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Department of Medicine

HYPERTHYROIDISM
DEFINITION- HYPERTHYROIDISM

Hyperthyroidism is a condition in which the thyroid gland


produces too much thyroid hormone (thyroxine)
The term thyrotoxicosis refers to the clinical
manifestations associated with serum levels of T4 or T3
that are excessive for the individual (hyperthyroidism).
EPIDEMIOLOGY

60-80% of cases of hyperthyroidism are caused by


Graves disease
Graves disease has a prevalence of up to 2% in women
but is less common in men. It typically occurs between
age 20-50 & can occur in the elderly
Hypothalamic-Pituitary-Thyroid axis

Diagnosis Hyperthyroidism
T3 and/or FT4
TSH
RISK FACTORS

Female sex
Smoking
History of other autoimmune diseases
Genetic
Pregnancy/ post partum ( can trigger hyperthyroidism in
those who are genetically susceptible)
SYMPTOMS

Symptoms
Sweats, tremors, palpitations
Weight loss, increased appetite
Insomnia
Heat intolerance
Diarrhoea
Oligomenorrhoea
Irritability/ labile motions/ anxiety
SIGNS OF HYPERTHYROIDISM
Tachycardia, irregular pulse ( atrial fibrillation)
Warm, moist skin
Fine tremor
Palmar erythema
Thin hair
Lid lag
Lid retraction
Goitre
Thyroid nodules
Thyroid bruit
Hyper-reflexia
SIGNS AND SYMPTOMS OF
HYPERTHYROIDISM
Hoarseness/
Nervousness/Tremor Deepening of Voice

Mental Disturbances/ Persistent Dry or Sore Throat


Irritability
Difficulty Swallowing
Difficulty Sleeping
Bulging Eyes/Unblinking Stare/ Palpitations/
Vision Changes Tachycardia

Enlarged Thyroid (Goiter) Impaired Fertility


Weight Loss or Gain
Menstrual Irregularities/
Light Period Heat Intolerance
Increased Sweating
Frequent Bowel Movements
Sudden Paralysis
Warm, Moist Palms

Family History of
First-Trimester Miscarriage/
Thyroid Disease
Excessive Vomiting in Pregnancy
or Diabetes
SIGNS OF GRAVES DISEASE

Exophthalmos
Ophthalmoplegia
Pretibial myxoedema
Thyroid acropachy ( extreme manifestation with
clubbing, painful finger & toe swelling & periosteal
reaction in limb bones)
THYROID EYE DISEASE

Seen in 25-50% of patients with Graves disease


Main risk factor if smoking
Retro- orbital inflammation & lymphocyte infiltration
results in swelling of the orbit
Signs:
Exophthalmos
Proptosis
Conjunctival oedema
Opthalmoplegia
Papilloedema
Loss of colour vision
Thyroid Ophthalmopathy

Department of Medicine,
RCSI
DIFFERENTIAL DIAGNOSIS

Common causes of Hyperthryoidism

Graves disease ( 60-80% of cases)


Toxic multi-nodular goitre
Solitary toxic thyroid nodule
Thyroiditis (Hashimotos; deQuervains)
Post-partum thyroiditis
Ectopic thyroid tissue eg. metastatic follicular thyroid cancer,
struma ovarii
Medications eg amiodarone, l-thyroxine excess
Jod-Basedow phenomenon
INVESTIGATIONS

Diagnosis of Hyperthyroidism
Thyroid functions tests ( TFTs)
TSH low
Free T4 elevated
SCREENING FOR AETIOLOGY

Establishing cause of Hyperthyroidism

Radionuclide scan

TSH receptor antibodies often raised in Graves disease

Anti-thyroid peroxidase antibodies ( may be raised in


autoimmune thyroid disease)

Thyroid ultrasound ( if nodules- if suspicious nodule, needs fine


needle aspiration to outrule malignancy)
Radionucleide scanning

Normal
Normal uptake Graves - diffuse uptake

Graves

Graves
Department of Medicine,
RCSI
MANAGEMENT- ACUTE SYMTPOMATIC

Beta blockers are used to manage the acute symptoms


of hyperthyroidism eg. Propranolol
Ensure no contra-indication to beta blocker use ( eg.
asthma) before commencing
MANAGEMENT- THERAPEUTIC

Graves Disease
3 main treatment modalities to reduce thyroid hormone
production

Medical
Radio-iodine
Surgical

The only prospective randomized trial between all three


modalities showed equal effectiveness of all 3 methods
& similar patient satisfaction levels.
MANAGEMENT- MEDICAL THERAPY

Carbimazole or Propylthiouracil (PTU)


Carbimazole 8-10x more potent than PTU
30mg CBZ = 300mg of PTU
Carbimazole is preferred due to longer duration
of action, more rapid efficacy & less side effects
Propylthiouracil is used in pregnancy as
carbimazole is associated with teratogenicity

Department of Medicine,
RCSI
MECHANISM OF ACTION

Carbimazole inhibits thyroid hormone synthesis by


blocking thyroid peroxidase
PTU inhibits the peripheral conversion of T4 to T3
SIDE EFFECTS

Agranulocytosis
Failure of bone marrow to make enough white cells(neutrophils)
Can result in profound sepsis
Most feared side effect
0.37% for PTU; 0.35% for Carbimazole
Usually occurs within 90 days of treatment
Warn patient to stop medication & get urgent medical review
including FBC if fever, sore throat, mouth ulcers
Cross reactivity do not use the second agent
Also check FBC/ stop medication if bruising/ bleeding/ symptoms
of pancytopaenia
MANAGEMENT-RADIOACTIVE IODINE

Radioactive iodine
used for treatment for 50 years.
first line therapy in America.
transient worsening of hyperthyroidism can occur as the
gland is destroyed.

