Thyrotoxicosis

Introduction

Thyrotoxicosis refers to the clinical, physiological and biochemical manifestation of the effect of excess thyroid hormone in tissues as opposed to hyperthyroidism which simply means hyperfunctioning of the thyroid gland.

There is a female preponderance due to the role of autoimmunity in the aetiology.

Causes of thyrotoxicosis

1. Grave’s disease (commonest cause)
2. Toxic nodule
3. Toxic multi-nodular goitre
4. Pituitary thyrotroph adenoma
5. Trophoblastic tumours producing HCG with thyrotrophic activity hormone resistance
6. Pituitary thyroid syndrome producing excess TSH and resultant excess T, and T
7. Thyroid cancers (rarely).
8. Thryroiditis (sub-acute or postpartum)
9. Iodine induced-drugs such as:
   • -Amiodarone
   • Radiographic contrast media
   • Iodine prophylaxis programmes
10. Extra-thyroidal sources of thyroid hormone excess
11. Factitious hyperthyroidism
12. Struma ovarii TSH-induced:

Symptoms and clinical features of thyrotoxicosis

1. A goitre may or may not be present
2. It may be diffuse or nodular
3. Heat intolerance
4. Dermatological:
   • Increased sweating and pruritus
   • Warm and moist skin
   • Pretibial myxoedema
   • Pigmentation, vitiligo
   • Palmar erythema
   • Onycholysis.
   • Hair loss
5. Cardiorespiratory:
   • Palpitation
   • Dyspnoea on exertion
   • Angina and cardiac failure
   • Increased pulse pressure (tachycardia)
   • Atrial fibrillation.
   • Exacerbation of asthma
6. Gastrointestinal:
   • Weight loss despite increased appetite (hyperphagia)
   • Weight gain in 10% of patients
   • Increased stool frequency
7. Neuromuscular:
   • Tremors, nervousness, irritability, emotional liability and psychosis
   • Muscle weakness and proximal myopathy
   • Hyperkinesia
   • Hyperreflexia
   • Insomnia
8. Reproductive:
   • Loss of libido, impotence
   • Amenorrhoea/ oligomenorrhoea
   • Infertility and spontaneous abortions
9. Ocular:
   • Lid lag lid retraction
   • Grittiness, excessive lacrimation
   • Exophthalmos diplopia
   • Papilloedema
10. Others:
    • Increased thirst
    • Polyuria
    • Fatigue and apathy
    • Triad of Proptosis, Nail changes (onycholyis) and Skin changes) strongly suggest Graves disease

Differential diagnosis:

• Active tuberculosis – weight loss, cough if in heart failure
• Advanced retroviral disease -weight loss, hyperdefeacation, skin changes
• Malnutrition-weight loss, proptosis
• Cancer cachexia- weight loss
• Malabsorption syndrome- weight loss
• Neuropsychiatric disorders- tremors, pressure of speech and talkativeness even frank psychosis.
• Poorly controlled Diabetes mellitus-weight loss, loss of libido, hyperphagia.

Complications of thyrotoxicosis

1. Hyperthyroid crisis (thyroid storm)
2. Compression of the trachea
3. Cardiac failure
4. Loss of visual acuity
5. Infertility
6. Periodic paralysis

Investigations:

Diagnostic investigations:

1. Thyroid Function Test with free T, and T, which is both expected to be high and TSH suppressed.
2. Thyroid antibodies
   • Thyroid Peroxidase
   • Antibodies which is elevated in most cases of autoimmune
     thyroid disease,
   • Thyroglobulin antibody elevated in most cases of thyroid diseases,
   • TSH Receptor antibodies especially Thyroid Stimulating Immunoglobulin specifically in Grave’s disease.
3. Radiolabelled thyroid scan with iodine 123 especially if diagnosis is not certain

Ancillary Investigations:

1. Full Blood Count with ESR- which may show anaemia; if megaloblastic -pernicious anaemia may coexist as an autoimmune
   disease. Elevated ESR.
2. Serum Electrolyte, urea and creatinine -electrolytes derangement
3. Fasting blood sugar which could be deranged
4. Electrocardiogram which may show sinus tachycardia, atrial fibrillation
5. Echocardiography may reveal evidence of congestive heart failure with poor ejection fraction, dilated heart chambers.

