Editing Hyperthyroidism (section)

== '''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