Approach to
Hyperthyroidism
LEE QIN ZHI (JOSIAH)
Physician
Hospital Queen Elizabeth I & II
Origin of thyroid?
Briefly about function of thyroid hormone?
Outline
Diagnosis
Etiology
Complications of disease
Complications of treatment
Diagnosis
Hyperthyroidism vs Thyrotoxicosis
Hyperthyroidism
• Diagnosed based on TFT TSH + serum free T4 / T3
• Scenarios:
• Overt hyperthyroidism Symptoms
• T3-toxicosis
• T4-toxicosis
• Subclinical hyperthyroidism
• TSH-induced hyperthyroidism
• Critically ill hyperthyroid patients
Hypothalamus
TRH +
T3 -
Pituitary
TSH +
Thyroid
T4, T3
T4, T3, rT3
Target
tissues
T3
Quick test
Hypothalamus
TRH +
T3 -
Pituitary
TSH +
Thyroid
T4, T3
T4, T3, rT3
Target
Iodinase tissues
T3
Activation of thyroid hormone synthesis and
Hypothalamus secretion of excessive thyroid hormone
TRH +
Graves disease (Toxic diffuse goitre)
T3 -
Pituitary • Most common cause of primary
hyperthyroidism
• Due to anti-TSH receptor antibodies
TSH +
Toxic multinodular goitre (Plummer’s disease)
• Focal/diffuse hyperplasia of thyroid
Thyroid follicular cells
• Independent of regulation by TSH
T4, T3
Toxic adenoma
• May co-exist with GD Marine-Lenhart
T4, T3, rT3
Target syndrome
tissues Others
T3
• Thyroid papillary carcinoma
Graves disease
Robert James Graves Karl Adolph von Basedow
(1835) (1840)
Graves disease
• Syndrome that consists of:
• Hyperthyroidism
• Goitre (usually diffuse)
• Thyroid eye disease (Graves orbitopathy)
• Pretibial myxedema
• Thyroid acropachy
Graves disease
• Syndrome that consists of:
• Hyperthyroidism
• Goitre (usually diffuse)
• Thyroid eye disease (Graves orbitopathy)
• Pretibial myxedema
• Thyroid acropachy
Graves disease
• Syndrome that consists of:
• Hyperthyroidism
• Goitre (usually diffuse)
• Thyroid eye disease (Graves
orbitopathy)
• Pretibial myxedema
• Thyroid acropachy
Graves disease
• Syndrome that consists of:
• Hyperthyroidism
• Goitre (usually diffuse)
• Thyroid eye disease (Graves
orbitopathy)
• Pretibial myxedema
• Thyroid acropachy
Graves disease
• Syndrome that consists of:
• Hyperthyroidism
• Goitre (usually diffuse)
• Thyroid eye disease (Graves orbitopathy)
• Pretibial myxedema
• Thyroid acropachy
• Antibodies to thyrotropin receptor
(TRAb)
Activation of thyroid hormone synthesis and
Hypothalamus secretion of excessive thyroid hormone
TRH +
Graves disease (Toxic diffuse goitre)
T3 -
Pituitary • Most common cause of primary
hyperthyroidism
• Due to anti-TSH receptor antibodies
TSH +
Toxic multinodular goitre (Plummer’s disease)
• Focal/diffuse hyperplasia of thyroid
Thyroid follicular cells
• Independent of regulation by TSH
T4, T3
Toxic adenoma
• May co-exist with GD Marine-Lenhart
T4, T3, rT3
Target syndrome
tissues Others
T3
• Thyroid papillary carcinoma
Activation of thyroid hormone synthesis and
Hypothalamus secretion of excessive thyroid hormone
TRH +
Graves disease (Toxic diffuse goitre)
T3 -
Pituitary • Most common cause of primary
hyperthyroidism
• Due to anti-TSH receptor antibodies
TSH +
Toxic multinodular goitre (Plummer’s disease)
• Focal/diffuse hyperplasia of thyroid
Thyroid follicular cells
• Independent of regulation by TSH
T4, T3
Toxic adenoma
• May co-exist with GD Marine-Lenhart
T4, T3, rT3
Target syndrome
tissues Others
T3
• Thyroid papillary carcinoma
