Hyperthyroidism

• Assessment of disease severity and underlying cause as determined by history, physical and investigations
• Factors that are important to consider in the choice of treatment:
  • Pregnancy
  • Breastfeeding
  • Planning pregnancy
  • Presence of ophthalmopathy
  • Patient’s age
• Obtain CBC and LFTs before the initiation of antithyroid medication.

Supportive care:

Regardless of etiology, beta blockers may be started as soon as in laboratory confirmed thyrotoxicosis, except in patients with significant history of asthma; where it is contraindicated.

Note: Calcium channel blockers (verapamil and diltiazem) may be used for rate control in patients intolerant to beta blockers, or in whom it is contraindicated.

Management of overt hyperthyroidism due to Graves’ disease:

Patients should be treated with any of the following modalities i.e.

• ¹³¹I therapy ( radioactive iodine)
• Antithyroid drugs (ATDs)
• Surgery

Typically in North America, physicians prefer radioactive iodine, while in Europe and Japan ATD’s/or surgery is preferred. However, the long-term quality of life following any one of the treatment modality is the same.

1. ¹³¹I therapy in the management of Graves’ disease is commenced as shown in the table:
2. Antithyroid drugs in the management of Graves’ disease as shown in the table:
3. Thyroidectomy in the management of Graves’ disease as shown in the table:

Management of thyroid nodule in patients with Graves’ disease:

Thyroid nodule larger than 1-1.5 cm should always be evaluated prior to radioactive iodine therapy in GD. The occurrence of thyroid cancer is approximately ≤2% in GD.

Following steps are recommended on discovery of a thyroid nodule:

• Any nonfunctioning or hypoactive nodule should be considered for fine needle aspiration
• If pathology is suspicious or confirms malignancy, surgery is advised after normalization of thyroid function

Management of thyroid storm associated complication:

Thyroid storm is a life-threatening disorder characterized by involving multiple systems with high mortality if not treated immediately and aggressively.

Criteria for thyroid storm has been defined by Burch- Wartofsky score; is solely based on clinical and physical assessment, which covers the following factors:

• Body temperature
• Central nervous effects
• Hepatic and gastrointestinal symptoms
• Cardiovascular dysfunction

Treatment comprises of:

• Provide immediate IV fluids, oxygen, ventilatory support, and ICU monitoring if needed
• Aggressive cooling with cooling blankets; followed by acetaminophen 15 mg/kg every 4 hrs, orally or rectally is administered in hyperthermia
• Administer antithyroid drugs to block the synthesis of new hormone; methimazole (MMI) 60-80 mg/day, or propylthiouracil (PTU) 500-1000 mg loading dose, then 250 mg every 4 hourly
• Beta-blockers (propranolol 60-80 mg every 4 hrs); it blocks T4 to T3 conversion and also used in patients with congestive cardiac failure (CCF)
• Iodine (SSKI) 5 drops (0.25 ml or 250 mg) PO every 6 hrs, to block thyroid hormone release and new hormone synthesis
• To further block the conversion of T4-T3, and avoid adrenal insufficiency; administer hydrocortisone 300 mg IV loading dose followed by 100 mg every 8 hrs

Management of overt hyperthyroidism due to TMNG or TA:

Treatment is focused to achieve rapid and sustained euthyroid state, there are two main treatment modalities recommended.

• ¹³¹I therapy
• Thyroidectomy

Note: Sometimes lifelong ATDs are the best choice for elderly patients who are in nursing homes, have increased surgical risk and are with limited life expectancy. The treatment requires frequent monitoring (every 3 months).

1. Factors and contraindications influencing the decision to choose particular modality:
2. ¹³¹I therapy in the management of overt hyperthyroidism due to TMNG or TA is commenced as shown in the table:
3. Thyroidectomy to manage TMNG or TA as shown in the table:

Management of subclinical hyperthyroidism:

Subclinical hyperthyroidism is defined by low TSH less than 0.3 mU/L (or undetectable) with normal free T4 estimates and normal total T3 or free T3 estimates.

