NES Pharmacy CPD: Thyroid  SpR in Endocrinology Glasgow Royal Infirmary February 2010 Amended by NES 2010 Developed and de...
Glands and Hormones <ul><li>Endocrine Glands:  Glands that secrete their products (hormones) directly into the bloodstream...
Thyroid gland <ul><li>Secrets two iodinated hormones T3 and T4. </li></ul><ul><li>Responsible for optimal growth, developm...
TRH/TSH Feedback Loop
TRH <ul><li>Thyrotrophin releasing hormone. </li></ul><ul><li>Tripeptide produced by hypothalamus. </li></ul><ul><li>Relea...
TSH <ul><li>Thyroid stimulating hormone. </li></ul><ul><li>Produced by the pituitary gland </li></ul><ul><li>Upregulated b...
Thyroid hormones (T4, T3) <ul><li>T3/T4 enter circulation transported to plasma proteins (99%).  </li></ul><ul><li>Thyroid...
Common diagnostic tools <ul><li>TSH </li></ul><ul><li>Free T 3 ,  </li></ul><ul><li>Free T 4 </li></ul><ul><li>Thyroid aut...
Hypothyroidism <ul><li>Clinical syndrome that results in deficiency of the thyroid hormones T4 and T3. </li></ul><ul><li>C...
Types of hypothyroidism <ul><li>Primary –  Thyroid gland failure </li></ul><ul><li>Secondary –  Pituitary failure </li></u...
Aetiology of hypothyroidism <ul><li>Agenesis </li></ul><ul><li>Thyroid destruction </li></ul><ul><ul><li>Hashimoto’s thyro...
Subclinical hypothyroidism <ul><li>Estimated to affect 10% of females > 50yrs </li></ul><ul><li>Normal FT4/FT3, mildly ele...
Clinical Presentation <ul><li>Symptoms –  Tiredness, cold intolerance, weight gain, constipation, aches and pains, depress...
Diagnosis of hypothyroidism <ul><li>Primary –  Low FT4/FT3 and high TSH </li></ul><ul><li>Secondary –  Low FT4/FT3 and low...
Management <ul><li>Apart from subacute and postpartum thyroiditis most require long term replacement in form of Levothyrox...
Management <ul><li>In  cardiac disease cautious replacement is required  to decompensation ie. Thyroxine 25mcg  with steps...
Management of subclinical cases <ul><li>If TSH>10  – treat with thyroxine </li></ul><ul><li>If TSH 4-10 and asymptomatic  ...
Nurse Led Management <ul><li>Patients often managed in nurse led clinics using questionnaire/algorithms. </li></ul><ul><li...
 
Hyperthyroidism <ul><li>Clinical syndrome associated with raised levels of the thyroid hormones T4 and/or T3. </li></ul><u...
Aetiology of hyperthyroidism <ul><li>Grave’s disease </li></ul><ul><li>Toxic multinodular goitre </li></ul><ul><li>Toxic a...
Clinical Presentation <ul><li>Symptoms –  Heat intolerance, weight loss, loose motions, tremor, increased appetite, amenor...
Diagnosis of thyrotoxicosis <ul><li>Primary –  High FT4 and/or FT3 and low TSH </li></ul><ul><li>Secondary –  High FT4 and...
Grave’s disease versus Toxic MNG <ul><li>Grave’s Disease </li></ul><ul><li>Female>male </li></ul><ul><li>Peak age 20-40 ye...
Management <ul><li>Carbimazole 20-40mg daily to render euthyroid (alternatively PTU). </li></ul><ul><li>Propanolol 40mg bd...
Drugs <ul><li>Carbimazole:  Inhibits hormone production, side effects include rash and agranulocytosis (0.1%). </li></ul><...
Pregnancy and lactation <ul><li>Increased risk of fetal and neonatal thyrotoxicosis. </li></ul><ul><li>PTU preferred to Ca...
Management <ul><li>In  Grave’s disease  option to treat with drugs for 18 months and stop (50% chance of remission). Can a...
Radio-iodine therapy <ul><li>131 I is a safe and effective means of treatment.  </li></ul><ul><li>Emits locally destructiv...
Nurse Led Management <ul><li>Patients often managed in nurse led clinics using questionnaire/algorithms. </li></ul><ul><li...
 
 
Pharmaceutical Care Issues – Hypothyroidism (examples) <ul><li>Monitoring for signs & symptoms for dosage </li></ul><ul><u...
Pharmaceutical Care Issues – Hyperthyroidism (examples) <ul><li>Explain dosage regime for carbimazole </li></ul><ul><li>Mo...
