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The Patient Y3 semester 1 > Therapeutics of thyroid disease > Flashcards

Therapeutics of thyroid disease Flashcards

1
Q

Where is the thyroid gland located?

A
  • Located in the neck region on the anterior surface of the trachea (just below the larynx)
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2
Q

Hormonal control pathway:

A

Hypothalamus –> pituitary –> thyroid gland –> T3 (most active) or T4 (given most in treatment, given in HYPOthyroidism)

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3
Q

What is the drug for T3?

A

liothyrinine

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4
Q

What is the drug for T4?

A

levothyroxine

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5
Q

What type of thyroid disease is the hypothalamus associated with?

A

tertiary thyroid disease

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6
Q

What type of thyroid disease is the pituitary gland associated with?

A

secondary thyroid disease (as a result of disease in the pituitary and is accompanied by a cohort of other diseases aswell)

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7
Q

What type of thyroid disease is associated with the thyroid?

A

Primary thyroid disease (T3 and T4 not produced)

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8
Q

Primary Hypothyroidism prevalence?

A
  • At the level of the thyroid gland
  • increased production of thyroid hormones
  • Prevalence 2%, 10-20x more common in women (3.5% in women and 0.6% in men
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9
Q

Causes of hypothyroidism?

A
  • Autoimmune disease (Hashimoto’s thyroiditis)
  • Result of previous treatment (e.g. surgery) for hyperthyroidism
  • Iodine imbalance (uncommon in UK as it is put in bread)
  • Congenital hypothyroidism – where a child is born without a thyroid gland or a very small one (1 in 4000 children affected) If untreated, major development problems.
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10
Q

Symptoms of hypothyroidism?

A
  • Lethargy, weakness
  • Dry scaly skin
  • Sensitive to cold weather
  • Depression
  • Hair loss
  • Memory loss
  • Weight gain
  • Constipation
  • Puffy face and gruff voice with untreated disease
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11
Q

What is a Thyroid Function Tests (TFTs)?

A
  • Thyroid Stimulating Hormone (TSH)
  • Free (unbound) T4
  • Thyroid peroxidase antibody (rarely measured outside secondary care because T4 levels and TSH are very good at measuring)
  • Primary Hypothyroidism:
    •  TSH,  free (unbound) T4
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12
Q

Initial treatment of hypothyroidism?

A
  • Adults ≤50 years – initially 50-100 mcg thyroxine daily, adjusted 25–50 mcg every 3–4 weeks according to response
  • Adults >50 years & in heart disease - initially 25 mcg once daily, adjusted 25 mcg every 4 weeks (Start at lower dose if CVD risk)
  • Congenital hypothyroidism – initially 10-15 mcg/kg for neonates (max 50 mcg), adjusted 5 mcg/kg every 2 weeks
  • Measure TSH after 8-12 weeks (T½ of T4 = 7days) and three monthly until stabilised
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13
Q

hypothyroidism treatment – maintenance

A
  • Usual maintenance dose
  • 100-200 mcg adults
  • 50-200 mcg children, depending on age
  • Monitor TSH yearly for adults and every 4-6 months until puberty for children; aim for
  • Lower half of reference range
  • Symptom free
  • Monitor for angina
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14
Q

Combination treatments for hypothyroidism?

A
  • Liothyronine (t3) and levothyroxine (t4)
  • Evidence shows no evidence of benefit over monotherapy
  • Rarely used, usually only by endocrinologist when patient not responding to monotherapy
  • Natural thyroid extract
  • Desiccated animal thyroid gland
  • Not recommended as no evidence of benefit
  • Long term adverse effects uncertain
  • Source of much debate on patient forums as available in US
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15
Q

Patient Counselling for hypothyroidism?

A
  • Life-long treatment
  • Single daily dose
  • Do not take at same time as calcium or iron preparations or caffeine containing beverages – can effect absorption
  • Three strengths of tablet – common cause of confusion as they look the same(25, 50, 100)
  • Need for monitoring
  • Entitled to medical exemption certificate for prescription charges (if primary or congenital)
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16
Q

Prevalence of hyperthyroidism?

