central nervous system disease. At 15.3 years, TUS showed complete atrophy of right lobe with involuting left lobe volume.

Conclusions: This is an unusual form of atrophic thyroiditis (AT) with coexisting neurological autoimmunity. GAD-65 CNS autoimmunity should be considered in children with AT presenting with neurological signs.
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http://dx.doi.org/10.1515/jpem-2020-0697DOI Listing
October 2021

Pre-treatment Neutropenia in Children and Adolescents with Autoimmune Hyperthyroidism

J Clin Res Pediatr Endocrinol 2021 08 2;13(3):263-268. Epub 2020 Dec 2.

New York University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, New York, USA

Objective: Neutropenia can occur in untreated autoimmune hyperthyroidism (AIH) or in association with treatment with the anti-thyroid drug, methimazole (MMI). Starting MMI in children and adolescents with AIH and pre-existing neutropenia could thus be worrisome. The aim was to describe the prevalence of neutropenia in pediatric AIH, prior to antithyroid drug therapy and to assess the effect of antithyroid drugs on neutrophil count.

Methods: Patients with AIH attending a pediatric endocrinology clinic were retrospectively reviewed. Absolute neutrophil count (ANC) data at presentation and during anti-thyroid treatment for up to 24 weeks was collected. AIH was defined as elevated free thyroxine (fT4) or free tri-iodothyronine (fT3), suppressed thyroid stimulating hormone, and positive thyroid autoantibodies. Neutropenia was defined as ANC <1500 cells/μL.

Results: Thirty-one patients (71% female) were included with a median interquartile range (IQR) age of 14.71 (11.89-17.10) years. Neither fT4 nor fT3 levels correlated with ANC at presentation (r=0.22, p=0.24 and r=0.13, p=0.54, respectively). 26/31 (84%) had normal baseline ANC. None developed neutropenia with thionamides. 5/31 (16%) had baseline neutropenia (median ANC 1,200/μL; IQR 874-1200). Four of these five started MMI at diagnosis while one was started on propranolol only but MMI was started one week later. All five normalized ANC within 24 weeks.

Conclusion: In this cohort, 16% of AIH patients had neutropenia at presentation, but this resolved in the short term and did not worsen with thionamides. Thionamides may be used with caution in these patients with close monitoring of blood counts.
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http://dx.doi.org/10.4274/jcrpe.galenos.2020.2020.0184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388046PMC
August 2021

Can preimplantation genetic diagnosis be used for monogenic endocrine diseases?

J Pediatr Endocrinol Metab 2019 Dec;32(12):1305-1310

Division of Pediatric Endocrinology, Department of Pediatrics, New York University School of Medicine, New York, NY, USA, Phone: +212-562-3793.

Context Preimplantation genetic diagnosis (PGD) is currently used for over 400 monogenic diseases. Some endocrine conditions that occur due to monogenic defects are either life-threatening or can cause severe morbidities; thus, PGD may be an option to avoid the occurrence of such diseases. Evidence acquisition An initial search in PubMed/Medline search was done to identify monogenic endocrine conditions using appropriate search terms. Eleven articles (1999-2018) reported 15 cases using PGD for monogenic endocrine diseases performed at major reproductive centers. Clinical and outcome data of these cases were reviewed with respect to the number of PGD cycles, successful pregnancy rates, live births and their genetic status. Evidence synthesis Fifteen couples underwent 32 PGD cycles (one to nine per couple), of which 17 resulted in a pregnancy. Seven couples underwent a single PGD cycle. Four couples had successful pregnancies each resulting in live births, one couple had an unsuccessful pregnancy, one needed medical termination of pregnancy and the outcome data were not reported in one. The remaining eight couples underwent multiple PGD cycles (two to nine per couple) and all had successful pregnancies in at least one cycle resulting in 16 live births. Of the total live births, 60% were genetically unaffected and 40% were carriers of the autosomal recessive gene mutation. Conclusions PGD may be a potential tool for preventing the inheritance of severe monogenic endocrine diseases in future generations. Currently, the use of PGD in endocrine disorders is rare but provides a promising option on a case-by-case basis, provided the optimal resources are available.
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http://dx.doi.org/10.1515/jpem-2019-0184DOI Listing
December 2019

Allergic and non-allergic skin reactions associated with growth hormone therapy: elucidation of causative agents.

J Pediatr Endocrinol Metab 2018 Jan;31(1):5-11

Department of Pediatrics, Division of Pediatric Endocrinology, New York University School of Medicine, New York, NY, USA.

Background: Allergic and non-allergic skin reactions to recombinant human growth hormone (rhGH) are uncommon and infrequently reported. However, physicians should be aware of these potential side effects to determine whether the reactions constitute true allergies and how to proceed with growth hormone therapy. To review allergic and non-allergic skin reactions caused by rhGH and subsequent diagnostic workup and management options.

Case Presentation: We report the case of a 12-year-old healthy male presenting with idiopathic short stature. He developed an itchy skin rash over the chest and abdomen, 15 min after administration of the first dose of rhGH, leading us to review allergic and non-allergic skin reactions to rhGH. In our patient, an immediate skin reaction after administration of rhGH prompted a concern about a type I hypersensitivity reaction (HS) and the discontinuation of rhGH. However, after a dermatologic evaluation and observed administration of rhGH without subsequent rash, the initial eruption was likely an exacerbation of his underlying atopic dermatitis and a type I HS was felt to be unlikely. The rhGH was resumed and he has been on rhGH for the past 1 year with no recurrence of rash and with improvement in growth velocity.

