Management of Hyperthyroidism

  • TNG:
    • Generally causes milder symptoms than Graves’ disease
  • In the absence of contraindications:
    • Beta-blockers may be used for symptomatic relief:
      • While awaiting results of definitive treatment
    • Beta-blockers may also be appropriate for patients with:
      • Atrial fibrillation and rapid ventricular response
    • Propranolol has been widely used to block T4 to T3 conversion:
      • A theoretic benefit
    • selective beta-blocker:
      • Such as atenolol:
        • May be used in patients who cannot tolerate propranolol
    • If beta-blockers are contraindicated:
      • A calcium channel blocker may be useful
  • Definitive Treatment:
    • Toxic Nodular Goiter:
      • RAI therapy (with 131I) and surgery:
        • Are effective options for the definitive treatment for TNG
      • The long-term use of thionamide antithyroid drugs (ATDs):
        • Is not favored:
          • Unless either 131I therapy or surgery is contraindicated
      • Thionamides, however, may be used before surgery:
        • Especially in older patients:
          • Until euthyroidism is restored
      • Radioactive iodine:
        • The clinical utility of RAI therapy in the management of TNG:
          • Is well established
        • If radioactive iodine uptake (RAIU) is adequate and the patient is not a good surgical candidate:
          • RAI is the treatment of choice 
        • Although the dose of 131I may be calculated on the basis of uptake determinations and gland weight:
          • TNGs are relatively resistant to 131I:
            • Because of their larger size and relatively lower uptake of iodine:
              • For these reasons, some clinicians increase the standard dose:
                • By 20% to 50%
        • Frequently, RAI doses between:
          • 15 and 50 mCi (555 and 1850 MBq) are administered
        • In a report from Mayo Clinic, Jensen et al:
          • Treated their patients with a mean dose of 37 mCi (1370 MBq) (range, 6.3 to 150 mCi [233 to 5550 MBq]):
            • After 1 year of follow-up:
              • 16% of patients were hypothyroid
        • Danaci et al. treated TNGs with a fixed dose of 16.6 mCi (631 MBq) 131I and reported:
          • cumulative relapse rate of:
            • 39% at 5 years
          • Cumulative incidence of hypothyroidism of:
            • 24% at 5 years
        • In a large prospective study involving 130 consecutive patients with TNGs and a mean follow-up of 6 years:
          • 92% of patients were cured after one or two treatments with 131I
          • Thyroid volume was reduced by a mean of 43%, and adverse effects were few
          • Patients were treated with a median dose of 10 mCi (370 MBq)
  • Generally, after RAI most patients are euthyroid within 2 to 4 months:
    • Although sometimes achieving euthyroidism may take longer
  • Although most patients treated with RAI achieve long-term euthyroidism:
    • 10% to 24% of these patients eventually become hypothyroid:
      • Regardless of the dose used
    • RAI is associated with a 20% chance of recurrence:
      • In which case patients may receive a second dose of 131I or opt for thyroidectomy
      • These patients should not be given iodide preoperatively:
        • Because of the risk of exacerbating thyrotoxicosis
  • Surgery:
    • Total thyroidectomy:
      • Is recommended for patients with:
        • Large goiters causing obstructive symptoms such as:
          • Choking
          • Dyspnea
          • Dysphagia:
            • Hoarsness
      • For those who refuse RAI therapy
      • Surgery may also be indicated when a suspicious cold or growing nodule is identified in a TNG
      • Surgery is an excellent option for patients who:
        • Decline RAI therapy and also for pregnant women 
    • Two issues with the operation:
      • The extent of thyroidectomy remains somewhat controversial
      • In the past, some clinics have preferred subtotal thyroidectomy to minimize complications such as:
        • Recurrent laryngeal nerve damage and hypoparathyroidism
      • In current practice, most surgeons perform:
        • A total thyroidectomy for bilateral benign nodular goiters:
          • This is what I recommend
      • Also, the trend in recent decades:
        • Suggests that RAI is being increasingly considered as:
          • An attractive, effective alternative to surgery in TNG
        • For example, a study from Mayo Clinic showed that between 1950 and 1974:
          • 83% of patients had surgical treatment
          • 17% had RAI treatment
        • Between 1990 and 1999, the figures were:
          • 53% for surgery and 47% for RAI
  • Thionamide antithyroid drugs:
    • Thionamide antithyroid drugs are the preferred transient treatment:
      • During pregnancyuntil delivery
    • They should also be considered for patients who are not candidates for or who decline definitive treatment
    • Treatment is generally indefinite with thionamide ATDs:
      • Generally because permanent remission is never achieved in TNG
  • Graves’ Disease:
    • In the management of Graves’ disease:
      • Treatment preferences vary substantially by geographic region
    • This was suggested by the outcome of an international survey of endocrinologists from the United States, Europe, and Japan:
      • Among physicians in the United States:
        • Thionamide ATDs were selected as the primary form of therapy for a “typical 43-year-old healthy woman” by only approximately 30%, whereas 69% chose RAI treatment and 1% opted for surgery
      • By contrast, 77% of European physicians and 88% of Japanese physicians selected thionamide ATDs as the preferred primary treatment, with RAI therapy as the second choice.
