Transcript Thyroid hormones

NES Pharmacy CPD: Thyroid
Developed and delivered
by Dr James Boyle
SpR in Endocrinology
Glasgow Royal Infirmary
February 2010
Amended by NES 2010
Glands and Hormones
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Endocrine Glands: Glands that secrete their
products (hormones) directly into the
bloodstream rather than through a duct
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Hormone: Chemical substance formed in the
body that is carried in the bloodstream to
affect another part of the body.
Thyroid gland
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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.
TRH/TSH Feedback Loop
TRH
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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.
TSH
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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
Thyroid hormones (T4, T3)
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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.
Common diagnostic tools
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TSH
Free T3,
Free T4
Thyroid autoantiboides
Thyroid ultrasound
Radio-isotope uptake and scan
Fine need aspiration of thyroid
Hypothyroidism
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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.
Types of hypothyroidism
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Primary – Thyroid gland failure
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Secondary – Pituitary failure
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Tertiary – Hypothalamic failure
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Sub-clinical
Aetiology of hypothyroidism
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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)
Subclinical hypothyroidism
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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
Clinical Presentation
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Symptoms – Tiredness, cold intolerance,
weight gain, constipation, aches and pains,
depression, psychosis, angina and
menorrhagia.
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Signs – Hair loss, hoarseness, goitre,
bradycardia, dry skin, slow relaxing reflexes,
anaemia, heart failure, effusions, carpal
tunnel syndrome, mxyoedema coma.
Diagnosis of hypothyroidism
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Primary – Low FT4/FT3 and high TSH
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Secondary – Low FT4/FT3 and low TSH
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Tertiary – Low FT4/FT3 and low TSH
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Sub-clinical – Normal FT4/FT3 and slightly
high TSH
Management
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Apart from subacute and postpartum
thyroiditis most require long term
replacement in form of Levothyroxine.
Starting dose usually 50 -100mcg/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
Management
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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 50-100% and
more monitoring is required. Use TSH to monitor at
least every trimester.
Management of subclinical cases
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If TSH>10 – treat with thyroxine
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If TSH 4-10 and asymptomatic – rpt TFT
6/12
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If TSH 4-10 and symptomatic or
antibodies +ve or dyslipidaemia or history
or radioiodine or surgery – treat with
thyroxine
Nurse Led Management
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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.
Hyperthyroidism
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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%
Aetiology of hyperthyroidism
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Grave’s disease
Toxic multinodular goitre
Toxic adenoma
Thyroiditis (sub-acute, postpartum)
Drug induced (amiodarone)
Over treatment of T4
TSH secreting adenoma
Clinical Presentation
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Symptoms – Heat intolerance, weight loss,
loose motions, tremor, increased appetite,
amenorrhoea, fatigue, anxiety, itch, angina.
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Signs – Goitre, tachycardia, AF, tremor,
warm hands, proximal myopathy, lid
lag/retraction, Grave’s opthalmopathy,
cardiac failure, hypertension, onycholysis,
acropachy, pretibial myxoedema, thyroid
storm .
Diagnosis of thyrotoxicosis
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Primary – High FT4 and/or FT3 and low TSH
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Secondary – High FT4 and/or FT3 and high
TSH
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Sub-clinical – Normal FT4/FT3 and low TSH
Grave’s disease versus Toxic MNG
Grave’s Disease
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Female>male
Peak age 20-40 years
Diffuse and smooth
Lid lag and retraction,
Grave’s eye signs,
pretibial mxyoedma
Acropachy, onycholysis
Autoantibodies usually
present
RAU scan uniform
increased uptake
Multinodular Goitre
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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
Management
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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.
Drugs
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Carbimazole: Inhibits hormone production,
side effects include rash and agranulocytosis
(0.1%).
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Propythiouracil: Inhibits hormone
production as well as blocking T4 to T3
conversion, side effects include rash and
agranulocytosis (0.4%).
Pregnancy and lactation
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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.
Management
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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.
Radio-iodine therapy
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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.
Nurse Led Management
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Patients often managed in nurse led clinics using
questionnaire/algorithms.
Very few if any patients discharged to GP on antithyroid 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.
Pharmaceutical Care Issues –
Hypothyroidism (examples)
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Monitoring for signs & symptoms for dosage
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Compliance can be a problem
Advise on treatment increments
Slow dose increments in heart disease
Anaemia can be associated with hypothyroid
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Macrocytic mild anaemia (responds to thyroxine)
Pernicious anaemia common (treatment)
Pharmaceutical Care Issues –
Hyperthyroidism (examples)
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Explain dosage regime for carbimazole
Monitor for side-effects of carbimazole
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skin rashes, sore throat or mouth ulcers
Monitor for side-effects of beta blockers
Block & replace – also on thyroxine
Eye grittiness ->hypromellose eyedrops