Conclusions: Though rare, allergic and non-allergic skin reactions are known to occur with rhGH. It is important to know if the allergic reaction was due to the growth hormone molecule or one of the preservatives. It is also important to consider a non-allergic reaction due to flare up of underlying skin disorders as in our patient.
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http://dx.doi.org/10.1515/jpem-2017-0309DOI Listing
January 2018

The CADMUS trial - Multi-parametric ultrasound targeted biopsies compared to multi-parametric MRI targeted biopsies in the diagnosis of clinically significant prostate cancer.

Contemp Clin Trials 2018 03 3;66:86-92. Epub 2017 Nov 3.

Division of Surgery, Department of Surgery and Cancer, Imperial College London, United Kingdom; Division of Surgery and Interventional Sciences, University College London, United Kingdom.

Objective: To compare the proportion of clinically significant prostate cancers (PCa) found in lesions detected by multiparametric MRI (mpMRI) with that found in lesions detected by multiparametric ultrasound (mpUSS), in men at risk.

Patients And Methods: CADMUS (Cancer Detection by Multiparametric Ultrasound of the prostate) is a prospective, multi-centre paired cohort diagnostic utility study with built-in randomisation of order of biopsies. The trial is registered ISRCTN38541912. All patients will undergo the index test under evaluation (mpUSS±biopsies), as well as the standard test (mpMRI±biopsies). Eligible men will be those at risk of harbouring prostate cancer usually recommended for prostate biopsy, either for the first time or as a repeat, who have not had any prior treatment for prostate cancer. Men in need of repeat biopsy will include those with prior negative results but ongoing suspicion, and those with an existing prostate cancer diagnosis but a need for accurate risk stratification. Both scans will be reported blind to the results of the other and the order in which the targeted biopsies derived from the two different imaging modalities are taken will be randomised. Comparison will be drawn between biopsy results of lesions detected by mpUSS with those lesions detected by mpMRI. Agreement over position between the two imaging modalities will be studied.

Discussion: CADMUS will provide level one evidence on the performance of mpUSS derived targeted biopsies in the identification of clinically significant prostate cancer in comparison to mpMRI targeted biopsies. Recruitment is underway and expected to complete in 2018.
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http://dx.doi.org/10.1016/j.cct.2017.10.011DOI Listing
March 2018

Spiral Fracture in Young Infant Causing a Diagnostic Dilemma: Nutritional Rickets versus Child Abuse.

Case Rep Pediatr 2017 19;2017:7213629. Epub 2017 Sep 19.

New York University School of Medicine, New York, NY, USA.

Fractures are uncommon in young, nonambulatory infants. The differential diagnosis includes nonaccidental injury (NAI) and metabolic bone disease, including rickets. While rickets typically present after six months of age, multiple cases have been reported in younger infants. We report a case of an 11-week-old male infant who presented with a spiral fracture of the humerus and no radiologic evidence of rickets. A detailed psychosocial assessment failed to reveal any risk factors for NAI. The patient had elevated alkaline phosphatase and PTH with low 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D levels. Additionally, the mother was noncompliant with prenatal vitamins, exclusively breastfeeding without vitamin D supplementation, and had markedly low vitamin D levels 15 weeks postpartum. The biochemical data and history were consistent with rickets. Given the diagnostic dilemma, the working diagnosis was rickets and the patient was started on ergocalciferol with subsequent normalization of his laboratory values and healing of the fracture. These findings are consistent with nutritional rickets largely due to maternal-fetal hypovitaminosis D. This case highlights that in young infants rickets should be considered even in the absence of positive radiologic findings. Additionally, it illustrates the importance of maintaining adequate vitamin D supplementation during pregnancy and early infancy.
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http://dx.doi.org/10.1155/2017/7213629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625808PMC
September 2017

Use of Chlorothiazide in the Management of Central Diabetes Insipidus in Early Infancy.

Case Rep Pediatr 2017 3;2017:2407028. Epub 2017 May 3.

Department of Pediatrics, Division of Pediatric Endocrinology, New York University School of Medicine, New York, NY, USA.

Management of central diabetes insipidus in infancy is challenging. The various forms of desmopressin, oral, subcutaneous, and intranasal, have variability in the duration of action. Infants consume most of their calories as liquids which with desmopressin puts them at risk for hyponatremia and seizures. There are few cases reporting chlorothiazide as a temporizing measure for central diabetes insipidus in infancy. A male infant presented on day of life 30 with holoprosencephaly, cleft lip and palate, and poor weight gain to endocrine clinic. Biochemical tests and urine output were consistent with central diabetes insipidus. The patient required approximately 2.5 times the normal fluid intake to keep up with the urine output. Patient was started on low renal solute load formula and oral chlorothiazide. There were normalization of serum sodium, decrease in fluid intake close to 1.3 times the normal, and improved urine output. There were no episodes of hyponatremia/hypernatremia inpatient. The patient had 2 episodes of hypernatremia in the first year of life resolving with few hours of hydration. Oral chlorothiazide is a potential bridging agent for treatment of central DI along with low renal solute load formula in early infancy. It can help achieve adequate control of DI without wide serum sodium fluctuations.
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http://dx.doi.org/10.1155/2017/2407028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434263PMC
May 2017

Salivary Testosterone during the Minipuberty of Infancy
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Horm Res Paediatr 2017 10;87(2):111-115. Epub 2017 Jan 10.

Background: The hypothalamic-pituitary-gonadal axis is transiently activated during the postnatal months in boys, a phenomenon termed "minipuberty" of infancy, when serum testosterone (T) increases to pubertal levels. Despite high circulating T there are no signs of virilization. We hypothesize that free T as measured in saliva is low, which would explain the absence of virilization.