• Usually, an incidental finding during a routine physical or sometimes signs and symptoms suggest the possibility of hyperthyroidism to the physician
• Once the results are confirmed by repeating the labs, determine the cause of low TSH by excluding other causes of decrease TSH levels such as:
  • Pituitary and hypothalamic disease
  • Euthyroid sick sinus syndrome
  • Drugs e.g. dobutamine, dopamine and steroids
  • Pregnancy: First trimester
  • Factitial TSH suppression e.g. excessive thyroid hormone ingestion
• In elderly TMNG is probably the most common cause of SH
• Patients with GD rather than a TMNG as the cause of SH may be more likely to spontaneously revert
• It is important to diagnose SH; because there is 2.8 folds risk of atrial fibrillation in individuals over the age of 60 yrs, likewise post-menopausal females with SH have increased risk of fractures

Who to Treat according to the age and TSH levels:

• Individuals who are >65 years with TSH <0.1 mU/L should be treated; while 0.1-0.5 mU/L should be considered for therapy
• Individuals aged <65 years with TSH < 0.1 mU/L with heart disease, osteoporosis and hyperthyroid symptoms should be treated while with TSH 0.1-0.5 mU/L with heart disease, menopausal females and hyperthyroid symptoms should consider treatment
• Individuals with aged <65 years and asymptomatic may consider treatment with TSH <0.1 mU/L

Treatment of subclinical hyperthyroidism will depend on its cause. In the case of clinical evidence for underlying Graves’ disease (goiter, ophthalmopathy, positive TSH (receptor antibodies), low-dose thiourea therapy with methimazole could be considered as well as radioiodine.

Management of hyperthyroidism in pregnancy:

• If GD is diagnosed during 1^st trimester of pregnancy, PTU is recommended treatment. Measure TRAb at diagnosis and if elevated repeat at 22-26 weeks of gestation; if thyroidectomy indicated then perform in 2^nd trimester
• If it is diagnosed after 1^st trimester methimazole is recommended; if surgery indicated it should be done in 2^nd trimester
• Diagnosed and treated females prior pregnancy; should switch to PTU from methimazole if pregnancy is confirmed
• Once in remission after stopping ATDs, TRAb monitoring is not required
• If previous treatment with radioiodine or surgery, TRAb are measured initially and if high then repeat 22-26 weeks of gestation

Management of Graves’ ophthalmopathy (GO):

Graves’ ophthalmopathy is defined as an inflammation of the orbital and periorbital soft tissues effecting on the eye; such as pain, itching, chemosis, retraction of the eyelids, and proptosis associated with hyperactivity of thyroid gland.

Approximately 50% of Graves’ hyperthyroidism presents with Graves’ ophthalmopathy, and 5% tend to suffer from severe disease.

Assessment of the disease activity is calculated by a clinical activity score (CAS)**. The score ranges from 0-10 and also predicts response to anti-inflammatory therapy. GO is considered active if the CAS ≥3.

The severity of disease is graded as follows:

• Mild GO: Features of GO, having very mild effects on daily life, insufficient to justify treatment
• Moderate to severe GO: Features having significant effects on daily life but without sight threatening GO; sufficient to justify treatment with immunosuppressive (inactive disease) or surgical intervention (if inactive disease)
• Sight threatening GO: patients with dysthyroid optic neuropathy and/or corneal breakdown, requiring immediate intervention

** Ref: Mourits MP, Koornneef L, Wiersinga WM, et al. Clinical criteria for the assessment of disease activity in Graves’ ophthalmopathy: a novel approach. Br J Ophthalmol. 1989;73:639-644.