Activation of thyroid hormone synthesis and
Hypothalamus secretion of excessive thyroid hormone
TRH +
Graves disease (Toxic diffuse goitre)
T3 -
Pituitary • Most common cause of primary
hyperthyroidism
• Due to anti-TSH receptor antibodies
TSH +
Toxic multinodular goitre (Plummer’s disease)
• Focal/diffuse hyperplasia of thyroid
Thyroid follicular cells
• Independent of regulation by TSH
T4, T3
Toxic adenoma
• May co-exist with GD Marine-Lenhart
T4, T3, rT3
Target syndrome
tissues Others
T3
• Thyroid papillary carcinoma
Thyroid stores of preformed hormone released in
Hypothalamus excessive amounts due to insult to thyroid gland
TRH +
T3 -
Autoimmune
Pituitary • Hashimoto’s thyroditis
TSH + Infective
• Subacute (viral), TB, cellulitis
Thyroid Chemical
• Drug-induced e.g. amiodarone, lithium
T4, T3
Physical
• Anaplastic thyroid carcinoma, lymphoma
T4, T3, rT3
Target
tissues Others
T3 • Radiation, postpartum thyroiditis
Hypothalamus
Excessive stimulation by trophic & other factors
TRH +
TSH-mediated
T3 -
Pituitary • TSH-producing pituitary adenoma
• Usually macroadenoma by time of diagnosis
TSH +
bHCG + Trophoblastic disease / germ cell
tumours
Thyroid • Hydatiform mole or choriocarcinoma
• Testicular germ cell tumour
• Secreting b-HCG with thytotropic activity
T4, T3
Drugs
T4, T3, rT3
Target • Amiodarone
tissues • Iodinated contrast material
• L-asparaginase chemotherapy
T3
Hypothalamus
Extrathyroidal sources of thyroid hormone
TRH +
T3 -
Pituitary Endogenous / ectopic
• Struma ovarii (teratoma of ovaries
TSH + comprising mainly thyroid tissue).
• Metastatic thyroid carcinoma (bony
metastases from follicular thyroid cancer
Thyroid Exogenous
• Over the counter thyroid-containing
T4, T3 supplements
• Ingestion of animal thyroid gland
• Factitious ingestion of thyroid hormone
T4, T3, rT3
Target • Levothyroxine overdose
tissues
T3
Determining Etiology
• Clinical history and physical examination
• TRAb
• Thyroid ultrasound
• Thyroid scintigraphy
TSH Receptor Antibodies (TRAbs)
• TRAbs are specific biomarkers for the diagnosis of Graves disease
• Useful for predicting risk of relapse and guide definitive treatment
• 99% sensitivity and specificity for diagnosis of Graves disease
Thyroid Ultrasound
• Recommended when expertise is available, no stigmata Recommended as ??
of Grave’s disease, etiology not clear by history. • Expertise IS available
• Useful to distinguish between Graves and Thyroiditis • Bedside?
• Conventional greyscale and colour flow Doppler
• Looks for co-existing
recommended
nodules
• Thyroid vascularity & peak systolic velocity (PSV) of
inferior thyroid artery comparable sensitivity of 96% • Pre-requisite for RAI
and specificity of 95% • Truly necessary?
• Useful when nuclear imaging is contraindicated:
pregnancy, lactation
• Limitations: may miss early Grave’s disease and
resolving thyroiditis
Thyroid Ultrasound
• Peak systolic velocity (PSV) of inferior thyroid
artery >40 cm/s is suggestive of Graves’ disease
Thyroid scintigraphy
• Only technique for assessment of thyroid regional function and
detection of autonomously functioning thyroid nodules.
• Suggested when nodularity coexists with hyperthyroidism
Complications of
Hyperthyroidism
Complications of Treatment
What are the goals of treatment?
What treatment options are available?
