Part 1 book “Recent advances in pediatric medicine” has contents: Update on the management of otitis media, contemporary management of children with hearing loss, overview of management of recurrent tonsillitis, therapies for pediatric chronic rhinosinusitis,… and other contents.
Recent Advances in Pediatric Medicine (Volume 1) (Synopsis of Current General Pediatrics Practice) Edited By Seckin Ulualp Division of Pediatric Otolaryngology, Department of Otolaryngology-Head and Neck Surgery, University of Texas Southwestern Medical Center, Children’s Health Dallas, Texas, USA Recent Advances in Pediatric Medicine Volume # Synopsis of General Pediatric Practice Editor: Seckin Ulualp eISSN (Online): 978-1-68108-520-3 ISSN( Print): 978-1-68108-521-0 eISBN (Online): 2543-2249 ISBN (Print): 2543-2257 © 2017, Bentham eBooks imprint Published by Bentham Science Publishers – Sharjah, UAE All Rights Reserved BENTHAM SCIENCE PUBLISHERS LTD End User License Agreement (for non-institutional, personal use) This is an agreement between you and Bentham Science Publishers Ltd Please read this License Agreement carefully before using the ebook/echapter/ejournal (“Work”) Your use of the Work constitutes your agreement to the terms and conditions set forth in this License Agreement 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will Bentham Science Publishers, its staff, editors and/or authors, be liable for any damages, including, without limitation, special, incidental and/or consequential damages and/or damages for lost data and/or profits arising out of (whether directly or indirectly) the use or inability to use the Work The entire liability of Bentham Science Publishers shall be limited to the amount actually paid by you for the Work General: Any dispute or claim arising out of or in connection with this License Agreement or the Work (including non-contractual disputes or claims) will be governed by and construed in accordance with the laws of the U.A.E as applied in the Emirate of Dubai Each party agrees that the courts of the Emirate of Dubai shall have exclusive jurisdiction to settle any dispute or claim arising out of or in connection with this License Agreement or the Work (including non-contractual disputes or claims) Your rights under this License Agreement will automatically terminate without notice and without the need for a court order if at any point you breach any terms of this License Agreement In no event will any delay or failure by Bentham Science Publishers in enforcing your compliance with this License Agreement constitute a waiver of any of its rights You acknowledge that you have read this License Agreement, and agree to be bound by its terms and conditions To the extent that any other terms and conditions presented on any website of Bentham Science Publishers conflict with, or are inconsistent with, the terms and conditions set out in this License Agreement, you acknowledge that the terms and conditions set out in this License Agreement shall prevail Bentham Science Publishers Ltd Executive Suite Y - PO Box 7917, Saif Zone Sharjah, U.A.E Email: subscriptions@benthamscience.org CONTENTS PREFACE i LIST OF CONTRIBUTORS ii CHAPTER UPDATE ON THE MANAGEMENT OF OTITIS MEDIA Emily Tignor, Bailey LeConte, Dayton Young and Tomoko Makishima INTRODUCTION Definition PATHOPHYSIOLOGY Anatomic Causes Environmental Causes Irritants Daycare Allergy Breast Feeding Infectious Causes Viruses Bacteria Genetic Causes Race, Ethnicities and Gender Heritability Genetic Alterations ACUTE OTITIS MEDIA Definition Epidemiology Clinical History and Physical Diagnosis Complications Treatment Acute Otitis Media, Single Episode Recurrent Acute Otitis Media OTITIS MEDIA WITH EFFUSION Definition Epidemiology Clinical History and Physical Diagnosis Complications Treatment Acute Treatment Recommendations for Tympanostomy Tubes TYMPANOSTOMY TUBES Effectiveness Indications (Table 4) Complex Cases Complications Otorrhea Myringosclerosis Tympanic Membrane Perforation 1 2 3 3 4 5 5 6 7 7 7 9 9 9 10 10 10 10 11 11 11 11 12 12 12 13 Follow-up Appointments Water Exposure CONCLUSION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES 13 13 13 13 13 13 14 CHAPTER CONTEMPORARY MANAGEMENT OF CHILDREN WITH HEARING LOSS Musaed Alzahrani and Issam Saliba INTRODUCTION DEFINITIONS AUDIOLOGY WORKUP Objective Tests Auditory Brainstem Responses (ABR) Otoacoustic Emissions (OAE) Immitancemetry Subjective Tests HEARING LOSS ETIOLOGIES HEARING LOSS REHABILITATION Medical/Surgical Rehabilitation Prosthetic Rehabilitation Components and Function Mechanical Stimulation Electrical Stimulation Cochlear Implants Auditory Brain Stem Implant (ABI) CONCLUSION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES 19 CHAPTER OVERVIEW OF MANAGEMENT OF RECURRENT TONSILLITIS Suparna N Shah and Harold Pine INTRODUCTION Anatomy Physiology Normal Flora Infections Fungal Pharyngitis Viral Pharyngitis Epstein Barr Virus Bacterial Pharyngitis Tonsiliths Complications of Tonsillitis Nonsuppurative Complications Suppurative Complications Clinical Guidelines [14] Management CONCLUSION CONFLICT OF INTEREST ACKNOWLEDGEMENTS 34 19 21 22 22 22 22 23 23 25 26 26 27 27 28 29 29 30 30 30 30 30 