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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.

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Thyroid Disease

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  1. Thyroid Disease PBL

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

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

  4. 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 (parafolliclarcells) that are scattered around the basement membrane and characteristically have a clear cytoplasm (secrete calcitonin).

  5. 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.

  6. 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).

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. Other causes of Thyrotoxicosis • De Quervain’sthyroiditis ‘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

  13. 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.

  14. 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

  15. 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).

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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)

  21. 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)

  22. 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.

  23. 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.

  24. 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.

  25. Prognosis • Good • 10 year survival: 80-95% • Factors that worsen prognosis: • Male, poor differentiation, local invasion, distant mets, advanced age, large tumour.

  26. 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’

  27. 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.

  28. 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

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