Editing Hyperthyroidism

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

== '''Epidemiology''' ==

* Prevalence 1.2% in USA

== '''Aetiology''' (most commonly those in bold) ==

* '''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''' ==

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

== '''Presentation''' ==

* 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''' ==

* 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''' ==

* 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)''' ==

* 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''' ==

* See [[thyroiditis]]