Dr. W A P S R WeerarathnaRegistrar in Medicine-WD 10/02

Hyperthyroidism/Thyrotoxicosis Causes of Thyrotoxicosis Graves’ disease-Pathology/presentation Common/rare complications of Graves’ disease Evaluation of a patient with Graves’ disease Management of Graves’ disease with recent

advances Graves’ opthalmopathy-management Graves’ disease in pregnancy Summary References

Thyrotoxicosis is a syndrome with excess FT4 & FT3

Hyperthyroidism indicates thyroid gland over activity resulting in thyrotoxicosis.

Thyrotoxicosis can result without hyperthyroidism when stored hormone is released from damaged thyroid.( subacutethyroiditis/ excess thyroid hormone ect..)

Primary Thyrotoxicosis Secondary hyperth.hyperthyoridism without hyperthyroidism

Graves disease (commonest cause 70-80%) Toxic multinodular goitre Toxic adenoma Functioning thyroid metastasis Struma ovarii-ectopic thyroid tissue Activating mutation of TSH receptor Activating mutation of Gsa (McCune-Albright

syndrome) Drugs: iodine excess (Jod-Basedow phenomenon)

TSH-secreting pituitary adenoma/TSHoma Thyroid hormone resistance syndrome Chorionic gonadotropin secreting tumors Gestational thyrotoxicosis. Testicular malignancies.

Subacute thyroiditis/de Quervain’s/post-partum

Silent thyroiditis Thyrotoxicosis factitia Thyroid destruction: use of amiodarone,

lithium, interferon-alpha & beta, interleukin-2, radiation & infarction of adenoma

Autoimmune disorder resulting increased synthesis & release of thyroid hormones

Female: male= 8:1 Common among 20-40 years Accompanied by infiltrative opthalmopathy in

60% specially in smokers! Subclinical opthalmopathy is detected by

CT/MRI.Infiltrative dermopathy /pretibial myxoedema in 1-2 % over shins, dorsum of foot. (5 P’s)

Thyroid acropatchy- uncommon <1% resembling finger clubbing & almost accompanied with opthalmopathy, pretibialmyxoedema

Painless palpable goitre more than 90% often with a bruit

Auto Ab’s bind to TSH receptors in thyroid cell membrane & stimulate the gland to hyperfuncton-TSI/TSHrAb

Familial tendency- H/O Graves’ disease or hashimoto’s thyroiditis

Associates with HLA-B8 & HLA-DR3 Thymus gland is typically enlarged & serum ANA

levels usually elevated showing underlying autoimmunity

Dietary supplementation can trigger the disease & treated with amioderone or KI have increased risk.

Other organ specific autoimmune diseases-sjogren’s syndrome/celiac disease/pernicious anemia/Addison’s disease/vitiligo/T1DM/hypoparathyroidism/MG/alopecia areata ect…

Opthalmopathy-20-40%upper eye lid retraction(Dalrymple sign)lid lag(von Graefe sign)staring appearance(Kocher sign)chemosisconjunctivitisperiorbital edemaproptosis( U/L in 5-10%)diplopia/extra ocular muscle dysfunctionimpaired visual acuity/fieldscorneal ulcerationgrittiness/increased tear production

Exopthalmos/proptosis

Staring appearance

Chemosis/periorbital swelling/conjuctivitis

Graves’ dermopathyglycoaminoglycans/lymphoid infiltrationskin-thickned/rough texturepre tibial/dorsum of footelephantiasis-rareassociated with high levels of

TSI/opthalmopathy

Pretibial myxoedema/elephantiasis

Presents with clubbing & swelling of fingers and toes.

Periosteal reaction of extremity bones Most are smokers! Strongly associated with thyroid dermopathy

that an alternative cause of clubbing should be sought in Graves patient without coincident skin and orbital involvement.

Onycholysis/Plummer’s nails

clinical• History and Physical examination.

labs

• Thyroid function test.

• Auto antibodies.

imaging

• Iodine uptake.

• Thyroid USS.

TFT-TSH/FT4 FT3 Second generation Anti TSH ab ->95% sensitivity

& specificity for diagnosis Anti TBG ab/ Anti TPO ab found in up to 80% of

Graves’ disease (also 15 % healthy women & 5% of men)

Thyroid scintiscanning with Tc 99 /I 131 in doubt about the nature of the goiter or thyrotoxicosiswithout hyperthyroidism is suspected.

ANA/ds DNA levels are elevated without evidence of SLE or other ARD’s.

