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Internal Medicine

Grave’s Disease

Autoimmune hyperthyroid disorder that classically comprises hyperthyroidism with a diffuse goitre, eye disease characterized by inflammation and involvement of intra-orbital structures, dermopathy to as pretibial myxoedema, and rare involvement of the nails, fingers and long bones known as acropachy.

Autoimmune hyperthyroid disorder that classically comprises hyperthyroidism with a diffuse goitre, eye disease characterized by inflammation and involvement of intra-orbital structures, dermopathy to as pretibial myxoedema, and rare involvement of the nails, fingers and long bones known as acropachy.

  • M/C cause of hyperthyroidism (60-80% cases)

History:

Robert James Graves
Robert James Graves, F.R.C.S. (1796 – 1853) was an eminent Irish surgeon after whom Graves’ disease takes its name. He was President of the Royal College of Physicians of Ireland, Fellow of the Royal Society of London and the co-founder of the Dublin Journal of Medical Science. He is also the uncredited inventor of the second-hand on watches.

Originally known as ‘exophthalmic goitre’, Graves’ disease owes its name to the Irish physician, Robert James Graves, who described the condition in 1835. Graves’ disease is a syndrome that classically comprises hyperthyroidism with a diffuse goitre, eye disease characterized by inflammation and involvement of intra-orbital structures, dermopathy referred to as pretibial myxoedema, and rare involvement of the nails, fingers and long bones known as acropachy. Prior to its description by Graves, others including the Greek philosopher Aristotle and the English physician Caleb Parry had noted unique aspects of the condition.


Etiology

Risk factors:

  • Genetic susceptibility
  • Stress
  • Smoking (esp associated with ophthalmopathy)
  • Female sex (sex steroids)
  • Post-partum period
  • Iodine (incl. amiodarone)
  • Lithium

Associated conditions:

  • Autoimmune conditions:
    • Diabetes mellitus type 1
    • Pernicious anaemia
    • Celiac disease
    • Vitiligo
    • Addison disease
    • Alopecia areata
    • Myasthenia gravis
  • Other conditions:
    • Hypokalemic periodic paralysis (particularly in Asian males)
    • Mitral valve prolapse

Presentation

Features of hyperthyroidism

Caused by thyroid-stimulating immunoglobulin (TSI), also known as thyroid-stimulating antibody (TSAb)
Graves disease
The Calgary Guide | http://calgaryguide.ucalgary.ca/

Graves dermopathy:

  • Pretibial myxedema (thyroid dermopathy)
  • Thyroid acropachy (clubbing of fingers & toes + soft-tissue swelling of hands & feet)
  • Patchy vitiligo (some)

Graves’ orbitopathy (ophthalmopathy):

Caused by inflammation, cellular proliferation and increased growth of extraocular muscles and retro-orbital connective and adipose tissues due to the actions of thyroid stimulating antibodies and cytokines released by cytotoxic T lymphocytes (killer cells).
  • Exophthalmos
  • Periorbital oedema
  • Diplopia, blurred vision, reduced colour perception

Complications

Congestive heart failure:

Differences between hyperthyroid and nonhyperthyroid heart failure
Differences between hyperthyroid and nonhyperthyroid heart failure. | Osuna, P. M., Udovcic, M., & Sharma, M. D. (2017). Hyperthyroidism and the Heart. Methodist DeBakey cardiovascular journal, 13(2), 60–63. doi:10.14797/mdcj-13-2-60

Osteoporosis

Thyroid storm:

Most commonly seen in the context of underlying Graves’ hyperthyroidism but can complicate thyrotoxicosis of any aetiology.
  • Occurs when hyperthyroid patient stops treatment/develops infection/has surgery
  • Clinical features represent manifestations of organ decompensation, with fever seen almost universally.
Causes of death in Japanese patients with TS
Causes of death in Japanese patients with TS. CHF, congestive heart failure; DIC, disseminated intravascular coagulation; GI, gastrointestinal; MOF, multiple organ failure. | Akamizu T. (2018). Thyroid Storm: A Japanese Perspective. Thyroid : official journal of the American Thyroid Association, 28(1), 32–40. doi:10.1089/thy.2017.0243

Management

Treatment for Grave's disease
Treatment for Grave’s disease | Ginsberg, J. (2003). Diagnosis and management of Graves’ disease. Canadian Medical Association Journal, [online] 168(5), pp.575-585. Available at: http://www.cmaj.ca/content/168/5/575.full [Accessed 24 May 2017]

Medical management:

  • Beta-adrenergic blocker: Propranolol
  • Antithyroid drugs (ATDs): PTU (Propylthiouracil), methimazole

Definitive management:

  • Radioiodine ablation: C/I Pregnancy & children
  • Subtotal thyroidectomy
Treatment algorithm for Graves' disease
Treatment algorithm for Graves’ disease. | Girgis, C. M., Champion, B. L., & Wall, J. R. (2011). Current concepts in graves’ disease. Therapeutic advances in endocrinology and metabolism, 2(3), 135–144. doi:10.1177/2042018811408488

Prognosis

Factors associated with either a higher likelihood of immunological remission following a course of ATDs or with increased resistance to RAI
Factors associated with either a higher likelihood of immunological remission following a course of ATDs or with increased resistance to RAI | Ginsberg, J. (2003). Diagnosis and management of Graves’ disease. Canadian Medical Association Journal, [online] 168(5), pp.575-585. Available at: http://www.cmaj.ca/content/168/5/575.full [Accessed 24 May 2017]

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