Hyperthyroidism

Introduction

• In serum T4:T3 ratio is 20:1
• Peripherally T4 is converted to active T3, which is 3-4 times more potent
• Hyperthyroidism refers to excessive circulating hormone levels resulting from thyroid gland hyperfunction
• Thyrotoxicosis refers to excessive circulating hormone originating from any cause (including thyroxine overdose)
• Thyroid storm  refers to extreme manifestation of thyrotoxicosis either due to adrenergic hyperactivity or altered peripheral response to thyroid hormone

Primary hyperthyroidism

• Excessive thyroid gland production of hormone
• Graves disease (85%)
  • IgG induced thyroid cell stimulation of thyroxine release + Graves ophthalmopathy
• Toxic multinodular goitre
• Toxic adenoma

Secondary hyperthyroidism

• Excessive TSH or TRH release
• Thyrotropin-secreting pituitary adenoma
• Thyroiditis
• Hashimoto thyroiditis (in early phase)
• Subacute painful thyroiditis (de Quervain’s)
• Subacute painless thyroiditis
• Radiation thyroiditis

Other causes

• Non-thyroidal disease
  • Ectopic thyroid tissue
  • Metastatic thyroid cancer
  • hCG from hydatidiform mole
• Drug-induced
  • Iodine-induced (Jod-Basedow disease)
  • Amiodarone
  • Thyroxine ingestion
  • Munchausen
  • Ingestion of beef thyroid tissue

Pathophysiology

• During thyroid storm, precipitants such as stress, infection, MI or trauma will multiply the effect of thyroid hormones via freeing from receptor binding sites or increased receptor sensitivity
• Precipitants of thyroid storm
  • Systemic: Infection, trauma, surgery, hyperosmolar coma
  • Endocrine: DKA, thyroid gland palpation
  • Drugs: Withdrawal of thyroxine, iodine delivery, thyroxine ingestion
  • CVS: MI, CVA, PE
  • Obstetrics: Delivery or eclampsia
  • Unknown in 25%

Clinical presentation

• Weakness, fatigue, heat intolerance, diaphoresis, weight loss, anxiety, emotional lability, palpitations, diarrhoea and hair loss
• May have thyrotoxic hypokalaemic periodic paralysis
• Examination
  • Often appear toxic and agitated i.e. like meth
  • Fever may be quite high (>41)
  • AF in 10-35% of cases; Sinus tachycardia in 40%
  • Fine tremor, hyperreflexia, periodic paralysis
  • Lid lag, dry eyes, ophthalmoplegia, exophthalmos (Graves)
  • Thyroid enlargement or bruit
  • Gynaecomastia and telangiectasia
  • Pretibial myxoedema, warm/moist skin, palmar erythema, onycholysis

• Thyroid storm
  • All of above +
  • Fever + CVS(tachycardia/arrhythmia/CCF) + CNS agitation/delirium/coma

Differential diagnosis

• Sepsis
• Cocaine
• Methamphetamine
• Psychosis
• Phaeochromocytoma
• Neuroleptic malignant syndrome
• Serotonin syndrome
• Anticholinergic delirium
• Hyperthermia

Thyroid storm

• Mostly due to uncontrolled Graves’ disease
• Clinical diagnosis (scoring system exists)
• No value of TFT’s is diagnostic
• Classic presentation:
  • Fever, tachycardia, tremor, diarrhoea, nausea and vomiting
  • Can range from apathetic hyperthyroidism (apathy, depression, hyporeflexia and myopathy) to MODS
  • DDx: Sepsis, serotonin syndrome, anticholinergic syndrome, sympathomimetics
  • Fever is rare in uncomplicated thyrotoxicosis
  • Initially systolic hypertension followed by hypotension
  • Atrial and polymorphic VT occur (due to prolonged QTc)
  • Also associated with hypokalaemic periodic paralysis

Investigations

• Primary hyperthyroidism – TSH low, T3/4 high
• Secondary hyperthyroidism – TSH high, T3/4 high
• Subclinical hyperthyroidism – TSH slightly low, T3/4 normal
• T3/4 may not necessarily be elevated during transition from thyrotoxicosis to thyroid storm
• Thyroid antibody titres
  • If Graves is suspected, anti-thyroid peroxidase and anti-thyroglobulin levels can confirm diagnosis
• Other labs
  • Hyperglycaemia is common due to hyperadrenergic state
  • LFT derangement is common due to hyperthyroidism
  • High serum cortisol is usual. If low, suspect coincident adrenal insufficiency
  • Leukocytosis with left shift
  • Hypokalaemia/hypomagnesaemia (particularly in apathetic thyrotoxicosis)

Treatment

• Supportive care
  • Thiamine 300mg IV
  • IV fluids with dextrose to replace fluid losses and glycogen stores
  • Resonium can inhibit enterohepatic circulation of thyroid hormone
  • Consider enhanced elimination of drugs
• Beta-blockers
  • Most important factor in decreasing morbidity and mortality
  • Propranolol inhibits peripheral effects AND inhibits conversion of T4 to T3
  • IV propranolol 0.5mg increments up to 10mg total then 40-120mg PO q6h
  • If underlying heart disease or asthma – consider IV esmolol 500mcg/kg IV then 50-200mcg/kg/min

• Inhibition of thyroid hormone release
  • Propylthiouracil 1200mg PO/NG then 300mg q4h
  • Blocks iodination of tyrosine to inhibit synthesis and inhibits peripheral conversion of T4 to T3
  • Does not prevent release of thyroid hormone
• Inhibition of new thyroid hormone production
  • Lugol’s iodine 30-60 drops daily in divided doses or IV sodium iodide 1g BD
  • Lithium is an alternative if allergic to iodine (300mg q8h)
  • Give 1 hour after PTU
• Prevention of peripheral conversion of T4 to T3
  • Hydrocortisone 100mg IV q6h (also treats relative adrenal insufficiency)
• Look for and treat any underlying precipitant

Prognosis

• Thyroid storm = 10-75% mortality
• Apathetic hyperthyroidism
  • Seen in the elderly with ALOC, cardiac failure and absence of most usual signs of hyperthyroidism
  • Treated the same but easily missed and much higher mortality

Last Updated on October 6, 2021 by Andrew Crofton