A
  • Autoimmune (Grave’s disease)
  • Toxic Nodules
  • Antibodies to TSH receptor stimulate the gland
  • increased production of thyroid hormones
  • Prevalence of 2% in women & 0.2% in men
17
Q

What does a hyperthyroid patient look like?

A
  • Anxious
  • Palpitations
  • Tremor
  • Weight loss
  • Tachycardia
  • Goitre
  • Heat intolerance
  • Warm moist skin
  • Difficulty sleeping
  • Diarrhoea
18
Q

Thyroid Function Tests (TFTs) for hyperthyroidism?

A

 Thyroid Stimulating Hormone (TSH)
 Free (unbound) T4
• Primary Hyperthyroidism
•  TSH,  free T4

19
Q

Treatment Options – Drug Therapy for hyperthyroidism?

A
  • Non-invasive
  • Low risk of long term hypothyroidism
  • Low long-term cure rate (<50%) for non-mild disease
  • Rare but serious side effects requiring monitoring
  • Drug treatment can be used either for suppression or to block and replace
  • Carbimazole is the most common drug therapy used and is a pro-drug, with methimazole as the active drug
20
Q

Drug therapy (thionamides) preferred for _____?

A
  • Children
  • Pregnancy, breast feeding (propylthiouracil only)
  • Uncomplicated, mild disease
  • Acute phase, prior to surgery or 131I
21
Q

Carbimazole (active metabolite: methimazole) or propylthiouracil mode of action ?

A

• Interfere with thyroid hormone synthesis by inhibiting thyroperoxidase activity in follicular lumen

22
Q

Carbimazole for hyperthyroidism?

A
  • First choice drug
  • Start with 15-40 mg daily (depends on severity of symptoms – can be higher)
  • Maintain high doses until TFTs normal (4-8 weeks)
  • Maintenance for 12-18 months
  •  by 25-30% monthly, until 5-15mg
  • Longer-term treatment may be required if relapse – occurs in up to 50% of patients with non-mild disease
23
Q

Blocking-replacement regimen (make the person completely hypothyroid)

A
  • Carbimazole 40-60 mg for approx 4 weeks
  • THEN Carbimazole 40-60 mg PLUS thyroxine 50-100 mcg
  • Makes patient temporarily hypothyroid
  • Not eligible for free prescriptions
  • Treat for up to 18 months
  • Thyroid gland returns to normal function when stop treatment
  • Not in pregnancy as only carbimazole crosses the placental barrier
24
Q

Pregnancy and carbimazole?

A
  • “Carbimazole is associated with an increased risk of congenital malformations when used during pregnancy, especially in the first trimester and at high doses (daily dose of 15 mg or more).
  • Women of childbearing potential should use effective contraception during treatment with carbimazole. It should only be considered in pregnancy after a thorough benefit-risk assessment, and at the lowest effective dose without additional administration of thyroid hormones—close maternal, fetal, and neonatal monitoring is recommended.” BNF
25
Q

Propylthoiuracil regimen?

A
  • 200-400 mg daily initially, in divided doses
  • 50 mg three times a day maintenance
  • Preferred in pregnancy, particularly in first trimester
  • Intolerant of carbimazole (rash, agranulocytosis)

Carbimazole is associated with an increased risk of foetal nail abnormalities

26
Q

CSM warning from BNF for Propylthoiuracil and Carbimazole:

A
  • Both can cause bone marrow suppression
  • decreased white cell count and increased infection
  • 0.3-0.5% – abrupt onset & not dose related
  • CSM warning BNF
  • “Doctors are reminded of the importance of recognising bone marrow suppression induced by carbimazole and the need to stop treatment promptly.
  • Patient should be asked to report symptoms and signs suggestive of infection, especially sore throat.
  • A white blood cell count should be performed if there is any clinical evidence of infection.
  • Carbimazole should be stopped promptly if there is clinical or laboratory evidence of neutropenia.”
27
Q

Patient Counselling (carbimazole)?

