Hyperthyroidism summary

1. Hyperthyroidism

Clinical features Goitre
ƒ Diffuse ± bruit
ƒ Nodular

GI
ƒ LOW ƒ N/↑ appetite
ƒ Diarrhoea ƒ Steatorrhoea
ƒ Anorexia ƒ Vomiting
Cardiorespiratory
ƒ Palpitation ƒ Sinus tachycardia ƒ AF
ƒ Dyspnoea ƒ Angina ƒ CMP ƒ Cardiac failure ƒ Ankle oedema in
absence of CF
ƒ ↑ pulse pressure ƒ Exacerbation of
asthma
Neuromuscular
ƒ Nervous / irritable ƒ Emotional lability ƒ Psychosis
ƒ Tremor ƒ Hyperreflexia ƒ Clonus
ƒ Proximal
myopathy
ƒ Muscle weakness
Dermatological
ƒ ↑ sweating ƒ Pruritus ƒ Alopecia ƒ Palmar erythema
ƒ Onycholysis ƒ Clubbing ƒ Pretibial
myxoedema
ƒ Spider naevi ƒ Pigmentation ƒ Vitiligo
Reproductive
ƒ Amenorrhoea /
oligomenorrhoea
ƒ Infertility /
spontaneous abortions
ƒ Loss of libido /
impotence
Ocular
ƒ Excessive
lacrimation
ƒ Grittiness
ƒ Lid lag / retraction ƒ Chemosis ƒ Corneal ulceration ƒ Exophthalmos
ƒ Ophthalmoplegia /
diplopia
ƒ Papilloedema ƒ Loss of visual acuity
Others
ƒ Heat intolerance ƒ Thirst
ƒ Fatigue / apathy ƒ Gynaecomastia
ƒ Lymphadenopathy ƒ Osteoporosis
• features unique to Graves’ dz are highlighted in blue • Important complications • Stigmata of hyperthyroidism: goitre, tremors, lid lag/retraction, myopathy
Causes • Graves’ disease • MNG • Toxic adenoma • Thyroiditis (subacute / de Quervain’s, or
post partum)
• Iodide induced (eg amiodarone,
contrast dye)
• Factitious hyperT4 • TSH induced (eg chorioCA,
hydatidiform mole)
• Follicular CA
Investigations TFT
Free T3 & T4, TSH
TRAb
Stimulating TSH-receptor Ab in Graves’ disease (>90%). May also be
blocking causing hypothyroidism
Other Abs
ƒ Anti-Thyroid Peroxidase Ab (TPO) & anti-Thyroglobulin Ab (TgAb) – high
levels are suggestive of GDz, Hashimoto’s, silent thyroiditis or post-
partum thyroiditis. <3% will be negative for all 3 autoimmune Abs
ƒ Anti-microsomal Ab – may be + in Hashimoto’s thyroiditis
TSI
Thyroid stimulating Immunoglobulin – used when Graves’ dz is suspected
by all other Abs are negative
Thyroid scan (I
131
or
Technetium
99)
Differentiate btwn types of ↑T4 ƒ Graves’ dz: Diffuse uptake ƒ MNG: maximal uptake by active nodules ƒ Toxic adenoma: uptake by adenoma, ↓ uptake by the remaining tissues
Thyroid U/S
Differentiate btwn cystic and solid thyroid nodules
FNAC
Differentiate nodule into benign, suspicious or malignant (5%) ƒ Follicular neoplasm – may be either follicular adenoma or CA.
Indistinguishable on FNAC
ƒ Interpreting TFT

T4
T3
TSH
Conventional hyperthyroidism
↑
↑
↓↓
T3 – hyperthyroidism
N
↑
↓↓
Subclinical hyperthyroidism
N
N
↓ / ↓↓
Primary hypothyroidism
↓
-
↑
Subclinical hypothyroidism
N
-
↑
Secondary hypothyroidism (eg hypothalamic or pituitary dz)
↓
-
↓↓


