Medscape is available in 5 Language Editions – Choose your Edition here.


Pediatric Graves Disease Clinical Presentation

  • Author: Lynne Lipton Levitsky, MD; Chief Editor: Stephen Kemp, MD, PhD  more...
Updated: Oct 08, 2013


Children with Graves disease are usually initially identified because of an enlarged thyroid, weight loss, or behavioral changes. Exophthalmos, which is common in adults with Graves disease, is less common in children. The reason for this difference is not clear; however, smoking is a well-recognized risk factor for exophthalmos.

The enlarged thyroid may be big enough to cause dysphagia, with reports of difficulty swallowing. Usually, the enlarged thyroid is identified by a parent or physician and is not overtly symptomatic. Weight loss accompanied by a voracious appetite and excessive growth in height can lead to initial evaluation. Often, children begin to have distractibility in the classroom, trouble sleeping, and mood changes, resulting in the identification of thyroid enlargement and elevated levels of circulating thyroid hormone.

The astute clinician may identify these children when they are referred for evaluation of symptoms of attention deficit disorder (ADD). Adolescents with this disorder may also report pruritus, temporal hair loss, thinning of the hair, darkening of the skin, palpitations, and, in girls, amenorrhea or infrequent or light menses. Frequent stools or frank diarrhea and symptoms of heat intolerance are common. A strong family history of Graves disease or other autoimmune thyroid disease may be noted.

Symptoms include the following:

  • Dysphagia
  • Irritability and emotional lability
  • Sleeplessness and restlessness
  • Inability to concentrate
  • Deterioration of handwriting and school performance
  • Frequent stools or diarrhea
  • Palpitations
  • Pruritus
  • Weight loss
  • Increased appetite
  • Nocturia, increase in urination, and thirst
  • Infrequent or light menses
  • Weakness and tiredness
  • Exercise intolerance
  • Heat intolerance

Physical Examination

Upon initial inspection, children and adolescents with thyrotoxicosis are usually tall and thin, with a fixed staring gaze and fidgety behavior. Children with thyrotoxicosis may sit on their hands or clasp their hands to control fidgeting. A widened pulse pressure and a rapid heart rate are typically found.

Ocular findings

Ocular findings are often independent of the degree of thyrotoxicosis and may appear before the onset of hyperthyroidism.[6, 7, 8, 9, 10]

Exophthalmos may be present and is usually mild. Weakness of the extraocular muscles is rare, but may be elicited by checking the capacity for convergence and looking for lid lag. Some adolescents may have true inability to close the eyelids because of more severe exophthalmos. Severe exophthalmos can be associated with a sandy, gritty feeling in the eyes upon awakening or with corneal irritation or ulceration (exceedingly rare). Exophthalmos may be unilateral.

Nonspecific signs include lid reaction, wide palpebral aperture (ie, Dalrymple sign, confirmed when the sclera is visible above the superior limbal margin), lid lag (von Graefe sign), stare or appearance of fright, infrequent blinking (Stellwag sign), and absent wrinkling of forehead skin on upward gaze (Joffroy sign). Signs unique to orbitopathy in Graves disease include the following:

  • Upper eyelid retraction (the most common sign of Graves ophthalmopathy)
  • Infrequent or incomplete blinking (Stellwag sign)
  • Lid lag upon infraduction (Von Graefesign) or globe lag on supraduction (Kocher sign)
  • Widened palpebral fissure during fixation (Dalrymple sign)
  • Incapacity to close eyelids completely (lagophthalmos)
  • Prominent stare (Binswanger sign)
  • Inability to keep the eyeballs converged (Mobius sign)
  • Limited extraocular gaze (especially upward)
  • Diplopia
  • Blurred vision due to inadequate convergence and accommodation
  • Swollen orbital contents and puffy lids
  • Chemosis
  • Irritated eye
  • Globe pain
  • Exophthalmos
  • Enlarged lacrimal glands (visible on inspection and palpable)
  • Visible swelling of lateral rectus muscles at insertion sites into the globe and injection of overlying vessels
  • Dysfunctional lacrimal glands with decreased quantity and abnormal composition of tears
  • Corneal injection, ulceration, punctate epithelial erosions, or superior limbic keratoconjunctivitis (rare)
  • Decreased visual acuity due to papilledema, retinal edema, retinal hemorrhages, or optic nerve damage (rare)

Always perform thyroid function tests (TFTs) in addition to local imaging studies in children with unilateral exophthalmos or proptosis to rule out orbital tumor.