A
  • Carbimazole as a single daily dose and Propylthiouracil in divided doses
  • Duration of treatment & tapering to maintenance dose
  • Report signs of agranulocytosis: sore throat, mouth ulcer, bruising
  • Report signs of hepatic dysfunction with Propylthiouracil: pruritis, jaundice, dark urine
  • Advise on contraception if on carbimazole
  • Need for regular review, tests
  • Patients with hyperthyroidism ARE NOT entitled to medical exemption certificate for prescription charges
  • Patients on carbimazole who come into community pharmacies with a sore throat or mouth ulcers should be referred immediately to their GP, rather than sold over-the-counter treatments
  • If on blocking-replacement regimen, then need counselling for both treatments
28
Q

Radioactive iodine as treatment?

A 
Radioactive iodine (131I)
–	Non-invasive
–	Excellent cure rate
–	Likelihood of long term hypothyroidism
–	Can worsen eye disease
–	Avoid pregnancy/fatherhood
Preferred for:
–	First-line treatment except for mild disease or if radioactivity means is unsuitable
–	Failure to respond to drug treatment
–	Relapse after drugs
–	Comorbid cardiac disease
–	Toxic nodular goitre
29
Q

Surgery for hyperthyroidism? (preferred for)

A 
–	Excellent and rapid cure rate
–	High likelihood of long term hypothyroidism
–	Invasive 
–	Risk of damage to parathyroid gland 
–	Scarring and possible swallowing difficulties
•	Surgery preferred for
–	Oesophageal obstruction
–	Intolerance to drug treatment
–	Young adults
30
Q

131I or surgery??

A

• Do not use either of these immediately after diagnosis
• Make patient euthyroid first using drugs for several weeks
• Prevent thyrotoxic crisis (thyroid storm) due to dangerously high levels of T4 released into system
– Hyperpyrexia, dehydration.
– Heart rate greater than 140 beats per minute, hypotension
– Nausea, vomiting, diarrhoea, abdominal pain.
– Confusion, agitation, delirium, psychosis, seizures or coma

31
Q

Hyperthyroidism – adjuvant therapy?

A

Beta-blockade
• rapid relief of symptoms within 4 days: palpitations, anxiety, tremor
• C/I in asthma
• Propranolol, nadolol
• May need to be given 3-4 times per day as metabolism increased in hyperthyroidism
• Usually only needed for initial stages of treatment, when still symptomatic

32
Q

Drug-induced Thyroid Disease. Iodine:

A
  • Overdose e.g. Radiographic contrast media
  • Acute - inhibits release of T3/T4 from thyroid
  • Prolonged – suppress T3/T4 production
  • Rarely, can cause thyrotoxicosis if there is an underlying defect in autoregulation
  • Iodine deficiency (very rare in UK) can cause hypothyroidism due to inability to produce T3/T4
33
Q

Drug-induced Thyroid Disease. Amiodraone? How?

A

• Contains organic iodine

Hypothyroidism
• Can occur at anytime in treatment – 1-10% of patients
• Inhibition of synthesis & release of T4 & T3
• usually continue amiodarone and start replacement T4 therapy if necessary

Mild Hyperthyroidism
• Blocks conversion of T4 to T3, therefore increases TSH & T4
• Transient when start treatment – normalises in 3-4 months

Severe hyperthyroidism
• Increased production of T4 because of iodine content
• Direct thyroiditis – excessive release of T4 into circulation
• Withdraw therapy, if possible or may use carbimazole

34
Q

Drug-induced Thyroid Disease. Lithium? How?

A

Hypothyroidism
• inhibits iodine uptake and prevents T3 & T4 release
• can be transient & subclinical
• monitor TSH
• start replacement T4 therapy if clinical

Hyperthyroidism
• Rare, paradoxical effect

The Patient Y3 semester 1 (17 decks)

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