    • Thionamide antithyroid drugs:
      • Thionamide ATDs inhibit biosynthesis of thyroid hormones:
        • Biochemical euthyroidism is usually achieved within 6 to 8 weeks after initiation of therapy
      • Currently, three thionamide ATDs are available
        • Methimazole
          • Available in the United States
          • Half-life of methimazole in plasma is:
            • 3 to 5 hours
        • Propylthiouracil 
          • Available in the United States
          • Half-life of  in plasma of propylthiouracil is 1 to 2 hours
        • Carbimazole:
          • Which is metabolized to methimazole:
            • Is sometimes used in Europe and Asia
      • Methimazole has a longer duration of action:
        • Although both drugs are effective for more than 5 hours because they accumulate in thyroid cells
      • Initial daily doses range from:
        • 10 mg to 40 mg of methimazole usually once daily
        • 100 to 150 mg of propylthiouracil every 6 to 8 hours daily
        • 15 to 45 mg daily of carbimazole usually in one dose up to three divided doses
      • The decision to use methimazole / carbimazole or propylthiouracil:
        • Is a matter of physician preference:
          • Because both agents are equally effective
        • However, observations over several decadeshave shown that methimazole and its prodrug carbimazole are better than propylthiouracil in controlling more severe hyperthyroidism;
          • But propylthiouracil should not be routinely used because of potential fatal hepatotoxicity
      • This has led to the recommendation that methimazole / carbimazole:
        • Be the first-line drug when ATD therapy is initiated:
          • Either for primary treatment or to prepare a patient for RAI therapy or surgery
        • An exception to this rule has been pregnancy:
          • During which propylthiouracil has been preferred:
            • Because of rare reports of birth defects associated with methimazole
          • Propylthiouracil has also been used in patients with:
            • Minor reactions to methimazole but who, nonetheless, prefer to continue ATD therapy 
          • Propylthiouracil may also be preferable in patients with:
            • Life-threatening thyrotoxicosis:
              • Because of its additional inhibition of T4 to T3 conversion
      • It is crucial to evaluate patients clinically and biochemically (with serum T4 and TSH measurements) regularly:
        • From 6 to 8 weeks after the initiation of ATD treatment:
          • Until the patient is biochemically euthyroid and every 8 to 12 weeks thereafter
        • Once the patient is euthyroid, the ATD dose may be reduced
      • Some clinicians favor adding levothyroxine to the ATD regimen as part of a block-replacement regimen:
        • Without reducing the original ATD dose:
          • To minimize the number of patient visits and maintain a more normal stable TSH:
            • This addition to the regimen causes no difference in the remission outcome compared with titration of ATD alone
          • The concern about compliance and the advantages of ATD alone have ensured that combination treatment (thyroxine and ATD) has not been widely adopted
      • It has been determined from various reports that treatment with thionamide ATDs for 12 to 18 months is optimal:
        • Resulting in long-term remission in 40% to 60% of patients with Graves’ disease:
          • With higher remission rates in women than in men
        • The likelihood of sustained remission:
          • Is greater in patients with:
            • Mild hyperthyroidism
            • Small goiter
            • Low or undetectable TSHR-Ab titers:
              • Than in those with moderate to severe hyperthyroidism or T3 toxicosis, large goiter, and high TSHR-Ab titers
        • If hyperthyroidism recurs:
          • Other modes of therapy (RAI or surgery) are considered
        • Most relapses following cessation of thionamide ATDs;
          • Occur shortly after the ATDs are discontinued:
            • Generally within the first few months:
              • Although they may occur several years later:
                • Therefore, clinical and biochemical evaluation is necessary 2 months after ATD withdrawal and periodically at regular intervals thereafter
      • As with all other drugs, thionamide ATDs may cause adverse effects:
        • As early as 2 weeks after initiation of therapy or later in the course of therapy:
          • It is essential to instruct patients on how to deal with these adverse reactions
