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Hyperthyroidism

From Surgopaedia

The clinical state of elevated thyroid hormone action in tissues, usually due to inappropriately high constitutive secretion of thyroid hormone from the thyroid

Epidemiology

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  • Prevalence 1.2% in USA

Aetiology (most commonly those in bold)

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  • Associated with normal or high RAI uptake (indicates de novo synthesis of hormone, so can be treated with a thionamide (i.e. carbimazole))
    • Graves disease
    • TMNG
    • Toxic adenoma
    • Trophoblastic disease
    • TSH-producing pituitary adenoma
    • Thyroid hormone resistance
  • Associated with no or minimal RAI uptake (indicates either inflammation and destruction of thyroid tissue with release of pre-formed hormone into the circulation, or an extra-thyroidal source of thyroid hormone; so thionamides won't help in these disorders)
    • Thyroiditis
      • Painless thyroiditis (silent or lymphocytic)
      • Amiodarone-induced thyroiditis
      • Subacute granulomatous thyroiditis
      • Acute thyroiditis
      • Palpation thyroiditis
    • Iatrogenic thyrotoxicosis - excessive, intentional replacement, or factitious
    • Struma ovarii
    • Follicular thyroid cancer metastases (ectopic)

Pathophysiology

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  • Divided into two groups
    • Overt - supressed TSH, elevated T3/T4
    • Subclinical - supressed TSH, normal T3/T4. Likely to be milder in presentation.

Presentation

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  • Tremor
  • Heat intolerance
  • Tachycardia/AF
  • Increased GIT motility
  • Muscle weakness
  • Anxiety
  • Embolic events
  • Rarely, severe cardiovascular complications
    • Cardiomyopathy
    • CCF
    • Cardiovascular collapse
    • Death
  • Thyroid storm
    • Rare life-threatening complication of hyperthyroidism - severe clinical manifestations
    • Can be precipitated by an acute event (cessation medications, infection, trauma, acute iodine load)
    • Tachycardia >140, febrile, agitation, delirium, progressing to psychosis, stupor, coma
    • Altered mentation is the main differentiating factor from 'normal' hyperthyroidism
    • Treat with ICU, beta blockers, medical treatment of cause of hyperthyroidism, glucocorticoids to reduce T4-T3 conversion, and treat the cause of the storm
    • The main indication for surgery is patients who had a severe reaction to medical management of hyperthyroidism, had to stop that agent, then get a thyroid storm, with no other treatment options available. Otherwise, it is really an endocrinology emergency.


Graves disease

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  • Epidemiology
    • Most common cause of hyperthyroidism
  • Risk factors
    • Female (8:1)
    • Typically presents between 20-40yo
    • Post-partum is a vulnerable period
  • Pathophysiology
    • Autoimmune systemic disorder
    • Caused by thyrotropin receptor antibody (TRAb) binding to and stimulating the TSH receptor, resulting in excessive synthesis and secretion of thyroid hormone
    • Associated with Hashimoto thyroiditis, SLE, RA, pernicious anaemia and Addison disease
  • Presentation
    • Gland feels diffusely and symmetrically enlarged and firm
    • Graves orbitopathy (25-30% of patients)
      • Associated with smoking, high levels of antibodies. RAI can worsen eye disease.
      • Pathophysiology
        • TSHRs (TSH receptors) are also found on orbital fibroblasts and adipocytes.
        • These can be activated by TRAb, which causes local inflammation, fibroblast proliferation, adipogenesis, and mucopolysaccharide deposition
        • This creates an overall higher volume of extra-orbital connective tissue and orbital connective tissue, leading to pressure within the orbit and displacement of the eyeball forward
        • That causes extra-ocular muscle dysfunction and impaired venous drainage, and worsens the swelling
      • Presentation
        • Ocular myopathy - diplopia, exophthalmos - due to the muscle fibrosis
        • Congestive ophthalmopathy - watery gritty eyes, periorbital oedema, conjunctival injection/chemosis
        • Can cause vision loss from corneal lesions or optic nerve compression
        • Loss of colour vision is an ophthalmologic emergency
      • Mild eye disease may resolve spontaneously, but mod-severe disease won't (only about 30% improve)
      • Should treat hyperthyroidism with thionamides (carbimazole/PTU) or surgery, not RAI (can cause worsening)
        • RAI is ok in mild eye disease
      • Treat eyes with glucocorticoids, or if proptosis/soft tissue involvement/diplopia are present, treat with teprotumumab if available (extremely expensive and not available yet in Australia as far as I know)
      • Total thyroidectomy is a good option
      • Local measures - artificial tears, raising head of bed at night (theoretically reduces orbital congestion), need to stop smoking
    • Skin manifestations - pretibial myxoedema and acropachy
  • Workup
    • TSH and free T4/T3
    • TRAb (diagnostic)
    • Technetium-99-pertechnetate scintigraphy can differentiate from toxic nodular disease based on uptake pattern
  • Treatment - three options
    • Antithyroid drugs
      • Methimazole (carbimazole) daily
        • Start on carbimazole 5mg daily and titrate upwards
        • Direct inhibition of TPO effect
        • Rapid clinical onset, but TSH rise may take weeks
        • Decreases thyroid hormone synthesis and control hyperthyroidism in 90% of patients within several weeks
        • Intent is to induce remission
        • Relapse occurs after stopping the drug in most patients
        • Side effects - bone marrow suppression - agranulocytosis/neutropaenia
        • Commonly used for pre-op preparation, or for temporary management of pregnant patients with Graves' disease
        • Propylthiouracil (PTU) is an alternative, mostly only used during first trimester and in thyrotoxic crisis now
          • Start at 50mg TDS in most cases
          • Inhibits TPO but also blocks conversion of T4 to T3 in target tissues
          • Risks agranulocytosis and fulminant liver failure
        • Long-term treatment with either is safe
      • Radioactive iodine (131-I)
        • Works in >90% with a single dose
        • Treatment of choice for most patients
        • RAI is taken up into cells by sodium iodide symporter - first step in thyroid hormone synthesis - and then causes cell death via emission of short-path length beta particles
        • Commonly become hypothyroid and have to take replacement afterwards
        • Side effects - neck pain from radiation thyroiditis (mild), sialadenitis, xerostomia, temporary worsening of thyrotoxicosis, and sometimes worsening of Graves' ophthalmopathy, which may be ameliorated with glucocorticoids
        • Small increased risk of secondary malignancy - at 30 years, the risk was 12.5% vs 10.2% in controls. Doses <100mCu are low-risk.
        • Contraindicated during pregnancy or lactating mothers, and used in relatively few adolescents/children
    • Surgery
      • Bilateral near-total or total thyroidectomy is virtually 100% effective
      • Will need levothyroxine
      • Resolves any questions of nodules/cancer
      • Safe in many pregnant women/breastfeeding
      • Pre-op preparation required
        • Goals: aim T3 ideally <15 or at least <20. TSH does not need to be normal, and it takes an extra few weeks to become normal.
        • Antithyroid drugs (methimazole) given for 3-6 weeks beforehand
        • Beta blockers can help control thyrotoxicosis/tachycardia if it still present.
        • Lugol's solution was used in the past for this - 5-7 drops TDS up to 10 days before surgery - reduces thyroid hormone secretion and decreases vascularity of the gland and surgical blood loss. Risk of hyperthyroidism via Jod-Basetow effect if continued longer than this.
        • Glucocorticoids can be given for refractory cases
        • Risk of thyroid storm - see above
        • Test for hypocalcaemia and give calcium/vitamin D if low
        • Consider ICU post-op
  • Note situations where surgery is the best options:
    • Patient factors
      • Need or desire for rapid reversal
      • Pregnancy or post-partum or wants to become pregnant
    • Disease factors
      • Active Graves ophthalmopathy
      • Periodic paralysis
      • Failure or contraindications to other options - fluctuating TSH or ongoing high dose requirement
    • Other indications for surgery
      • Known or suspected thyroid malignancy
      • One or more large thyroid nodules
      • Co-existing primary hyperparathyroidism requiring surgery
      • Large goitres with compressive symptoms

