Diffuse Toxic Goiter (Graves Disease) Guidelines

Updated: Dec 10, 2020
  • Author: Bernard Corenblum, MD, FRCPC; Chief Editor: George T Griffing, MD  more...
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Guidelines Summary

2016 American Thyroid Association Guidelines

In 2016, the American Thyroid Association updated the 2011 hyperthyroidism/thyrotoxicosis guidelines it had codeveloped with the American Association of Clinical Endocrinologists. The following is a sampling of the 124 recommendations included in the guideline [1] :

  • Beta-adrenergic blockade is recommended in all patients with symptomatic thyrotoxicosis, especially elderly patients and thyrotoxic patients with resting heart rates in excess of 90 beats per minute or coexistent cardiovascular disease
  • Patients with overt Graves hyperthyroidism should be treated with any of the following modalities: radioactive iodine therapy, antithyroid drugs, or thyroidectomy
  • If methimazole is chosen as the primary therapy for Graves disease, the medication should be continued for approximately 12-18 months and then discontinued if the serum thyrotropin and thyrotropin receptor antibody levels are normal at that time
  • If surgery is chosen as the primary therapy for Graves disease, near-total or total thyroidectomy is the procedure of choice
  • If surgery is chosen as treatment for toxic multinodular goiter, near-total or total thyroidectomy should be performed
  • If surgery is chosen as the treatment for toxic adenoma, a thyroid sonogram should be done to evaluate the entire thyroid gland; an ipsilateral thyroid lobectomy (or isthmusectomy, if the adenoma is in the thyroid isthmus), should be performed for isolated toxic adenomas
  • Children with Graves disease should be treated with methimazole, radioactive iodine therapy, or thyroidectomy; radioactive iodine therapy should be avoided in very young children (< 5 years); radioactive iodine therapy in children is acceptable if the activity is over 150 μCi/g (5.55 MBq/g) of thyroid tissue and for children between ages 5 and 10 years if the calculated radioactive iodine administered activity is under 10 mCi (< 473 MBq); thyroidectomy should be chosen when definitive therapy is required, the child is too young for radioactive iodine, and surgery can be performed by a high-volume thyroid surgeon
  • If methimazole is chosen as the first-line treatment for Graves disease in children, it may be tapered in those children requiring low doses after 1-2 years to determine if a spontaneous remission has occurred, or it may be continued until the child and caretakers are ready to consider definitive therapy, if needed
  • If surgery is chosen as therapy for Graves disease in children, total or near-total thyroidectomy should be performed
  • In patients with Graves hyperthyroidism who have mild active ophthalmopathy and no risk factors for deterioration of their eye disease, radioactive iodine therapy, antithyroid drugs, and thyroidectomy should be considered equally acceptable therapeutic options

Graves Orbitopathy

2016 American Thyroid Association Recommendations

The 2016 American Thyroid Association guidelines recommendations on Graves orbitopathy include the following [1] :

  • Euthyroidism should be expeditiously achieved and maintained in hyperthyroid patients with Graves orbitopathy or risk factors for the development of orbitopathy
  • In Graves disease patients with mild Graves orbitopathy who are treated with radioactive iodine, steroid coverage is recommended if there are concomitant risk factors for Graves orbitopathy deterioration

2016 European Thyroid Association Recommendations

In 2016, the European Thyroid Association/European Group on Graves' Orbitopathy (EUGOGO) released their updated guidelines for the management of Graves orbitopathy (GO) which included the following key recommendations [6] :

  • Activity and severity of GO should be categorized as active or inactive and as mild, moderate to severe or sight threatening
  • Euthyroidism should be restored and maintained in all patients 
  • All patients should be treated with nonpreserved artificial tears with osmoprotective properties unless corneal exposure requires the higher protection that gels or ointment can offer
  • In mild GO, a 6-month course of selenium supplementation is effective in improving mild manifestations and preventing progression to more severe forms.
  • High-dose glucocorticoids (GCs), preferably via the intravenous route, are the first line of treatment for moderate-to-severe and active GO
  • Rehabilitative surgery (orbital decompression surgery, squint surgery or eyelid surgery) should be offered when the disease is associated with a significant impact on visual function or quality of life after the disease has been inactive for at least 6 months. 
  • Severe corneal exposure should be treated medically or by means of progressively more invasive surgeries as soon as possible to avoid progression to corneal breakdown. The latter should be immediately addressed surgically.