Treatment for thyrotoxicosis

Treatment objectives

1. Achieve normal metabolic rates
2. Obtain normal serum T3, T, and TSH Levels
3. Prevent complications

Drug treatment

1. Antithyroid drugs

Carbimazole

Adult:

• Starting dose 30 – 60 mg orally in divided doses daily
• Maintenance: 10-15 mg oral daily

Child:

• Neonate, initially 250 micrograms/kg orally every 8 hours until euthyroid then
  adjust as necessary
• 1 month -12 years: initially
  250 micrograms/kg (maximum 10 mg every 8 hours) until euthyroid then adjusted as
  necessary
• 12 18 years: initially 10 mg every 8 hours until euthyroid then adjusted as necessary

Higher initial doses occasionally required, particularly in thyrotoxic crisis.

Child and carers to inform doctor immediately if sore throat, mouth ulcers, bruising, fever, malaise or nonspecific illness develops.

Propylthiouracil

• (This is preferred in pregnancy)

Adult:

• Starting dose 300 – 450 mg orally in divided doses daily
• Maintenance: 100 – 150 mg orally in 2 or 3 divided doses daily

Child:

• Neonate, initially 2.5 – 5 mg/kg orally every 12 hours until euthyroid, then adjusted as necessary 1 month – 1 year: initially 2.5 mg/kg every 8 hours until euthyroid;
• 1-5 years: 20 mg/kg 8 hourly until euthyroid;
• 5- 12years: initially 50mg every 8hours until euthyroid;.12 – 18 years: initially 100 mg every 8 hours until euthyroid.

Higher doses occasionally required particularly in thyrotoxic crisis.

Duration of treatment usually is 18 – 24

2. B-adrenergic blocking drugs

Propranolol 

• 80 – 160 mg orally daily in divided doses.

Symptoms and signs of hyperthyroidism
due to adrenergic stimulation may respond to these agents

3. Iodine used in:

• The emergency management of thyroid storm
• Thyrotoxic patients undergoing
  emergency surgery
• For the preoperative preparation of
  thyrotoxic patients selected for subtotal thyroidectomy

Aqueous iodide oral solution (Lugol’s solution):

Iodine 5%, potassium iodide 10% in
purified water; total iodine 130 mg/mL

Adult:

• 23 drops of saturated potassium  iodide solution orally 3 or 4 times daily (300-600 mg/day)

Child:

• Neonate 0.1-0.3 mL orally every 8 hours;
• 1 month -18 years: 0.1 0.3 mL every 8 hours

Thyrotoxic crisis:

Child 1 month -1 year: 0.2 – 0.3 mL 8 hourly

• Dilute with milk or water.

4. Use of steroids in autoimmune cases of thyrotoxicosis 

Radioactive sodium iodine

• Used in patients who are past child bearing age
• Dosage difficult to gauge; the response of the gland is unpredictable
• Up to 25% of patients given enough
  radioactive iodine to achieve
  euthyroidism, may develop hypothyroidism within one year
• High incidence of recurrence of hyperthyroidism if smaller doses are used

Surgery

Indications include:

• Patients < 21 years who should not receive radio iodine
• Persons who cannot tolerate other agents because of hypersensitivity, or for other reasons
• Patients with very large goitres, having compressive symptoms or signs
• Some patients with toxic adenoma and multinodular goitres

Supportive measures

• Appropriate care of any system affected e.g. eye care, treatment of heart failure
• Thyroid storm would require judicious intravenous fluid use, corticosteroids and treatment of the precipitating cause

Notable adverse drug reactions, caution and contraindications

Carbimazole and propylthiouracil

• May cause severe bone marrow
  suppression (including pancytopemia and agranulocytosis)
• They are contraindicated in
  breastfeeding mothers