Toxic single adenoma

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  • Single benign monoclonal thyroid tumours that autonomously oversecrete thyroid hormone, existing within an otherwise normal or non-toxic nodular thyroid gland
  • Risk factors
    • Mild female predominance
    • Median age 50-60yo
  • Pathophysiology
    • Constitutively active mutations in the TSH receptor gene
    • Usually >3cm
    • Evolves through a course of subclinical to clinical hyperthyroidism
    • Virtually never malignant
  • Workup
    • As per Toxic MNG
  • Treatment
    • Antithyroid drugs - seldom if ever chosen, as recurrence is guaranteed, and remission does not occur
    • Radioactive iodine - effective, and euthyroidism is re-established in 80% with a single dose. Not ok in pregnancy/lactation. Can have recurrence.
    • Surgery - virtually 100% effective
      • Can be unilateral thyroidectomy, unless bilateral suspicious nodules and/or symptomatic goitre
    • Percutaneous ablative techniques
      • Either ethanol or RFA
      • Requires much further study before being accepted - not very well understood currently with decent complication rate

Toxic MNG (Plummer's Disease)

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  • An enlarged nodular thyroid containing one or more autonomously functioning nodules leading to a state of hyperthyroidism
    • Second most common cause of hyperthyroidism
  • Risk factors
    • Older age - uncommon <50yo
    • Iodine deficient region
    • Female (5:1)
  • Pathophysiology
    • Autonomously functioning nodules occur after a mutation in TSH receptor gene leads to constitutive synthesis and secretion of thyroid hormones
    • Rarely malignant, do not generally require biopsy
  • Presentation
    • Develops slowly from subclinical hyperthyroidism into thyrotoxicosis
  • Workup
    • TFTs and thyroid Abs
    • Exclude Graves and autoimmune thyroiditis
    • Nuclear scintigraphy - first-line imaging
      • Identifies location and distribution of autonomously functioning nodules and/or regions
    • USS
      • Also useful to characterise any nodules that may require biopsy
  • Management - three options
    • Antithyroid drugs - virtually never used for definitive treatment, but can help as pre-op preparation
      • Use methimazole before both RAI and surgery, with or without beta blockade
      • Start on carbimazole 5mg daily
    • Radioactive iodine - effective, but generally takes about 6 months to work. Especially good in settings of high operative risk. Second dose necessary in about 25%.
      • Most common option in USA
      • Need higher dose than in Graves disease because of lower uptake
    • Surgery - prompt, permanent cessation of hyperthyroidism (within a month). Removal of Goitre. Treatment of any nodules/malignancy. Will need thyroxine. Can be more difficult operation than normal thyroidectomy due to size of goitre. Need near-total or total thyroidectomy.

Amiodarone-induced thyrotoxicosis

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