Graves’ Disease

Epidemiology ƒ Usually 30-50 YO ƒ Genetic factors: a/w HLA-B8, DR3 & DR2 ƒ Trigger: ?viruses / bacteria (E. coli & Yers inia enterocolitica – may possess cell-membrane
TSH receptor, causing cross-reactivity of Abs vs host TSH receptor)
ƒ a/w IDDM & pernicious anaemia ƒ cause of >90% of hyperthyroidism in Singapore Features ƒ Diffuse thyroid enlargement + thrill / bruit. May be nodular ƒ Ophthalmopathy
∼ Lid retraction ∼ Excessive lacrimation ∼ Conjunctivitis ∼ Corneal ulceration (due to increased
exposure)
∼ Proptosis ∼ Loss of visual acuity ± visual field defect
due to corneal oedema or optic n. compression
∼ Diplopia
ƒ Pretibial myxoedema (rare): raised pink / purplish plaques on anterior shin to dorsum of foot.
a/w pruritis, peau d’orange and coarse hair

2. Pathogenesis ƒ TRAb (TSH-receptor IgG Abs) vs thyroid follic ular cell stimulates thyroid hormone production ƒ Ophthalmopathy & dermopathy: immunologically mediated proliferation of fibroblasts which
secrete hydrophilic glycosaminoglycans causing in creased interstitial fl uid content + chronic
inflammatory cell infiltrate (usually lym phocytic). May cause optic nerve compression.
Clinical course 1. Prolonged periods of ↑T4 of fluctuating severity 2. Periods of relapses and remission of ↑T4 3. Single short-lived episode with prolonged remission ± eventual onset of ↓T4 Assoc. Non-specific Biochemical Abnormalities ƒ LFT: ↑ bilirubin, ALT, AST, GGT, ALP

ƒ Mild ↑ Ca

ƒ Glycosuria

Management 1.
Carbimazole ƒ Inhibit tyrosine iodination + immunosuppression (↓ serum TRAb conc) ƒ Duration: 6-18 mths then try stopping. Consider other Rx if relapse occurs (70%) ƒ Onset of efx: 3-12 wks. Meanwhile, use propanolol for symptomatic control ƒ 2 dosing strategy: either give just enough CBZ to keep PT euthyroid, or give excess CBZ
& correct hypothyroidism with L-thyroxine replacement
ƒ ADR: **Agranulocytosis (reversible, requires WBC monitoring. Stop drug and consult Dr
immediately in the event of a sore thr oat / fever!), rash, cholestatic hepatitis,
thrombocytopenia, vasculitis, lupus-like syndrome
ƒ Preferred over propylthiouracil due to lower dose (once daily vs tds dosing)
2.
Subtotal thyroidectomy ƒ Change antiT4 drug to potassium iodate PO 2 wks pre-Sx: short term inhibition of thyroid
hormone release and reduce gland size and vascularity

ƒ Outcome 1 yr post-Sx: 5% ↑T4, 15% permanently ↓T4, 80% euthyroid. Late onset ↓T4 or
↑T4 common, therefore require continued follow-up.

3.
Radioiodine
ƒ Indications: failed medical/Sx Rx, PT w cardiac dz, PT’s preference ƒ 4-12 wks for onset of effects ƒ Interim symptom control with β-blocker or carbimazole ƒ No a/w

↑ freq of malignancy or congenital malformation in offspring

ƒ Majority devt hypothyroidism (50% in 1
st
yr) – need f/u with TFT & thyroxine replacement

ƒ CI: pregnant, breastfeeding, severe Graves’ Ophthalmopathy (may worsen it)

4.
β-blocker (eg propranolol) ƒ For short term alleviation of symptoms. ƒ Useful for pre-thyroidectomy, or before onset of effects of radioiodine or carbimazole
5.
Ophthalmopathy ƒ Eyedrops / glasses + side shields ƒ Lateral tarsorrhaphy – for corneal ulceration ƒ Extra-ocular muscle Sx: for persistent diplopia. Alternative: prism glasses.
ƒ Papilloedema, loss of visual acuity or vi sual field defect: Urgent Rx with Prednisolone
60mg daily. Surgical orbital decompression if no improvement.