34 34 36 37 37 38 38 38 39 40 41 41 42 42 45 48 49 49 REFERENCES 49 CHAPTER THERAPIES FOR PEDIATRIC CHRONIC RHINOSINUSITIS Anthony Sheyn INTRODUCTION DIAGNOSIS MEDICAL MANAGEMENT OF PCRS Antibiotics Steroids Nasal Irrigation Antihistamines Gastroesophageal Reflux Biofilms Surgical Therapy Adenoidectomy Balloon Catheter Dilation Endoscopic Sinus Surgery Special Considerations Cystic Fibrosis CONCLUSION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES 51 CHAPTER PRACTICAL MANAGEMENT OF CHILDREN WITH STRIDOR Anil Gungor INTRODUCTION Definitions Evaluation of the Stridorous Child Craniofacial Anomalies and Nasal Obstruction Choanal Atresia-Stenosis and CNPAS (Congenital Nasal Piriform Aperture Stenosis) Mandibular Glossopexy for Tongue Base Obstruction Synchronous Airway Lesions (SAL) Premature Babies CONCLUSION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES 64 CHAPTER UPDATE ON THE MANAGEMENT OF LARYNGOMALACIA Mohamed Akkari, Catherine Blanchet and Michel Mondain INTRODUCTION DIAGNOSTIC MANAGEMENT History Physical Examination Severity Classification Associated Diseases Gastroesophageal Reflux Disease (GERD) Synchronous Airway Lesions (SAL) Neurological Disorders (ND) Heart Disease Congenital Syndrome 77 51 52 53 54 55 55 55 55 56 56 56 57 58 59 59 60 60 60 60 64 65 65 68 69 71 72 73 74 74 74 74 77 78 78 78 79 80 80 80 80 81 81 Atypical Laryngomalacias Complementary Examinations Measurement of PO2 and PCO2 Chest X-ray Rigid Laryngotracheal Endoscopy under General Anaesthesia Polysomnography (PSG) Drug Induced Sleep Endoscopy (DISE) Swallow Studies Twenty Four-hour PH Study Echocardiogram Polymalformative Assessment THERAPEUTIC MANAGEMENT Mild Laryngomalacia Moderate Laryngomalacia Severe Laryngomalacia Transoral Supraglottoplasty Tracheotomy Noninvasive Ventilation (NIV) CONCLUSION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES 81 81 82 82 82 82 82 83 83 83 83 83 83 83 84 84 86 87 87 87 87 87 CHAPTER SYNOPSIS OF MANAGEMENT OF DIABETES MELLITUS TYPES AND Eric Velazquez and Bethany A Auble INTRODUCTION Epidemiology Physiology TYPE DIABETES MELLITUS Multiple Daily Injection Insulin Regimens Continuous Subcutaneous Insulin Injection (Insulin Pumps) Continuous Glucose Monitors New Advances in Technology Family Questions you may be asked TYPE DIABETES MELLITUS Lifestyle Modifications Pharmacotherapy in Type Diabetes Bariatric Surgery Comorbidities and Complications CONCLUSION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES 93 CHAPTER PEDIATRIC TYPE DIABETES MELLITUS Carisse Orsi, Maria Rayas, Jessica Hutchins and Elia Escaname INTRODUCTION EPIDEMIOLOGY DIAGNOSIS TREATMENT LONG-TERM COMPLICATIONS Hypertension 105 93 94 94 95 96 97 98 98 99 100 100 100 101 102 102 103 103 103 105 105 106 108 111 111 Nephropathy Retinopathy Dyslipidemia Non-alcoholic Fatty Liver Disease Depression Neuropathy CONCLUSION CONFLICT OF INTEREST ACKOWLEDGEMENTS REFERENCES 112 112 113 113 114 114 114 114 114 114 CHAPTER PRACTICAL GUIDE FOR MANAGEMENT OF CHILDREN WITH OBESITY Neslihan Gungor INTRODUCTION DEFINITION ETIOLOGY AND RISK FACTORS PREVALENCE AND EPIDEMIOLOGY COMORBIDITIES AND COMPLICATIONS 1- Endocrine 2-Cardiovascular Comorbidities 3-Gastrointestinal Problems 4-Pulmonary Comorbidities 5-Orthopedic Complications 6-Neurologic Complications 7-Dermatologic Complications 8-Psychosocial Complications CLINICAL EVALUATION Diagnosis History Review of Systems Family History Psychosocial History Physical Examination LABORATORY STUDIES TREATMENT CONCLUSION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES 117 CHAPTER 10 CURRENT CONCEPTS IN THE MANAGEMENT OF HYPERTHYROIDISM Abha Choudhary INTRODUCTION Epidemiology Pathogenesis Etiology CLINICAL PRESENTATION DIAGNOSTIC EVALUATION Laboratory Evaluation Imaging Studies Thyroid Ultrasound Thyroid Uptake Studies 117 118 118 120 120 122 124 124 125 125 125 125 126 126 127 127 128 128 128 129 131 133 136 137 137 137 144 144 144 145 146 147 148 148 148 148 148 Management of Hyperthyroidism Recent Advances in Pediatric Medicine, Vol 145 children, while it is per 100,000 person-years in adolescents The prevalence in United States is in 10,000 person-years GD is rare in less than years of age and has a peak incidence at 10 to 15 years of age, more common in females than males (5:1) GD is more common in children with other autoimmune conditions and in those with family history of autoimmune thyroid disease [3, 4] Pathogenesis The cause of GD is unclear, but it is thought to result from a complex interaction of genetic, immune and environmental factors The immune system produces the thyroid stimulating hormone receptor antibody (TRAb), which is directed against the thyroid stimulating hormone receptor (TSHR) The TRAb can either stimulate or inhibit thyroid hormone secretion GD occurs from formation of stimulating antibodies to the TSHR called the thyrotropin stimulating immunoglobulins (TSI) It is a functional assay which measures the production of cyclic adenosine monophosphate in cultured thyroid follicular cells TSI binds to and also stimulates the TSHR on the thyroid follicular cells, leading to increased vascularity of the gland, follicular hypertrophy/ hyperplasia and increased