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  1. 1. NES Pharmacy CPD: Thyroid SpR in Endocrinology Glasgow Royal Infirmary February 2010 Amended by NES 2010 Developed and delivered by Dr James Boyle
  2. 2. Glands and Hormones <ul><li>Endocrine Glands: Glands that secrete their products (hormones) directly into the bloodstream rather than through a duct </li></ul><ul><li>Hormone: Chemical substance formed in the body that is carried in the bloodstream to affect another part of the body. </li></ul>
  3. 3. Thyroid gland <ul><li>Secrets two iodinated hormones T3 and T4. </li></ul><ul><li>Responsible for optimal growth, development and function of body tissues. </li></ul><ul><li>The synthesis of T3 and T4 requires iodine. </li></ul><ul><li>Release of T3 and T4 controlled by negative feedback. </li></ul>
  4. 4. TRH/TSH Feedback Loop
  5. 5. TRH <ul><li>Thyrotrophin releasing hormone. </li></ul><ul><li>Tripeptide produced by hypothalamus. </li></ul><ul><li>Release is pulsatile. </li></ul><ul><li>Downregulated by T 3. </li></ul><ul><li>Travels through portal venous system to adenohypophysis. </li></ul><ul><li>Stimulates TSH synthesis and release. </li></ul>
  6. 6. TSH <ul><li>Thyroid stimulating hormone. </li></ul><ul><li>Produced by the pituitary gland </li></ul><ul><li>Upregulated by TRH </li></ul><ul><li>Downregulated by T 4 , T 3 </li></ul><ul><li>Travels through portal venous system to cavernous sinus and body. </li></ul><ul><li>Stimulates several processes synthesis and release of hormones from the gland as well as gland growth </li></ul>
  7. 7. Thyroid hormones (T4, T3) <ul><li>T3/T4 enter circulation transported to plasma proteins (99%). </li></ul><ul><li>Thyroid only contributes 20% of the free circulating T3 with the rest produced by peripheral conversion of T4 to T3. T4 may be deiodinated to inactive reverse T3. </li></ul><ul><li>Regulation is based on the free component of thyroid hormone. </li></ul><ul><li>Action not understood but thought to involve high affinity binding sites in plasma membrane, mitochondria and nucleus resulting in protein synthesis and increased energy metabolism. </li></ul>
  8. 8. Common diagnostic tools <ul><li>TSH </li></ul><ul><li>Free T 3 , </li></ul><ul><li>Free T 4 </li></ul><ul><li>Thyroid autoantiboides </li></ul><ul><li>Thyroid ultrasound </li></ul><ul><li>Radio-isotope uptake and scan </li></ul><ul><li>Fine need aspiration of thyroid </li></ul>
  9. 9. Hypothyroidism <ul><li>Clinical syndrome that results in deficiency of the thyroid hormones T4 and T3. </li></ul><ul><li>Common, prevalence 1-2% </li></ul><ul><li>F:M preponderance of 10:1 </li></ul><ul><li>Congenital hypothyroidism is 1:4000 live births in the UK. </li></ul>
  10. 10. Types of hypothyroidism <ul><li>Primary – Thyroid gland failure </li></ul><ul><li>Secondary – Pituitary failure </li></ul><ul><li>Tertiary – Hypothalamic failure </li></ul><ul><li>Sub-clinical </li></ul>
  11. 11. Aetiology of hypothyroidism <ul><li>Agenesis </li></ul><ul><li>Thyroid destruction </li></ul><ul><ul><li>Hashimoto’s thyroiditis </li></ul></ul><ul><ul><li>Surgery </li></ul></ul><ul><ul><li>Radio-iodine ablation </li></ul></ul><ul><ul><li>Infiltration (tumour, sarcoidosis) </li></ul></ul><ul><li>Inhibition of function </li></ul><ul><ul><li>Iodine deficiency </li></ul></ul><ul><ul><li>Anti-thyroid medications (Carbimazole, PTU, lithium, amiodarone) </li></ul></ul><ul><ul><li>Inherited defects </li></ul></ul><ul><li>Transient </li></ul><ul><ul><li>Postpartum </li></ul></ul><ul><ul><li>Sub-acute thyroiditis </li></ul></ul><ul><li>Secondary/Tertiary (pituitary, hypothalamic) </li></ul>
  12. 12. Subclinical hypothyroidism <ul><li>Estimated to affect 10% of females > 50yrs </li></ul><ul><li>Normal FT4/FT3, mildly elevated TSH </li></ul><ul><li>Few report symptoms </li></ul><ul><li>High risk of developing primary hypothyroidism </li></ul><ul><li>Can be associated with dyslipidaemia and subtle cardiac abnormalities. </li></ul><ul><li>Management a matter of clinical judgement </li></ul>