MNG

ƒ Usually women around 60 YO ƒ a/w AF and cardiac failure due to older age group ƒ Rx:
1. Radioiodine – hypoT4 less common 2. Partial thyroidectomy – for tracheal compression or retrosternal extension of goitre 3. Antithyroid drugs NOT useful as relapse occurs after drug withdrawal.
Toxic Adenoma

ƒ Follicular adenoma autonomously secreting excess thyroid hormone – negative feedback
inhibits TSH secretion and causes atrophy of the rest of the thyroid gland.
ƒ Usually females >40YO ƒ Hyperthyroidism may be mild, and 50% have isolated elevation of T3 only (T3 thyrotoxicosis) ƒ Rx: Hemithyroidectomy, radioiodine. Post-Rx hypoT4 uncommon due to compensation of
remaining thyroid gland. Antithyroid drugs not useful as relapse invariably follow drug
withdrawal.
Subacute (de Quervain’s) Thyroiditis

ƒ Virus induced (Coxsackie, mumps, adenovirus) thyroid inflammation. ƒ Usually females 20-40YO ƒ a/w pain radiating to angle of jaw and ears, worse on swallowing, coughing, neck movt.
Tender enlarged thyroid
ƒ Raised thyroid hormone levels for 4-6 wks followed by asymptomatic hypoT4. Full recovery
within 4-6 mths
ƒ Rx: Aspirin / NSAID for pain, propranolol for ↑T4 symptoms, ± prednisolone. Post-partum Thyroiditis

ƒ Unmasking of subclinical autoimmune thyroid disease ƒ Usually presents with ↑T4 symptoms for the first time within 6 mths post-partum. ƒ Recurs in subsequent pregnancies, progressing to permanent hypoT4 in the long term. ƒ Rx: Propranolol.

Indications for surg:

• Thyrotoxicosis not controlled by drugs • Compressive symps • CA • Cosmesis

3. Special Problems in Hyperthyroidism

Hyperthyroidism & Pregnancy

ƒ ↑T4 usually cause anovulatory cycles and infertility ƒ Carbimazole: crosses placenta causing treats fetus which is exposed to TRAb as well. Use
smallest dose possible to prevent fetal hypothyroidism & goitre
ƒ Breastfeeding: use PTU which is excreted in breast milk to a lesser extent c.f carbimazole. ƒ Radioiodine: absolute CI – causes fetal hypothyroidism. Atrial Fibrillation

ƒ Dysrhythmias present in 10% of thyrotox ic patients. Increasing incidence with age. ƒ Establish euthyroidism, then consider cardioversion (establish stable sinus rhythm in 50%).
β-blocker helps control ventricular rate as well.
ƒ Anticoagulation: aspirin in the elderly, warfarin in younger PTs and those with Cardiomegaly
/ atrial thrombus.


Thyroid Storm

Presentation Fever
From underlying sepsis or thyroid storm (uncontrolled ↑T4 /
post-subtotal thyroidectomy / post-radioiodine Rx)
Agitation / confusion

Tachycardia / AF

Accentuated thyrotoxic S/S
LOW, tremors etc
Multiorgan dysfunction
CNS: altered mental state, confusion, agitation, coma etc GI: abdo pain, diarrhoea, vomiting CVS: AF, heart failure, hyper/hypotension
Volume depletion
From fever, diarrhoea and increased metabolism
S/S of precipitating event
Eg sepsis, recent surgery
Management ™ Supportive 1. High flow O2

2. Monitor
ECG, vital signs q10mins, pulse oximetry
3. IV lines and fluid
Dextrose-saline with appropriate electrolytes. Beware of
precipitating heart failure.
4. Lab invxs
FBC U/E/Cr LFT TFT CXR: heart failure and infection ECG; ischaemia, infarction or dysrrhythmia Urinalysis ± C/S if sepsis suspected
5. Correct precipitating factors
eg sepsis, MI
6. Relieve fever
Paracetamol, tepid sponging
™ Drugs 1. β-blockers
IV esmolol, or IV / PO propranolol
2. PTU (propylthiouracil)
Blocks iodination and conversion of T4 to T3
3. Iodine solution
Inhibit thyroid hormone release
4. Dexamethasone
IV 2mg for glucocor ticoid support & to block conversion
of free T4 to T3
5. Treat CVS Cx accordingly
Eg digoxin, diuretics
6. Carbimazole
Long term control of ↑T4 with carbimazole.
Thyrotoxic periodic paralysis

• Periodic weakness a/w hypo K - Cause of hypoK is due to K shift intracellularly • usu Asian males, onset in early adulthood • episodic limb weakness lasting hrs to days • weakness ppted by exercise, onset usu at night during sleep (after strenuous exercise) • strength normal btwn attacks • ECG: ST depression, flattened T waves, U waves