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Review endocrine physiology of
thyroid gland
Five selected types of thyrotoxicosis-
understand:
Pathophysiology
Clinical presentation
Investigations
Treatment
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Multiple Etiologies
5 are common
Diagnosis needed for
appropriate
management
Differentiation can
often be made through
history and physical
examination
23 woman presents for care
Chief Complaint:
“I went to the fitness club and a guy came up to
me and said that I should get my thyroid
checked!”
“I looked on the internet- I think that it’s
overactive!”
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Some findings of
thyrotoxicosis are present
regardless of the etiology
What symptoms?
What physical findings?
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She wants you to know that
her mother and sister have
“overactive thyroids”.
She has noticed that her
eyes have become more
prominent
She’s pretty sure from her
reading that she has
Graves’ disease
What findings are specific
to this condition?
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Weetman, A. P. N Engl J Med 2000;343:1236-1248
Clinical Manifestations of Graves' Disease
Pathogenesis of Graves' Disease.
Weetman AP. N Engl J Med 2000;343:1236-1248.
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Weetman, A. P. N Engl J Med 2000;343:1236-1248
Bahn, R. S. et al. N Engl J Med 1993;329:1468-1475
Computed Tomographic Scans of the Orbits (Axial Views) in a Patient with Graves' Ophthalmopathy
(Panel A) and a Normal Subject (Panel B)
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>60% of cases of thyrotoxicosis
HLA-DR, CTLA-4, but 20% concordance
monozygotic twins
Women in North America: 0.5/1000 (20 year
incidence)
Women:Men 10:1
Peak: age 40-60, but any age possible
Disease Etiology Specific
Symptoms
Signs Lab Tests Other tests
Graves’ TSI Orbitopathy,
Dermopathy
Firm, rubbery
gland +/-
orbitpathy
↓ TSH
↑ Free T4
TSH receptor
antibody*
Third generation assay sens 97%, spec 99%. JCEM 98, 6, June 2013, Barbesino
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Radioiodine
Two day procedure
Isotope limited:
Tuesday, Wednesday
Good for etiology
Good for structure
Good if planning
iodine therapy
Pertechnetate
Same day procedure
Short notice
Quick result
Good for high uptake
Not good for structure
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Contra-indicated in pregnancy and breast-
feeding
Can’t be performed in the face of recent radio-
contrast dye:
IVP
CT
Angiography
Tracer can’t compete with large exogenous
iodine dose for uptake
Kelp pills
57 year old woman
Chief Complaint:
“It’s the worst flu I’ve
ever had! I’ve got a
fever, I ache all over
and I’ve got the worst
sore throat and
earache!”
“Can I get some
antibiotics?”
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“Flu” started with
runny nose and cough
Progressed to fever,
generalized myalgia,
ear pain, pain with
swallowing
Thyroid is enlarged,
tender, firm, no nodes
Pearce, E. N. et al. N Engl J Med 2003;348:2646-2655
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Disease Etiology Specific
Symptom
s
Signs Lab Tests Uptake #
Pattern
Graves’
Disease
TSI Orbitopathy,
Dermopathy
Rubbery
gland +/-
orbitpathy
↓ TSH
↑ Free T4
High
Diffuse
Sub-acute
Thyroiditis
Auto-
immune+/-
viral
Pain,
tenderness
Firm,
tender
gland
↓ TSH
↑ Free T4
None
None
58 year old woman
Symptoms of
thyrotoxicosis
Enlarged neck for
many years
2010:
TSH 0.1 (0.5-5.5),
Free T4 20 (11-22)
2014:
TSH < 0.01, Free T4 35
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General Appearance: thyrotoxic
HR 100, BP 150/80
Lid-lag, stare, no proptosis
