Thyroid Disease

Physiology

Complex diagram detailing tyrosine and iodine metabolism

 

Hormone

Secretion
mg/day

Level
mg/dl

t 1/2

Onset

Max effect

Biological Effect

T 4

80-100

4.5-10

7 dys

3 dys

10 dys

T 4 Exerts its effect by conversion to T 3 . This is dependent on nutritional, illness and hormonal factors unrelated to thyroid status

T 3

10

0.2

1 dy

6 hrs

2 dys

rT 3

35

0

Biologically inactive

T 3 becomes cellular protein bound to increase nuclear transcription of genes leading to
  1. Increased Basal Metabolic Rate with Increased oxygen consumption,
  2. Increased respiratory rate and tidal volume
  3. Increased heat production.
  4. Increased blood supply with vasodilatation
  5. Increased blood volume
  6. Increased cardiac output and heart rate
  7. Increased protein catabolism leading to creatinuria, muscle weakness, osteoporosis and increasing calcium and phosphate levels. 
  8. Increased number of beta receptors and decreased number of cardiac cholinergic receptors.
  9. Increased and uncoupled mentation.
 

Thyrotoxicosis

Myxoedema

Causes

Graves disease (TSI - ?LATS), Paranodular graves, Multinodular goitre, Toxic nodule, Hypersecretion of TSH, Excessive replacement - iatrogenic, intentional.

Idiopathic, Iatrogenic - Surgery, Radioactive iodine. Antithyroid R x. Iodine deficiency. Hashimotos, DeQuivaines, Reidals thyroiditis

Drugs - Li, cholestryramine, SNP, Amiodarone, phenytoin, phenobarb

Symptoms

Fatigue, Weight loss, Increased appetite, Heat intolerance, Palpitations, sweating, anxiety, irritability, diarrhoea, Oligo/Amenorrhoea

Weight gain, Anorexia, Cold intolerance, fatigue, constipation, Menorrhagia, Dry skin, Hair loss

Signs General

Thin, anxious pt, warm moist skin, palmar erythema, telangectasia, fine soft skin, hair, nails, clubbing (acropachy), pretibial myxoedema

Hypothermia, Puffy face, Periorbital odema, large tongue, coarse dry skin, carotenaemia, hoarseness, deafness, slow mentation, confusion,
coarse sparse hair, loss of outer third of eyebrows

Cardiac

SVT with atrial fibrillation

Resting pulse > 90bpm

High output failure

Sinus bradycardia, small complexes,

CCF pleural and pericardial effusions

Peripheral

Fine static tremor, Proximal myopathy

Carpal tunnel syn. Pendular reflexes

Eye

Lid retraction and lag, Exopthalmos

 

Other

Osteoporosis

Megaloblastic anaemia

Peri-operative management

Physiologically euthyroid state

Localisation of suspected hormone secreting tumours with documentation of hormonal excess or deficiency

 

 

T 4

TSH

Thyrotoxicosis

1 o Hypothryroid

2 o Hypothyroid

Pregnancy

N

 

Thyrotoxicosis

Medical normalisation of hormonal status

  1. 2-6 weeks of stabilisation on a thionamide antithyroid agent.

    They inhibit oxidation and organification of iodide and the coupling of iodotyrosines. In high doses can inhibit the peripheral conversion of T4 to T3 Carbimazole (Neomercazole) converted to Methimazole (Trapazole) 5mg tablet 4-14hour half life. 20-60mg/day in 1-3 doses Propylthiouracil 50mg tablet 1-2hour half life. 300-1200mg/day in 4 doses.

  2. Adrenergic antagonists to control the excessive autonomic stimulation.

    Propanolol (Inderal) 10mg tablet. 3-6 hour half life. 40-240mg/day in 4 doses Nadolol 16-24 hour half life (Drug Of Choice - Hammilton, Forrest, Gunn - due to the long half life) Esmolol 50 microg/Kg ivi loading dose then 25-300 microg/Kg/min ivi until HR < 90bpm and hypertension controlled

  3. Iodine acutely inhibits the release of T4 and transiently inhibits organification (Wolff - Chaikoff effect).

    Iodine was used to decrease the vasularity and the size of the gland but it is not used by surgeons any more as it is associated with release of stored hormone causing severe storm (Reed, Bradley).

Assessment and treatment of end organ disease

Cardiovascular

Resting heart rate is excellent guide to when to perform surgery.

ECG for arrhythmias, ischaemia and digoxin changes (Important in apathetic mxyoedema)

ECHO for Left Ventricular function as prolonged exposure to excess catecholamine secretion will result in a cardiomyopathy

Respiratory

Careful history for symptoms of tracheal compression - Treat as for anterior mediastinal mass.  Careful examination for ease of intubation

  1. Chest X ray - Position and compression of trachea
  2. Flow volume loops lying and sitting
  3. CT scan of the Trachea
  4. ENT indirect laryngoscopy for documentation of recurrent laryngeal nerve involvement

Metabolic

  1. Haemoglobin - Anaemia contributes to cardiac decompensation.
  2. Platelets
  3. Coagulation status
  4. Urea and electrolytes

Mxyoedema

Medical normalisation of hormonal status

Assessment and treatment of end organ disease

Cardiovascular

Depression of the myocardial function is due to protein and mucopolysaccharide deposition within the myocardium and depression of intracellular myocardial metobolism. The cardiac output is decrease because of a bradycardia and a decreased stroke volume, decreased blood volume and baroreceptor dysfunction. Pericardial effusions may accompany the hypothyroidism.