Methods: We measured serum total T and free T in saliva using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 30 infant boys, aged 1-6 months, and in 12 adolescents, aged 11-17 years.

Results: Total serum T in all infants was, as expected, high (172 ± 78 ng/dL) while salivary T was low (7.7 ± 4 pg/mL or 0.45 ± 0.20%). In contrast, salivary T in the adolescents was much higher (41 ± 18 pg/mL or 1.3 ± 0.36%) in relation to their total serum T (323 ± 117 ng/dL). We provide for the first time reference data for salivary T in infants.

Conclusion: Measurement of salivary T by LC-MS/MS is a promising noninvasive technique to reflect free T in infants. The low free T explains the absence of virilization. The minipuberty of infancy is more likely of intragonadal than peripheral significance.
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http://dx.doi.org/10.1159/000454862DOI Listing
June 2017

Transdermal testosterone gel for induction and continuation of puberty in adolescent boys with hepatic dysfunction.

J Pediatr Endocrinol Metab 2017 Jan;30(1):105-109

Treatment to induce puberty in boys is indicated in those who do not undergo spontaneous development at a normal age. Stimulating development of the secondary sex characteristics is possible using gradually increasing doses of testosterone esters (TEs) via intramuscular (IM) administration, which is the most widely used method of testosterone (T) supplementation. When TEs are administered as monthly injection, serum T levels exhibit large fluctuations with supraphysiologic levels seen immediately after the injection followed by a decrease into the low range. Transdermal T (TT) has also been used for replacement therapy in adult males with hypogonadism and this provides steadier serum T levels. We report three adolescent boys with delayed puberty who were treated with TT gel for pubertal induction/continuation. This route was chosen as an alternative therapy due to their hepatic dysfunction, as is known that TT avoids the hepatic first-pass metabolism.
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http://dx.doi.org/10.1515/jpem-2016-0201DOI Listing
January 2017

Unusual phenotype of congenital adrenal hyperplasia (CAH) with a novel mutation of the CYP21A2 gene.

J Pediatr Endocrinol Metab 2016 Jul;29(7):867-71

Gonadotropin independent sexual precocity (SP) may be due to congenital adrenal hyperplasia (CAH), and its timing usually depends on the type of mutation in the CYP21A2 gene. Compound heterozygotes are common and express phenotypes of varying severity. The objective of this case report was to investigate the hormonal pattern and unusual genetic profile in a 7-year-old boy who presented with pubic hair, acne, an enlarged phallus, slightly increased testicular volume and advanced bone age. Clinical, hormonal and genetic studies were undertaken in the patient as well as his parents. We found elevated serum 17-hydroxyprogesterone (17-OHP) and androstenedione that were suppressed with dexamethasone, and elevated testosterone that actually rose after giving dexamethasone, indicating activity of the hypothalamic-pituitary-gonadal (HPG) axis. An initial search for common mutations was negative, but a more detailed genetic analysis of the CYP21A2 gene revealed two mutations including R341W, a non-classical mutation inherited from his mother, and g.823G>A, a novel not previously reported consensus donor splice site mutation inherited from his father, which is predicted to be salt wasting. However, the child had a normal plasma renin activity. He was effectively treated with low-dose dexamethasone and a GnRH agonist. His father was an unaffected carrier, but his mother had evidence of mild non-classical CAH. In a male child presenting with gonadotropin independent SP it is important to investigate adrenal function with respect to the androgen profile, and to carry out appropriate genetic studies.
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http://dx.doi.org/10.1515/jpem-2015-0457DOI Listing
July 2016

Progression of nonmotor symptoms in subgroups of patients with non-dopamine-deficient Parkinsonism.

Mov Disord 2016 Mar 11;31(3):344-51. Epub 2016 Feb 11.

Division of Brain Sciences, Imperial College London, UK.

Background: Ten to fifteen percent of Parkinson's disease (PD) patients recruited to clinical trials have scans without evidence of dopaminergic deficit, whose presence represents a heterogeneous patient population.

Methods: A cohort of 41 patients with parkinsonism and scans without evidence of dopaminergic deficit at baseline, were subdivided into groups according to their final clinical diagnoses and nigrostriatal dopamine function assessed after 2 years of study. At follow up, 23 patients had clinically probable PD or unclassified parkinsonism with normal nigrostriatal dopamine imaging ("true" scans without evidence of dopaminergic deficit), nine were diagnosed with another tremulous condition, five had psychogenic parkinsonism, and four had phenoconverted to PD with reduced nigrostriatal dopamine function. We analyzed nonmotor symptoms at baseline and follow-up in subgroups of patients with scans without evidence of dopaminergic deficit in comparison with a random sample of 62 PD patients and 195 healthy controls (HCs). All patients were enrolled in the Parkinson's Progressive Marker's Initiative.

Results: Patients who had true scans without evidence of dopaminergic deficit had more severe rapid eye movement sleep disorder, depression, anxiety, and autonomic dysfunction than HCs in addition to more frequent depressive symptoms and worse cardiovascular dysfunction than patients with PD (P = 0.038, P = 0.047, respectively). Patients with true scans without evidence of dopaminergic deficit had normal olfaction that was significantly better than that of patients with PD (P < 0.001). Subgroup analysis of the cohort with scans without evidence of dopaminergic deficit revealed that all patients shared similar nonmotor features irrespective of their final clinical diagnoses. Follow-up of subject groups showed stable nonmotor symptoms over 2 years of study.