production of the thyroid hormone The thyroid gland displays lymphocytic infiltration with T-lymphocyte abnormalities and an absence of follicular destruction T cells activate local inflammation and tissue remodeling by producing cytokines, leading to B-cell dysregulation and autoantibody formation An imbalance between pathogenic and regulatory T cells is thought to be involved in both the development of GD and its severity [3] Graves’ ophthalmopathy, an immune mediated condition is caused by crossreactivity of TSI with a TSHR like protein in retro-orbital tissue and extraocular muscle This leads to local inflammation and infiltration of glycosaminoglycans resulting in edema, muscle swelling and increase in intraorbital pressure causing the characteristic eye findings [5, 7] Transient hyperthyroidism may result from destruction of thyroid follicular cells by an autoimmune or infectious process, which leads to unregulated release of preformed hormone into the circulation Subacute thyroiditis occurs from an infection or inflammation and usually resolves in a few months with normalization of thyroid functions Hyperthyroidism is also seen in McCuneAlbright syndrome (somatic-activating mutation of the GNAS gene) It results in increased stimulatory G protein signaling that causes hyperfunction of glycoprotein hormone receptors, autonomous cell proliferation and hormone hypersecretion Thyrotropin stimulating hormone (TSH) secreting pituitary adenoma and pituitary resistance to thyroid hormone are caused by unregulated overproduction of TSH [6, 7] 146 Recent Advances in Pediatric Medicine, Vol Abha Choudhary Etiology The most common cause of hyperthyroidism in children is GD Other causes include acute or sub-acute thyroiditis, T4 ingestion and thyrotoxic phase of chronic lymphocytic thyroiditis (Hashitoxicosis) Hyperthyroidism is also seen in autonomously functioning thyroid nodule, toxic adenoma, multinodular goiter, McCune Albright syndrome, struma ovarii and TSH producing pituitary adenomas [5, 7, 8] Etiology is listed in Table Table Causes of Hyperthyroidism Condition Mechanism Thyroid Exam Antibody RAIU Increased Secretion of Thyroid Hormone Graves’ disease Thyrotropin receptorstimulating antibodies (TRAb) Symmetric, non tender goiter TSI+ Anti-thyroglobulin and thyroid peroxidase antibody +/- Diffusely ↑ Toxic multinodular goiter Autonomous overproduction of thyroid hormone Multiple nodules Negative ↑ multifocal uptake Toxic adenoma Autonomous overproduction of thyroid hormone Single nodule Negative ↑ uptake in a single focus TSH secreting pituitary adenoma Autonomous production of TSH Normal or symmetric goiter Negative ↑ Pituitary resistance to thyroid hormone Overproduction of TSH Symmetric goiter Negative Diffusely ↑ Excess Secretion of Preformed Thyroid Hormone Chronic lymphocytic thyroiditis (Hashitoxicosis) Autoimmune Release of preformed hormone Firm goiter Anti-thyroglobulin and thyroid peroxidase antibody + ↓ Subacute thyroiditis Viral Release of preformed hormones Painful goiter Negative ↓ Negative, low TSH ↓ Drug Induced Hyperthyroidism Factitious thyroiditis Iodine induced Intake of thyroxine No goiter Exposure to contrast Often Negative ↑ agent multinodular TSH: Thyroid stimulating hormone; TSI: thyrotropin stimulating immunoglobulins; TRAb: thyroid stimulating hormone receptor antibody Management of Hyperthyroidism Recent Advances in Pediatric Medicine, Vol 147 CLINICAL PRESENTATION The onset of symptoms is subtle and a high index of suspicion is needed in diagnosing children Prompt treatment is important due to its unique effects on growth, pubertal development and neurodevelopmental outcomes in children GD can present insidiously with emotional lability, fatigue, sleep disturbances and increased appetite School aged children are sometimes brought to medical attention for evaluation of attention deficit hyperactivity disorder because of their inability to concentrate and poor school performance Prepubertal children most commonly present with poor weight gain and diarrhea, whereas adolescents present with irritability, fatigue, palpitations, heat intolerance, fine tremors and a goiter Younger children typically have a delay in diagnosis and this leads to increased height, advanced bone age and poor weight On physical examination, thyromegaly is present in 95% of the cases The gland is symmetrically enlarged, smooth and non-tender Other signs include tachycardia, fine tremors, warm skin, muscle weakness, increased pulse pressure and exaggerated deep tendon reflexes Ophthalmic abnormalities such as staring eyes, proptosis, retraction of upper eye lid and wide palpebral fissure can occur in 40% of children and adolescents and is less severe than seen in adults Pretibial myxedema and dermopathy are rare in children Thyroid storm is also rare in children and is characterized by increased metabolism with excessive release of thyroid hormones leading to severe hyperthyroid symptoms [4, 5, 8, 9] Signs and symptoms of GD are listed in Table Table Signs and Symptoms of Graves’ disease in children Signs Symptoms Smooth, symmetric, non- tender goiter Hyperactivity Tachycardia, rarely atrial fibrillation Palpitations Weight