Graves' disease

long term

medium

Hyperthyroidism causes bone mineral loss, and the degree of bone loss is related to the duration of untreated hyperthyroidism.[174] This would need to be prolonged to cause definite osteoporosis.

Osteoporosis

variable

medium

Graves’ orbitopathy occurs in around 25% of cases and is usually mild.[1] It is important to assess and classify the activity and severity of orbitopathy to help guide treatment.[58][155] Guidelines providing recommendations for initial assessment and management have been published.[58][155][156]

In children, orbitopathy is frequently mild and will often regress once euthyroid status is restored. A 'wait and see' strategy may be appropriate.

Risk factors should be addressed to prevent progression of Graves’ orbitopathy, including ensuring adequate control of thyroid dysfunction and supporting patients who smoke to stop.[58]

Mildly active orbitopathy is managed with lubricant eye drops and ointments, or sunglasses for surface symptoms, or prisms for diplopia.[155] Some patients with mild Graves’ orbitopathy of short duration may benefit from a 6-month course of selenium supplements.[157][158]

Patients with active moderate-to-severe orbitopathy should be managed by an expert multidisciplinary team consisting of ophthalmologists and endocrinologists; first-line treatment is intravenous corticosteroid pulse-dose therapy (e.g., methylprednisolone).[155][159][160] Use of other agents, including a combination of a corticosteroid plus mycophenolate, or targeted immunotherapy (e.g., teprotumumab) is recommended in some countries.[58][155][161][162][163][164][165][166] Adverse effects associated with teprotumumab include inflammatory bowel disease, otological symptoms including hearing loss, and hyperglycaemia.[165][167] Monoclonal antibody therapies (e.g., rituximab and tocilizumab) have shown mixed results and are considered second- or third-line options.[155][168][169][170]

Orbital irradiation, with or without corticosteroids, is also used for moderate-to-severe active orbitopathy; there is limited evidence to suggest that orbital radiation may prevent compressive optic neuropathy.[171][172][173] Rehabilitative surgery has an important role in moderate-to-severe orbitopathy when the disease is stable and inactive.

variable

medium

Atrial fibrillation may occur after the age of 40 and could be the presenting symptom even in subclinical hyperthyroidism. Atrial fibrillation may result in thromboembolic complications and stroke.[2]

Acute atrial fibrillation

variable

medium

Congestive or high-output failure can occur in severe cases, especially in older patients.[2]

Acute exacerbation of congestive heart failure

variable

low

Sight-threatening orbitopathy usually occurs in the first year after diagnosis of hyperthyroidism, but it may occur prior to diagnosis of hyperthyroidism or years later in some cases. These complications are rare and include corneal ulcers and optic neuropathy.

Optic neuropathy should be treated urgently with very high doses of intravenous corticosteroids.[58] Patients who respond well to initial treatment with corticosteroids can switch to intravenous corticosteroid pulse-dose therapy. Surgical orbital decompression is recommended if corticosteroids fail.[58][155][175] Rehabilitative surgery (to reduce proptosis and for correction of diplopia) and eyelid surgery may also be needed once orbitopathy is stable and inactive.[10][118][176]

Sight-threatening features (e.g., optic neuropathy, corneal breakdown) are an occasional complication in children and may require immediate surgical intervention. Multidisciplinary involvement (including paediatric endocrinology and ophthalmology) is required.[177][Figure caption and citation for the preceding image starts]: Orbitopathy and elephantiasisCourtesy of Dr Vahab Fatourechi [Citation ends]. com.bmj.content.model.Caption@58127743

variable

low

Dermopathy usually occurs 1 year after orbitopathy. Dermopathy (pretibial myxoedema) occurs in 10% to 20% of patients with moderate-to-severe orbitopathy. It is usually mild and resolves spontaneously or with local corticosteroid therapy.[18][178] A dermatologist should be consulted if dermopathy is persistent, extensive, and/or troublesome. In severe cases with associated moderate-to-severe orbitopathy, systemic corticosteroid therapy may be beneficial, although long-term evidence is lacking.[18] There are currently no treatments for acropachy. Elephantiasis occurs in 5% of dermopathy cases and is difficult to treat. Elephantiasis may create cosmetic and functional problems.[18][59][179][Figure caption and citation for the preceding image starts]: ElephantiasisCourtesy of Dr Vahab Fatourechi [Citation ends]. com.bmj.content.model.Caption@66ccd1ed

Complications

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