  1. ECG - Will show small complexes which do not distinguish between poor myocardial contraction and pericardial effusion
  2. ECHO - to assess LV function and the degree of myocardial compromise due to a pericardial effusion.

Respiratory

There is always some degree of hypoventilation with the ventilatory response to hypoxia and hypercarbia being significantly impaired. These patients are increadibly sensitive to all sedative drugs with the possibility of precipitating respiratory failure.

  1. Chest X Ray for evidence of aspiration
  2. Arterial blood gas for baseline oxygenation and ventilation

Hepatic and Renal function

Thermoregulation

These patients are very prone to hypothermia because of lowered metabolic rate and lowered heat production.

Intra-operative management

All necessary drugs available especially for thyroid storm (Lugol's, PTU, cortisol, Esmolol, Digoxin, Verapamil, Lasix) or myxoedema coma.

Check all machines and anaesthetic equipment

Monitoring

  1. Temperature for hypo or hyperthermia
  2. ECG for arryhthmias and ischaemia
  3. Non Invasive Blood pressure
  4. Peripheral oxygen saturation
  5. End tidal carbon dioxide
  6. Muscle relaxation
  7. Blood glucose
  8. Central venous pressure and arterial line are indicated in patients with decreased cardiac reserve

Anaesthetic aims

Positioning

  1. Limited access to the patient mandates careful attention to good intravenous access
  2. Excellent eye protection especially with proptosis and exopthalmos
  3. Careful padding around an inflatable shoulder support. This allows the support to be deflated at the end of the surgery, allowing good surgical closure.
  4. 30 o head up tilt int he neutral position with elevation of the legs minimise venous congestion and surgical bleeding. This can be associated with venous air embolism

Airway management

Post operative management

  1. Recurrent Laryngeal Nerve paralysis or tracheomalacia may result in airway obstruction needing emergency re-intubation or tracheostomy
  2. Haematoma formation may result in associated laryngeal oedema and or spasm causing respiratory distress
  3. Hypocalcaemia following parathyroid removal may be transient and asymptomatic or may present as stridor due to laryngospasm.
  4. Lymphatic duct damage,
  5. Damage to the cervical sympathetic trunk, phrenic nerve or spinal accessory nerve.
  6. Thyroid storm
  1. Thionamide antithyroid drugs are continued for 6-7 days post surgery
  2. Adrenergic blockade is continued for 7-10 days post surgery
  3. T4 is re-instituted when the patient can take orally
  1. Morphine patient controlled analgesia
  2. Pethidine 1-2 mg/kg intramuscularly every 4 hours
  3. Cyclizine (Valoid) 50mg intramusculary 6 hourly

Thyroid Storm

Definition
Thyroid storm is a life threatening, abrupt exacerbation of hyperthyroidism caused by the sudden excessive release of thyroid gland hormones into the circulation. It can be precipitated by surgical stress, but is more common 6-18 hours post operatively. The highest risk is in patients undergoing emergency surgery.

Diagnosis

  1. High degree of clinical suspicion.
    1. No diagnostic laboratory tests
    2. Rapid elevation in core temperature >41oC - generally regarded as essential to the diagnosis
    3. Abrupt onset of sinus tachycardia (often >160 beats per minutes)
    4. Arrhythmias - atrial fibrillation, premature ventricular contractions and ventricular fibrillation
    5. Sudden onset of cardiac failure with profound hypotension and pulmonary oedema
    6. Mental changes ranging from agitation to psychosis and coma
    7. Patient appearance (enlarge thyroid; exopthalmos)
    8. Electrolyte abnormalities
      1. Hypercalcaemia
      2. Hypokalaemia
  2. Differentiate from malignant hyperthermia
    1. Metabolic acidosis less severe
    2. Rhabdomyolosis less severe
    3. Hypoxaemia less severe
  3. Other differential diagnoses
    1. Sepsis
    2. Phaeochromocytoma
    3. Acute drug intoxication - cocaine and amphetamines
    4. Central anticholinergic syndrome
    5. Delirium tremens
    6. Neuroleptic malignant syndrome

Treatment

As with all flow diagrams the following is presented step by step. Help should be sent for immediately and as many steps as possible should be performed simultaneously