loss Fatigue Heat intolerance Poor school performance, decreased attention span Tremor Emotional lability Hypertension Increased appetite Hair loss Increased frequency of bowel movements Advanced bone age and height velocity Excessive sweating Eye findings- staring, lid lag, exophthalmos Difficulty sleeping Proximal muscle weakness and wasting Amenorrhea or oligomenorrhea 148 Recent Advances in Pediatric Medicine, Vol Abha Choudhary DIAGNOSTIC EVALUATION Laboratory Evaluation Laboratory evaluation includes serum thyroid stimulating hormone (TSH), free thyroxine (FT4), total triiodothyronine (TT3), TSI, thyroid peroxidase and antithyroglobulin antibody levels Complete blood count and liver function tests are obtained at baseline Serum TSH level is suppressed and FT4 and TT3 values are elevated in hyperthyroidism TSI is positive in 90% of the cases of GD Thyroid peroxidase and thyroglobulin antibodies are positive in autoimmune thyroiditis and maybe positive in GD as well [9] Imaging Studies Thyroid Ultrasound It is performed if the thyroid gland is asymmetric or a palpable nodule is noted If a nodule is confirmed, a fine needle aspiration biopsy should be performed as well as 123I or 99Tc scan Differentiated thyroid cancer may be seen concurrently with GD or in an autonomous nodule Thyroid Uptake Studies Thyroid uptake scan is performed in cases of unclear etiology of hyperthyroidism The thyroid gland can actively concentrate iodine and radioactive iodine (RAI) 123 I is the radionucleotide of choice for thyroid uptake since it has a short half-life and delivers a smaller radiation dose as compared with 131I Radiolabelled technetium (99Tc) can also be used since technetium is trapped by the thyroid gland but not organized 99Tc scan is sometimes preferred because it is less expensive, quicker and involves less total body radiation The uptake scan shows increased uptake to 50 to 80% throughout the gland in GD Conditions such as sub-acute thyroiditis or early phase of autoimmune thyroiditis are associated with decreased uptake as low as ≤ 2% [8, 9] TREATMENT OPTIONS Current treatment approaches for GD include antithyroid drugs (ATDs), surgery and radioactive iodine ablation (131I) There is no specific cure for the disease and each treatment option is associated with complications ATDs are the initial treatment options in GD They palliate the hyperthyroid state until it spontaneously resolves or definitive treatment is done Refer to Fig (1) and Table for Management of Hyperthyroidism Recent Advances in Pediatric Medicine, Vol 149 an overview on the management options Child with hyperthyroidism Obtain TSH, FT4 and TT3 Obtain TSI and Thyroid antibodies Establish diagnosis of GD Treatment with ATD for to years Side effects/noncompliance In childern > 10 years Definitive treatment - RAI or thyroidectomy can be offered in selected cases Trial off ATD Recurrence Remission Definitive treatmentRAI or throidectomy Drug treatment of hypothyroidism with Levothyroxine Long term surveillance (particullary during pregnancy) Fig (1) Algorithm for diagnosis and management of Graves’ disease in children TSH: Thyroid stimulating hormone; FT4: free thyroxine, TT3: Total triiodothyronine, TSI: thyrotropin stimulating immunoglobulins; GD: Graves’ disease; ATD: anti-thyroid drugs; RAI: radioactive iodine ablation Table Treatment options Indications Contraindications Advantages Antithyroid drugs First line of treatment in children If greater chances of remission (mild disease, small goiter, low titers of TRAb) Major adverse drug reaction Non invasive No hospital stay needed Less initial cost Low risk of permanent hypothyroidism Possible remission Radioactive iodine >10 years of age If child not in remission after to years of MMI Major adverse drug reaction to ATD Pregnancy Breastfeeding Coexisting thyroid cancer Unable to follow radiation safety precautions Definitive cure of hyperthyroidism No surgical/ anesthesia risk No effect on infertility, birth defects, cancer Reduction in goiter size 150 Recent Advances in Pediatric Medicine, Vol Abha Choudhary (Table ) contd Indications Contraindications Advantages Surgery Large goiter (>80gm) Coexisting conditions which Rapid control of Suspicion of thyroid increase the anesthesia and hyperthyroidism malignancy surgery risk If planning a pregnancy in to months TRAb: thyroid stimulating hormone receptor antibody; MMI: methimazole; ATD: antithyroid drugs Adapted from Management Guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists (2011) [11] Antithyroid Drugs ATDs are Thionamide derivatives which were introduced in early 1940s by Astwood Thiouracil, the first compound used clinically was associated with toxic side effects and was replaced by Propylthiouracil (PTU) in 1947 Methimazole (MMI) has been the treatment option for GD since 1950 MMI is 10 to 20 times more potent than PTU and has a longer half- life In 2008, a number of cases describing PTU- induced liver failure requiring transplant emerged The risk was estimated to be in 2000 children In April 2010, the United States Food and Drug Administration issued a black box warning stating that PTU should not be used in children, except in special