Pediatric Graves Disease Clinical Presentation
- Author: Lynne Lipton Levitsky, MD; Chief Editor: Stephen Kemp, MD, PhD more...
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:
Irritability and emotional lability
Sleeplessness and restlessness
Inability to concentrate
Deterioration of handwriting and school performance
Frequent stools or diarrhea
Nocturia, increase in urination, and thirst
Infrequent or light menses
Weakness and tiredness
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.
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)
Blurred vision due to inadequate convergence and accommodation
Swollen orbital contents and puffy lids
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.
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.
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.
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.
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.
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].
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].
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].
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].
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].
Wiersinga WM. Thyroid associated ophthalmopathy: pediatric and endocrine aspects. Pediatr Endocrinol Rev. 2004 Aug. 1 Suppl 3:513-7. [Medline].
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].
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].
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].
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].
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].
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].
FDA MedWatch Safety Alerts for Human Medical Products. Propylthiouracil (PTU),updated April 21, 2010. US Food and Drug Administration. [Full Text].
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].
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].
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].
[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].
[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].
[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].