  13. 13. Clinical Presentation <ul><li>Symptoms – Tiredness, cold intolerance, weight gain, constipation, aches and pains, depression, psychosis, angina and menorrhagia. </li></ul><ul><li>Signs – Hair loss, hoarseness, goitre, bradycardia, dry skin, slow relaxing reflexes, anaemia, heart failure, effusions, carpal tunnel syndrome, mxyoedema coma. </li></ul>
  14. 14. Diagnosis of hypothyroidism <ul><li>Primary – Low FT4/FT3 and high TSH </li></ul><ul><li>Secondary – Low FT4/FT3 and low TSH </li></ul><ul><li>Tertiary – Low FT4/FT3 and low TSH </li></ul><ul><li>Sub-clinical – Normal FT4/FT3 and slightly high TSH </li></ul>
  15. 15. Management <ul><li>Apart from subacute and postpartum thyroiditis most require long term replacement in form of Levothyroxine. </li></ul><ul><li>Starting dose usually 50 -100mcg/daily. </li></ul><ul><li>Increased in steps of 25-50mcg every 4-6 weeks until FT4 is above middle of normal range and TSH normal/low normal. </li></ul><ul><li>Usual maintenance is 100mcg-200mcg/daily. </li></ul><ul><li>Suppressed TSH acceptable in certain cases </li></ul>
  16. 16. Management <ul><li>In cardiac disease cautious replacement is required to decompensation ie. Thyroxine 25mcg with steps of 25mcg only. </li></ul><ul><li>In secondary/tertiary cases ensure good adrenal reserve before commencing thyroxine replacement and dont use TSH to assess response. </li></ul><ul><li>In pregnancy requirements go up 50-100% and more monitoring is required. Use TSH to monitor at least every trimester. </li></ul>
  17. 17. Management of subclinical cases <ul><li>If TSH>10 – treat with thyroxine </li></ul><ul><li>If TSH 4-10 and asymptomatic – rpt TFT 6/12 </li></ul><ul><li>If TSH 4-10 and symptomatic or antibodies +ve or dyslipidaemia or history or radioiodine or surgery – treat with thyroxine </li></ul>
  18. 18. Nurse Led Management <ul><li>Patients often managed in nurse led clinics using questionnaire/algorithms. </li></ul><ul><li>Once patients with primary hypothyroidism are stable for 6 months (12 months for post radioiodine) they are discharged to GP for annual check. </li></ul><ul><li>Majority of patients unlikely to need to change dose of levothyroxine in the community. </li></ul>
  19. 20. Hyperthyroidism <ul><li>Clinical syndrome associated with raised levels of the thyroid hormones T4 and/or T3. </li></ul><ul><li>Can be increased production, release from damaged gland or exogenous T4. </li></ul><ul><li>Prevalence 1-2% </li></ul><ul><li>Incidence 3 per 1000 per year </li></ul><ul><li>Secondary hyperthyroidism due to increased TSH secretion is very rare (>1% of all cases) Common, prevalence 1-2% </li></ul>
  20. 21. Aetiology of hyperthyroidism <ul><li>Grave’s disease </li></ul><ul><li>Toxic multinodular goitre </li></ul><ul><li>Toxic adenoma </li></ul><ul><li>Thyroiditis (sub-acute, postpartum) </li></ul><ul><li>Drug induced (amiodarone) </li></ul><ul><li>Over treatment of T4 </li></ul><ul><li>TSH secreting adenoma </li></ul>
  21. 22. Clinical Presentation <ul><li>Symptoms – Heat intolerance, weight loss, loose motions, tremor, increased appetite, amenorrhoea, fatigue, anxiety, itch, angina. </li></ul><ul><li>Signs – Goitre, tachycardia, AF, tremor, warm hands, proximal myopathy, lid lag/retraction, Grave’s opthalmopathy, cardiac failure, hypertension, onycholysis, acropachy, pretibial myxoedema, thyroid storm . </li></ul>
  22. 23. Diagnosis of thyrotoxicosis <ul><li>Primary – High FT4 and/or FT3 and low TSH </li></ul><ul><li>Secondary – High FT4 and/or FT3 and high TSH </li></ul><ul><li>Sub-clinical – Normal FT4/FT3 and low TSH </li></ul>