circumstances PTU can sometimes be used short term with extreme caution in patients who have had a toxic reaction to MMI while waiting for definitive therapy If started on PTU, patient and families should be informed of the risk of liver failure If they note signs and symptoms of liver toxicity like itching, jaundice, abdominal pain, light colored stools, dark urine or anorexia, the medication should be stopped and medical attention should be sought promptly [10] Mechanism of Action ATDs act by inhibiting oxidation and organic binding of thyroid iodine thus impairing thyroid hormone synthesis [8, 10] MMI and Monitoring Therapy MMI is the drug of choice for GD The typical dose is 0.2 to 0.5 mg/kg/day once a day or in divided doses The dose can range from 0.1 to mg/kg/day It is available in 5, 10 and 20 mg tablets The following doses can be used in guiding therapy In infants: 1.25 mg/day; to years: 2.5 to mg/day; to 10 years: to 10 mg/day and 10 to 18 years: 10 to 20 mg/day The doses can be doubled in severe hyperthyroidism Complete blood counts, liver function tests, pregnancy test (for girls in the reproductive age group), should be performed prior to starting therapy [11] Thyroid function tests should be obtained month after starting Management of Hyperthyroidism Recent Advances in Pediatric Medicine, Vol 151 therapy After FT4 levels normalize, the MMI dose is reduced by 50% to maintain a euthyroid state TSH takes months to normalize and hence should not be used in guiding the change in dose Two approaches have been discussed Some use the “block and replace” approach and add levothyroxine while not changing the MMI dose to achieve euthyroidism With this approach, there is a greater risk of side effects since there is a dose response relationship for some MMI related complications The other approach is the dose titration which involves adjusting the doses of the MMI to achieve euthyroidism Compliance may also be an issue in some children, who may find it easier to take one drug rather than two drugs The American Thyroid Association guidelines suggest using the dose titration method by using the lowest dose of MMI rather than the block and replace approach [3, 10 - 12] Adverse Drug Reaction Minor side effects can occur in 17% of the children on MMI which includes rash, hives, arthralgia and nausea Major side effects include Stevens- Johnson syndrome, agranulocytosis, neutropenia, thrombocytopenia, cholestatic jaundice, hepatitis and vasculitis These typically occur in the first months of starting therapy but can occur anytime during the course of therapy [13] Agranulocytosis is dose dependent and typically develops in the first 100 days of therapy Pediatric patients and their families should be informed of the side effects, the necessity of stopping the medications and informing their physician if they develop pruritic rash, jaundice, acolic stools or dark urine, arthralgias, abdominal pain, nausea, fatigue, fever or pharyngitis [11] In the pediatric population, anti-neutrophilic cytoplasmic antibody (ANCA) - mediated disease has been described with PTU or MMI These antibodies can cause serious vasculitis event, hence it is reasonable to check ANCAs on children who have been on ATDs for greater than years ATDs can cross the placenta and has an increased risk of birth defects MMI embryopathy causes choanal atresia, esophageal atresia, growth retardation and developmental delay PTU is the drug of choice during the first trimester of pregnancy because of the potential teratogenic effects of MMI [9] Remission Remission of GD is defined as biochemical euthyroidism or hypothyroidism for one year or more after discontinuation of ATDs The remission rates in children are reported to be 20 to 30% after many years of ATDs [14, 15] A French study showed that prolonged ATDs were associated with 50% remission rates 154 children with GD diagnosed between 1997 and 2002 were examined following treatment with carbimazole The estimated remission rates were 20%, 37%, 45% and 49% after 4, 6, and 10 years of therapy respectively [16] The chance of 152 Recent Advances in Pediatric Medicine, Vol Abha Choudhary remission after years of ATDs is low if the thyroid gland is large (more than 2.5 times normal size for age), young child (4 ng/dl) [11, 15, 17, 18] The 2011 American Thyroid Association (ATA) and American Association of Clinical Endocrinologist (AACE) management guidelines recommend continuing ATD in children for two years if there are no major side effects If children develop serious allergic reaction to MMI, radioactive iodine or surgery should be considered [11] Beta Adrenergic Antagonists Beta adrenergic antagonists are useful in the management of GD because it helps to decrease sympathetic symptoms like sweating, tremor, palpitations and anxiety Propranolol, atenolol or metaprolol can be used to control GD symptoms Atenolol is preferred for its cardioselective nature When the thyroid hormone levels normalize, they can be stopped [8, 9] Radioactive Iodine Radioactive iodine (RAI; 131I) use for thyroid ablation was introduced in 1940s by Saul Hertz and co-workers at the Massachusetts Institute of Technology and Massachusetts General Hospital