Thyroid Emergencies And The Acute Take - RCP London

Thyroid Emergencies And The Acute Take

Dr Sutapa Ray.

Consultant Endocrinologist.

Harrogate And District Foundation Trust.

Lesson Plan : Case based discussions

Acute illness.

Thyroid storm

Drugs – Amiodarone

Pregnancy

Thyroid Follicle

Thyroid Hormone Synthesis

Peripheral Circulation and Conversion

T3 & T4 binds to globulin (TBG), transthyretin & albumin.

Only free hormone is biologically active.

T4 converted to T3 ( potent) and reverse T3 (inactive).

Central Regulation

Hypothalamus –

Pituitary –

Thyroid-

Axis

Interpreting TFTs

Primary Hypothyroidism

– T3 and T4 ∴TSH

Secondary Hypothyroidism – TSH ∴ T3 and T4

Primary Hyperthyroidism – T3 and T4 ∴ TSH

Secondary Hyperthyroidism

– TSH ∴ T3 and T4

Peripheral regulation of hormone production

T4 to T3 conversion

Illness

Nutrition

Drugs

Propylthiouracil

Glucocorticoids

Beta blockers

David

72 yr male.

– Smoker, COPD, IHD.

– Admitted with pneumonia and dehydration

– Noted tachycardia

– TSH < 0.05 miu/ l ( 0.05 – 4.5 miu/l)

David : Management ?

TSH :- < 0.05 mIu/l (0.05- 4.5 mIu/l) Supressed

T3 :- 1.6 pmol/l ( 2.3 – 5.6 pmol/l) Low

T4 :- 12.2 pmol/l (10- 20 pmol/l) Low normal

TFTs in non-thyroidal illness :- “Sick euthyroid”

T3 : reduced peripheral conversion

T4 : normal or reduced or spuriously high.

TSH : normal or reduced.

rT3: increased.

TFTs in acute illness

DO NOT check unless strong suspicion. Pyrexia , tachycardia, altered mental ( not responding to therapy)

AND

History of thyroid disease / Recent exposure to iodine contrast medium.

– ( Exception acute tachy-arrhythmias.)

TSH alone inadequate.

? Protective to reduce catabolism.

Supplements of no benefit.

45 yr old

– Admitted with UTI and acute confusion

– Temp 40 °C, BP 110/60, AF 160.

– Graves’s. Due clinic next week.

TSH < 0.05 ( 0.01 – 4.5 mIu/ l)

T4 > 70 ( 10- 20) pmol ,

T3 > 35 (2.5-6.5) pmol.

– Carbimazole 20 mgs OD, concordant.

Thyroid

>45 :- highly suggestive

25 - 44 :- likely

<25 :- unlikely

Adapted from: Burch HB, Wartofsky L.

Life-threatening thyrotoxicosis. Thyroid storm.

Endocrinol Metab Clin North Am 1993; 22:263.

Treatment Strategy

Reduce hormone production and release

Lower conversion of T4 to T3

Block peripheral action

Remove circulating hormones

Treat precipitating factors

Symptomatic treatment

Prevent synthesis :- Thionamides

Carbimazole/ Propylthiouracil (PTU)

Both act to blocks de-novo production.

No effect on hormone release.

PTU also reduces T4 to T3 conversion.

Quicker onset

Wolff–Chaikoff Effect and Escape: Iodine

Temporary inhibition of synthesis.

Effect exaggerated in auto-immune disease.

Escape in 2- 4 weeks.

Lugol’s Iodine: An hour after thionamides.

Rapidly blocks hormone release

Reduces hormone synthesis

Prevent peripheral conversion T4 to T3

Glucocorticoids Hydrocortisone 100mgs , IV, TDS

Iodinated radio-contrast agent Also blocks hormone release.

Give an hour after thionamides

Propylthiouracil (PTU)

Beta Blockers

Propranolol 60- 80 mgs 4- 6 hrly

Cardio-selective blockers

? Calcium channel blockers

Bile acid sequestrants

Hepatic conjugation

Secreted in bile

Free hormones released

Cholestyramine ↓ reabsorption

4 gm, oral, QDS

Plasmapheresis :- If all else fails!

Removes

– cytokines, antibodies, T3 and T4

Effective within 2 - 3 sessions

Prepare for urgent surgery

Thyroid Storm

Life-threatening. Mainly CVS:- Heart failure, arrhythmia

Mortality 10-30%.

Hormone levels may not be profoundly raised.

Precipitating factors Surgery, trauma, infection, parturition, Iodine load.

Multi-pronged approach

Effect of Amiodarone on Thyroid Hormones

Amiodarone and the Thyroid Gland

Intrinsic effect

↓ T4 to T3 conversion

Blocks T3 receptor binding

Destructive thyroiditis

Effect due to iodine content

Failure of Wolff Chakoff effect

Jod Basedow effect

– ↑ hormone production as

increased substrate (iodine)

Amiodarone and Hypothyroidism

Wolff–Chaikoff Effect - Failure to escape

Amiodarone induced Hyperthyroidism

Type 1

Pre-existing thyroid disease

Excess iodine as substrate

Increased T4 and T4 synthesis

Thionamides

Type 2

Without known disease.

Direct toxicity

Excess release of T3 & T4

Glucocorticoids

Expected changes with Amiodarone?

Expected changes with Amiodarone

At 0– 3 mths

T4 rises by 20 to 40

T3 decreases by up to 30

TSH may exceed the upper

limit of normal.

Beyond 3 mths.

T4 remains slightly elevated

or in the upper normal range.

T3 concentrations remain in

the low normal range.

TSH normalises

Kiran

Primi, 6/40 gestation.

Vomiting. Dehydration. Recent weight loss.

Admitted to Obstetrics for IV fluids.

TSH < 0.01 miu/l ( 0.01 – 4.5)

T4 22. pmol/l ( 10- 20 )

T3 6.7 pmol/l (2.5 – 6.3)

Diagnosis? Medication ?

Thyroid Physiology and Pregnancy

hCG and TSH similar structure

As hCG , TSH levels .

T4 / T3 transient elevation.

Exaggerated in hyperemesis

hCG stimulates TSH receptor

Lisa

Para 0, Gravida 2 , 9/ 40 gestation.

Recent UTI

TFTs done earlier TSH 6.5 miu/l ( 0.01 – 4.5)

T4 11.2pmol/l ( 10- 20 )

T3 3.8 pmol/l (2.5 – 6.3)

TPO antibodies elevated.

Diagnosis?

? Intervention – holiday for 3 weeks tomorrow

Subclinical Hypothyroidism and Pregnancy

TPO antibodies associated with spontaneous miscarriage and preterm labour

Treatment with Thyroxine may improve outcomes

Pregnancy and pre-existing hypothyroidism

T3 and T4 circulate bound to TBG

Dose of thyroxine ↑ to maintain free hormone level

Reduce to usual dose post delivery

Summary

Acute illness.

Thyroid storm

Effect of Amiodarone

Pregnancy.