Thyrotoxicosis

  • Aetiology
    • Graves’ - most common
  • Common
    • Toxic multinodular goitre - 5%
      • Toxic solitary thyroid adenoma
  • Uncommon
    • Acute Thyroiditis
    • viral - de Quervain's
      • acute inlflmn, pyrexia, malaise, neck+thyroid pain, inc ESR+plasma viscosity - aspirin; prednisolone if bad long term
    • autoimmune
    • post-irradiation
    • post-partum
    • Gestational - hCG stim'd
    • Exogenous iodine
    • Drugs, eg. Amiodarone, Thyroxine
    • Thyrotoxicosis factitia - secret T 4consumption
  • Rare
    • TSH-secreting pituitary adenoma (1% of hyperthyroidism)
    • Metatstatic differentiated thyroid carcinoma
    • hCG producing tumours
    • Hyperfunctioning ovarian teratoma - struma ovarii
Clinical Features
  • Older present: Tachycardia ± AF ± HF
  • Lid lag
  • Periorbital oedema
  • Goitre, bruit
  • Diarrhoea
  • Weight loss (can also have paradoxical weight gain)
  • Increase appetite
  • Hyperkinesia
  • Sweating
  • Heat intolerance
  • Palpitations
  • Tremor
  • Irritability
  • Oligomenorrhoea
  • Infertility
  • Psychosis, panic
  • Lost libido
  • Tall kids
  • Grave's only
  • eye signs
  • pretibial myoedema
  • Grave's demopathy
  • thyroid acropachy
  • extreme cases; soft tissue swelling, finger clubbing and periosteal reaction of the extremities.
Graves’ Disease
Autoimmune disease in which the thyroid is overactive due to TSH-stimulating auto-antibodies
  • Hashimotos and Grave’s are two ends of the same spectrum, can even co-exist.
    • Epidemiology
      • 1% of the population
  • peak incidence 30-50y
    • F>M
      • Most common cause of endogenous hyperthyroidism
  • Aetiology
    • Unknown
      • Genetic predisposition: HLA-DR3, -B8, DR2
  • CTLA-4 polymorphisms
    • Potentially environmental factors: viral or bacterial infection
  • Pathogenesis
    • Breakdown of self-tolerance to thyroid autoantigens, esp. TSH R
      • TSH stimulating auto-antibodies activate TSH-R (=> cAmp) => increased release of thyroid hormones
  • Thyroid growth stimulating Ig => thyroid proliferation => Hyperplasia of thyroid follicular epithelium
    • TSH inhibiting Ig => bind free TSH, not unusual to have both inhibition and activation => possible to swing between hyper and hypothyroidism
      • Unregulated secretion of thyroid hormones
  • Exopthalmos
    • Infiltration of retroorbital space by mononuclear cells
      • inflammation and oedema of extraocular muscles
        • accumulation of ECM
  • increased numbers of adipocytes
    • Macroscopic Features
      • Diffuse enlargement of the thyroid
  • Firm red cut surface
    • Potentially nodular
  • Microscopic Features
    • Hyperplastic follicular epithelium with small papillae projecting into follicular lumen
      • Little colloid, pale
  • Lymphoid infiltrate with or without germinal centres
    • Clinical Features
      • Triad
        • Thyrotoxicosis
  • Opthalmopathy (40% of patients)
    • Dermopathy, e.g. pretibial myxedema
      • Diffuse goitre
  • Bruit of the thyroid gland due to increased blood supply
    • Lid lag
      • Complications – thyroid storm
        • Hyperpyrexia
  • Dehydration
    • Cardiac failure
  • Investigations
    • Radioactive iodine: diffuse increased
      • serum TSH <0.05 mU/L (v rare: hyperTSH)
      • raised serum / free T4
      • raised free T3 more sens for rare 'T3 toxicosis' (not Grave's!)
  • Prognosis
    • Good with treatment but remission and relapse common
  • Increased incidence of other autoimmune diseases: SLE, T1DM, Addison’s
  • Treatment
    • Medical
      • B-blockers for rapid symptom control
  • Titration of carbimazole (reduces T3 and T4 by inhibiting thyroid peroxidase)
    • Block and replace – carbimazole and thyroxine
      • T4 t½ 7 days so observable benefit after 10-20 days
  • Carbimazole can cause agranulocytosis => sepsis (is also immunosuppressive)
    • Propylthiouracil PTU inhibits thyroid peroxidase that generates I0 from Iodine in the colloid
      • Usually for 18m-2y
  • Surgical: thyroidectomy
    • Radioiodine
  • Long term: many patients (post surgery, radioiodine tx) become hypothyroid
Robbins Basic Pathology, Robbins Pathologic Basis of Disease, Robbins Review of Pathology (MCQs - very path-y), Robbins Flash Cards, Baby Robbins, Robbins Atlas - some exact same images come up in the exam, 100 Cases in ClinicalPathology - possibly the best Qbank for the practical