RAI uptake by the thyroid is not distinguishable from ordinary iodine, thus RAI is trapped in the thyroid cell After being taken up by the thyroid cells, beta- emission causes destruction of the iodine trapping cells It results in fibrosis and glandular atrophy If 131I therapy is chosen, it should be administered as a single dose to render the patient hypothyroid [7, 11, 12] It should not be used to cause euthyroidism in children as this leads to partially irradiated residual thyroid tissue which can be associated with a risk of thyroid cancer Typically administered thyroid doses of 150µCi/gm generate radiation doses of 12,000 cGy to the thyroid Larger doses (>150 µCi of 131I per gram of thyroid tissue) are preferred over smaller doses of radioactive iodine Hypothyroidism is achieved in approximately 60 to 95% of patients with a dose of 131 I 150 – 200 µCi per gram of thyroid tissue [11, 19, 20] Dosages of radioiodine administered are based on iodine uptake and gland size using the Quimby-Marinelli equation: dosage (radiation; in Gy) = 90 × oral 131 Idose (μCi) × oral 24-hr uptake (%) / gland mass (gm) × 100%) This calculation assumes an effective half life of days for 131I Thyroid size is estimated by palpation or ultrasound (ultrasound volume = 0.48 × length × depth × width) [10] An advantage of calculated dose is that it may be possible to administer lower doses if the iodine uptake is high Management of Hyperthyroidism Recent Advances in Pediatric Medicine, Vol 153 Preparation The ATDs are discontinued 3–5 days before 131I is administered The circulating levels of thyroid hormones may increase to 10 days after the ablation when the thyroid hormones are released from degenerating follicular cells Following the ablation, TSH and FT4 levels should be obtained every month Biochemical euthyroidism or hypothyroidism is achieved in to 12 weeks after 131I treatment Until then, the symptoms of hyperthyroidism can be controlled using beta adrenergic antagonists MMI or Lugol’s solution can be used one week after 131I to decrease biochemical hyperthyroidism without affecting the outcome of RAI [8] Children with FT4 >5ng/dl should be pretreated with MMI and beta adrenergic antagonists until FT4 normalizes before proceeding with 131I therapy [11] Side Effects Side effects of 131I therapy include mild tenderness over the thyroid in the first week after ablation This can be treated with acetaminophen or non-steroidal antiinflammatory drugs for 24 to 48 hrs There are rare reports of thyroid storm in children with severe hyperthyroidism receiving 131I RAI Precautions RAI is excreted in saliva urine and stool Significant radioactivity is retained within the thyroid for several days Hence radiation precautions are recommended which include absence from school, not sharing utensils and not kissing or sitting next to pregnant women and babies for week [11] Follow Up If hyperthyroidism persists months after 131I, a second dose can be given Patients with very large thyroid gland (>80 gm) and high TRAb levels have lower responses to 131I therapy Indications I is an effective therapy for GD and may be considered for children who are not in remission after - years of MMI therapy or in those who have major adverse side effects to the ATDs [19] It can also be offered as the initial therapy in adolescents [19] 131 Outcome The benefits of RAI is the ease of administration, reduced need for long term follow up and absence of long term side effects [9, 21] The most extensive study 154 Recent Advances in Pediatric Medicine, Vol Abha Choudhary in children involved 36 year outcomes of 116 patients who were < 20 year old when treated with 131I therapy for GD There was no evidence of increased cancer risk in this population There has been no evidence of adverse effects to offspring of children treated with 131I, increase in rate of infertility, spontaneous abortion or congenital anomalies in offspring of patients treated with 131I [22] The risk of thyroid cancer after external radiation is highest in children < years of age and decline with advancing age The American Thyroid Association recommends to avoid RAI in children 150 µCi/g of thyroid tissue The need for 131I in a young child may occur when the child develops a toxic reaction to an ATD, proper surgical expertise is not accessible, or the child is not a suitable surgical candidate Surgery The oldest form of definitive GD therapy is thyroidectomy The Nobel Prize in Physiology and Medicine was awarded to Koker in 1909 for development in this field When surgery is chosen as therapy, near total or total-thyroidectomy is recommended and should be performed by a high volume thyroid surgeon Surgery leads to hypothyroidism in children who undergo total thyroidectomy, whereas after subtotal thyroidectomy, hyperthyroidism recurs in 10-15% of the patients Indications Surgery is preferred in children < years when definitive therapy is needed, in individuals with large thyroid glands (>80 gm) where the response to 131I is poor and in a late adolescent who is considering pregnancy It should be performed by an experienced and high volume thyroid surgeon [11, 23] Preparation for Surgery The patient should be