Thyroid Disorders

Summary

Goitre- enlarged palpable thyroid gland, moves on swallowing

o   Best way to assess is via USS

o   Not necessarily indicative of disease

o   Simple Goitre - normal level of hormones, no treatment necessary

o   Multinodular Goitre - progresses with age, secrete autonomously, many nodules can cause hyperthyroidism

o   Most common causes;          Problems with thyroid function (hypo or hyperthyroidism)

endemic

sporadic non-toxic

Endemic – when over 5% of the children in a population have a goitre (can exceed 30%)

o   Affects over 200 million people worldwide, caused by iodine deficiency or ‘goitrogens’ (chemicals found in food that exaggerate the effects of iodine deficiency eg. Cassava, selenium, cabbage). 

o   Usually diffuse goitre, becoming nodular with age, rarely compressing.

o   Treated with iodine supplements, iodized salt/water.

Sporadic – unknown cause

o   5% population, M:F – 1:4. Incidence declines with age.

o   Usually changes from diffuse to multinodular. TSH levels are normal. Nodules from an entire follicle rather than a single cell. Mostly visible, with compression on the neck.

o   Should be left alone unless causing pain or significant compression.

 

Hyperthyroidism(aka thyrotoxicosis- the state produced by excessive thyroid hormone)

·         M:F – 1:5 (2-5% females, 0.2-0.3% males)

·         99% caused by thyroid disease (<1% by pituitary)

·         Graves Disease accounts for 60-80% cases

·         Toxic nodular thyroid disease 20-40% cases

·         Rarer causes; thyroid carcinoma, iodine excess, TSH receptor mutation.

·         Results in higher mortality, increased risk osteoporosis

·         Low serum TSH <0.05mU/L

·         Increased T3/T4 (T3 more sensitive)

Symptoms	Signs
§ Hyperactivity, irritability, altered mood § Heat intolerance, sweating § Palpitations § Fatigue, weakness § Weight loss (with increased appetite) § Diarrhoea, steatorrhoea § Polyuria § Loss of libido § Altered periods (oligomenorrhea or menorrhagia)	§ Heart : sinus tachycardia, atrial fibrillation (particularly in elderly) § Visible: fine tremor, diffuse pigmentation palmar erythema, goitre § On examination: warm, moist skin,muscle weakness and wasting, gyanaecomastia, eyelid retraction § Rarely: psychosis, periodic paralysis (common in Asian males),impaired consciousness

Thyrotoxic storm (acute illness) 20-30% mortality rate

·         Fever >38.5

·         Seizures

·         Vomiting

·         Diarrhoea

·         Jaundice

·         Death through arrhythmias, heart failure or hyperthermia

Ø Treat immediately with propranolol, antithyroid drugs, potassium iodide (reduces vascular flow to thyroid gland) and corticosteroids

Toxic Multinodular Thyroid Disease

Ø Commonly occurs in old women

Ø Linked with increase in iodine intake

Ø Nodules are adenomatous

Ø Develops from single sporadic goitre

Ø >50% due to mutation TSH receptor

Ø Some hyperplasia and colloid filled nodules with fibrosis, haemorrhage and calcification

Ø Can get solitary nodules, this is rarer, only accounts for 5%

Graves Disease

Ø Detectable TSH receptor stimulating antibodies (often thyroglobulin and TPO antibodies also).

Ø Cause unknown, but E-Coli and gram negative bacteria contain TSH binding sites.

Ø Environment triggers:

§ High iodine intake

§ Smoking (also a risk in thyroid associated ophthalmopathy)

§ Stress

Ø Genetic factors (20-50% concordance monozygotic twins). Related to other autoimmune diseases (myasthenia gravis and pernicious anaemia)

Ø Relapsing remitting course (<40% have single episode)

Ø Bruit can be heard as increased blood flow to gland.

Ø Clubbing (10-20%), Pretibial myxoedema (5%) (NB. Only on shin)

Ø Thyroid hypertrophy and hyperplasia, reduced colloid, follicle cells become columnar, lymphocytic infiltrate, lymph node hyperplasia (especially spleen).

Ø Eye signs(thyroid associated ophthalmopathy)

-          Occurs in 50% Graves patients. -          Immune response - Retro-orbital inflammation (swelling and oedema of extraorbital muscles) -          Causes proptosis (protrusion from orbit). -          Pressure on the optic nerve results in optic atrophy. Get lid lag, corneal damage. -          Severity of eye disease not related to severity of thyrotoxicosis.

-          5-10% threaten patients sight. -          In 10% signs are unilateral. -          More common in smokers. -          May not resolve with thyrotoxicosis treatment – can be worsened by hypothyroidism. -          Treatment: Surgery, eye drops and systemic steroids (glucocorticoids or prednisolone).

 
Treatment for hyperthyroidism

Medication

Beta-blockers (eg. Propranolol)- reduce symptoms (tachycardia, dysrhythmias, tremor and agitation) before antithyroid drugs take effect. Also reduce peripheral conversion T4 to T3.

