Thyroid Disease

Thyroid Disease

PBL

Basic Anatomy

• Level C5 – T1• Surrounded by thin fibrous capsule• Highly vascular• 15 – 30 g Norm

Basic Histology

• Has numerous spherical follicles – cuboidal epithelium (follicular cells) surrounding the secreted colloid in the centre.

Further Histology

• Thyroid follicles lined by simple cuboidal epithelium.• Size of follicles vary depending on activity of the

gland – active = smaller follicles lined by tall cuboidal/columnar cells, less activy = larger follicles lined by flattened epithelial cells.

• Has C cells (parafolliclar cells) that are scattered around the basement membrane and characteristically have a clear cytoplasm (secrete calcitonin).

Thyroid Hormones

• Triiodothyronine (T3): – 4X more potent than T4, but a smaller pool of it

(7%).– Most of it formed from iodine cleavage of T4 at

peripheral tissues– Less strongly protein bound.– Half life – 1 to 2 days.

Thyroid Hormones

• Thyroxine (T4):– Less potent but larger pool (93%) – acts as a reservoir

pool as it has a longer half life.– Half life – 7 days.

Function of T4 and T3:– Increase basal metabolic rate.– Mimic B adrenergic action (heart, gut motility, CNS

activation) (upregulates B adrenergic receptors).

Thyrotoxicosis & Hyperthyroidism

• Thyrotoxicosis: Clinical syndrome characterised by elevated serum levels of T3 and T4. It can also be elevated TSH from a pituitary tumour (this is rare). (Excessive thyroid hormone)– Affects 2-5% of females at some point in their life.– Sex ratio= 5-10 : 1 (F:M)

• Hyperthyroidism: Excessive thyroid function.

Graves Disease

• Most common form of hyperthyroidism. • Autoimmune process where serum IgG

antibodies stimulate the TSH receptors (mimic TSH) to stimulate thyroid hormone production.

• Antibody known as Long Acting Thyriod Stimulator (LADS)

• Specific Graves disease Ix: Anti-thyroid Peroxidase (TPOAb) presence.

Graves: cardinal signs and symptoms

• Graves Eye disease: Lid retraction/lag +/- exophthalmos (due to immune response that causes retro-orbital inflammation).

• Pre-tibial myxoedema: Accumulation of mucopholysaccharides in the dermis of the skin.

• Clubbing.• Thyroid often has bruit.

Other Sx of Hyperthyroidism

• Weight loss but increased appetite.• Mood disturbances, irritability, agitation• Sympathetic overdrive: sweating, tachycardia,

darrhoea, AF, hypertension, tremor, palpitations, warm vasodilated peripheries

• Menstrual changes• Muscle weakness +/- Proximal myopathy

Other causes of Thyrotoxicosis

• Toxic Adenoma:– Soliary nodule producing T3 and T4.– <1% of adenomas produce enough hormone to

cause thyrotoxicosis.

Toxic multi-nodular goitre– Rarely 1-2 nodules may become hypersecretory.– More common in the elderly and iodine deficient.

Other causes of Thyrotoxicosis

• De Quervain’s thyroiditis ‘subacute thyroiditis’:– Transient hyperthyroidism from an acute

inflammatory process, probably viral. – Usually also fever, malaise, pain in the neck

• Thyroid cancer• Small cell carcinoma of the lung• Secondary causes: drugs – amiodarone

Management

• Aim: reduce thyroid hormone over production and to block its peripheral effects

• Stages– Use anti-thyroid medication to induce euthyroid

state– Surgery/Radioactive iodine/ to block and replace.– Maintain euthyroid state and replace if necessary.

Also: symptomatic relief by using B-blockers.

Anti-Thyroid Medication

• Controls hyperthyroidism, but does not cure it. • Often used to shrink thyroid gland before

surgery.

• Include: – Thyionamides– Radioactive Iodine– Iodine/Iodide treatment– B-adrenoreceptor agonists

Thionamides• Inhibits iodination of tyrosine on thyroglobulin, so

decreases T3, T4. • Carbimazole and propylthiouracil usually preferred (these

also reduce breakdown of T4 to T3 in peripheral tissue).• Can be taken orally, good for long term use in Graves.• Crosses the placenta, can be found in breast milk, can

cause hypthyroidism in babies (carbimazole chosen over propylthiouracil to minimise this).

