Hypothyroidism

For Congenital Hypothyroidism please see separate article called Childhood and Congenital Hypothyroidism.

• Incidence:
  • Overt form - 2% women, 0.2% men.¹
  • Sub-clinical - 6-8% women, 3% men.
  • 2.5% of pregnant women develop hypothyroidism.²
• Hypothyroidism increases with age and is commonest around the age of 60 years.
• Autoimmune hypothyroidism is more common in Japan.
• The commonest cause of hypothyroidism worldwide is iodine deficiency.
• In areas where iodine deficiency is not a problem, autoimmune and iatrogenic hypothyroidism are more commonly the cause.

Hypothyroidism results from insufficient secretion of thyroid hormones and can be due to a variety of abnormalities. The severest form is myxoedema where there is accumulation of mucopolysaccharides in the skin and other tissues, causing thickening of the facial features, and associated with ventilatory dysfunction and coma.³

Primary hypothyroidism

• Autoimmune hypothyroidism - Hashimoto's thyroiditis (associated with a goitre) and atrophic thyroiditis
• Iatrogenic - radio-iodine treatment, surgery, radiotherapy to neck, e.g. lymphoma (no goitre usually)
• Iodine deficiency - commonest cause worldwide and goitre is present
• Drugs - amiodarone, contrast media, iodides, lithium and antithyroid medication
• Congenital defects, e.g. absence of thyroid gland or dyshormonogenesis
• Infiltration of thyroid, e.g. amyloidosis, sarcoidosis and haemochromatosis

Secondary hypothyroidism

• Isolated TSH deficiency
• Hypopituitarism - neoplasm, infiltrative, infection and radiotherapy
• Hypothalamic disorders - neoplasms and trauma

Transient hypothyroidism

• Withdrawal of thyroid suppressive therapy
• Post-partum thyroiditis
• Subacute/chronic thyroiditis with transient hypothyroidism

Often insidious onset with non-specific symptoms.

Symptoms

• Tiredness, lethargy, intolerance to cold
• Dry skin and hair loss
  
  
• Slowing of intellectual activity, e.g. poor memory and difficulty concentrating
• Constipation
• Decreased appetite with weight gain
• Deep hoarse voice
• Menorrhagia and later oligo- or amenorrhoea
• Impaired hearing due to fluid in middle ear
• Reduced libido

Signs

• Dry coarse skin, hair loss and cold peripheries.
• Puffy face, hands and feet (myxoedema)
• Bradycardia
• Delayed tendon reflex relaxation
• Carpal tunnel syndrome
• Serous cavity effusions, e.g. pericarditis or pleural effusions

In autoimmune hypothyroidism patients may have features of other autoimmune diseases, such as, vitiligo, pernicious anaemia, Addison's disease and diabetes mellitus.¹

Furthermore, 5% of patients will have ophthalmopathy as in Grave's disease.

Other presentations

• Acute renal failure⁴
• Female sexual dysfunction⁵
• Hypercholesterolaemia

This can develop into myxoedema:

• Expressionless dull face with peri-orbital puffiness, swollen tongue, sparse hair
• Pale, cool skin with rough, doughy texture
• Enlarged heart
• Mega-colon/intestinal obstruction
• Cerebellar ataxia
• Psychosis
• Encephalopathy

Patients can go on to develop myxoedema coma (see below):

Hashimoto's and atrophic thyroiditis

• Sub-clinical autoimmune thyroiditis probably represents the early stages of chronic thyroiditis with a soft or firm thyroid gland which is usually normal in size or slightly enlarged.
• Sub-clinical autoimmune thyroiditis is associated with normal thyroid function.
• Hashimoto's thyroiditis and atrophic thyroiditis probably represent two ends of the same spectrum of chronic thyroiditis. In Hashimoto's thyroiditis there is a painless goitre of varying size with a rubber consistency and irregular surface. Thyroid function varies from normal to sub-clinical or overt hypothyroidism.
• Atrophic thyroiditis represents the end stage of autoimmune hypothyroidism and patients are overtly hypothyroid.
• Interestingly, excessive iodine intake can lead to autoimmune hypothyroidism.⁶
• Autoimmune hypothyroidism is uncommon in children. It presents as delayed growth and facial maturation. Puberty may also be delayed. In very young children there may be intellectual impairment.

Post-partum thyroiditis

This occurs in 5-7% of pregnancies within the first 6 months post-partum.² Most women show complete remission but some may progress to permanent hypothyroidism.