  1. Provision of supportive measures
    1. Ensure oxygenation and ventilation
    2. Establish invasive cardiovascular monitoring - Central Venous Pressure, arterial line
    3. Optimise haemodynamics
      1. Furosemide and morphine for the treatment of pulmonary oedema
      2. Monitored fluid supplementation against the central venous pressure
      3. Inotropic support under ECG monitoring
    4. Collect blood for thyroid hormone and TSH assays prior to treatment
    5. Identification and treatment of precipitating cause, usually infections
    6. Actively cool the patient
      1. Avoid Acetylsalicylate (displaces T4 from TBG)
      2. Iced saline infusion and lavage body cavities with iced saline (PNGT and rectal catheter irrigation)
      3. Place ice over the neck, in the axilla and in the groin. To avoid causing an ice burn it is best to use an ice slurry.
  2. Additional support
    1. Maintain high caloric intake with dextrose containing fluids
    2. Monitor and treat electrolyte abnormalities
    3. Vitamin supplementation - especially thiamine infusions (100mg per 24 hour period)
  3. Prevention of thyroid hormone effects
    1. Start intravenous infusion of a beta blocker.
      1. Propanolol (0.05-0.1mg/Kg/6hourly) Start with small doses (0.5mg) to avoid precipitating cardiac failure, Maintain the heart rate at an acceptable level Antagonises the effect of thyroid hormones and the hypersensitivity to the action of the catecholamines. Inhibits the peripheral conversion of T4 to T3
      2. Esmolol (5-300 microg/Kg/min) Does not prevent the conversion of T4 to T3 Advantageous in reactive airways disease and cardiac failure
      3. Reserpine 2.5-5.0mg IMI 4-6 hourly should be reserved for propanolol resistant storm
    2. Intravenous steroids
      1. Cortisol 100-200mg 8 hourly
      2. Dexamethasone 5mg 12 hourly Inhibits the conversion of T4 to T3

      Correction concommitant glucocorticoid deficiency

    3. Specific antithyroid drugs
      1. Propylthiouracil 1g PNGT followed by 200mg 6 hourly PNGT Inhibits the conversion of T4 to T3 (Effect apparent within 24 hours) Prevents the release of further thyroid hormones (Effect apparent within 24 hours) Prevents the iodination and oxidative coupling, preventing the formation of further thyroid hormones (Requires several days for effect)
      2. Methimazole 100mg PNGT followed by 20mg 12 hourly PNGT Not well absorbed It does not inhibit peripheral conversion of T4
      3. Iodide - 30mg (5drops) of lugol's iodine one hour after propylthiouracil. Repeated eight hourly until the patient is stable Prevents the release of T4 by TSH (Effect apparent within 24 hours) Transiently inhibits iodine organification and prevents the formation of further thyroid hormones (Wolff-Chaikoff effect)
      4. Lithium 500-1500mg daily Blocks thyroid hormone release Plasma exchange Reserved for refractory cases, following 24-48hours of aggressive conventional therapy.
    4. Dantrolene 2.5mg/kg starting dose Symptomatic improvement when used to treat "MHS"

Mxyoedemic Coma

Definition

A rare complication of hypothyroidism manifesting as profound lethargy or coma, spontaneous hypothermia (less than 35oC), hypoventilation and congestive cardiac failure

Diagnosis

  1. Features of chronic hypothyroidism are usually present Puffy face, large tongue, coarse dry skin, carotenaemia, coarse sparse hair
  2. Additional features often present Seizures, stupor, coma
  3. Hypoventilation with airway obstruction
  4. Psychotic behaviour
  5. Hypothermia
  6. Hypotension
  7. Bradycardia
  8. Markedly delayed tendon reflexes
  9. Laboratory findings
    1. Hyponatraemia
    2. Hypoglycaemia
    3. Acidosis
    4. Elevated TSH with low T4

Treatment

  1. Ensure oxygenation and ventilation
  2. Establish invasive cardiovascular monitoring - CVP, art line
  3. Thyroxine (T4 = Eltroxin) 500 microg PNGT followed by 100 microg PNGT per day
    1. Large doses are needed initially to saturate the thyroid binding globulin
    2. Tri-iodothyrodine (T3 = Tertroxin) IVI creates supraphysiological levels associated with arrythmias and ischaemia
    3. Peripheral conversion of T4 to T3 is unrelated to thyroid status and is regulated differently in different tissues.
  4. Careful maintenance of blood pressure
    1. Careful fluid replacement is mainstay of treatment
    2. Poor response to inotropic agents
    3. Combination of inotropes and thyroid hormones can cause severe arrhythmias
  5. Correct hyponatraemia
    1. Free water restriction
    2. If Na+ <115mmol/l use Normal saline or Hypertonic saline 200mls 5% NaCl over 6 hours
    3. Hydrocortisone 300mg/day IVI
  6. Stabilise glucose with a glucose infusion associated with 100mg Thiamine a day
  7. Non aggressive rewarming over 2-4 days
    1. Prevention of further heat loss
    2. Warmed fluids
    3. No External warming devices
  8. Careful titration of sedation
    1. Increased sensitivity to narcotics, anaesthetics and tranquillisers
  9. Identification and treatment of precipitating factor, usually infection