• SE: rashes (2-25%), headache, nausea, jaundice, joint pains, agranulocytosis (dec WBC).

Radioactive Iodine Treatment

• Used for hyperthyroidism and thyroid carcinoma.• Given orally, radioactive iodine taken up by thyroid

and incorporated into thyroglobin, where it has a localized cytotoxic effect, killing nearby cells.

• Single dose: cytotoxic effects seen in 1-2 months, peaks at 3-4 months.

• SE: hypothyroidism, small increased risk of thyroid cancer.

• C/I: pregnancy and childhood.

Iodine/Iodide treatment

• Most rapid treatment.• High dose of Iodine inhibits release of T3, T4 (via

inhibition of TSH and TRH).• Very useful for short term managment of

hyperthyroidism: thyrotoxic crisis and preparation for thyroidectomy. – Takes 24 hours for effect to be seen.– Reduction in vascularity and gland size in 10-14 days.

• Allergy reaction can occur.

B Adrenoreceptor Agonists

• Symptomatic treatment• Used when waiting for the effects of

radioactive iodine and thionamides to be seen.

• Sx such as tachycardia, angina, arrhythmia, agitation.

Thyroidectomy

• Not usually used as medical treatment usually successful.

• Indications:– Elective– Persistent medication SE– Large goitres that will not remit after medical

management– Poor compliance with drugs

Thyroidectomy - complications

• Post op bleeding can cause tracheal compression and asphyxiation (but rare)

• Laryngeal nerve palsy (1%)• Transient hypocalcaemia (10%)• Hypothyroidism (10% of pt)• Recurrent Hyperthyroidism• Damage/ removal of parathyroid glands (1%

permanent hypoparathyroidism)

Goitre

• Goitre – an enlarged thyroid gland, can be diffuse or nodular.

• Hypothyroidism (increase TSH):– Dietary deficiency of iodine causes reduced levels of

thyroid hormones, which leads to increased secretions of TSH from ant pituitary, causing thyroid gland to hypertrophy and cause goitre.

• Hyperthyroidism (hypertrophy):– The follicules are overactive, causing them to

hypertrophy (not hyperplasia)

Tumours

• Benign• Tumours of the thyroid usually benign• Follicular adenoma is the most common cause

of a solitary thyroid nodule.• Sometimes may be ‘hot’ on radio-isotope

scans, and can cause thyrotoxicosis.

Tumour - malignant

• Thyroid cancer not common accounts for <1% of all cancer deaths.

• 90% present as thyroid nodules, occasionally with cervical LAD (5%), or with lung, hepatic, bone or cerebral mets.

• Very rarely cause hyperthyroidism, but 90% secrete thyroglobulin – good tumour marker.

Malignant nodule Rx

• Surgery: total thyroidectomy indicated for any malignancy greater than 1 cm diameter.

• Remnant ablation: thyroid tissue remaining is destroyed with orally administered radioiodine.

• NB: this is where thyroglobulin is handy – after thyroidectomy and further radio iodine administratin, there should be no thyroid tissue, hence no thyroglobulin – if there is some, may be from secondary mets.

Prognosis

• Good• 10 year survival: 80-95%

• Factors that worsen prognosis:• Male, poor differentiation, local invasion,

distant mets, advanced age, large tumour.

Investigations

• Specific thyroid antibodies:• TPOAb (thyroid peroxidase antibody):– Present in Hashimoto’s and Graves’

• TgAb (thyroglobulin antibody):– Present in Hashimoto’s and Thyroid cancer

• TRAb (thyroid stimulating hormone receptor antibody):– Present in Graves’

Further Ix• U/S• Useful for nodules – can see if they are cyctic or solid. • Can help determine multi-nodular goitre when only a single

nodule is palpable.• Unfortunately, even cystic lesions can be malignant and tumours

can arise in multi-nodular goitre, so FNA is usually also done.• • FNA:• In pt with a solitary nodule or dominant nodule in multi-nodular

goitre, there is a 5% risk of malignancy. • 5% false negative rate – counsel pt.

Further Ix• Chest and thoracic inlet x-rays • To detect tracheal compression and retrosternal extensions. • • Thyroid scan• FNA largely replaced isotope scans in diagnosing thyroid

nodules.• Can be useful to distinguish between functioning (hot) and

non-functioning (cold) nodules. • Hot nodule rarely malignant.• 10% of cold nodule malignant