Therapeutic approaches to GO include:

• Local measures
• Corticosteroids
• Orbital radiation
• Surgery

Since quality of life may not be significantly improved by these measures, it is important to prevent development and/or progression of GO by identifying and treating of risk factors as follows:

• High pretreatment T₃ and TRAb levels: Achieve euthyroid state as soon as possible
• Smokers: Advised to stop
• Radioiodine- induced hypothyroidism should be corrected

In patients receiving RAI for hyperthyroidism, use of glucocorticosteroids may help prevent the development of GO.

Use of glucocorticoids for prevention of Graves’ ophthalmopathy in patients receiving radioactive iodine (RAI) for Graves’ hyperthyroidism:

Management of drug induced thyrotoxicosis:

More than one mechanism can be induced by a single drug. Medications which may interfere and affect thyroid function to cause hyperthyroidism or thyrotoxicosis involve following mechanisms:

• Iodine induced
• Destructive thyroiditis
• Thyroid autoimmunity

Management of destructive thyroiditis:

Destructive thyroiditis results from the subacute release of preformed thyroid hormone, and is self-limited.

Common causes include:

• Subacute thyroiditis
• Painless thyroiditis (including postpartum thyroiditis, amiodarone-associated destructive thyroiditis, and lithium-associated thyroiditis)
• Acute thyroiditis- referred to suppurative thyroiditis or thyroid abscess, is usually euthyroid, occasionally may present as destructive thyrotoxicosis

a) Patients with mild symptomatic subacute thyroiditis are treated with:

• Beta-blockers
• Non-steroidal anti-inflammatory drugs (NSAIDs)

Note: Non-responders may require steroids for moderate to severe symptoms.

b) Patients with painless thyroiditis treated with:

• Beta-blockers for symptoms of thyrotoxicosis
• ATD has no role because new thyroid hormone synthesis is already low in these patients
• In severe cases, corticosteroids may be used

c) Patients with acute thyroiditis:

• Cause is usually bacterial infection requiring systemic antibiotics
• In the presence of abscess drainage is required
• Beta blocker is given for supportive therapy in case of thyrotoxicosis
• No role of ATD

Management of unusual causes of thyrotoxicosis:

As discussed earlier there are other uncommon causes that may cause hyperthyroidism or thyrotoxicosis.

[/cq_vc_tab_item][cq_vc_tab_item tabtitle=”Medication Dose”]MEDICATIONS:

Radiopharmaceutical, Antithyroid agent

• ➣ Sodium iodide I¹³¹

Mechanism:

• Destroyed the overactive thyroid gland; brings back to normal function
• Small amount is used for diagnostic purpose by measuring the uptake by the thyroid gland
• Larger doses of sodium iodide I¹³¹ are used in certain thyroid cancer to destroy the remaining thyroid tissues after surgery

Doses:

Sodium Iodide I¹³¹

Graves’ disease

• Typically (10-15 mCi) is a sufficient single dose to achieve hypothyroid state

Toxic multinodular goiter (TMNG)

• Activity of radioiodine should be calculated according to the size of the goiter to deliver 150-200 µCi per gram of tissue corrected for 24 hrs RAIU

Toxic thyroid adenoma (TA)

• Approximately 10-20 mCi, or calculated on the bases of nodule size using 150-200 µCi per gram corrected for 24-hour RAIU

Thionamides, Antithyroid agent

• ➣ Propylthiouracil (PTU)
• ➣ Methimazole (MMI)

Mechanism

• Inhibits the conversion of iodide to iodine by binding to thyroid peroxidase
• Thus blocks synthesis of thyroxine and triiodothyronine
• Does not inactivate already formed, circulating and exogenous thyroid hormones

Doses:

Propylthiouracil (PTU)

• 50-150 mg PO TID; once the thyroid functions return to normal; it is maintained 50 mg PO TID

Thyroid storm

• Initial 500-1000 mg, then 250 mg every 4 hourly

Methimazole (MMI)