  23. 24. Grave’s disease versus Toxic MNG <ul><li>Grave’s Disease </li></ul><ul><li>Female>male </li></ul><ul><li>Peak age 20-40 years </li></ul><ul><li>Diffuse and smooth </li></ul><ul><li>Lid lag and retraction, Grave’s eye signs, pretibial mxyoedma </li></ul><ul><li>Acropachy, onycholysis </li></ul><ul><li>Autoantibodies usually present </li></ul><ul><li>RAU scan uniform increased uptake </li></ul><ul><li>Multinodular Goitre </li></ul><ul><li>Female>male </li></ul><ul><li>Peak age >50 years </li></ul><ul><li>Multinodular goitre </li></ul><ul><li>Lid lag and retraction </li></ul><ul><li>No skin, nail or finger changes </li></ul><ul><li>Autoantibodies usually absent </li></ul><ul><li>RAU patchy, irregular appearance </li></ul>
  24. 25. Management <ul><li>Carbimazole 20-40mg daily to render euthyroid (alternatively PTU). </li></ul><ul><li>Propanolol 40mg bd/tds to control symptoms in the short term. </li></ul><ul><li>Dose titration or “block and replace” regimen depending on individual practice. </li></ul><ul><li>Decision of definitive therapy needs to be made. </li></ul>
  25. 26. Drugs <ul><li>Carbimazole: Inhibits hormone production, side effects include rash and agranulocytosis (0.1%). </li></ul><ul><li>Propythiouracil: Inhibits hormone production as well as blocking T4 to T3 conversion, side effects include rash and agranulocytosis (0.4%). </li></ul>
  26. 27. Pregnancy and lactation <ul><li>Increased risk of fetal and neonatal thyrotoxicosis. </li></ul><ul><li>PTU preferred to Carbimazole due to less found in breast milk and less crossing placenta. </li></ul><ul><li>Carbimazole has been associated with aplasia cutis. </li></ul><ul><li>Requirements fall in Grave’s. </li></ul><ul><li>Lowest dose possible should be used. </li></ul><ul><li>Radio-iodine contra-indicated during pregnancy </li></ul><ul><li>TSH receptor titres should be determined early in third trimester to assess risk of neonatal thyroid dysfunction. </li></ul>
  27. 28. Management <ul><li>In Grave’s disease option to treat with drugs for 18 months and stop (50% chance of remission). Can also opt for radioiodine or surgery. </li></ul><ul><li>In toxic multinodular goitre/toxic adenoma need to use radioiodine or surgery to cure. Small number opt for long term drug therapy. </li></ul>
  28. 29. Radio-iodine therapy <ul><li>131 I is a safe and effective means of treatment. </li></ul><ul><li>Emits locally destructive beta particles to lead to cell damage and death over months. </li></ul><ul><li>Render euthyroid with drugs first and stop before to allow uptake of isotope. </li></ul><ul><li>In Glasgow, antithyroid drugs are not restarted afterwards unless thyrotoxicosis confirmed. </li></ul><ul><li>High risk of subsequent hypothyroidism. </li></ul>
  29. 30. Nurse Led Management <ul><li>Patients often managed in nurse led clinics using questionnaire/algorithms. </li></ul><ul><li>Very few if any patients discharged to GP on anti-thyroid drugs </li></ul><ul><li>Nurse led management appropriate if diagnosis made, decision of definitive therapy made and no complications. </li></ul><ul><li>Majority of patients unlikely to need to change dose of anti-thyroid drug in the long term. </li></ul>
  30. 33. Pharmaceutical Care Issues – Hypothyroidism (examples) <ul><li>Monitoring for signs & symptoms for dosage </li></ul><ul><ul><li>Compliance can be a problem </li></ul></ul><ul><li>Advise on treatment increments </li></ul><ul><li>Slow dose increments in heart disease </li></ul><ul><li>Anaemia can be associated with hypothyroid </li></ul><ul><ul><li>Macrocytic mild anaemia (responds to thyroxine) </li></ul></ul><ul><ul><li>Pernicious anaemia common (treatment) </li></ul></ul>
  31. 34. Pharmaceutical Care Issues – Hyperthyroidism (examples) <ul><li>Explain dosage regime for carbimazole </li></ul><ul><li>Monitor for side-effects of carbimazole </li></ul><ul><ul><li>skin rashes, sore throat or mouth ulcers </li></ul></ul><ul><li>Monitor for side-effects of beta blockers </li></ul><ul><li>Block & replace – also on thyroxine </li></ul><ul><li>Eye grittiness ->hypromellose eyedrops </li></ul>

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