Avoid in pregnancy
SIDE EFFECT OF RADIOACTIVE IODINE

Hypothyroidism
often of gradual onset after RAI
~2-5% per year
requires life long monitoring
treat with L-thyroxine
Can worsen thyroid eye disease
Radiation is emitted from gland post treatment-
avoid prolonged contact with children/ pregnant
women until same subsides
Caution in active hyperthyroidism as risk of thyroid
storm/ hyperthyroid crisis
MANAGEMENT- SURGERY

Used mostly if obstructive goitre or for those unable to


tolerate medications/ radio- iodine or those who have
contraindications to same
Can be used if co-existing suspicious nodule that needs
removal to exclude malignancy
Risk of complications including nerve damage, bleeding,
infection, hypoparathyroidism, hypothyroidism ( will need
thyroxine replacement therapy)
MANAGEMENT- THERAPEUTIC

If toxic multinodular goitre or solitary toxic nodule-initially


can treat with suppressive medication but need surgery
or radio- iodine as definite treatment
Toxic Multinodular Goitre

Initially-
control the thyrotoxic state with medication

Definitive
Radioactive iodine or Surgery
Solitary Toxic Nodule

Treatment: Radioactive iodine / Surgery


COMPLICATIONS OF HYPERTHROIDISM

Atrial fibrillation
Heart failure
Angina
Osteoporosis
Ophthlamopathy
Oligomenorrhoea/ amenorrhoea
Gynaecomastia
PROGNOSIS-MEDICAL THERAPY

Medication for Graves disease

Therapy for 12 to Remission rate


18 months
50%
PROGNOSIS- RADIOIODINE

Approximately 10 to 20 percent of patients fail the first


radioiodine treatment and require a second or
subsequent dose.
These patients usually have more severe
hyperthyroidism or larger goitres.
THYROIDITIS:
DE QUERVAINS

Clinical
Sub-acute, self limiting, post viral.
Flu-like illness, fever
Painful tender goitre
Initially hyperthyroid phase followed by hypothyroid
phase. TFTs usually normalise subsequently
Diagnosis
High ESR
TFT ( T4, TSH initially)
Radionucleotide scan no uptake

Department of Medicine,
TREATMENT OF THYROIDITIS

Analgesia- NSAIDS to reduce inflammation in gland

Beta-blockers

Steroids (taper over 2 weeks)

May need L- thyroxine if become hypothyroid

Monitor TFTs closely- every 2-4 weeks until normalise


SUBCLINICAL HYPERTHYROIDISM
Subclinical Hyperthyroidism
Normal T3 and FT4
TSH
Usually asymptomatic

Relatively common (1.3% of population)


Prevalence among patients with a goitre is 5%.
Approximately 1:16 will develop clinical
hyperthyroidism in 1 year.

Department of Medicine,
RCSI
SUB-CLINICAL HYPERTHYROIDISM

Reasons to treat:
1. Atrial fibrillation
2. Osteoporosis
3. Increased cardiovascular disease risk
4. Progression to clinical hyperthyroidism

Department of Medicine,
RCSI
SUB-CLINICAL HYPERTHYROIDISM

Repeat TFT after 8 weeks


If definite, than consider therapy in:
1. Atrial fibrillation +/- cardioversion to NSR
2. Possible hyperthyroid symptoms
3. Post menopausal women with osteoporosis
4. Multi-nodular goitre
Always aim for normal TSH

AACE Thyroid Task Force 2002


MCQ 1

A 45 year old lady presented to her GP with a 4 month


history of palpitations & weight loss & was found to be
hyperthyroid. She was commenced on carbimazole 20mg
po od 3 weeks ago for this. She returns today complaining
of a sore throat. Which test should be performed
immediately?
A. Free T4
B. FBC
C. TSH
D. Monospot
E. Throat swab
Answer= B ( important to outrule agranulocytosis)
MCQ 2

A 28 year old lady who is 6 months post partum presents


to her GP with weight loss, heat intolerance &
palpitations. On examination, she has a fine tremor,
diaphoresis & notable exophthalmos. Which of the
following is most likely to represent her thyroid function
test results?
A. Elevated T4, Normal TSH
B Elevated T4, Elevated TSH
C. Low T4, Elevated TSH
D. Elevated T4, Low TSH
E. Low T4, low TSH
Answer= D ( elevated T4 with suppressed TSH)
MEQ

A 45 year old lady attends her GP with anxiety, weight loss & heat intolerance.
The GP suspects hyperthyroidism.

Q1. List 7 signs that the GP should look for on exam to support the diagnosis of
hyperthyroidism ( 7 marks)
Answer= See slide 7

Q2. What is the most common cause of hyperthyroidism? ( 3 marks)


Answer= Graves disease ( 80% cases)

Q3. Thyroid function tests confirm hyperthyroidism. List 2 tests that can be subsequently
performed to confirm the aetiology of the hyperthyroidism. ( 4 marks)
Answer = Radionuclide scan ,TSH receptor antibodies often raised in Graves disease,Anti-
thyroid peroxidase antibodies ,ultrasound & FNA if nodule present

Q4. List 3 treatment options for hyperthyroidism & give 1 side effect of each. ( 6 marks)
Answer= Medications ( carbimazole or propylthiouracil), radio-iodine & surgical. See slides
for side effects
REFERENCES

Uptodate.com
Kumar & Clark- Clinical Medicine 2012
Harrisons clinical medicine 2012
Oxford handbook of clinical medicine 8th edition