Rapid and durable elimination of hyperthyroid state
General principles of treatment
• Acute management
• Symptom control
• Definitive treatment
• Long term plan
Symptom control
• Beta blocker: propranolol, atenolol, metoprolol, others
• Decreased heart rate
• Decreased systolic blood pressure
• Decreased muscle weakness
• Decreased tremors
• Improvement in degree of irritability, emotional lability
• Improvement in exercise tolerance
• Recommended in ALL patients with symptoms
• Especially elderly, patients with HR >90 bpm, coexisting CV disease
• Calcium channel blockers i.e. Verapamil or Diltiazem
• Affect heart rate control - if contraindicated for beta-adrenergic blockers
Comparing MMI + BB vs MMI alone showed
symptom improvement with addition of BB
• Propranolol in high doses >160mg/day also slowly decreases T3 by
30% via inhibition of 5’-monodeiodinase
• Takes 7-10 days, contributes little to therapeutic effects of drug
• Atenolol, metoprolol, bisoprolol are reasonable alternatives
• Anti-thyroid drugs (ATDs) / Thionamides
Definitive • Radioactive iodine (RAI)
treatment • Thyroidectomy
Anti-thyroid drugs / Thionamides
• Achieve euthyroidism quickly, BUT not cure
FT4 levels Methimazole Carbimazole
(9.01-19.05 pmol/L) (ATA 2016) (3mg MMZ=5mg CBZ)
1 to 1.5 X ULN (20-30) 5 - 10 mg daily 10 - 15mg daily
1.5 to 2 X ULN (30-40) 10 - 20 mg daily 15 - 30mg daily
2 to 3 X ULN (40-60) 20 - 40 mg daily 30 - 60mg daily
• Carbimazole preferred choice
• OD dose, faster onset, lower risk of major side effects
• Immunosuppresive role in Graves disease
• If pregnant, switch/start with Propylthiouracil (5mg CBZ = 50mg PTU)
• Block and replace regime not routinely used
Anti-thyroid drugs / Thionamides
• Pre-treatment
• FBC (with differential), LFT
• Complications (rare) – need to counsel educate patients
• Agranulocytosis (0.1-0.5% - rare BUT serious). Cross reactivity of CBZ and PTU.
• Counsel to seek healthcare advice and do FBC at earliest sign on fever, sore throat or other infection
• Hepatotoxicity (PTU > CBZ)
• Cutaneous / allergic reactions
• *Provide pamphlet
• Less common
• Pancreatitis
• ANCA-vasculitis (PTU)
Anti-thyroid drugs / Thionamides
• Monitoring
• TFT repeated at 2-6 weeks - take at week 6, review at week 8
• Once T4 normal, can reduce dose by 30-50%
• Repeat 3-6 monthly if stable on maintenance dose (5-10mg)
• 12-18 (up to 24) months, or 2-5 years of ATD for Graves disease trial stop
• Not to stop for Toxic MNG or Adenoma
• Considerations
• If started on high dose, can taper earlier – prevent iatrogenic hypothyroidism
• TSH may lag behind (misleading during initial period)
• T3-thyrotoxicosis
Radioactive Iodine
(RAI)
• Cost
• Government referral: RM125 + RM5
• Private referral: RM750 + RM30
• Non-Malaysian: RM800 + RM120
• Goal of treatment: Render the patient
HYPOTHYROID
• Can be administered as initial therapy,
without pre-treatment
• Elderly, co-morbidities, severe
hyperthyroidism require pre-treatment
• Complications: Rare
Post RAI monitoring
Thyroidectomy
• Goal of treatment: Render the patient HYPOTHYROID
• High cure rate for Graves disease
• Common complications:
• Hypocalcemia due to hypoPTH (transient or permanent)
• Recurrent or superior laryngeal nerve injury (temporary or permanent)
• Bleeding
• GA-related complications
• Ideally at centre with high-volume thyroid surgeons
Indications / preferences
How to choose?
ATD vs RAI vs Thyroidectomy
Graves disease long term plan
When is definitive treatment indicated?
• What to do if ATD does not work? – next lecture
• When should you refer to Endocrine?
A not-so-short note about
Subclinical
Hyperthyroidism