Conclusions: At an early symptomatic stage, patients with scans without evidence of dopaminergic deficit and long-standing parkinsonism exhibit nonmotor features that differ from those of patients with PD on mood and cardiovascular and olfactory function, but remain similar to patients with scans without evidence of dopaminergic deficit with alternative final diagnoses.
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http://dx.doi.org/10.1002/mds.26456DOI Listing
March 2016

Clinical correlates of raphe serotonergic dysfunction in early Parkinson's disease.

Brain 2015 Oct 23;138(Pt 10):2964-73. Epub 2015 Jul 23.

1 Division of Brain Sciences, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK 3 Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus, Denmark

Post-mortem and neuroimaging studies suggest that the serotonergic system, which originates from the brainstem raphe nuclei, is disrupted in Parkinson's disease. This could contribute to the occurrence of non-motor symptoms and tremor, which are only partially explained by dopamine loss. However, the level of involvement of the serotonergic raphe nuclei in early Parkinson's disease is still debated. (123)I-FP-CIT single photon emission computed tomography is a marker of dopamine and serotonin transporter availability. While (123)I-FP-CIT binds primarily to dopamine transporters in the striatum, its binding in the brainstem raphe nuclei reflects serotonin transporter availability. We interrogated baseline single photon emission computed tomography scans of subjects recruited by the Parkinson's Progression Markers Initiative to determine: (i) the integrity of the brainstem raphe nuclei in early Parkinson's disease; and (ii) whether raphe serotonin transporter levels correlate with severity of tremor and symptoms of fatigue, depression, and sleep disturbance. Three hundred and forty-five patients with early drug-naïve Parkinson's disease, 185 healthy controls, and 56 subjects with possible Parkinson's disease without evidence of dopaminergic deficit were included. In the Parkinson's disease cohort, 37 patients had a tremulous, 106 patients had a pure akinetic-rigid, and 202 had a mixed phenotype. Patients with Parkinson's disease had significantly lower serotonin transporter availability in the brainstem raphe nuclei compared to controls (P < 0.01) and subjects without evidence of dopaminergic deficit (P < 0.05). However, only 13% of patients with Parkinson's disease individually had reduced signals. Raphe serotonin transporter availability over the entire Parkinson's disease cohort were associated with rest tremor amplitude (β = -0.106, P < 0.05), rest tremor constancy (β = -0.109, P < 0.05), and index of rest tremor severity (β = -0.104, P < 0.05). The tremulous Parkinson's disease subgroup had significantly lower raphe serotonin transporter availability but less severe striatal dopaminergic deficits compared to akinetic-rigid patients with no resting tremor (P < 0.05). In tremulous patients, raphe serotonin transporter availability was also associated with rest tremor constancy (β = -0.380, P < 0.05) and index of rest tremor severity (β = -0.322, P < 0.05). There was no association between raphe serotonin transporter availability and fatigue, depression, excessive daytime sleepiness, or rapid eye movement sleep behaviour disorder in early Parkinson's disease. We conclude that the raphe nuclei are affected in a subgroup of early drug-naïve Parkinson's disease patients and that reduced raphe serotonin transporter availability is associated with the severity of resting tremor but not non-motor symptoms.
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http://dx.doi.org/10.1093/brain/awv215DOI Listing
October 2015

Evaluation of puberty by verifying spontaneous and stimulated gonadotropin values in girls.

J Pediatr Endocrinol Metab 2015 Mar;28(3-4):387-92

Background: Changes in pharmacological agents and advancements in laboratory assays have changed the gonadotropin-releasing hormone analog stimulation test.

Objective: To determine the best predictive model for detecting puberty in girls.

Subjects: Thirty-five girls, aged 2 years 7 months to 9 years 3 months, with central precocious puberty (CPP) (n=20) or premature thelarche/premature adrenarche (n=15).

Methods: Diagnoses were based on clinical information, baseline hormones, bone age, and pelvic sonogram. Gonadotropins and E2 were analyzed using immunochemiluminometric assay. Logistic regression for CPP was performed.

Results: The best predictor of CPP is the E2-change model based on 3- to 24-h values, providing 80% sensitivity and 87% specificity. Three-hour luteinizing hormone (LH) provided 75% sensitivity and 87% specificity. Basal LH lowered sensitivity to 65% and specificity to 53%.

Conclusions: The E2-change model provided the best predictive power; however, 3-h LH was more practical and convenient when evaluating puberty in girls.
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http://dx.doi.org/10.1515/jpem-2014-0135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767152PMC
March 2015

Is ultrasound useful in the diagnosis of adolescents with polycystic ovary syndrome?

J Pediatr Endocrinol Metab 2015 May;28(5-6):605-12

Background: Diagnosis of adolescent polycystic ovary syndrome (PCOS) remains a challenge despite several existing criteria, and may be difficult to distinguish from pubertal changes. Different parameters to study ovarian function using ultrasonography have been proposed, but there is still no consensus about their diagnostic value.

Objective: To evaluate the role of ultrasonography in the diagnosis of adolescent PCOS by reviewing available studies that assessed the ovarian volume (OV) and other ovarian morphological features such as location and number of follicles, stromal area, and volume.

Methods: MEDLINE/PubMed database were searched to identify studies that assessed ovarian characteristics of adolescent PCOS patients by ultrasound. Studies on adults were also reviewed if study population included adolescents and stromal characteristics were assessed by three-dimensional (3D) sonogram.

Results: Five studies, including 262 PCOS adolescents (10-19 years of age) and two-dimensional (2D) ultrasound analysis, were identified. Mean OV was 9.29 cm³ for PCOS patients and 4.77 cm³ for controls. The morphology of ovarian follicles, when reported, showed multiple (>10) peripheral follicles in 83% of cases. Two studies, including 157 PCOS adolescents and young women (15-35 years of age) and 2D and 3D ultrasound analysis, were identified. Patients with PCOS patients had a MOV 13.1 cm³, multiple follicles (>15), and a statistically significant greater S/A ratio compared to controls. Stromal volume indices were positively correlated with hyperandrogenemia in PCOS patients.

