Briefly covers causes of hyperthyroidism with focus on Grave’s disease and its treatment.

1. Hyperthyroidism
- Grave’s Disease
Internal Med GOOT champions
-Dr. L Perez Monserrat

2. Contents:
A) Case discussion
B) Background- causes of
hyperthyroidism
C) Management
D) Article comparison

3. Case summary
52 year old female, known RVD
Presented to OPD and then casualty
℅ of: abdominal pains, nausea, dizziness,
shortness of breath, painful lower limbs, loss
of appetite, noted to have protruding eyes,
emaciated
Taken bloods and reviewed: assessed as renal
failure, anaemia
Plan: crossmatch and t/f 2u RBC, admit,
augmentin, renal friendly arvs, pyridoxine
Results:
WCC 12.07
HB: 4.9__
MCV: 111.0
MCH: 36.0
Plts: 676
CRP: 90___
Na: 125___
K: 4.2
Ur: 32.3___
Cr: 244___
Egfr: 18

4. Day 2 Hospital Admission
Assessed as AKI, anaemia, RVD.
℅ of fatigue and palpitations
Exam noted as unremarkable
Put on normal saline @ 80ml/hr, ferrous sulphate

5. Day 4 Hospital Admission
Grand round
Noted to have exopthalmos and ‘stare’. Also scarring around thyroid gland with hyperpigmented changes. Patient admits to previous thyroid disease with radioactive
iodine treatment.
Vitals: afebrile, sats 98% ra, HR: 111, BP: 93/58
Pale with dry mucus membranes, no peripheral oedema, wasted
CVS: S1/S2. No added. Regular rhythm with slight tachycardia.
Chest: diffuse creps bilaterally
Abdomen: SNT no HSM
Thyroid: scar as above, normal in size, no nodules, or goiter felt
CXR: reviewed with ill-defined opacities bilaterally. No sputum
Assessed: RVD, to exclude PTB, with likely background hyperthyroidism- Grave’s Disease and? Current tfts, with AKI and a macrocytic anaemia
Plan: took bloods, continued arvs, continued augmentin and azithro, continued fluid replacement

6. Progress in ward
Continued to have a tachy, AKI improved on
fluids, dipstick normal, ECG done
Completed course of Augmentin, crepitations
improved,
Taken over by another doctor. Infective
markers decreased, aki resolved and dc to be
f/u at OPD.
Bloods for TFTs and B12, Folate taken 3
different times and not processed. To f/u tfts
at that week's OPD
Results:
CD4: 1217
VL:160
U&E normalised
Post-tf 7.1
MCV:109
ESR:37
ECG: sinus tachy, normal rhythm, otherwise
normal

7. Review at OPD
Came for review:
Vitals BP: 107/77 HR: 134 Sats: 99% RA
Exam was normal. Assessed as: RVD, resolved LRTI,
resolved AKI,? Megaloblastic anaemia, with
hyperthyroidism- thyrotoxicosis on bloods likely due
to Grave’s Disease
Plan: started on carbimazole 20mg dly, propanolol
20mg dly, continued arvs
Took bloods for B12 and Folate, anti- TSH receptor
antibodies, TPO antibodies. Will call patient if
abnormal.
Otherwise to f/u in 6wks to rpt lfts, fbc, tfts.
TSH: < 0.01 (0,34-5,60)
T4: 26.1 (7,6-16,1)
T3: 6.7 (4,3- 6,8))

8. Hyperthyroidism
Excessive thyroid hormones T4 and T3.
Symptoms:
Weight loss, malaise, sweating, palpitations, heat intolerance, stiffness, muscle weakness, vomiting, diarrhoea, eye complaints,
oligomenorrhoea, goitre, tremor
Signs: tremor, hyperkinesia, psychosis, tachycardia, afib, full pulse, warm vasodilated peripheries, systolic hpt, cardiac failure, wasting, eye
signs, goitre, bruit, proximal myopathy, palmar erythema
Eye signs: ‘ lid lag and stare’
Grave’s dermopathy: rare, occur on any extensor surface - - > pretibial myxoedema : infiltration of skin on shin - - > thyroid acropachy:
clubbing, swollen fingers, peri- osteal new bone formation
Atrial fibrillation, tachycardias and/or heart failure
Children: excessive height or growth, behavioral problems
‘Apathetic’ thyrotoxicosis

9. Investigations
● Serum TSH <0.05
● Increased free T4 or T3
● TSH- receptor Antibodies
specific for Grave’s disease
● TPO & thyroglobulin
antibodies
● Scintiscan 99Tm: antibody
negative patients to look for
toxic nodular disease

