eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Graves Disease: Follow-up

Author: Robert J Ferry Jr, MD, Chief, Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children's Medical Center, University of Tennessee Health Science Center at Memphis, and St Jude Children's Research Hospital; Field Surgeon (Medical Corps), 162nd Area Support Medical Company, Army National Guard
Coauthor(s): Lynne Lipton Levitsky, MD, Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor, Department of Pediatrics, Harvard University Medical School
Contributor Information and Disclosures

Updated: Jun 4, 2009

Follow-up

Further Inpatient Care

• Inpatient care is only indicated in the event of thyroid storm or for a few days of the postoperative period after subtotal thyroidectomy.
• See Thyroid Storm for management of this disorder.
• Post–subtotal thyroidectomy, assess serum calcium and laryngeal nerves. Damage to these tissues is very unusual in the hands of an experienced thyroid surgeon; nonetheless, having calcium for injection by the bedside is reasonable to treat severe acute hypocalcemia. If the patient is hypocalcemic because of transient or permanent hypoparathyroidism, commence treatment with calcium and vitamin D as soon as necessary. See Hypoparathyroidism for treatment of that condition.

Further Outpatient Care

Outpatient care is predicated on the treatment option chosen.

• Antithyroid drug therapy
  • Monitor the patient at 6-week to 3-month intervals with TFTs, liver function tests (LFTs), and CBC count. Assess other potential adverse effects of the agent by history.
  • If beta-adrenergic blocking agents have been started, discontinue when the patient is euthyroid.
  • At each visit, assess thyroid gland size and firmness. Risk of recurrence upon discontinuation of therapy is great unless the thyroid gland is close to normal in size. After 1-2 years of therapy, if the thyroid is still large and the drug dose has not been able to be decreased to relatively low levels (eg, one half to one fourth of the initial dose), consider alternative therapies.
• Radioactive iodine treatment
  • The purpose of this treatment should be to render the patient hypothyroid and, therefore, decrease risk of recurrence. In severe thyrotoxicosis, adding Lugol solution or SSKI drops to the regimen 5-7 days after treatment may enhance the speed of remission. Antithyroid drugs may also be started or restarted after 5-7 days, and beta-adrenergic blocking agents may be continued until remission, which may take 4-6 months for full effect.
  • If the patient is not in remission by 6 months, consider a second treatment. Repeat thyroid hormone and TSH levels at about 4- to 6-week intervals and start supplementation with levothyroxine (L-T4) when indicated by these tests. Long-term follow-up is essential for adjustment of thyroid hormone.
• Subtotal thyroidectomy
  • TFTs performed after surgery should provide evidence of hypothyroidism.
  • Individuals who are euthyroid have a very high recurrence rate.
  • Start thyroid hormone treatment as indicated and monitor the appropriate dose at 3-month intervals for several visits and then at 6-month intervals during childhood.

Inpatient & Outpatient Medications

• Treat all symptomatic patients with beta-adrenergic blocking agents unless a exacerbation of severe bronchospastic disease is a strong concern even with a selective beta1 antagonist. Other treatment plans depend on the therapeutic approach chosen.
• Begin antithyroid drug therapy with methimazole or PTU promptly and carefully monitor. L-T4 can be added to the regimen when the dose of methimazole or PTU decreases and the thyroid gland is still large and firm in order to establish an equilibrium during therapy. This addition of T4 does not enhance the rapidity of remission.
• Discontinue antithyroid drugs 4 days before RAI therapy. Antithyroid drugs can be restarted 1 week after treatment or, alternatively, iodine drops can be administered until remission.
• In most cases, L-T4 therapy is started within 4-7 days after subtotal thyroidectomy.

Transfer

• An experienced pediatric endocrinologist should care for children with Graves disease.
• If care involves RAI therapy, transfer to the temporary care of the treating endocrinologist or nuclear medicine physician is indicated.
• If care involves surgery, transfer to the care of an experienced thyroid surgeon is warranted.

Deterrence/Prevention

• Presently, no means of preventing this disorder are recognized.