Exophthalmos can be quantitated using an exophthalmometer, which measures the extension of the eye beyond the bony socket. This measurement is standardized for adults. Values for young children are not readily available, but these findings may still be useful to measure progression of the eye disease.

Thyroidal findings

The thyroid is firm and usually smooth and rubbery. A bosselated gland may suggest the thyrotoxic phase of chronic lymphocytic thyroiditis.

A gland with a single nodule suggests an autonomously functioning nodule inducing thyrotoxicosis, whereas a multinodular gland indicates a multinodular goiter, a reasonably rare finding in children living in an iodine-replete environment. Malignancy is rarely associated with such hyperfunctioning lesions.

The finding of hyperthyroidism without a goiter suggests the possibility of exogenous administration of thyroid hormone.

Cardiopulmonary manifestations

Cardiac examination may reveal the murmur of mitral valve prolapse. A rapid heart rate and prominent precordium are noted. Atrial fibrillation may rarely be induced by thyrotoxicosis in children. In the most severe form of thyrotoxicosis associated with Graves disease, thyroid storm, high-output heart failure is observed.

Neuromuscular findings

Deep tendon reflexes are exaggerated. Thenar and hypothenar wasting may be noted. Muscle weakness can be profound.

In some genetically prone individuals, periodic paralysis associated with hypokalemia may be induced by thyrotoxicosis. Although thyrotoxic periodic paralysis is described as an adult disorder, it has been observed in adolescents.

Dermal manifestations

The skin is usually fine and moist. Excoriations may be present because of pruritus. Skin darkening may be observed in some darker-skinned individuals. Thyrotoxicosis may intensify the lesions of acanthosis nigricans. The presence of irregular café au lait spots may suggest the diagnosis of thyrotoxicosis associated with McCune-Albright syndrome rather than Graves disease.

Contributor Information and Disclosures

Lynne Lipton Levitsky, MD Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Received grant/research funds from Eli Lilly for pi; Received grant/research funds from NovoNordisk for pi; Received consulting fee from NovoNordisk for consulting; Partner received consulting fee from Onyx Heart Valve for consulting.


Sunil Sinha, MD Assistant Professor, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Sunil Sinha, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD Former Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.


George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece; UNESCO Chair on Adolescent Health Care, University of Athens, Greece

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Robert J Ferry Jr, MD Le Bonheur Chair of Excellence in Endocrinology, Professor and Chief, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Eli Lilly & Co Grant/research funds Investigator; MacroGenics, Inc Grant/research funds Investigator; Ipsen, SA (formerly Tercica, Inc) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Grant/research funds Investigator; Bristol-Myers-Squibb Grant/research funds Other; Amylin Other; Pfizer Grant/research funds Other; Takeda Grant/research funds Other

Thomas A Wilson, MD Professor of Clinical Pediatrics, Chief and Program Director, Division of Pediatric Endocrinology, Department of Pediatrics, The School of Medicine at Stony Brook University Medical Center

Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Pediatric Endocrine Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Lynne L. Levitsky, MD, to the original writing and development of this article.

  1. Ohye H, Minagawa A, Noh JY, Mukasa K, Kunii Y, Watanabe N, et al. Antithyroid Drug Treatment for Graves' Disease in Children: A Long-term Retrospective Study at a Single Institution. Thyroid. 2013 Aug 8. [Medline].

  2. Chu X, Pan CM, Zhao SX, et al. A genome-wide association study identifies two new risk loci for Graves' disease. Nat Genet. 2011 Aug 14. 43(9):897-901. [Medline].

  3. Cassio A, Corrias A, Gualandi S, Tato' L, Cesaretti G, Volta C, et al. Influence of gender and pubertal stage at diagnosis on growth outcome in childhood thyrotoxicosis: results of a collaborative study. Clin Endocrinol (Oxf). 2006 Jan. 64(1):53-7. [Medline].

  4. Lavard L, Ranløv I, Perrild H, Andersen O, Jacobsen BB. Incidence of juvenile thyrotoxicosis in Denmark, 1982-1988. A nationwide study. Eur J Endocrinol. 1994 Jun. 130(6):565-8. [Medline].