Thyroid asymmetrically enlarged
It is quite firm, irregular, non-tender with no
adenopathy
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Worldwide: iodine deficiency
Developed world: genetic and non-immune
Early: diffuse goitre
Later: nodularity
Slow growth with gradual functional
“autonomy”- dropping TSH with normal T4
Minority: biochemical and clinical
thyrotoxicosis
Some may have local obstructive signs
Avoid exogenous iodine
Jod-Basedow phenomenon
Iodine causes autonomous nodules to overproduce
thyroxine
Often older patients
Weight loss, atrial fibrillation, palpitations
No increased risk of malignancy
Biopsy if dominant nodule or increasing size
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49 year old man with
history major
depression treated
with medication
Improved mood, but
weight loss,
tachycardia,
diaphoresis, tremour
TSH < 0.01
Sertraline
Cytomel
TSH <0.01
Free T4 8 (11-22)
Free T3 9.3 (3.5-6.5)
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Disease Etiology Specific
Symptoms
Signs Lab Tests Uptake #
Pattern
Graves’
Disease
TSI Orbitopathy,
Dermopathy
Rubbery gland
+/- orbitpathy
↓ TSH
↑ Free T4
High
Diffuse
Sub-acute
Thyroiditis
Auto-
immune+/-
viral
Pain,
tenderness
Firm, tender
gland
↓ TSH
↑ Free T4
None
None
Toxic Multi-
nodular Goitre
“Autonomy”
Multifactorial
Slow goitre
growth
Asymmetric,
nodular
↓ TSH
↑ Free T4
High
Patchy
Toxic Nodule TSH receptor
mutation
Single nodule? Nodule,
remainder of
thyroid small
↓ TSH
↑ Free T4
High
Nodule
Factitious,
Iatrogenic
Exogenous
thyroid
hormone
History may
not be
obvious
Thyroid not
palpable
↓ TSH
↑ Free T4 or T3
None
None
Surgery
Sub-total
thyroidectomy
Rarely performed
Special cases:
Pregnancy and
intolerance of anti-
thyroid drugs
<2% recurrence rate
Hypothyroidism
common
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Thionamides:
propylthiouracil,
carbimazole and active
metabolite methimazole
(Tapazole)
Inhibit TPO: reducing
oxidation and
organification of iodide
This image cannot currently be displayed.
Methimazole Propylthiouracil
Serum Half-life 4-6 hrs 75 minutes
Tissue concentration 100X serum (gives 20 hr
duration of action)
Dosing Single daily 3X/day
Time to normalization
T3,T4
5.8 weeks 16.8 weeks
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Measure Free T4
monthly (TSH
unreliable)
Titrate dose down to
maintenance
Maximum remission
rate by 18-24 months
Discontinue and monitor
for relapse
Methimazole
starting dose: 20-40 mg
daily
Maintenance: 2.5-10
PTU
Starting dose: 100-200
TID
Maintenance: 50-100
daily in divided doses
~4%: rash, urticaria
<3:1,000 agranulocytosis
“Sore throat, high fever- notify physician”
Less common with low dose methimazole
Rarer:
PTU: hepatocellular necrosis
Methimazole: reversible cholestatic jaundice
PTU: vasculitis
Methimazole: scalp defect in neonates
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Either as initial treatment or second-line after
relapse following drugs
Progressive destruction of thyroid cells
Calculated dose based on uptake value and
size of gland
Hypothyroidism common
Time to normalization 4- 8 weeks
Worsen orbitopathy?
Radioiodine is treatment of choice
Concentrates within toxic nodule
Remainder of thyroid is suppressed and unaffected
Normal thyroid tissue recovers
Surgical resection is also effective
Some centres use repeat injection of ethanol
solutions
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During acute inflammation:
If marked local or systemic symptoms:
Prednisone 40-60 mg daily tapered over 6-8 weeks
If less symptomatic:
NSAIDs or ASA
If hypothyroid phase is prolonged and
symptomatic:
Thyroxine at modest dose 50-100 ug daily 2-3
months
Three additional references?