Conclusion: Pelvic ultrasound is an increasingly important aid in the diagnosis of PCOS in adolescents. Besides ovarian volume, ovarian morphology must be assessed with 2D ultrasound to look for peripherally located multiple follicles. Further studies are warranted to evaluate the utility of 3D ultrasonographic assessment in adolescents with PCOS.
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http://dx.doi.org/10.1515/jpem-2014-0307DOI Listing
May 2015

Evaluation of the pro-inflammatory cytokine tumor necrosis factor-α in adolescents with polycystic ovary syndrome.

J Pediatr Adolesc Gynecol 2014 Dec 23;27(6):356-9. Epub 2014 Sep 23.

Division of Pediatric Endocrinology, Department of Pediatrics, New York University School of Medicine, New York, New York. Electronic address:

Background: Patients with polycystic ovary syndrome (PCOS) often suffer from comorbidities associated with chronic inflammation characterized by elevations in pro-inflammatory cytokines. There is limited data on markers of chronic inflammation, in particular Tumor Necrosis Factor-alpha (TNF-α), in adolescents with PCOS.

Objectives: To compare serum levels of TNF-α in overweight or obese adolescents with PCOS and obese controls. In the PCOS group, to correlate serum TNF-α levels with body mass index (BMI) z-score, severity of hyperandrogenism, degree of insulin resistance, and ovarian ultrasonographic characteristics.

Methods: We performed a cross-sectional retrospective analysis of clinical and biochemical findings in 23 overweight or obese adolescent females with PCOS (mean BMI z-score 2, mean age 15.2 yrs) and 12 obese age- and sex-matched controls (mean BMI z-score 2, mean age 14.1 y). All subjects were post-menarchal. Serum TNF-α levels were compared between groups. In the PCOS group, cytokine levels were correlated with BMI z-score, androgen levels, fasting insulin and glucose levels as well as ovarian ultrasonographic features.

Results: Both groups were comparable in age, BMI z-score, fasting glucose, and fasting insulin. Mean free testosterone was 9.76 ± 5.13 pg/mL in the PCOS group versus 5 ± 2.02 pg/mL in the control group (P = .0092). Serum TNF-α was 7.4 ± 4 pg/mL in the PCOS group versus 4.8 ± 3.16 pg/mL in the control group (P = .0468). There was no significant correlation between serum TNF-α and BMI z-score, free testosterone, fasting insulin, or fasting glucose. No correlation existed between serum TNF-α and ovarian follicle number, distribution, or volume.

Conclusions: Serum TNF-α is elevated in overweight/obese adolescents with PCOS. Chronic inflammation in adolescents with PCOS render them at a potential increased risk for the development of atherosclerosis, type 2 diabetes, cancer, infertility, and other comorbidities. Every effort should be made to identify adolescents with PCOS early and initiate aggressive therapy to prevent future complications.
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http://dx.doi.org/10.1016/j.jpag.2014.01.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536070PMC
December 2014

Growth patterns in pubertal HIV-infected adolescents and their correlation with cytokines, IGF-1, IGFBP-1, and IGFBP-3.

J Pediatr Endocrinol Metab 2013 ;26(7-8):639-44

Objective: This study aims to describe the final adult height (FAH) and pubertal growth patterns in human immunodeficiency virus (HIV)-infected adolescents and to compare these to an age-matched population of seroreverting HIV-exposed, uninfected (HEU) adolescents. It further aims to evaluate the interplay of proinflammatory cytokines with insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), and IGFBP-1 during the pubertal growth spurt.

Methods: HIV-infected (n=34) and HEU (n=12) adolescents who had achieved FAH were evaluated. Auxologic data, viral load, CD4+ T-lymphocyte (CD4) count, and the use of highly active antiretroviral therapy were obtained via a retrospective chart review. Serum interleukin (IL)-1α, IL-6, tumor necrosis factor (TNF)-α, IGFBP-1, IGFBP-3, and IGF-1 were assessed.

Results: The mean FAH standard deviation score for the HIV-infected group was -0.78 (±1.1) compared to 0.05 (±0.78) for the HEU (p=0.034). There was a positive correlation between CD4 count and FAH (p=0.019). The mean age and magnitude of peak growth velocity (GV) was within normal limits. IL-1α, IL-6, TNF-α, IGFBP-3, and IGF-1 were not significantly correlated with HIV RNA or height. IGFBP-1 was detectable in 100% of poorly controlled HIV-infected patients and 25% of the HEU cohort (p=0.0003).

Conclusions: The FAH of HIV-infected patients was significantly shorter than that of HEU patients, and it positively correlated with CD4 count. Our cohort demonstrated normal timing and magnitude of peak GV during puberty.
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http://dx.doi.org/10.1515/jpem-2011-0464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012610PMC
December 2013

Elevated serum anti-Müllerian hormone in adolescents with polycystic ovary syndrome: relationship to ultrasound features.

J Pediatr Endocrinol Metab 2012 ;25(9-10):983-9

Department of Pediatrics, New York University School of Medicine, New York, NY, USA.

Context: Serum anti-Müllerian hormone (AMH) is linked to the ovarian follicle pool. Little is known about the relationship between serum AMH and ovarian ultrasound (US) features in adolescents with polycystic ovary syndrome (PCOS).

