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Hyperthyroidism

Sub-section: Thyroid Section: Endocrine

Definition

  • Increased thyroid hormone secretion results in hyper metabolic state

Symptoms

Classic symptoms:

  • Sweating
  • Unintentional weight loss
    • Despite increased appetite
  • Heat intolerance
  • Increased thirst
  • Menstrual disturbance
  • Anxiety
  • Diarrhoea
  • Palpitations
  • Hair loss
  • Sleep disturbance Other symptoms:
  • Bulging eyes
  • Hepatomegaly
  • Nausea, vomiting
  • Loss of libido
  • Hand tremors
  • Severe thyrotoxicosis can cause heart failure, peripheral oedema, arrhythmias (VT of AF)

Causes

  • Primary alterations in the gland (most common)
  • CNS disorders and increased TSH produced thyroid stimulation
  • Other hyperthyroid states
    • Mismanaged thyroxine ingestion
    • Molar pregnancy with increased hCG
    • Thyroid malignancy with overproduction of thyroid hormone
      • Very rare!

Diagnosis of Hyperthyroidism

  • Enlarged smooth thyroid mass with signs/symptoms of hyperthyroidism
  • Elevated T3 and T4
  • With decreased or undetectable TSH
  • I123 radionucleotide scan
    • Graves
      • High uptake throughout entire gland
    • Hyperfunctioning nodule
      • Isolated area of increased uptake
    • Thyroiditis or exogenous thyroxine misuse
      • Low uptake throughout
  • USS or CT of neck to evaluate clinical landmarks prior to surgery
    • Caution with IV contrast if hyperthyroidism untreated

Toxic Nodular Goitre & Toxic Adenoma

  • “Plummer Disease”
  • Overview
    • Toxic adenoma and MNG are the result of focal and/or diffuse hyperplasia of thyroid follicular cells whose functional capacity is independent of regulation by TSH
      • Get increased thyroid hormone production independently of TSH control
    • Symptoms usually milder, and in older people, than Grave’s
    • Thyroid may be diffusely enlarged or associated with retrosternal goitres
  • Initially
    • Mild symptoms
    • fT4/T3 elevated, TSH suppressed
    • Antithyroid antibodies not usually detected
  • Diagnosis
    • Clinical suspicion leads to Radioactive iodine uptake scan with I-123 or I-131 scan
      • Graves disease
        • The uptake will be high and diffuse
      • Toxic nodule
        • The uptake will be focal known as a hot nodule
      • Toxic multinodular goiter
        • Patchy uptake
      • Subacute thyroiditis
        • Low uptake, factitious hyperthyroidism
  • Management
    • Three options
      • Thionamides (i.e. Carbimazole, PTU)
        • Nodules rarely resolve with this
      • RAI therapy
        • RAI preferentially accumulates in the hyper-functioning nodule
        • Surrounding thyroid tissue doesn’t take it up as TSH suppressed
        • Net result is euthyroid state
      • Surgery
        • Lobectomy or Near-Total Thyroidectomy

Grave’s Disease

Definition

  • Autoimmune disease
  • Caused by thyroid-stimulating hormone-receptor antibodies
  • Stimulating growth of the thyroid and overproduction of thyroid hormone

Overview

  • Most common cause of hyperthyroidism

Risk

  • autoimmune disease
  • family hx
    • Women > Men, age 20-40
  • smokers

Aetiology

  • TSH Receptor autoantibodies stimulate TSH-R
  • ? Genetic cause (twin studies)
  • Cross reactivity with the retro-orbital tissue
    • Leads to mucopolysaccharides deposition in the extra ocular fat
    • Inflammation and swelling of occular muscles

Symptoms

  • Triad of symptoms
    • Signs and symptoms of thyrotoxicosis
    • Goitre (may have bruit related to increased vascular flow)
    • Ophthalmopathy + Exophthalmos
      • Ocular symptoms can be severe, including proptosis, periorbital oedema, lid retraction, tearing, blurry vision, eye pain, chemosis (conjunctival swelling), optic nerve damage, blindness, diplopia
      • Retro-orbital tissue has over-expressed TSH-R
      • Severe symptoms rarely seen now with screening assays

Treatment

  • Beta-adrenergeric blocker
  • There are three options to reduce thyroid hormone synthesis. These options are:
  1. Antithyroid drugs which block thyroid hormone synthesis and release
  2. Radioactive iodine (RAI) treatment of the thyroid gland
  3. Total or subtotal thyroidectomy
    • Should be euthyroid
      • If unable to be give Lugols iodine

Management of Hyperthyroidism

  • Initial medical therapy
    • Beta blockers
    • Thionamides
    • Corticosteroids
    • Iodine
  • Long-term/Definitive management
    • Continue Thionamides
      • 1/3 in long term remission after 1-2 yrs treatment
    • RAI
    • Thyroidectomy

Beta-blockers

  • Thyrotoxicosis causes increased adrenergic stimulation
  • Peripheral adrenergic effects can be modulated with beta blockers
  • Propranolol
    • Should be initiated in patients with tachycardia and in elderly
  • Beta blockers don’t inhibit thyroid hormone synthesis
  • Hypermetabolic state can remain or even progress