rendered euthyroid with ATDs or inorganic iodine Iodine drops (5 to 10 drops three times a day) are given to 10 days prior to surgery This stops the thyroid hormone production and causes the gland to become firm and less vascular, facilitating surgery Complications Postoperatively, children are at a high risk for acute complications such as hypocalcemia, hemorrhage and recurrent laryngeal nerve paresis In children, rates from 0–6 years were 22%, from 7–12 years, 11%; and from 13 to 17 years, Management of Hyperthyroidism Recent Advances in Pediatric Medicine, Vol 155 11% [24, 25] Long term complications include hypoparathyroidism and recurrent laryngeal nerve injury Follow Up Follow up is essential for all patients treated for GD It should include regular examination of the thyroid gland and thyroid function tests once to twice a year OTHER CAUSES OF HYPERTHYROIDISM AND MANAGEMENT Chronic Lymphocytic Thyroiditis- to 10% of children present with a thyrotoxic phase called Hashitoxicosis The hyperthyroidism is due to inflammation and autonomous release of preformed and stored thyroid hormones It typically lasts for a few months The hyperthyroidism is mild and transient The thyroid peroxidase and anti-thyroglobulin antibodies are positive and TSI is negative RAI uptake is low or absent Symptomatic treatment with beta adrenergic antagonists is recommended in children with palpitations, tremors, tachycardia and hypertension Sub-acute Thyroiditis- It is also known as De Quervain’s disease and is due to a viral infection of the thyroid The inflammation results in autonomous release of preformed and stored hormones which leads to hyperthyroidism Fever, thyroid tenderness and hyperthyroidism may last for several weeks The erythrocyte sedimentation rate is elevated The TSH is suppressed and the FT4 and TT3 are high Thyroid antibodies are negative and RAI uptake is low or absent Nonsteroidal anti-inflammatory drugs and beta adrenergic antagonists are used for symptomatic treatment This disease is self-limited, running its course over a period of to months Acute Thyroiditis- It is characterized by fever, sore throat, painful thyroid swelling and erythema of the overlying skin Surgical incision and drainage with appropriate antibiotics are required Toxic Adenoma or Solitary Thyroid Nodule- These are uncommon and are suspected in the setting of hyperthyroidism and presence of a thyroid nodule Warm or hot nodules can lead to excessive production of thyroid hormone Activating mutations of TSHR and stimulatory G protein have been described in hyperfunctioning nodules Thyroid antibodies are negative RAI uptake will show uptake only in the functioning nodule The treatment is ATDs but ultimately surgical excision is required Toxic Multinodular Goiter- These are also uncommon cause of hyperthyroidism in children They are suspected in the setting of hyperthyroidism and multiple 156 Recent Advances in Pediatric Medicine, Vol Abha Choudhary nodules Thyroid antibodies are negative and RAI shows uptake in multiple nodules It can be treated with ATDs and eventually thyroidectomy or 131I should be considered TSH-secreting Pituitary Adenoma- Hypersecretion of TSH from a pituitary adenoma is a rare cause of hyperthyroidism in children Laboratory evaluation shows an elevated FT4 and TT3 with inappropriately normal or slightly elevated TSH with a high serum TSH alpha subunit concentration This diagnosis is confirmed on magnetic resonance imaging and treatment is resection of the pituitary tumor Iodine-induced Hyperthyroidism- Contrast agents can induce thyrotoxicosis Radiation Induced Hyperthyroidism- Childhood cancer survivors can have thyrotoxicosis associated with radiation Resistance to Thyroid Hormone- It is an autosomal dominant disorder due to mutation in the thyroid hormone beta receptor gene (TRβ) Children present with a goiter, elevated FT4 and normal to slightly elevated TSH Children with generalized resistance to thyroid hormone are usually euthyroid, while those with pituitary resistance can have thyrotoxic clinical features Most patients with generalized resistance require no treatment Mutation in the TSH Receptor Gene- It is an autosomal disorder caused by mutations in the thyrotropin receptor gene on the long arm of chromosome 14 It is also called non autoimmune hereditary hyperthyroidism FT4 and TT3 are increased with a suppressed TSH The TSI is negative Diffuse goiter is present with a negative maternal history of thyroid disease Treatment is with ATD’s McCune- Albright Syndrome- It is a sporadic disease characterized by the triad of polyostotic fibrous dysplasia, cutaneous pigmentation (Café- au-lait macule) and precocious puberty It is caused by an activating mutation of the alpha subunit of the stimulatory G protein Diffuse enlargement of the thyroid occurs early which then evolves into a multinodular goiter The TSH is suppressed with increased RAI uptake Surgical excision is indicated Factitious Thyrotoxicosis- can be seen in adolescents who ingest thyroxine to lose weight RAI uptake will be low or absent Thyroid Storm- It is an endocrine emergency and is a life-threatening condition It is characterized by multisystem organ failure