  5. Klatka M, Grywalska E, Partyka M, Charytanowicz M, Rolinski J. Impact of methimazole treatment on magnesium concentration and lymphocytes activation in adolescents with Graves' disease. Biol Trace Elem Res. 2013 Jun. 153(1-3):155-70. [Medline]. [Full Text].

  6. Wiersinga WM. Thyroid associated ophthalmopathy: pediatric and endocrine aspects. Pediatr Endocrinol Rev. 2004 Aug. 1 Suppl 3:513-7. [Medline].

  7. Durairaj VD, Bartley GB, Garrity JA. Clinical features and treatment of graves ophthalmopathy in pediatric patients. Ophthal Plast Reconstr Surg. 2006 Jan-Feb. 22(1):7-12. [Medline].

  8. Bradley EA, Gower EW, Bradley DJ, Meyer DR, Cahill KV, Custer PL, et al. Orbital radiation for graves ophthalmopathy: a report by the American Academy of Ophthalmology. Ophthalmology. 2008 Feb. 115(2):398-409. [Medline].

  9. Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, et al. Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol. 2008 Mar. 158(3):273-85. [Medline].

  10. Przemyslaw P, Janusz M, Alina BL, Maria G. Pattern electroretinogram (PERG) in the early diagnosis of optic nerve dysfunction in the course of Graves' orbitopathy. Klin Oczna. 2013. 115(1):9-12. [Medline].

  11. Mittra ES, Niederkohr RD, Rodriguez C, El-Maghraby T, McDougall IR. Uncommon causes of thyrotoxicosis. J Nucl Med. 2008 Feb. 49(2):265-78. [Medline]. [Full Text].

  12. Ben-Skowronek I, Szewczyk L, Kulik-Rechberger B, Korobowicz E. The differences in T and B cell subsets in thyroid of children with Graves' disease and Hashimoto's thyroiditis. World J Pediatr. 2013 Aug. 9(3):245-50. [Medline].

  13. Slyper AH, Wyatt D, Boudreau C. Effective methimazole dose for childhood Graves' disease and use of free triiodothyronine combined with concurrent thyroid-stimulating hormone level to identify mild hyperthyroidism and delayed pituitary recovery. J Pediatr Endocrinol Metab. 2005 Jun. 18(6):597-602. [Medline].

  14. FDA MedWatch Safety Alerts for Human Medical Products. Propylthiouracil (PTU),updated April 21, 2010. US Food and Drug Administration. [Full Text].

  15. Read CH Jr, Tansey MJ, Menda Y. A 36-year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves' patients. J Clin Endocrinol Metab. 2004 Sep. 89(9):4229-33. [Medline]. [Full Text].

  16. Sugino K, Ito K, Mimura T, Fukunari N, Nagahama M, Ito K. Surgical treatment of Graves' disease in children. Thyroid. 2004 Jun. 14(6):447-52. [Medline].

  17. Bahn Chair RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011 Jun. 21(6):593-646. [Medline].

  18. [Guideline] Bahn Chair RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011 Jun. 21(6):593-646. [Medline].

  19. [Guideline] Kahaly GJ, Bartalena L, Hegedüs L. The American Thyroid Association/American Association of Clinical Endocrinologists guidelines for hyperthyroidism and other causes of thyrotoxicosis: a European perspective. Thyroid. 2011 Jun. 21(6):585-91. [Medline].

  20. [Guideline] Sisson JC, Freitas J, McDougall IR, Dauer LT, Hurley JR, Brierley JD, et al. Radiation safety in the treatment of patients with thyroid diseases by radioiodine 131I : practice recommendations of the American Thyroid Association. Thyroid. 2011 Apr. 21(4):335-46. [Medline].

A 16-year-old girl with thyrotoxicosis for 3 years is shown. Note her thyrotoxic stare (infrequent blinking with exophthalmos) and enlarged thyroid gland (goiter).
Neonate with thyrotoxicosis secondary to transplacental passage of maternal thyroid-stimulating immunoglobulins (TSI). The baby has a noteworthy stare. Upon examination, a small goiter and a rapid heart rate could be appreciated.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.