      • The most serious and rare complication:
        • Agranulocytosis:
          • Should be ruled out:
            • By obtaining white blood cell and differential counts:
              • If fever and signs of infection such as sore throat occur while the patient is on thionamide ATD therapy
Adverse EffectPropylthiouracil
(100 to 150 mg/day)
Methimazole
(10 to 40 mg/day)
Minor reactions
Fever, rash, arthralgia5% to 20%5% to 20% (dose related)
Major reactions
Agranulocytosis0.2%-0.5% (not clearly dose related)0.2%-0.5% (dose related)
Hepatotoxicity (hepatitis)30% (< 1% severe)Cholestatic (usually reversible, with few deaths reported)
VasculitisANCA +Rare

ANCA, antineutrophil cytoplasmic antibody
  • Inorganic Iodine:
    • Iodine given in pharmacologic doses (as Lugol solution or as a saturated solution of potassium iodide):
      • Inhibits the release of thyroid hormones for a few days or weeks:
        • After which its antithyroid action is lost
      • For this reason it is not used routinely:
        • But short-term iodine therapy is useful in:
          • The preparation of patients for surgery
          • After RAI therapy to hasten the fall in serum T3 and T4 concentrations to normal:
            • Although this is not a routine indication
        • In the treatment of thyrotoxic crisis
      • The usual dose of Lugol solution (5% iodine and 10% potassium iodide in water) is:
        • 0.1 to 0.3 mL three times daily
      • The usual dose of potassium iodide is:
        • 60 mg (1 drop) three times daily
  • Radioactive iodine therapy:
    • In use for more than 60 years:
      • RAI therapy is established as an effective, relatively inexpensive, and safe treatment option for Graves’ disease
    • The objective of RAI therapy is to:
      • Destroy sufficient thyroid tissue to cure hyperthyroidism
    • The goal of treatment is to:
      • Render the patient either euthyroid or hypothyroid:
        • Depending on the willingness of the physician to risk the possibility of persistent hyperthyroidism
    • Much attention has focused on achieving euthyroidism:
      • By adjusting the RAI dose:
        • But there is little consensus regarding the most appropriate dose schedule
    • The regimens used include the traditional method of:
      • Repeated low doses (2 mCi)
      • Fixed doses
      • Doses calculated on the basis of:
        • The size of the thyroid
        • The RAIU
        • The turnover of 131I
    • Because it has proved impossible to titrate doses for individual patients accurately to guarantee a euthyroid state:
      • The majority of physicians in the United States:
        • Prefer to administer a single, relatively large dose:
          • 10 to 20 mCi initially with the intent of:
            • Inducing thyroid ablation and the development of hypothyroidism
        • Thyroid function is then assessed 6 to 8 weeks after RAI administration and possibly every month thereafter:
          • To monitor the development of hypothyroidism:
            • Especially during the first 6 months after RAI treatment
        • When hypothyroidism is detected by TSH elevations:
          • Levothyroxine treatment should be initiated:
            • To maintain the TSH level in the normal range (0.5 to 3 mIU/L)
        • However, if hyperthyroidism persists:
          • Another RAI dose may be delivered:
            • But should not be given until at least 6 months after the first dose
    • Before RAI treatment is started:
      • Patients should be informed of the precautions needed after RAI
      • Rarely patients may experience:
        • Mild anterior neck pain after RAI
        • short-lived exacerbation of hyperthyroid symptoms:
          • Caused by the leakage of preformed thyroid hormones from a damaged thyroid gland
        • Worsening of Graves’ ophthalmopathy:
          • Especially among smokers:
            • May be observed after 131I treatment
          • Risk is reduced by:
            • Cessation of smoking and the administration of glucocorticoids, namely, prednisone:
              • Different regimens are available, but most agree on the regimen of oral prednisone:
                • Administration 1 to 3 days after RAI treatment at 0.3 to 0.5 mg/kg daily, and the dose is tapered until withdrawal about 3 months later
    • Whether to pretreat patients with thionamide ATDs:
      • Until they are euthyroid before 131I administration is a matter of debate:
        • Retrospective studies have shown that the efficacy of treatment with 131I:
