In the Name of God, Most Gracious, Most Merciful

A KALEIDOSCOPIC

PRESENTATION

OF THYROID

DISEASE- Dr.Mohammed Sadiq Azam

Postgraduate MD (Int Med)

Dept Of Internal Medicine, DCMS

Case 1

35/F presented with c/o diarrhoea, palpitations and a feeling of restlessness. She has been having increased sweating since 3 months. Complaints of increased appetite and decreased weights over 6 months.

On examination: Irregular pulse, 106pbm, PD 20 bpm.

Thyroid Profile revealed:T3: 210 ng/dl (high)T4: 15 ug/dl (high)TSH: <0.01 (low)

THE HYPERTHYROID STATE- Diagnosis & Treatment

EVALUATION THYROTOXICOSISMeasure TSH, unbound T4

TSH ↓unbound T4 ↑

TSH ↓ unbound T4 - N

TSH - N/↑unbound T4 ↑

TSH & unbound T4 - N

No further testsPrimarythryrotoxicosis

F/S/O Graves?

Unbound T3

High Normal

T3 toxicosis

Subclinicalhyperthyroidism

Follow up 6-12 weeks

TSH secreting pituitary adenoma or thyroid hormone resistance syndrome

Yes, Graves

MNG or Toxic adenoma

Yes, Toxic nodularhyperthyroidism

No, Low RNuptake

Yes, Destructive thyroiditisIodine excess or thyroid hormone excess

Rule out other causes including Stimulation by hCG

THYROTOXICOSIS

MANAGEMENT

3 approaches 1. Antithyroid drugs

2. Radioactive Iodine I131

3. Subtotal thyroidectomy

THYROTOXICOSIS

MEDICAL MANAGEMENT

1. ANTITHYROID DRUGS: > Carbimazole

> Propyl thiouracil

Dosage of Carbimazole:

0-3 weeks 40-60 mg daily

4-8 weeks 20-40 mg daily

Maintainence 5-20 mg daily for 18-24 months

ADR: Rash, Agranulocytosis

C/I: Lactating Mothers

MEDICAL MANAGEMENT

2. RADIOACTIVE I131 :

MOA: > Destroys functioning thyroid cells

> Inhibits their ability to replicate

Dose:

180-370 MBq (5-10mCi) orally (Dep. on goitre size)

• 4-6 weeks to be effective (long lag period)

• -blockers control symptoms in lag period.

• Severe cases: Carbimazole within 48 hrs of I131

THYROTOXICOSIS

MEDICAL MANAGEMENT

3. Role of -blockers: ONLY SYMPTOMATIC RELIEF

(within 12-24 h)

Propronolol: 160 mg/day

Nadolol: 40-80 mg/day

T3 toxicosis : I131(555-110Mbq), Hemithyroidectomy

THYROTOXICOSIS

MANAGEMENT OF ATRIAL FIBRILLATION

• Ventricular Rate responds little to Digoxin.• Good response to addition of - blockers.• CARDIOVERSION to revert to sinus rhythm.

(Only after TSH/T4 )• Anti coagulation with Warfarin / Aspirin.

• Generally control of serum T4 causes a return to sinus rhythm.• Drugs provide symptomatic relief.

THYROTOXICOSIS

GRAVES’ OPTHALMOPATHY

• Gritty sensation, Discomfort, lacrymation

• Exopthalmous

• Periorbital oedema, Chemosis, Scleral injection

THYROTOXICOSIS

MANAGEMENT - GRAVES’ OPTHALMOPATHY

1. Reassurance

2. Methyl cellulose drops grittiness, discomfort

3. Tinted glasses / Side shields excess lacrymation

Complications:1. Corneal Ulcer: Lid lengthening Sx

2. Papilloedema/Loss of acuity/Field defects:

URGENT trt. with PREDNISOLONE 60mg/d

THYROTOXICOSIS

GRAVES’ OPTHALMOPATHY

EFFECT OF THERAPY

BEFORE AFTER

Case 2

32/F come to hospital for routine physical examination and master heath checkup. Healthy. No specific complaints.

Thyroid profile:T3: 124 ng/dl (normal)T4: 9.1ug/dl (normal)TSH: 7.5 uIU/ml (high)

SUBCLINICAL THYROID DYSFUNCTION- A Tricky situation

INCLUDES:

Subclinical hypothyroidism

Commonly encountered

Subclinical hyperthyroidism

Rare entity

SUBCLINICAL HYPOTHYROIDISM Defined as:

“Biochemical evidence of thyroid hormone

deficiency in patients who have few or no

apparent clinical features of hypothyroidism.”

Previously called:

Mild hypothyroidism

Early thyroid failure

Preclinical hypothyroidism

Decreased thyroid reserve

SUBCLINICAL HYPOTHYROIDISM

Associated with risk of cardiac,

neuropsychiatric and dyslipidemic

abnormalities.

Risk of neonatal hypothyroidism if

encountered in pregnancy.

Risk of progression to overt hypothyroidism

is high when TSH is elevated and Anti TPO

Ab+

SUBCLINICAL HYPOTHYROIDISM

Recent guidelines do not recommend

routine treatment when TSH levels are

< 10 mU/L. (Har 18th ed, Pg 2922)

Confirm sustained elevation of TSH over a

3 month period prior to initiating therapy.

