1. NES Pharmacy CPD: Thyroid
Developed and delivered by Dr James Boyle
SpR in Endocrinology
Glasgow Royal Infirmary
February 2010
Amended by NES 2010

2. Glands and Hormones
Endocrine Glands: Glands that secrete their products (hormones) directly into the bloodstream rather than through a duct
Hormone: Chemical substance formed in the body that is carried in the bloodstream to affect another part of the body.

3. Thyroid gland Secrets two iodinated hormones T3 and T4.
Responsible for optimal growth, development and function of body tissues.
The synthesis of T3 and T4 requires iodine.
Release of T3 and T4 controlled by negative feedback.

4. TRH/TSH Feedback Loop 4

5. TRH Thyrotrophin releasing hormone.
Tripeptide produced by hypothalamus.
Release is pulsatile.
Downregulated by T3.
Travels through portal venous system to adenohypophysis.
Stimulates TSH synthesis and release.

6. TSH Thyroid stimulating hormone. Produced by the pituitary gland
Upregulated by TRH
Downregulated by T4, T3
Travels through portal venous system to cavernous sinus and body.
Stimulates several processes synthesis and release of hormones from the gland as well as gland growth

7. Thyroid hormones (T4, T3)
T3/T4 enter circulation transported to plasma proteins (99%).
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.
Regulation is based on the free component of thyroid hormone.
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.

8. Common diagnostic tools
TSH
Free T3,
Free T4
Thyroid autoantiboides
Thyroid ultrasound
Radio-isotope uptake and scan
Fine need aspiration of thyroid

9. Hypothyroidism
Clinical syndrome that results in deficiency of the thyroid hormones T4 and T3.
Common, prevalence 1-2%
F:M preponderance of 10:1
Congenital hypothyroidism is 1:4000 live births in the UK.

10. Types of hypothyroidism
Primary – Thyroid gland failure
Secondary – Pituitary failure
Tertiary – Hypothalamic failure
Sub-clinical

11. Aetiology of hypothyroidism
Agenesis
Thyroid destruction
Hashimoto’s thyroiditis
Surgery
Radio-iodine ablation
Infiltration (tumour, sarcoidosis)
Inhibition of function
Iodine deficiency
Anti-thyroid medications (Carbimazole, PTU, lithium, amiodarone)
Inherited defects
Transient
Postpartum
Sub-acute thyroiditis
Secondary/Tertiary (pituitary, hypothalamic)

12. Subclinical hypothyroidism
Estimated to affect 10% of females > 50yrs
Normal FT4/FT3, mildly elevated TSH
Few report symptoms
High risk of developing primary hypothyroidism
Can be associated with dyslipidaemia and subtle cardiac abnormalities.
Management a matter of clinical judgement

13. Clinical Presentation
Symptoms – Tiredness, cold intolerance, weight gain, constipation, aches and pains, depression, psychosis, angina and menorrhagia.
Signs – Hair loss, hoarseness, goitre, bradycardia, dry skin, slow relaxing reflexes, anaemia, heart failure, effusions, carpal tunnel syndrome, mxyoedema coma.

14. Diagnosis of hypothyroidism
Primary – Low FT4/FT3 and high TSH
Secondary – Low FT4/FT3 and low TSH
Tertiary – Low FT4/FT3 and low TSH
Sub-clinical – Normal FT4/FT3 and slightly high TSH

15. Management
Apart from subacute and postpartum thyroiditis most require long term replacement in form of Levothyroxine.
Starting dose usually mcg/daily.
Increased in steps of 25-50mcg every 4-6 weeks until FT4 is above middle of normal range and TSH normal/low normal.
Usual maintenance is 100mcg-200mcg/daily.
Suppressed TSH acceptable in certain cases

16. Management
In cardiac disease cautious replacement is required to decompensation ie. Thyroxine 25mcg with steps of 25mcg only.
In secondary/tertiary cases ensure good adrenal reserve before commencing thyroxine replacement and dont use TSH to assess response.
In pregnancy requirements go up % and more monitoring is required. Use TSH to monitor at least every trimester.

17. Management of subclinical cases
If TSH>10 – treat with thyroxine
If TSH 4-10 and asymptomatic – rpt TFT 6/12
If TSH 4-10 and symptomatic or antibodies +ve or dyslipidaemia or history or radioiodine or surgery – treat with thyroxine

18. Nurse Led Management
Patients often managed in nurse led clinics using questionnaire/algorithms.
Once patients with primary hypothyroidism are stable for 6 months (12 months for post radioiodine) they are discharged to GP for annual check.
Majority of patients unlikely to need to change dose of levothyroxine in the community.