Thyrotoxicosis in Pregnancy

2017 American Thyroid Association Guidelines

In 2017, the American Thyroid Association (ATA) released guidelines pertaining to the diagnosis and management of thyroid disease in women during pregnancy and the postpartum period, as well as prior to conception. Recommendations regarding thyrotoxicosis in pregnancy included the following [16] :

  • When a suppressed serum thyroid stimulating hormone (TSH) is detected in the first trimester (TSH less than the reference range), a medical history, physical examination, and measurement of maternal serum free thyroxine (FT4) or total thyroxine (T4) concentrations should be performed; measurement of thyroid-stimulating antibody (TSab) and maternal total triiodothyronine (T3) may prove helpful in clarifying the etiology of thyrotoxicosis
  • Radionuclide scintigraphy or radioiodine uptake determination should not be performed in pregnancy
  • The appropriate management of abnormal maternal thyroid tests attributable to gestational transient thyrotoxicosis and/or hyperemesis gravidarum includes supportive therapy, management of dehydration, and hospitalization if needed; antithyroid drugs are not recommended, though beta blockers may be considered
  • In all women of childbearing age who are thyrotoxic, the possibility of future pregnancy should be discussed; women with Graves disease seeking future pregnancy should be counseled regarding the complexity of disease management during future gestation, including the association of birth defects with antithyroid drug use; preconception counseling should review the risks and benefits of all treatment options and the patient’s desired timeline to conception
  • Thyrotoxic women should be rendered stably euthyroid before attempting pregnancy; several treatment options exist, each of which is associated with risks and benefits; these include  131I ablation, surgical thyroidectomy, and antithyroid drug therapy
  • Women taking methimazole or propylthiouracil should be instructed to confirm potential pregnancy as soon as possible; if the pregnancy test is positive, pregnant women should contact their caregiver immediately
  • In pregnant women with a high risk of developing thyrotoxicosis if antithyroid drugs were to be discontinued, continued antithyroid medication may be necessary; factors predicting high clinical risk include being currently hyperthyroid or requirement of >5-10 mg/d methimazole or >100-200 mg/d propylthiouracil to maintain a euthyroid state; in such cases, propylthiouracil is recommended for the treatment of maternal hyperthyroidism through 16 weeks of pregnancy, and when shifting from methimazole to propylthiouracil, a dose ratio of approximately 1:20 should be used (eg, methimazole 5 mg/d = propylthiouracil 50 mg twice daily)
  • In women being treated with antithyroid drugs in pregnancy, free thyroxine (FT4)/total thyroxine (T4) and TSH should be monitored approximately every 4 weeks; antithyroid medication during pregnancy should be administered at the lowest effective dose of methimazole or propylthiouracil, targeting maternal serum free thyroxine (FT4)/total thyroxine (T4) at the upper limit of or moderately above the reference range.
  • A combination regimen of levothyroxine (LT4) and an antithyroid drug should not be used in pregnancy, except in the rare situation of isolated fetal hyperthyroidism
  • Thyroidectomy in pregnancy may be indicated for unique scenarios; if required, the optimal time for thyroidectomy is in the second trimester of pregnancy; if maternal thyroid-stimulating antibody (TSab) concentration is high (>3 times the upper reference for the assay), the fetus should be carefully monitored for development of fetal hyperthyroidism throughout pregnancy, even if the mother is euthyroid postthyroidectomy
  • The ATA concurs with the American College of Obstetricians and Gynecologists’ (ACOG) Committee on Obstetric Practice consensus guidelines (written in 2011 and revised in 2015), which state the following: ‘‘1) A pregnant woman should never be denied indicated surgery, regardless of trimester. 2) Elective surgery should be postponed until after delivery. 3) If possible, nonurgent surgery should be performed in the second trimester when preterm contractions and spontaneous abortion are least likely.’’ In the setting of a patient with Graves disease undergoing urgent, nonthyroid surgery, if the patient is well controlled on antithyroid medication, no other preparation is needed; beta blockade should also be utilized if needed
  • If the patient has a past history of Graves disease treated with ablation (radioiodine or surgery), a maternal serum determination of thyroid-stimulating antibodies (TSabs) is recommended at initial thyroid function testing during early pregnancy
  • If maternal thyroid-stimulating antibody (TSab) concentration is elevated in early pregnancy, repeat testing should occur at weeks 18-22
  • If the patient requires treatment with antithyroid drugs for Graves disease through midpregnancy, a repeat determination of thyroid-stimulating antibody (TSab) concentration is again recommended at weeks 18-22
  • If elevated thyroid-stimulating antibody (TSab) is detected at weeks 18-22 or the mother is taking antithyroid medication in the third trimester, a TSab measurement should again be performed in late pregnancy (weeks 30-34) to evaluate the need for neonatal and postnatal monitoring
  • Fetal surveillance should be performed in women who have uncontrolled hyperthyroidism in the second half of pregnancy and in women with high thyroid-stimulating antibody (TSab) levels detected at any time during pregnancy (>3 times the upper limit of normal); a consultation with an experienced obstetrician or maternal–fetal medicine specialist is recommended; monitoring may include ultrasonography to assess heart rate, growth, amniotic fluid volume, and the presence of fetal goiter
  • If antithyroid drug therapy is given for hyperthyroidism caused by autonomous nodules, the fetus should be carefully monitored for goiter and signs of hypothyroidism during the second half of pregnancy; a low dose of antithyroid medication should be administered with the goal of maternal free thyroxine (FT4) or total thyroxine (T4) concentration at the upper limit of or moderately above the reference range