Objectives: To confirm that serum AMH is elevated in adolescents with PCOS and to correlate serum AMH with ovarian US features in this population are the objectives of this study.

Design: A retrospective chart review of clinical, biochemical, and ultrasonographic data in adolescents with PCOS and normal controls is the design of the study. Serum AMH was measured and compared between groups and correlated with ovarian US findings.

Setting: The study was done in two urban tertiary academic medical centers.

Participants: Study groups included 23 adolescent females with PCOS and 12 age and BMI-matched female controls.

Main Outcome Measures: We hypothesized that serum AMH would be elevated in the PCOS group compared with the controls and would positively correlate with the follicle number, distribution, and ovarian volume.

Results: Serum AMH was 6.78±3.55 ng/mL in the PCOS group vs. 3.38±1.48 ng/mL in the controls (p=0.0004). AMH positively correlated with ovarian volume (left ovary r=0.65, p=0.0007, right ovary r=0.55, p=0.0065) and peripheral follicle distribution (p=0.0027). Ten or more follicles were observed in 83% of USs.

Conclusions: There is a positive relationship between serum AMH and ovarian volume as well as peripheral follicular distribution in adolescents with PCOS. Our findings support the use of serum AMH as a useful marker to reflect ovarian US features typical of PCOS in cases where accurate USs are not available and for follow-up.
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http://dx.doi.org/10.1515/jpem-2012-0013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763943PMC
April 2013

Early occurrence of cerebral white matter abnormality detected in a neonate with salt-wasting congenital adrenal hyperplasia.

J Pediatr Endocrinol Metab 2013 ;26(1-2):13-7

Department of Radiology, Bellevue Hospital Center, New York, NY, USA.

The development of white matter signal abnormalities on magnetic resonance brain imaging (MRI) in children and young adults with congenital adrenal hyperplasia has been well documented. Existing theories regarding the development of these findings include effects of electrolyte imbalances, effects of disease-related hormone abnormalities, and non-physiologic long-term administration of corticosteroids. Many of the patients previously described were normal neurologically. We describe the case of white matter signal abnormalities in a neonate with salt-wasting congenital adrenal hyperplasia who presented with seizures during the first week of life, possibly due to a transient blood calcium disturbance. This case suggests that white matter changes are not simply the result of chronic insults and that they may not always be subclinical.
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http://dx.doi.org/10.1515/jpem-2012-0154DOI Listing
June 2013

Oral fluid nanosensor test: saliva as a diagnostic tool for oral health.

J Calif Dent Assoc 2012 Sep;40(9):733-6

Department of Oral Medicine and Radiology, Dr. Syamala Reddy Dental College Hospital and Research Centre affiliated to Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka, India.

High-impact diseases, especially cancer, are challenging to diagnose without supplementing laboratory testing. Even with laboratory tools, definitive diagnosis often remains elusive. The oral fluid nanosensor test technology platform combines cutting-edge technologies--such as self-assembled monolayers, bionanotechnology, cyclic enzymatic amplification, and microfluidics--with several well-established techniques including microinjection molding, hybridization-based detection, and molecular purification. The intended use of the OFNASET is for the point-of-care multiplex detection of salivary biomarkers for oral cancer.
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September 2012

Improved long-term glucose control in neonatal diabetes mellitus after early sulfonylurea allergy.

J Pediatr Endocrinol Metab 2012 ;25(3-4):353-6

Division of Pediatric Endocrinology, Department of Pediatrics, New York University Langone Medical Center, New York, NY 10016, USA.

Background: Activating mutations of the ABCC8 gene can lead to permanent neonatal diabetes mellitus (PNDM). Glucose variability in infants with NDM treated with insulin can be extreme. We report long-term glycemic control in a patient with PNDM on sulfonylurea therapy, despite initial allergic reaction.

Methods: A Chinese girl presented on the first day of life with persistent hyperglycemia. Despite treatment with various insulin regimens, hemoglobin (Hb)A1c (normal 4.8%-6.3%) increased from 5.0% at 14 days of age to a peak of 9.7% at 15 months of age. Her average insulin dose was 0.5 units/kg/day. Genetic analysis revealed two novel ABCC8 gene activating mutations encoding the beta-cell sulfonylurea-1 receptor of the ATP-sensitive potassium channel. At age 3 years 2 months, transition from insulin to the oral sulfonylurea glyburide was initiated. After 8 days, she developed urticaria, palmar erythema, and a diffuse maculopapular rash, which resolved when medication was discontinued. At age 3 years 11 months, glyburide was reintroduced at a very low dose and was increased with concomitant weaning of insulin over the following 6 months.

Results: Normoglycemia (HbA1c 5.6%) was achieved on glyburide without any further allergic reaction at the age of 4 years 5 months with improved metabolic control. For the next 3 years, HbA1c measurements, and glucose means and variability were significantly lower compared with values during insulin therapy.

Conclusions: As compared with subcutaneous insulin, oral sulfonylureas improved long-term metabolic control in a patient with NDM caused by novel activating mutations in the ABCC8 gene. Desensitization permitted safe oral sulfonylurea therapy in our patient with NDM despite initial allergic reaction. Fewer episodes of hypoglycemia occurred on sulfonylurea than on insulin therapy, which is an advantage in a very young child.
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http://dx.doi.org/10.1515/jpem-2011-0449DOI Listing
July 2012

Exogenous pubertal induction by oral versus transdermal estrogen therapy.

J Pediatr Adolesc Gynecol 2013 Apr 23;26(2):71-9. Epub 2011 Nov 23.

Department of Pediatrics, Division of Pediatric Endocrinology, NYU School of Medicine, New York, NY 10016, USA.