20. Hyperthyroidism
Clinical syndrome associated with raised levels of the thyroid hormones T4 and/or T3.
Can be increased production, release from damaged gland or exogenous T4.
Prevalence 1-2%
Incidence 3 per 1000 per year
Secondary hyperthyroidism due to increased TSH secretion is very rare (>1% of all cases) Common, prevalence 1-2%

21. Aetiology of hyperthyroidism
Grave’s disease
Toxic multinodular goitre
Toxic adenoma
Thyroiditis (sub-acute, postpartum)
Drug induced (amiodarone)
Over treatment of T4
TSH secreting adenoma

22. Clinical Presentation
Symptoms – Heat intolerance, weight loss, loose motions, tremor, increased appetite, amenorrhoea, fatigue, anxiety, itch, angina.
Signs – Goitre, tachycardia, AF, tremor, warm hands, proximal myopathy, lid lag/retraction, Grave’s opthalmopathy, cardiac failure, hypertension, onycholysis, acropachy, pretibial myxoedema, thyroid storm .

23. Diagnosis of thyrotoxicosis
Primary – High FT4 and/or FT3 and low TSH
Secondary – High FT4 and/or FT3 and high TSH
Sub-clinical – Normal FT4/FT3 and low TSH

24. Grave’s disease versus Toxic MNG
Multinodular Goitre
Female>male
Peak age years
Diffuse and smooth
Lid lag and retraction, Grave’s eye signs, pretibial mxyoedma
Acropachy, onycholysis
Autoantibodies usually present
RAU scan uniform increased uptake
Female>male
Peak age >50 years
Multinodular goitre
Lid lag and retraction
No skin, nail or finger changes
Autoantibodies usually absent
RAU patchy, irregular appearance

25. Management
Carbimazole 20-40mg daily to render euthyroid (alternatively PTU).
Propanolol 40mg bd/tds to control symptoms in the short term.
Dose titration or “block and replace” regimen depending on individual practice.
Decision of definitive therapy needs to be made.

26. Drugs
Carbimazole: Inhibits hormone production, side effects include rash and agranulocytosis (0.1%).
Propythiouracil: Inhibits hormone production as well as blocking T4 to T3 conversion, side effects include rash and agranulocytosis (0.4%).

27. Pregnancy and lactation
Increased risk of fetal and neonatal thyrotoxicosis.
PTU preferred to Carbimazole due to less found in breast milk and less crossing placenta.
Carbimazole has been associated with aplasia cutis.
Requirements fall in Grave’s.
Lowest dose possible should be used.
Radio-iodine contra-indicated during pregnancy
TSH receptor titres should be determined early in third trimester to assess risk of neonatal thyroid dysfunction.

28. Management
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.
In toxic multinodular goitre/toxic adenoma need to use radioiodine or surgery to cure. Small number opt for long term drug therapy.

29. Radio-iodine therapy 131I is a safe and effective means of treatment.
Emits locally destructive beta particles to lead to cell damage and death over months.
Render euthyroid with drugs first and stop before to allow uptake of isotope.
In Glasgow, antithyroid drugs are not restarted afterwards unless thyrotoxicosis confirmed.
High risk of subsequent hypothyroidism.

30. Nurse Led Management
Patients often managed in nurse led clinics using questionnaire/algorithms.
Very few if any patients discharged to GP on anti-thyroid drugs
Nurse led management appropriate if diagnosis made, decision of definitive therapy made and no complications.
Majority of patients unlikely to need to change dose of anti-thyroid drug in the long term.

33. Pharmaceutical Care Issues – Hypothyroidism (examples)
Monitoring for signs & symptoms for dosage
Compliance can be a problem
Advise on treatment increments
Slow dose increments in heart disease
Anaemia can be associated with hypothyroid
Macrocytic mild anaemia (responds to thyroxine)
Pernicious anaemia common (treatment)

34. Pharmaceutical Care Issues – Hyperthyroidism (examples)
Explain dosage regime for carbimazole
Monitor for side-effects of carbimazole
skin rashes, sore throat or mouth ulcers
Monitor for side-effects of beta blockers
Block & replace – also on thyroxine
Eye grittiness ->hypromellose eyedrops