10. Causes:
Most common: Grave’s
Other common causes:
Solitary toxic adenoma/nodule: 5% of
cases. Most cases will be controlled by
anti-thyroid drugs but no remission usually.
Toxic multinodular goitre: older women,
usually also controlled by anti-thyroid drugs
but no remission
Uncommon causes:
De Quervain’s thyroiditis:
Transient from a viral inflammatory process.
Fever, malaise, pain in neck, tachycardia,
localized tenderness
Increased septic markets
Thyroid uptake scans: suppression of uptake
then hypothyroidism
Treat with aspirin and prednisone if severe
-TPO antibodies

11. Causes continued
Other uncommon:
Post-partum thyroiditis:
Pregnancy can cause hypothyroidism or hyperthyroidism
Amiodarone-induced thyrotoxicosis
Caused by the class 3 antiarrhythmic drug
2 types:
A) Type 1: pre-existing Grave’s disease or MNG. Triggered by high iodine content.
B) Type 2: no previous thyroid disease

12. Grave’s disease
Most common cause
● Autoimmune process:serum IgG antibodies bind to
TSH receptors stimulating thyroid hormone
● TSH Receptor-Antibodies: specific for Grave’s
● Associated with HLA- B8, DR3 and DR-2
● ? Molecular mimicry in genetically-susceptibke
individuals: Y.enterocolitica, E.coli & other gram - ves
contain TSH binding sites
● Thyroid eye disease: even though may be euthyroid
or hypothyroid
● Grave's dermopathy, lymphadenopathy or
splenomegaly
● Associated with pernicious anaemia, vitiligo &
myasthenia gravis
● Relapse & remission is common. 40% single
episode.
● Also associated with TPO antibodies

13. UpToDate Treatment of Grave’s
● Rapid amelioration of treatment: Beta-blocker
● Anti-thyroid: thionamide, radioiodine ablation, surgery
● Atenolol: 25-50mg initial, increase to 200mg prn
● Significant symptoms or at increased risk (older, CVS risks)=Start with methimazole
● Once euthyroid: radioiodine ablation, surgery or 1-2 year tx of methimazole or
long-term methimazole
● In absence of orbitopathy: suggest radioiodine over surgery
● If mild hyperthyroidism: can go straight to radioiodine or
● Large or obstructive goitre: surgery
● Wanting to fall pregnant: radioiodine or surgery preferred 6m prior; if want anti-thyroid
drugs: PTU during first trimester and continued
● Future: immunotherapy with thyrotropin receptor peptides??

15. Anti- thyroid drugs
Carbimazole
● Immunosuppressive
● Clinical benefit not apparent for 10-20
days
● TSH often remains suppressed for many
months after clinical improvement and
normalised t4/t3
● 20-40mg dly starting dose
● SEs: rash, n&v, arthralgia, agranulocytosis,
jaundice
Propylthiouracil
● 100-200mg 8hrly
● Similar SEs
● Additionally blocks conversion of
t4–t3
Thiamazole (methimazole) in US

16. Dosage regimen
Gradual dose titration
Start at doses then review after 4-6 wks
and reduce carbimazole
Once clinically and biochemically
euthyroid stop beta blocker
Reduce carbimazole if ft4 falls below or
TSH above normal (18 months)
Stop tx at end of course if euthyroid on
5mg carbimazole
Block and replace regimen
Full doses Ie 40mg carbimazole with
100ug of levothyroxine once euthyroid
Contraindicated in preg

17. Cochrane Review
Analysed 2 RTC: total 425 patients, with 204 to radioiodine and 211 to
methimazole
-did not look at propylthiouracyl
-single dose of radioiodine or 18 months of methimazole
-higher rates of worsening Grave’s orbitopathy with radioiodine (38%)
vs methimazole (19%)
But low quality evidence
Confounding factors:differing rates of smokers which is associated with
worsened orbitopathy
-euthyroidism not achieved by any radioiodine, but 94% with methimazole
-relapse more often with methimazole
-hypothyroidism was an adverse event with radioiodine (95%), 11%
drug-events related to methimazole
-cost comparison : without relapse : +- USD 1100 for methimazole, USD 1800
for radioiodine, similar trend for relapse

18. References
1) Feather, A. Randall, D and Waterhouse, M. 2021. Kumar & Clark’s Clinical
Medicine. 10th ed. London: Elsevier, pp 614-620.
2) Ma, C. Xei, J. Wang, H. Li, J and Chen, S. 2016. Radioiodine therapy versus
antithyroid medications for Grave’s disease [online] [Accessed 23 February
2022]
3) S Ross, D. 2022. Grave’s hyperthyroidism in nonpregnant adults: overview of
treatment. UpToDate.