 

Radioiodine ¹³¹I given as sodium salt, taken up into thyroglobulin, emits both beta and gamma radiation, beta has powerful cytotoxic action. Half life of 8 days. Effects not seen for 1-2 months. Often causes hypothyroidism. Can be used to treat thyroid cancer. Thyroid eye disease may be worse after radioiodine. Monitor closely for 1 year after, and yearly after that. Avoid in childhood and pregnancy. Slightly increases risk of thyroid cancer.

 

Antithyroid drugs (thiourelenes) eg. Carbimazole, propylthyrourazil, thiamazole

Given orally.

Takes just hours for drug action but can take 3-4 weeks for clinical effects due to long half life T4.

Reduce thyroid hormone production by inhibiting thyroid peroxidise enzyme.

Propylthyrourazil (PTU) acts quicker than carbimazole as also inhibits peripheral conversion T4 to T3. It is used in pregnancy over carbimazole. The child is monitored throughout for signs of hyperthyroidism (if left untreated this is associated with hyperactivity at a later stage).

50% relapse after treatment.

Unwanted side effects; agranulocytosis (low levels circulating WBCs especially neutrophils) – immunosuppression. Can change type of thiourelene.

Treatment regimes; block and replace or titration

Block and replace; High dose carbimazole, completely stop thyroid hormone production and replace with thyroxine. Do not use in pregnancy.

Titration; takes longer, start on high dose, gradually reduce until you find the dose that holds them stable with close to normal thyroid function.

 

Surgery

Total thyroidectomy. Usually only done if patient is euthyroid and has poor compliance/persistent side effects on the drugs, recurrent hyperthyroidism or a large obstructive goitre.

 

Hypothyroidism -(sometimes called myxoedema)

Ø Occurs especially in women >40. (Mean age diagnosis 60)

Ø Prevalence 1% women, 0.1% men. Higher lifetime risk.

Ø Congenital hypothyroidism occurs 1/4000 births. Screening programme.

Ø Primary thyroid disease (autoimmune, congenital, damage by radioiodine, effects of antithyroid drugs, iodine deficiency.)

Ø Rarely: pituitary/hypothalamic disorders/peripheral resistance

Ø Gradual onset, rise in TSH, free T4 falls. Once TSH >10u/L symptoms are apparent.

Symptoms	Signs
-          Tiredness / malaise, cold intolerance -          Weight gain, poor appetite, constipation -          Poor memory / mental slowness, depression -          Change in periods Menorrhagia or oligomenorrhoea -          Overweight / obese -          Deep voice -          Cold peripheries -          Dry, brittle, unmanageable hair	-          Hypertension -          Hypothermia -          Peripheral oedema -          Carpal tunnel syndrome -          Bradycardia (<60bpm) -          Appearance; puffy eyes, loss of eyebrows. Dry skin, ‘peaches and cream’ complexion -          Myxoedema (subcutaneous mucopolysaccharide accumulation)

Complications

o   Anaemia (usually normocytic)

o   AST raised due to liver and kidney myopathy

o   Hypercholesterolaemia

o   High creatinine kinase

o   Hyponataemia

 

Clinical emergency; Myxoedema coma –rare, mortality 50%. Hypothermia (sometimes as low as 23’), coma and possibly seizures. Patients are usually old, and there is often an additional condition.

 

Autoimmune hypothyroidism

o   Most common type

o   T-cell mediated cytotoxicity

o   Antibodies block TSH receptors

o   Massive fibrosis

o   Very little lymphocyte infiltrate

o   Few follicles remaining by diagnosis

o   No goitre

 

Hashimotos Thyroiditis

o   Autoimmune

o   Massive goitre

o   Initially causes Hashi-toxicity

o   Infiltration by lymphocytes

o   Increased concentration mitochondria

o   High levels TPO (thyroid peroxidise) antibody

o   Treat with thyroxine (shrinks goitre)

 

Congenital hypothyroidism

o   Mainly due to thyroid aplasia or hypoplasia

o   Once suspected immediately commence thyroxine

o   Review at 3-4 years once critical neurological risk stage has passed

 

Iodine deficiency

o   Common in mountainous areas (often where there is ‘endemic goitre’).

o   Underlying iodine deficiency increases TSH which stimulates and enlarges the gland.

 

Post-partum thyroiditis

o   May present as hyperthyroidism (lymphocytic thyroiditis) during pregnancy

o   Later progresses to permanent hypothyroidism.

 

Treatment for hypothyroidism;

 Levothyroxine (for life) adjust dose until the patient has normal TSH levels. For completely non-functioning thyroid tissue, you need about 150µg T4/day for normal functioning. Higher than this you risk atrial fibrillation. Slightly increased risk pernicious anaemia and Addisons Disease. Increase thyroxine dose in pregnancy. Often develop depression shortly after commencing treatment, this subsides over time.

 

Thyroid carcinoma

o   5 main types

o   Only account for 400 deaths/year (not very common)

o   Frequency of occurrence Papillary>Follicular>Medullary>Anaplastic>Lymphoma (the last 3 often have poor prognosis)

o   Sites of spread; lymph nodes, lungs and brain

o   Treatment;
For some types surgery, radio-iodine and thyroxine (to lower TSH) will be highly effective treatments.
For other types prognosis is poor, the care given is mainly palliative and multiple metastases are common.