and clinical features including nausea, vomiting, diarrhea, tachycardia, hepatic dysfunction, hyperthermia, hypotension, arrhythmias and congestive heart failure Neuropsychiatric Management of Hyperthyroidism Recent Advances in Pediatric Medicine, Vol 157 manifestations are agitation, delirium, psychosis, stupor and coma Factors that precipitate thyroid storm include acute cessation of ATDs, surgery in inadequately treated hyperthyroidism and acute illnesses The recommendations for treatment are monitoring in intensive care unit, treatment with beta adrenergic antagonists, ATDs, inorganic iodine and glucocorticoids [11] Neonatal Thyrotoxicosis- Neonatal GD is due to transplacental passage of maternal TSI antibodies The incidence is estimated to be in 25,000 neonates It occurs in infants of mothers with active GD or in those previously treated with RAI or surgery due to persistant TSI It is most likely if maternal TSI exceeds 500% Clinical features include tachycardia, irritability, hyperactivity, restlessness, diarrhea and poor weight gain Severe neonatal thyrotoxicosis can be complicated by congestive heart failure Management includes use of inorganic iodine which inhibits organification of iodine and thyroid hormone release, ATDs and beta adrenergic antagonists Neonatal GD resolves to 12 weeks after birth [3, 4, 7, 8] CONCLUSIONS GD is the most common cause of hyperthyroidism in children ATDs are the first line of treatment, although ultimately definitive treatment is needed Selecting a treatment approach for childhood GD can be challenging It is important to discuss the risks and benefits of each therapeutic option to help the patient and family select a treatment plan For children less than years of age, MMI should be considered as the first-line therapy Young children are less likely to have remission on drug treatment and prolonged drug therapy may be necessary If there are no adverse side effects with MMI, it is reasonable to continue MMI until the child is old enough for 131I If adverse drug reaction occurs, or there is the desire to avoid prolonged drug use, thyroidectomy or 131I can be considered 15% of children with GD present between years and 10 years of age MMI is the first line drug therapy for this age group Children who are 10 years of age and older constitute 80% of GD For this age group, either MMI therapy can be considered if prognostic factors suggest likelihood of remission or radioactive iodine can be considered as an initial therapy if the chances of remission appear poor [8, 11, 19, 23] CONFLICT OF INTEREST The author declares no conflict of interest, financial or otherwise 158 Recent Advances in Pediatric Medicine, Vol Abha Choudhary ACKNOWLEDGMENTS Declared none REFERENCES [1] Abraham-Nordling M, Byström K, Törring O, et al Incidence of hyperthyroidism in Sweden Eur J Endocrinol 2011; 165(6): 899-905 [http://dx.doi.org/10.1530/EJE-11-0548] [2] Williamson S, Greene SA Incidence of thyrotoxicosis in childhood: a national population based study in the UK and Ireland Clin Endocrinol (Oxf) 2010; 72(3): 358-63 [http://dx.doi.org/10.1111/j.1365-2265.2009.03717.x] [3] Léger J, Kaguelidou F, Alberti C, Carel JC Graves' disease in children Best Pract Res Clin Endocrinol Metab 2014; 28(2): 233-43 [http://dx.doi.org/10.1016/j.beem.2013.08.008] [4] Zimmerman D, Lteif AN Thyrotoxicosis in children Endocrinol Metab Clin North Am 1998; 27(1): 109-26 [http://dx.doi.org/10.1016/S0889-8529(05)70302-9] [5] Cooper DS Hyperthyroidism Lancet 2003; 362(9382): 459-68 [http://dx.doi.org/10.1016/S0140-6736(03)14073-1] [6] Brent GA Clinical practice Graves' disease N Engl J Med 2008; 358(24): 2594-605 [http://dx.doi.org/10.1056/NEJMcp0801880] [7] Srinivasan S, Misra M Hyperthyroidism in children Pediatr Rev 2015; 36(6): 239-48 [http://dx.doi.org/10.1542/pir.36-6-239] [8] Rivkees SA Thyroid Disorders in Children and Adolescents In: Ma S, Ed Pediatric Endocrinology Philadelphia: Elsevier 2014; pp 444-70 [9] Bansal S, Umpaichitra V, Desai N Perez- Colon S Pediatric graves’ disease Int J Endocrinol 2015; 1(1) [http://dx.doi.org/10.16966/ ijemd.104] [10] Rivkees SA Pediatric Graves' disease: management in the post-propylthiouracil Era Int J Pediatr Endocrinol 2014; 2014(1): 10 [http://dx.doi.org/10.1186/1687-9856-2014-10] [11] Bahn RS, Burch HB, Cooper DS, et al American Thyroid Association American Association of Clinical Endocrinologists Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists Endocr Pract 2011; 17(3): 456-520 [http://dx.doi.org/10.4158/EP.17.3.456] [12] Hegedüs L 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Uptake Studies 11 7 11 8 11 8 12 0 12 0 12 2 12 4 12 4 12 5 12 5 12 5 12 5 12 6 12 6 12 7 12 7 12 8 12 8 12 8 12 9 13 1 13 3 13 6 13 7 13 7 13 7 14 4 14 4 14 4 14 5 14 6 14 7 14 8 14 8 14 8 14 8 14 8 TREATMENT OPTIONS ... Clinical Features of Pediatric OSAS Diagnostic Testing 17 7 17 7 17 8 17 8 17 8 17 9 17 9 17 9 17 9 18 0 18 0 18 1 18 1 18 1 18 2 18 2 18 2 18 2 18 2 18 7 18 7 18 8 19 0 19 1 19 1 19 2 19 3 19 4 19 4... OF INTEREST ACKNOWLEDGMENTS REFERENCES 14 8 15 0 15 0 15 0 15 1 15 1 15 2 15 2 15 3 15 3 15 3 15 3 15 3 15 3 15 4 15 4 15 4 15 4 15 5 15 5 15 7 15 7 15 8 15 8 CHAPTER 11 RECENT