Management of Hyperthyroidism, Subclinical hypothyroidism, Thyroid dysfunction in pregnancy & Sick euthyroid syndrome

1. In the Name of God, Most Gracious, Most Merciful

2. A KALEIDOSCOPIC
PRESENTATION OF
THYROID DISEASE
- Dr.Mohammed Sadiq Azam
Postgraduate MD (Int Med)
Dept Of Internal Medicine, DCMS

3. Case 1

4. 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)

5. THE
HYPERTHYROID
STATE
- Diagnosis & Treatment

6. EVALUATION
THYROTOXICOSIS
Measure TSH, unbound T4
TSH ↓ TSH ↓ TSH - N/↑ TSH &
unbound T4 ↑ unbound T4 - N unbound T4 ↑ unbound T4 - N
Primary Unbound T3 No further tests
thryrotoxicosis
TSH secreting pituitary
High Normal adenoma or thyroid
hormone resistance
T3 toxicosis syndrome
F/S/O Graves?
Subclinical Follow up
Yes, Graves
hyperthyroidism 6-12 weeks
MNG or
Toxic adenoma Yes, Destructive thyroiditis
Iodine excess or
No, thyroid hormone excess
Yes, Toxic nodular
hyperthyroidism Low RN
Rule out other causes including
uptake
Stimulation by hCG

7. THYROTOXICOSIS
MANAGEMENT
3 approaches 1. Antithyroid drugs
2. Radioactive Iodine I131
3. Subtotal thyroidectomy

8. 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

9. THYROTOXICOSIS
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

10. 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

11. THYROTOXICOSIS
MANAGEMENT OF ATRIAL FIBRILLATION
• Generally control of serum T4 causes a return to sinus rhythm.
• Drugs provide symptomatic relief.
• 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.

12. THYROTOXICOSIS
GRAVES’ OPTHALMOPATHY
• Gritty sensation, Discomfort, lacrymation
• Exopthalmous
• Periorbital oedema, Chemosis, Scleral injection

13. 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

14. GRAVES’ OPTHALMOPATHY
EFFECT OF THERAPY
BEFORE AFTER

15. Case 2

16. 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)

17. SUBCLINICAL
THYROID
DYSFUNCTION
- A Tricky situation

18. INCLUDES:
 Subclinical hypothyroidism
 Commonly encountered
 Subclinical hyperthyroidism
 Rare entity

19. 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

20. 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+

21. 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.

22. Case 3

23. 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/dl
T4: <0.30 ug/dl
TSH: >150.00 uIU/ml

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

25. 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

26. 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

27. 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

28. HYPERTHYROIDISM - PREGNANCY
 Rare
 Pregnancy has an attenuating influence
on hyperthyroidism due to associated
immunosuppression
 Medical therapy is the trt of choice

29. 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.

30. 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)

31. Case 4

32. 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)

33. SICK
EUTHYROID
SYNDROME
- To treat or not to treat?

34. 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.

35. 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)

36. 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.

37. 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.

38. 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.

39. THANK YOU