Hypogonadal adolescent girls need estrogen therapy for the induction of puberty. For years, oral conjugated estrogens have been used for this purpose, starting at a very low dose, with gradual increments over time, to allow for the maturation of the reproductive organs, in order to mimic physiologic conditions. Several concerns, mainly due to first pass through the liver, are manifest with oral estrogen therapy. With the advent of transdermal estrogens and its improved efficacy profile as well as reduced side effects, it seems reasonable to consider it for pubertal induction. The primary objective of this study was to compare and contrast oral versus transdermal estrogen with regard to metabolism and physiology and to review current available data on transdermal estrogens with respect to exogenous pubertal induction.
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http://dx.doi.org/10.1016/j.jpag.2011.09.012DOI Listing
April 2013

Radiologic findings of pelvic venous congestion in an adolescent girl with angiographic confirmation and interventional treatment.

Pediatr Radiol 2012 May 13;42(5):636-40. Epub 2011 Sep 13.

Department of Radiology, New York University Langone Medical Center, New York, NY 10016, USA.

We present a case of pelvic venous congestion in a 13-year-old girl who complained of pelvic pain for 9 months. The diagnosis of pelvic congestion syndrome was suggested by imaging modalities, including sonography, CT and MRI, with classically described imaging findings. The girl underwent diagnostic laparoscopy, where visual inspection demonstrated congested pelvic veins and endometriosis. After removal of endometrial implants, the child's pain persisted and she subsequently underwent venography and embolization of the ovarian veins. We found no literature describing pelvic venous congestion (PVC) in children. Knowledge that PVC exists in children is important, particularly for pediatric radiologists who are imaging patients with complaints of pelvic pain.
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http://dx.doi.org/10.1007/s00247-011-2232-yDOI Listing
May 2012

Obese Adolescents with Type 2 Diabetes Mellitus Have Hippocampal and Frontal Lobe Volume Reductions.

Neurosci Med 2011 Mar;2(1):34-42

Department of Psychiatry, New York University School of Medicine, New York, USA.

The rates of type 2 diabetes (T2DM) continue to parallel the rising rates of obesity in the United States, increasingly affecting adolescents as well as adults. Hippocampal and frontal lobe reductions have been found in older adults with type 2 diabetes, and we sought to ascertain if these brain alterations were also present in obese adolescents with T2DM. In a cross-sectional study we compared MRI-based regional brain volumes of 18 obese adolescents with T2DM and 18 obese controls without evidence of marked insulin resistance. Groups were matched on age, sex, school grade, ethnicity, socioeconomic status, body mass index, and waist circumference. Relative to obese controls, adolescents with T2DM had significantly reduced hippocampal and prefrontal volumes, and higher rates of global cerebral atrophy. Hemoglobin A1c, an index of long-term glycemic control, was inversely associated with prefrontal volume and positively associated with global cerebral atrophy (both p < 0.05). Brain integrity is negatively impacted by T2DM already during adolescence, long before the onset of overt macrovascular disease. Paralleling the findings of greater vascular and renal complications among obese adolescents with severe insulin resistance and T2DM relative to their age-matched peers with type 1 diabetes, we find clear evidence of possible brain complications. Our findings call for aggressive and early intervention to limit the negative impact of obesity-associated insulin resistance leading to T2DM on the developing brains of adolescents.
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http://dx.doi.org/10.4236/nm.2011.21005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117471PMC
March 2011

Age of onset of polycystic ovarian syndrome in girls may be earlier than previously thought.

J Pediatr Adolesc Gynecol 2011 Feb;24(1):15-20

Department of Pediatrics, New York University School of Medicine, New York, NY, USA.

Objectives: To study the age at diagnosis of polycystic ovarian syndrome (PCOS) in a pediatric population. To compare risk factors involved in causing PCOS in preadolescent and adolescent girls. To review the current literature on the reported age of PCOS in girls.

Design: A retrospective chart review and systematic review of the literature.

Participants: Patients included 58 girls (age ≤ 18 yrs) with a diagnosis of PCOS based on the Rotterdam criteria. Girls were grouped as preadolescents (<13 yrs) or adolescents (13-18 yrs). Clinical and biochemical data were reviewed from the time of diagnosis.

Main Outcome Measures: Age at diagnosis. Differences in risk factors for PCOS (Ethnicity, obesity, family history of PCOS, birth weight, age at pubarche, thelarche and menarche, evidence of hyperandrogenism and/or insulin resistance) were compared between the two groups.

Results: There were 26% (15/58) preadolescent girls (9-12 yrs) vs 74% (43/58) adolescents (13-18 yrs). There was no significant difference between the two groups in ethnicity, BMI z-score, family history of maternal PCOS, birth weight, hyperandrogenism, or insulin resistance. Preadolescents with PCOS had significantly earlier onset of pubarche and thelarche than adolescents with PCOS, by 1.9 and 1.5 yrs, respectively (P = 0.018, 0.030). In addition to earlier puberty, PCOS developed 2.1 years sooner after thelarche in preadolescents than in adolescents. (P = 0.008) Preadolescents were significantly taller for age than adolescents (72nd % vs 43rd %) (P = 0.005). A review of the 28 studies published in the last 3 years that included PCOS patients with age <=18 yrs described only 6.4% (27/425) of pediatric subjects with age <13 yrs. Four were primarily pediatric studies that included patients under the age of 13 yrs, with 9.4% (12/127) of the patients <13 yrs.