          • Is decreased after propylthiouracil:
            • It is best to discontinue ATDs a few days before RAI is given
      • Previously RAI was reserved for adults because of the lack of long-term data in children and adolescents:
        • More recently, in properly administered doses, data have shown that RAI is the ideal form of therapy for Graves’ disease in children
      • It remains absolutely contraindicated:
        • During pregnancy and lactation
  • Surgery:
    • Because of the higher relapse rates seen with subtotal thyroidectomy, or near-total thyroidectomy:
      • Total thyroidectomy:
        • Is the recommended surgical procedure for the treatment of Graves’ hyperthyroidism
    • It usually results in postoperative hypothyroidism:
      • Requiring lifelong levothyroxine replacement
    • Thyroidectomy is preferred in patients with:
      • Large goiters:
        • Especially those with tracheoesophageal compression symptoms)
      • Coincidental suspicious thyroid nodules
      • Contraindications to 131I or ATDs
      • In those who refuse RAI treatment or are pregnant when hyperthyroidism is difficult to control
    • Surgical morbidity, including:
      • Permanent hypoparathyroidism
      • Vocal cord dysfunction caused by recurrent laryngeal nerve injury,
      • Infection
      • Hematoma
        • Is low in experienced centers
    • Any patient with hyperthyroidism scheduled to undergo surgery:
      • Should be treated with thionamide ATDs:
        • To restore euthyroidism
    • Alternative methods of preoperative therapy include:
      • Thionamide ATDs combined with beta-blockers:
        • Propranolol:
          • 40 to 80 mg three times a day or
        • longer-acting beta-adrenergic antagonist:
          • Atenolol, 50 mg/day
      • Potassium iodide:
        • 40 mg three times a day for 10 days
      • Potassium iodide (several drops per day for 10 days) in combination with propranolol (40 to 120 mg per day):
        • May be another alternative:
          • Any of these regimens virtually eliminates the risk of postoperative thyrotoxic crisis
    • Indefinite follow-up is essential after thyroidectomy:
      • With an adequate replacement dose of levothyroxine that maintains TSH within the range of normal
  • Pregnancy:
    • Appropriate management of hyperthyroidism during pregnancy is important for the mother’s health and for the course of the pregnancy
    • Moreover, the quality of management may have considerable impact on the progeny:
      • Both in fetal and in neonatal life and on the long-term health of the child
    • The most common form of hyperthyroidism during pregnancy:
      • Is mostly the result of Graves’ disease:
        • Its adequate control is essential
    • Pregnant hyperthyroid women should be treated with:
      • Thionamide ATDs:
        • Most clinicians prefer propylthiouracil:
          • Although both propylthiouracil and methimazole:
            • Are shown to cross the placenta equally
        • As noted previously, rare reports of birth defects associated with methimazole exist
        • The minimum dose of ATD that keeps maternal thyroid function around or slightly above the upper limit of normal should be used:
          • To avoid fetal hypothyroidism and fetal goiter:
            • Therefore, frequent monitoring of the mother and the fetus is necessary
        • Mothers may experience:
          • Exacerbation of thyrotoxicosis after delivery
        • Newborns may have:
          • Transient thyroid dysfunction when exposed to ATDs or may develop transient neonatal hyperthyroidism resulting from the passage of TSHR antibodies through the placenta
    • Postpartum propylthiouracil:
      • Is also preferred for nursing mothers:
        • Because less drug appears in breast milk than with methimazole
    • Surgical thyroidectomy:
      • In the second trimester of a pregnant woman with Graves’ disease:
        • Is performed only in the case of uncontrollable hyperthyroidism:
          • That threatens the health of the woman or when ATDs are not tolerated
      • If thyroidectomy is performed, this should be followed by a systematic and a careful follow-up evaluation of the thyroid state of the fetus

#Arrangoiz #ThryoidExpert #ThyroidSurgeon #HeadandNeckSurgeon #SurgicalOncologist #ParathyroidSurgeon #CancerSurgeon #Hyperthyroidism #Goiter #GravesDisease #ToxicNodularGoiter #PlummersDisease #ThyroidNodules #Miami #MountSinaiMedicalCenter

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