The thyroid gland is diffusely enlarged, and often homogeneous.

parenchymal hypervascularity is observed. Goiter size is variable,

Carbimazole(CBZ)/methimazole/propylthiouracil(PTU)

Inhibits iodine organification by thyroid peroxidase(TPO), reducing T4 & T3

PTH- inhibits T4T3 Also inhibits TSI levels accounting for

sustained remission in 40-50% of GD

Titration regimen-initial high doses CBZ(40-60mg/d) or PTU(300-450mg/d)

initially/divided doses/3-4 per day Tail off every 4-8 weeks based on FT4 FT4 normalizes-CBZ-once/day with

maintenance dose 5-15mg/day & PTU 50-150mg/day

Treat for 18-24 months/monitor FT4 & TSH

Block-replace regimen-CBZ 40mg/d or PTU 300mg/d is maintained throughout

Hypothyroidism is avoided by giving T4-adding T4 100mic/d , needed 3-4 wks after starting.

T4 dose is adjusted based in T4 levels Continued for about 6mths with remission

rate similar to titration regimen! Needs few visits/control is smoother Only the dose of T4 is altered to optimize TFT NOT used in pregnancy!

Patients are reveiwed regularly in the year after stopping drugs-70% of relapses!

Supervenes 15% of autoimmune hypothyroidism.

Other drugs- Beta blockers(BB) Propanolol 20-40mg/ tds or other non-

selective BB used temporarily in sever thyrotoxicosis or thyroid crisis.

MAJORMINOR

Agranulocytosis (<0.1%) –within 3/12Papular or urticarial skin rashes(1-5%)

Vasculitis (lupus-like syndrome) Arthralgias

PolyarthritisNausea/vomiting

HepatitisPruritis

Cholestatic jaundiceHair loss

Liver failureAbnormal taste sensation

ThrombocytopeniaDrug fever

Stevens-Johnson syndrome *Lymphandenopathy

I 131 concentrates in the thyroid & damage it. 400-600 MBq, higher doses for larger goitres C/I – pregnancy & breast feeding Pregnancy is safe after 6 mths/avoid

fathering within 4 mths Avoid close contacts with children for several

weeks A/E- transient thyroiditis/exacerbation of

thyrotoxicosis/sialoadenitis- occasionally ATD’s given before & or shortly after RAI to

prevent thyroid crisis

ATD’s stopped before RAI-CBZ for 2 days/PTU for 2 weeks

NO overall risk of malignancy after RAI RAI acts slowly- wait 4-6 mths before

repeating for persisting thyrotoxicosis Transient hypothyroidism within 3 mths/

persistent in about 10% in 1st year TFT’s checked annually Poor response- large goiter/opthalmopathy

Remove sufficient thyroid tissue-more than less, hypothyroidism is treatable!

Recurrence 2-4% in best centers Complications(1%) are uncommon-

hypoparathyroidism/RLN palsy/bleeding/laryngeal edema

Ensure euthyroidism-avoid crisis-lugol’siodine 10 days before surgery to reduce vascularity & inhibit hormone synthesis

<50 years- initial course of ATD’s vs RAI Relapse is treated with RAI or surgery (ATD’s

seldom results in remission!) In elderly – indefinite treatment with low dose

ATD’s with risk of recurrence >50 years- RAI is the choice! RAI may worsens opthalmopathy, specially in

smokers & caution in opthalmopathy Try long-term ATD’s/ surgery/RAI combined with

tapering regimen of steroids

Eye discomfort-artificial rears(day)/oinments(night),glasses

Periorbital edema-elevate head end/diuretics(co-amilozide)/radiotheraphy(RT

Eye protective measures-eye tapes(night),severe-RT/surgery/corticosteroids

Congestive opthalmopathy-mild-selenium 100 mic bd

Severe-high dose prednesolone(40-60mg/d with tapering or

IV methylprednesolon pulse theraphy-500mg/wk for 6wks & 250mg/wk for 6wks

Other immunosupressives-rituximab Progressive/active disease-decompressive

surgery or retrobulbar RT Optic nerve compression- high dose

prednesols-80-120mg daily with a tapering regimen.

Lowest possible dose of ATD’s used to maintain euthyroidism

Some prefer PTU >CBZ-due to A/E like aplasiacutis 7 choanal atresia

Block-replace regimen is C/I- due to insufficient T4 crossing the placenta & causing neonatal hypothyroidism

<5% sufficient maternal TSHRab crossing the placenta causing fetal & neonatal hyperthyroidism

Inutero- tachycardia(.160/min) & poor growth Can check maternal TSHRab levels in T3 Mx- ATD’s to mother & monitor fetal

response by cordocentesis samples Neonatal hyperthyroidism is self limiting, due

to disappearance of maternal Ab’s within 3mths

BF-possible during ATD’s provided low doses are used

Thyrotoxicosis is a syndrome caused by excessive thyroid hormone & is commonly due to GD

ATD’s are usually initial treatment of GD & RAI or surgery being for relapses

TSHRab’s are sensitive & specific for GD RAI in the presence of opthalmopathy should

avoid unless prophylactic CS are given Care is needed in managing GD in pregnancy

to avoid A/E for fetus % mother.

Medicine international-vol 41:9 september2013

CMDT-2014,1069-1076