Conclusion: Increased awareness of PCOS in young females is needed. PCOS may occur at a younger age in girls who develop early pubarche and thelarche. Therefore, the diagnosis and workup should be considered in young girls with risk factors suggestive of PCOS.
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http://dx.doi.org/10.1016/j.jpag.2010.06.003DOI Listing
February 2011

Outcomes of children and adolescents with well-differentiated thyroid carcinoma and pulmonary metastases following ¹³¹I treatment: a systematic review.

Thyroid 2010 Oct;20(10):1095-101

Department of Pediatrics, Division of Pediatric Endocrinology, New York University School of Medicine, 530 1st Avenue, New York, NY 10016, USA.

Background: The optimal dose and efficacy of ¹³¹I treatment of children and adolescents with well-differentiated thyroid carcinoma (WDTC) and pulmonary metastases are not well established. A therapeutic challenge is to achieve the maximum benefit of ¹³¹I to decrease disease-related morbidity and obtain disease-free survival while avoiding the potential complications of ¹³¹I therapy.

Summary: We systematically reviewed the published literature on children and adolescents with WDTC and pulmonary metastases treated with ¹³¹I to examine outcomes after ¹³¹I administration and the risks and benefits of therapy. After reviewing 14 published articles, 9 articles met our inclusion criteria encompassing 112 pediatric and adolescent patients with WDTC and pulmonary metastases 21 years of age or younger at diagnosis spanning a follow-up period of 0.6–45 years. ¹³¹I therapy after surgery and thyrotropin suppression resulted in complete, partial, and no disease response in 47.32%, 38.39%, and 14.29% of patients, respectively. Five studies provided data on disease response in relation to ¹³¹I dose. In general, nonresponders received the highest ¹³¹I doses and complete responders received a higher dose than partial responders. The disease-specific mortality rate was 2.68%. Survival was 97.32%. A second primary malignancy occurred in one patient. One out of 11 patients studied experienced radiation fibrosis.

Conclusions: This review confirms that the majority of pediatric and adolescent patients with WDTC and pulmonary metastases treated with ¹³¹I do not achieve complete response to therapy, yet disease-specific morbidity and mortality appear to remain low. It is therefore prudent to use caution in the repeated administration of ¹³¹I to such patients to ensure that adverse effects of therapy do not cause more harm than good in a disease that has an overall favorable natural course. Long-term prospective studies are needed to analyze disease-specific morbidity and mortality, recurrence rate, dose-specific response, and dose-related adverse effects of ¹³¹I in this patient population.
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http://dx.doi.org/10.1089/thy.2009.0446DOI Listing
October 2010

Thyrotropin-secreting pituitary adenoma in an adolescent boy: challenges in management.

Pediatrics 2010 Aug 12;126(2):e474-8. Epub 2010 Jul 12.

Department of Pediatrics, New York University Medical Center, New York, NY 10016, USA.

Thyrotropinomas tend to be aggressive, invasive tumors that are difficult to resect because of their marked fibrosis and their proximity to vital structures such as the optic chiasm. The latter characteristic also limits the use of radiation therapy. In the few cases reported of children younger than 18 years whose thyrotropinomas were treated surgically, the results were disappointing. We present here the case of a 16-year-old boy with a thyrotropin-secreting pituitary macroadenoma who underwent partial resection via a transsphenoidal approach and was left with significant residual tumor and continued hyperthyroidism. He subsequently received 4 years of long-acting release somatostatin therapy, during which he has remained euthyroid without requiring antithyroid medication. To our knowledge, this is thus far the longest duration of somatostatin therapy in the pediatric age group. This regimen also achieved a decrease in compression of the optic nerve and prevented further tumor growth. We review here the current literature on somatostatin analog treatment including molecular mechanisms and promising new treatment modalities, such as the heterodimerization of dopamine and somatostatin receptors. We conclude that this has been a useful adjuvant treatment for our adolescent patient.
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http://dx.doi.org/10.1542/peds.2009-2354DOI Listing
August 2010

Unilateral ovarian enlargement in adolescents with polycystic ovary syndrome: a variant of bilateral disease.

J Pediatr Endocrinol Metab 2010 Jan-Feb;23(1-2):87-95

Department of Pediatric Endocrinology, NYU School of Medicine, New York, NY, USA.

Aims: To evaluate clinical, biochemical and radiological features in adolescent females with unilateral polycystic ovary (UniPCO) versus bilateral polycystic ovary (BiPCO) in patients with polycystic ovarian syndrome (PCOS), and to compare the association of insulin resistance (IR) and metabolic syndrome (MS) between the two groups.

Setting: Pediatric endocrine clinic.

Methods: A retrospective chart review of girls with the diagnosis of PCOS was performed. They were divided into two groups: PCOS with UniPCO and BiPCO.

Results: No difference was seen between the two groups in regard to clinical parameters. LH/FSH ratio was significantly higher in patients with BiPCO. No difference was seen in free testosterone, lipids, MS or IR between groups. Ultrasound showed a mean ovarian volume of 13.2 +/- 1.5 ml on the affected side in UniPCO and 16.1 +/- 1.2 ml in BiPCO. Ovarian follicle location was mostly peripheral in both UniPCO and BiPCO. Multiple follicles were found in the majority of cases. IR and MS were present in 40% of girls with UniPCO and 38% and 23%, respectively, in girls with BiPCO.

Conclusion: UniPCO may be a forerunner of BiPCO and may represent an early point along the continuum. Later, the unaffected ovary continues to increase in volume, resulting in BiPCO. Metabolic abnormalities of patients with UniPCO highlights that as well as being a precursor of BiPCO, it also imparts considerable health risks.
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http://dx.doi.org/10.1515/jpem.2010.23.1-2.87DOI Listing
May 2010
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