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Pediatric Graves Disease Workup

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

Approach Considerations

The following laboratory studies may be indicated:

  • Thyroid-stimulating hormone
  • Thyroxine
  • Thyroid hormone binding index
  • Triiodothyronine
  • Antithyroid antibodies
  • Thyroid-stimulating or thyroid-binding immunoglobulins
  • Complete blood count (CBC)
  • Liver function tests (LFTs, such as circulating levels of SGPT, SGOT, GGT, and bilirubin)
  • Antinuclear antibody
  • Serum calcium, urine calcium-to-creatinine ratio

Thyroid-stimulating hormone

TSH levels are suppressed in Graves disease and in all forms of thyrotoxicosis except thyrotoxicosis due to a TSH-secreting tumor of pituitary or other origin. Children with pituitary thyroid hormone resistance also have elevated TSH levels.

Thyroxine

Total serum thyroxine (TT 4 ) levels are elevated in almost all patients with thyrotoxicosis except those with pure elevations in T 3 (T 3 toxicosis) and individuals with decreased T 4 binding. Acutely ill individuals with sick syndrome may appear euthyroid when they are thyrotoxic.

FT 4 may also be measured and is elevated except in patients with pure T 3 toxicosis or the sick syndrome. T 4 and FT 4 are elevated in patients with pituitary insensitivity to thyroid hormone.

Triiodothyronine

T 3 is elevated in all patients with thyrotoxicosis unless they are acutely or chronically ill, malnourished, or taking medication (eg, PTU) that interferes with the conversion of T 4 to T 3 peripherally.

T 3 is slightly elevated in obesity and in overfeeding. Also, T 3 levels are higher in children in the first several years of life than in older children. Children with pituitary resistance to thyroid hormone also have elevated serum T 3 .

Thyroid hormone binding index

The thyroid hormone binding index (THBI), sometimes referred to as the T 3 resin uptake (T 3 RU), measures binding of thyroid hormone to serum proteins. In combination with the TT 4 , THBI estimates FT 4 .

THBI is elevated in almost all patients with thyrotoxicosis except for those with pure T 3 toxicosis. THBI is also elevated in patients with decreased serum thyroid binding proteins (TBG deficiency).

THBI may not be elevated in acutely ill individuals with sick syndrome. Like T 4 , THBI is elevated in patients with pituitary insensitivity to thyroid hormone.

Antithyroid antibodies

Graves disease is almost always associated with measurable markers of autoimmunity in the form of suppressive or destructive antibodies.

Elevated levels of anti-TPO, antimicrosomal, or antithyroglobulin antibodies (in order of sensitivity) usually confirm the autoimmune nature of the thyrotoxicosis without recourse to the more difficult in vitro bioassays for TBI or TSI.

Thyroid-stimulating or thyroid-binding immunoglobulins

Measures of these antibodies by in vitro bioassay confirm Graves disease but are rarely necessary for diagnosis. Occasionally, these are not measurable even in patients with clinically proven Graves disease. Maternal titers of these antibodies may be predictive of the severity of neonatal thyrotoxicosis.

CBC

Graves disease may be associated with a leukopenia and relative increase in lymphocytes, as well as a mild anemia. In a child who is treated with an antithyroid drug, a baseline CBC may be reassuring if later CBC counts reveal a slight leukopenia, because PTU or methimazole may induce neutropenia.

Liver function tests

Severe thyrotoxicosis may be associated with elevations in liver enzymes and in bilirubin (thyroid storm).

If antithyroid drugs are to be used to treat thyrotoxicosis, initial liver enzyme levels (aspartate aminotransferase [AST] or SGPT is usually sufficient) that are within the reference range are reassuring, because these drugs can induce hepatitis.

Other measures of autoimmune function, including antinuclear antibody

Thyrotoxicosis may be associated with lupus. In patients with nonspecific symptoms of joint and muscle pain, a negative antinuclear antibody (ANA) can be reassuring. The ANA may become positive during treatment with antithyroid drugs if an immune response to the medication occurs, and this is associated with arthritis or arthralgia.

Serum calcium, urine calcium-to-creatinine ratio

Rare individuals have symptoms of polyuria, nocturia, and thirst as a result of hypercalcuria. Documentation of hypercalcuria and reference range serum calcium levels may be useful.

Additional tests

Ultrasonography of the thyroid may help to define anatomy in puzzling cases but is almost never indicated in classic Graves disease.

Fine-needle aspiration biopsy of the thyroid is rarely indicated in the diagnosis of Graves disease, but biopsy of a suspicious nodular lesion can usually be conducted without incident, even in the presence of the vascular gland of Graves disease.

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Thyroid Scanning and Radioactive Iodine Uptake

Thyroid scanning is rarely indicated for the diagnosis of classic Graves disease. If a thyroid nodule is identified and autonomously functioning nodular disease is suspected, perform iodine I-123 (123 I) scanning.

Technetium scans reveal the thyroid, but quantitation of uptake is not usually possible. Technetium is taken up by the thyroid but not organified; thus, discrepancies between iodine and technetium scanning results may be observed. Administration of123 I also facilitates calculation of RAIU, which is not necessary for the diagnosis of Graves disease.

Because iodine sufficiency in the North American diet widely varies, standards for RAIU are quite wide and may be confusing in the diagnosis of thyrotoxicosis. However, RAI scanning and uptake can be useful when a goiter is not noted in a hyperthyroid patient or other disorders are suspected. For instance, the hyperthyroidism of subacute thyroiditis is associated with the release of thyroid hormone from a damaged thyroid gland. Therefore, despite thyrotoxicosis, the RAIU is very low. Similarly, in factitious hyperthyroidism because of thyroid hormone ingestion or the rare hyperthyroidism associated with struma ovarii, the RAIU is suppressed.

Because of higher radiation exposure, RAIUs using iodine I-131 (131 I) are now limited to patients who undergo RAI therapy for treatment of thyrotoxicosis or for visualization of residual thyroid malignancy.

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Histologic Findings

The TSH receptor antibodies that are etiologic in Graves disease stimulate the thyroid gland and produce diffuse hyperplasia. Loss of normal thyroid colloid and a hyperemic gland is observed. The formation of many small, new follicles is noted, and the thyroid cells form tall, columnar structures. The blood vessels are larger than normal. Patchy lymphocytic infiltrates are found between follicles, and lymphoid hyperplasia may be seen. T cells and B cells may be identified.[12] The outflow from the thyroid gland is enriched with anti-TSH receptor antibodies, suggesting that these mononuclear cells are a major source of the autoantibodies that maintain the disorder.

Fluid accumulates in periorbital tissues. Extraocular muscles may be infiltrated with lymphocytes.

Thickening of the subcutaneous tissues because of deposition of glycosaminoglycans (pretibial myxedema) may rarely be found in children.

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Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

Acknowledgements

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.

References
  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].

 
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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.
 
 
 
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