Sub-acute thyroiditis

Also referred to as granulomatous, giant cell or de Quervain thyroiditis - a viral infection produces local symptoms and exquisite tenderness of the thyroid gland with nodularity. Initially patients are thyrotoxic but later they become hypothyroid.⁷

• Anti-thyroid peroxidase (anti-TPO) antibodies or anti-thyroglobulin antibodies are found in 90-95% of patients with autoimmune thyroiditis.
• Untreated hypothyroidism may be associated with a raised CK, raised cholesterol and triglycerides and anaemia (normocytic or macrocytic). These abnormalities usually resolve with treatment.
• If the patient has an asymmetrical goitre then they may need imaging of their thyroid gland, e.g. ultrasonography to rule out neoplastic lesions.

Neonates - investigations include ultrasonography or ¹²³I scintigraphy, serum thyroglobulin and low molecular weight iodopeptides to differentiate different types of defects. Total urinary iodine excretion will differentiate between inborn errors of metabolism and hypothyroidism due to iodine deficiency or excess.

Clinical hypothyroidism

• The aim is to restore normal metabolic state gradually, as rapid increase may precipitate cardiac arrhythmias.
• Levothyroxine in the dose range of 100-150 mcg per day is used for maintenance.
• In younger patients start at 100 mcg thyroxine.
• In elderly with IHD start with 25-50 mcg and increase by 25 mcg increments at 4-8 weekly intervals until normal metabolic state reached.
• Patients with iatrogenic causes of hypothyroidism usually require lower doses for maintenance.
• Determine optimum dose by clinical criteria and TSH (check every 2 months after any dose change).
• Ideally want to normalise TSH and keep it in the lower half of the reference range.
• Once stabilised, check TSH annually. Free T4 is more useful in secondary hypothyroidism.
• Need to inform the patient that symptom relief may take many months and even up to 6 months after TSH levels have normalised.
• Drugs, such as ferrous sulphate, calcium supplements, rifampicin and amiodarone can interfere with T4 absorption.

Sub-clinical hypothyroidism

• Sub-clinical hypothyroidism occurs when there is biochemical evidence of hypothyroidism, i.e. raised TSH levels with normal free T4 and T3, but few or no clinical features.⁸Sub-clinical hypothyroidism is associated with reduced exercise capacity but there is some controversy over whether to treat these patients - symptoms may improve on T4 but concerns over risk of reduced bone mineral density and atrial fibrillation.^1,8,9
• Treat patients with history of radio-iodine treatment or positive thyroid antibody test, as this subgroup will nearly always progress to overt hypothyroidism.
• Also treat if previous treatment of Grave's disease or other organ-specific autoimmune disease or TSH > 10. Levothyroxine is used to maintain TSH within the normal range.⁸
• If none of the above is present, then monitor TSH every 6-12 months. If symptomatic, then a trial of thyroxine may be warranted.

Children

• Very rarely levothyroxine therapy can cause pseudotumor cerebri in children.
• It is an idiosyncratic reaction and presents raised intracranial pressure and can occur months after treatment.

Pregnancy

• Women of child-bearing age should be encouraged to wait until they are euthyroid before trying to conceive.¹⁰
• It is important to maintain euthyroid throughout pregnancy, especially during the first trimester.²
• Measure thyroid function tests during first, second and third trimesters. There is continuing debate as to whether there is a need to screen pregnant women for thyroid disorders.¹
• Levothyroxine dose may need to be increased by more than 50% during pregnancy. The dose can usually be reduced post-partum.¹⁰

Elderly

• Patients with known coronary artery disease need to be started on levothyroxine cautiously.
• For example, use a start dose of 12.5-25 mcg and increase by similar amounts every 2-3 months.

• Myxoedema coma is seen mostly in elderly patients and is associated with a high mortality rate.
• Patients may be on treatment for hypothyroidism or be previously undiagnosed.
• Poor adherence may also predispose to myxoedema coma.
• Patients present with reduced level of consciousness, seizures,¹¹ hypothermia and features of hypothyroidism.
• Precipitating factors include sedative drugs and anything that impairs the respiratory system, e.g. pneumonia, cardiac failure and myocardial infarction.¹²
• Hypoventilation plays a major role with resulting hypoxia and hypercapnia.
• Metabolic disturbances are also prominent including, hyponatraemia and hypoglycaemia.

Treatment

• Intravenous levothyroxine is used - usually start with a loading dose and then a lower dose for maintenance on a daily basis.¹³
• Other treatments that have been used are liothyronine (T3) but this can cause arrhythmias.
• Combinations of levothyroxine and liothyronine can also be used - but the mainstay of therapy is levothyroxine alone.
• Other therapy is usually supportive, e.g. correct metabolic disturbances, patient warming if hypothermic and treatment of precipitating factors.
• Patients may need to be intubated and ventilated if respiratory impairment is severe.¹²
• Intravenous hydrocortisone is also required, as impaired adrenal function is present in profound hypothyroidism (but send a random blood cortisol first).¹³