Thionamides

  • Propylthiouracil (PTU) and Methimazole
    • NB: Carbimazole is completely metabolised to methimazole
  • Function
    • Blocks synthesis of thyroid hormone (inhibit thyroid peroxidase)
    • Inhibit
      • Oxidation of iodide
      • Organification (block binding of iodine to thyroglobulin)
      • Coupling of iodotyrosine molecules to form T3 and T4
    • PTU has additional action of preventing extra-thyroidal conversion of T4 ⇒ T3
    • Methimazole is preferred over PTU
      • Because it can reverse hyperthyroidism more quickly, can be dosed once daily, and has less hepatotoxicity
      • Also has less effect on subsequent RAI therapy
    • PTU preferred in some special circumstances
      • 1st trimester of pregnancy
      • Life-threatening thyroid storm (because also prevents peripheral conversion of T4 ⇒ T3)
      • Previous minor reactions to methimazole, and don’t want RAI or surgery
  • Side effects
    • Main concern is agranulocytosis, but this occurs in less than 1% of cases
    • Other side effects include
      • Rash
      • Arthralgias
      • Neuritis
      • Hepatotoxicity (potentially worse with PTU)
  • Contraindications
    • Previous severe reactions (agranulocytosis, hepatotoxicity)
    • Potentially teratogenic so needs discussion

Corticosteroids

  • Can effectively suppress the pituitary-thyroid axis
  • Also act in the periphery to inhibit the peripheral conversion of T4 to T3
  • Effectively lowers serum T3 levels
    • Allows steroids to be used as a rapid inhibitory agent for hyperthyroid conditions
  • Steroids can also lower serum TSH concentration
  • Due to rapid action, good for
    • Primary treatment of severe, previously untreated, or resistant hyperthyroidism
    • Usually in conjunction with supportive care and the other above-mentioned agents

Iodide

  • Given in large doses in the form of Potassium iodide (SSKI) or Lugol solution
  • After the administration of an antithyroid medication
  • Wolff-Chaikoff Effect
    • Iodide excess causes down-regulation of NaIS symporter
      • Usually transports Iodide into the cell on basolateral membrane
    • Iodide also decreases amount and activity of TPO
      • Less organification
    • Reduces vascularisation of the thyroid
  • Effect transient
    • Normal thyroids get escape after 2-5 days
    • Can be longer in autoimmune/Graves thyroids – up to 10 days
      • NIS no longer down regulated because iodide in thyrocytes so low
    • Organification resumes
  • Can be used to treat hyperactivity of the gland in preparation for surgery
  • Handy for reducing vascularity

RAI Ablation - Therapeutic I-131

  • Indications
    • Considered as Gold standard for Grave’s
    • Also option for Toxic Adenoma and Toxic Multinodular Goitre
  • Ablates the thyroid within 6 to 18 weeks
  • Patients with mild, well-tolerated hyperthyroidism can safely proceed to RAI ablation immediately
  • Patients who are older or severely thyrotoxic may require pretreatment with a thionamide
  • Overall cure rate with RAI is 90%
  • Hypothyroidism develops post rx
    • Needs monitoring of thyroid hormone and TSH levels at regular intervals
  • Most patients are candidates for RAI
  • Contraindications:
    • Pregnancy or lactation
    • Suspicious nodule
  • Advantages
    • Avoidance of surgery and the associated risks of RLN damage, hypoparathyroidism or post-op recurrence
    • Might be more cost-effective over time, but the financial advantage is not as clear if repeated 131I therapy is needed
  • Disadvantages
    • Can exacerbate cardiac arrhythmias, particularly in older patients
    • Possible foetal damage in pregnant women
    • Worsening ophthalmic problems
    • Rare but possibly life-threatening thyroid storm

Thyroidectomy

  • Candidates for Thyroidectomy in the setting of Grave’s disease
    • Large Goitres
    • Pregnant (or may become pregnant within the next 6 months) and breastfeeding mothers
    • Thyroid nodule concerning for malignancy
    • Concomitant hyperparathyroidism needing operative intervention
    • Social factors that would expose family members to RAI
    • Ophthalmopathy may be transiently worsened by RAI therapy
      • Surgery may more rapidly stabilize ophthalmopathy
    • Grave’s disease refractory to RAI
  • Advantages
    • Rapid, effective treatment of thyrotoxicosis without the necessity for long-term antithyroid medications and their potential side effects
  • Amount of residual tissue uncertain
    • Complete ablation of thyroid tissue requires Total Thyroidectomy
      • Associated with the highest rates of Hypoparathyroidism and RLN damage
      • Also has the lowest likelihood of recurrent Grave’s disease
    • Other subtotal resections include near-total thyroidectomy or subtotal thyroidectomy
  • Need to correct hyperthyroidism pre-op otherwise at risk of thyroid storm

Thyroid Storm

  • Thyrotoxicosis must be managed medically before thyroidectomy
    • Tachycardia and other clinical thyrotoxic symptoms must be controlled
    • Circulating levels of thyroid hormone should be in normal range
      • TSH may remain suppressed
  • If not properly treated pre-op, thyroid storm can be life-threatening
    • Rarely encountered if appropriately anticipated
  • Thyroid storm is precipitated by an acute event on top of hyperthyroidism
    • Thyroid or non-thyroidal surgery, trauma, infection, an acute iodine load, parturition
    • Or irregular/under use of anti-thyroid drugs, prolonged uncontrolled Graves etc
  • Treatment of a patient with overt thyroid storm includes
    • Rapid fluid replacement
    • Close monitoring
    • Institution of
      • Antithyroid drugs (prevent synthesis of new thyroid hormones)
      • Beta blockers (counteract peripheral adrenergic stimulation)
      • Iodine solutions (block release of thyroid hormone)
      • Steroids (prevent peripheral conversion of T4 –> T3)
    • In life-threatening circumstances
      • Plasmapheresis or plasma exchange may be effective in reducing T4 and T3
  • Signs and symptoms
    • Severe tachycardia
    • Fever
    • Confusion
    • Vomiting
    • Adrenergic overstimulation to the point of mania and coma

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