Start with low dose of 25-50ug/day with

the goal of normalising TSH.

Case 3

23/F, Primi Gravida, no past history of thyroid disease. TFT during ANC (12 weeks GA) revealed a normal T3, T4 but raised TSH 6.4uIU/ml.

No treatment done, at term (36 weeks) her TSH increased to 8.2 uIU/ml (T3, T4 Normal).8 months postpartum:T3: <10ng/dlT4: <0.30 ug/dlTSH: >150.00 uIU/ml

THYROID FUNCTION IN PREGNANCY - An Enigma in its own right!

FACTORS ALTERING THYROID FUNCTION

Transient increase in hCG during first trimester

stimulates TSH-R

Estrogen induced rise in TBG during Trimester I

sustained throughout pregnancy

Alterations in immune system expression of an

underlying thyroid disease

Increased thyroid hormone metabolism by placenta

Increased urinary excretion of iodide high risk of

deficiency in women taking <50ug of iodide/day

The hCG phenomenon Rise in hCG in first trimester is accompanied by a

reciprocal fall in TSH that persists upto the middle of

pregnancy.

Weak binding of hCG, which is present at very high

levels to the TSH-R

hCG induced changes in thyroid function can result in:

Transient gestational hyperthyroidism

Hyperemesis gravidarum

Rarely warrants use of antithyroid drugs

HYPOTHYROIDISM - PREGNANCY

Maternal hypothyroidism occurs in 2-3% of women of

child-bearing age.

All pregnant women & those planning pregnancy

(esp with family history) must be screened for

hypothyroisism in first & third trimester.

Most pregnant women with primary hypothyroidism

require an additional 25-50ug increase to their dose.

Subclinical hypothyroidism must be treated

TSH Target to treat in pregnacy: 2.5-3.0uIU/ml

HYPERTHYROIDISM - PREGNANCY

Rare

Pregnancy has an attenuating influence

on hyperthyroidism due to associated

immunosuppression

Medical therapy is the trt of choice

HYPERTHYROIDISM - PREGNANCY

PTU or Carbimazole?

Both cross placenta, can cause low T4 and high TSH in

fetus

Maternal T4 flux across placenta is highly variable

PTU > 200mg / Carbimazole >15mg is undesirable

(esp in III trim)

Serum free T4 should be maintained in upper limit of

normal and no attempt at normalisation must be made.

HYPERTHYROIDISM - PREGNANCY

In most cases maintainence dose must be 200mg

PTU or less in early pregnancy.

PTU preferred to methimazole due to risk of fetal

aplasia cutis with the latter.

Emerging reports of a “carbimazole

embryopathy” have made PTU the drug of

choice. (LeBeau et al. Thy dis dur preg. Endo

Clin North Am 2006;35:117-136, vii)

Case 4

65/M, admitted with c/o severe abdominal pain and vomintings. High grade fever+.On examination, RIF tenderness + with Guarding and rigidiity +. Patient was taken up or emergency laparotomy for perforated appendix.Post op case kept in SICU, Thyroid profile revealed:T3: 43 ng/dl (low)T4: 8.7 ug/dl (normal)TSH: 3.8 uIU/ml (normal)

SICK EUTHYROID SYNDROME- To treat or not to treat?

SICK EUTHYROID SYNDROME

Abnormalities of circulating TSH or thyroid

hormone levels as a consequence of any

acute, severe illness.

Major cause of these hormonal changes is the

release of cytokines such as IL-6.

Unless a thyroid disorder is strongly suspected,

the routine testing of thyroid function should

be avoided in acutely ill patients.

SICK EUTHYROID SYNDROME (SES)

Most common hormone pattern in SES:

Low T3 (total & free)

Normal T4

Normal TSH

Magnitude of fall in T3 correlates with the severity of

the illness.

Decreased peripheral conversion of T4 T3. leading

to increased rT3 (more due to decreased clearance

rather than increased production).

Low T3 also seen in fasting. (Decreased catabolism)

SICK EUTHYROID SYNDROME (SES)

Very sick patients exhibit a fall in total T4

as well (low T4 syndrome).

Poor prognosis

Fall in T4 is due to altered binding to

TBG. (Normal unbound fraction)

TSH may range from <0.1 to >20 mIU/L.

These alterations maybe due to IL-12 and

IL-18.

SICK EUTHYROID SYNDROME (SES) Acute liver failure:

Initial rise in total T3 and T4 (but not unbound hormone), due to

TBG release.

Levels become subnormal with progression to liver failure.

Acute psychiatric states (5-30%):

Transient increase in total & unbound T4

Normal T3, Low, normal or high TSH

HIV:

Early disease T3, T4 rise, TSH normal. T3 falls with progression

to AIDS.

Renal disease:

Low T3, normal rT3 (NOT increased rT3) due to increased rT3

uptake by liver.

SICK EUTHYROID SYNDROME (SES)

Based on history, severity of patient state,

thyroid hormone assays (including rT3)

Diagnosis is frequently presumptive

Treatment is controversial. Most of the

abnormalities recover with recovery from the

acute crisis.

Monitor TFT during recovery. No need of

hormonal replacement unless clinical evidence

of hypothyroidism + or low T4 levels.

THANK YOU