Complications

• Hyperthyroidism leads to hypercalciuria and loss of bone mineral during childhood and adolescence. In severely thyrotoxic individuals, assessment of bone mineral by dual energy x-ray absorptiometry (DEXA) may be advisable.
• Severe school problems because of inattention and restlessness may seriously harm children.
• Thyroid storm is the most severe form of thyrotoxicosis and can be provoked by surgical or medical stress in an undiagnosed thyrotoxic individual.
• Other autoimmune disorders can be associated with Graves disease, including diabetes mellitus type 1, Addison disease, vitiligo, alopecia, and lupus.
• Treatment complications include the following:
  • Severe drug reaction to methimazole or PTU, including liver disease, lupus, and agranulocytosis
  • Surgical complications, including hypoparathyroidism or recurrent laryngeal nerve damage
  • Rare induction of hypoparathyroidism post-RAI therapy and a questionable slight increase in the risk of thyroid cancer
  • Fetus with thyroid ablation in women treated with RAI during pregnancy

Prognosis

Graves disease is a chronic illness without a true cure. None of the management options for this disorder actually remove the underlying immunologic disorder. Therefore, the prognosis of the disorder greatly depends on the form of therapy chosen.

• Antithyroid drug therapy
  • In one review, 46.8% of patients had a permanent remission following drug treatment for a variable number of years, and 29% had a relapse. Of this population of 651 children, culled from a number of reports, 5.6% of patients developed granulocytopenia, 2.3% had arthritis, 1.9% had liver disease, and 8% developed a skin rash. Likelihood of remission is greater if the thyroid gland is smaller, the RAIU is relatively low, and TSI levels are lower.
  • A statistical analysis of children who had long-term drug treatment suggests that approximately 25% of children have remission every 2 years. This remission rate is generous and is lower than the remission rate observed in adults.
• Subtotal thyroidectomy: A recent review of outcomes in 555 children, taken from several large series, suggests that 42% of patients become hypothyroid, and 10% have recurrence. In this combined series, 2% of patients had hypoparathyroidism, 1.2% had vocal cord paralysis, 0.2% had bleeding, 1.7% had keloid formation, and 1.5% were discovered to have papillary cancer by histology.
• Radioactive iodine therapy: In a recent review of outcomes of 555 children, taken from several large series, 69% of children became hypothyroid, 98% experienced cure of hyperthyroidism, 12% required re-treatment, and 4.4% had histologically benign nodules. The practice today in most centers is to aim for hypothyroidism, which would change these figures.

Patient Education

• Instruct patients treated with antithyroid drugs as to possible adverse effects and the need for close follow-up.
• Patients treated with surgery and RAI must understand the rationale for the development of hypothyroidism and the need for close follow-up.
• For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

Miscellaneous

Medicolegal Pitfalls

• Graves disease can be masked by the presence of concurrent illness, such as diabetic ketoacidosis.
• Neonates with Graves disease as a result of transplacental passage of maternal antibodies may be missed unless the maternal history is carefully assessed and the diagnosis is considered.
• Graves disease may be confused with ADHD, leading to delays in treatment.
• The adverse effects of all treatments for Graves disease, but particularly antithyroid drug therapy, are considerable, and obtaining true collaborative informed consent is important.
• Children with pituitary resistance to thyroid hormone, a rare genetic disorder, have been diagnosed mistakenly with hyperthyroidism and treated with antithyroid drug therapy or thyroid ablative therapy. The diagnosis is predicated on the finding of elevated thyroid hormone levels, elevated or reference range TSH levels, and no evidence of pituitary disease. Diagnosis can be confirmed by identification of family history and of a mutation in the thyroid hormone receptor gene.

Special Concerns

• Neonatal thyrotoxicosis caused by transplacental passage of maternal TSI is transient but leads to prenatal deaths due to arrhythmia and cardiac failure. Postnatally, poor weight gain, rapid heart rate, and jaundice may indicate the severity of the disorder. These children require special attention after treatment of thyrotoxicosis and remission because TSI have been attenuated and long-term TSH suppression may render them hypothyroid for variable periods.
• Assess adolescent girls treated for Graves disease for pregnancy risk and start contraception if indicated.
• Management of Graves disease during pregnancy requires careful therapy with PTU and maintenance of thyroid hormone levels in the high range typical of pregnancy. Overtreatment can lead to fetal hypothyroidism and goiter with concomitant poor intellectual outcome. Undertreatment can lead to fetal loss. Surgery can lead to fetal loss and should be carried out only if absolutely necessary. Do not administer RAI therapy to a sexually active adolescent girl until she is known to have a negative pregnancy test result. Destruction of the fetal thyroid by RAI produces severe in utero hypothyroidism.

• Search for CME/CE on This Topic »

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