• Start 10-20 mg/day PO daily; maintenance dose: 5-10 mg once daily

Thyroid storm

• 60-80 mg/day

Drug induced thyrotoxicosis

• 20-40 mg daily

Beta-adrenergic blocking agents

β₁ selectivity

• ➣ Atenolol
• ➣ Metoprolol

Nonselective

• ➣ Nadolol
• ➣ Propranolol

Mechanism:

• Blocks response to beta-adrenergic stimulation
• β₁-selective beta-blocker inhibits β-adrenergic receptors within the myocardium at normal doses
• But can inhibit β-adrenergic receptors within bronchial and vascular smooth muscle at higher doses
• Nonselective beta-blocker inhibits β-adrenergic receptors within the myocardium and within bronchial and vascular smooth muscle
• Decrease heart rate and cardiac output
• Decrease renin release

Doses:

β₁-selective:

Atenolol

• 25-100 mg/day PO once daily or BID; Max 200 mg/day

Esmolol

Thyrotoxicosis/thyroid storm

• IV pump 50-100 mcg/kg/min

Metoprolol

• 25-50 mg PO QID

Nonselective:

Nadolol

• 40-160 mg/day once daily

Propranolol

• Oral: 10-40 mg TID-QID
• Intravenous: 1-3 mg single dose

Thyroid storm

• Oral: 60-80 mg every 4 hrs
• Intravenous: 0.5-1 mg over 10 minutes every 3 hrs

Calcium channel blocking agents (CCBs)

Non-dihydropyridine

• ➣ Diltiazem
• ➣ Verapamil

Mechanisms:

• Blocks the inward movement of calcium by binding to the L-type calcium channels in the heart and in smooth muscle of the peripheral vasculature
• This decreases intracellular calcium leading to a reduction in muscle contraction
• Significant reduction in afterload but not preload

Doses:

Diltiazem

• 120 mg PO every 8 hrs

Verapamil

• 40-80 mg/day PO every 8 hrs

Non-steroidal anti-inflammatory drugs (NSAIDs)

• ➣ Ibuprofen
• ➣ Aspirin

Mechanism:

• Prostaglandins are believed to be a common factor in the production of pain, fever, and inflammation
• These drugs inhibit cyclooxygenase-1 and 2 (COX-1 and 2) enzymes
• This results in decreased formation of prostaglandin precursors

Doses:

Ibuprofen

• 1200 to 3200 mg/day in divided doses

Aspirin

• 2600 mg/day in divided dose

Glucocorticoids

• ➣ Methylprednisolone
• ➣ Prednisone

Mechanism:

• Decreases inflammation and the normal immune response through multiple mechanisms, such as
• Inhibition of macrophage accumulation in inflamed areas
• Decreases permeability of capillary wall and edema formation
• Stabilizes leukocyte lysosomal membranes
• Also suppresses adrenal function in higher doses

Doses:

Hydrocortisone

Thyroid storm

• 300 mg IV loading dose followed by 100 mg every 8 hrs

Prednisone

Subacute thyroiditis

• 40 mg/day PO for 1-2 weeks; followed by gradual taper over 2-4 weeks or longer, depending upon clinical response

Antithyroid agent; Expectorant

• ➣ Saturated solution of potassium iodide (SSKI)

Mechanism:

• Decreases viscosity of mucus by increasing respiratory tract secretions
• Inhibits thyroid hormone synthesis and release
• Also blocks or reduces accumulation of radioactive iodine in the thyroid gland
• Antifungal activity is not known exactly

Doses

Saturated solution of potassium iodide (SSKI)

Thyroidectomy Graves’ disease

• Potassium iodide 5-7 drops (0.25-0.35 mL), or saturated solution of potassium iodide (SSKI); 1-2 drops (0.05-0.1 mL) PO TID mixed in water for 10 days prior to surgery should be given

Thyroid storm:

• 5 drops (0.25 mL or 250 mg) PO every 6 hrs

Note: Do not start until 1 hour after antithyroid drugs[/cq_vc_tab_item][/cq_vc_tabs]