Hyperthyroidism (burden of new era)##causes__features ##treatment ###treament of hyperthyroidism in pregnancy

 Hyperthyroidism

Thyrotoxicos is defined as the state of thyroid hormone excess and is not synonymous with hyperthyroidism, which is the result of excessive thyroid function. 

I.e., Thyroid hormone excess due to any cause if Thyrotoxicosis but hormone excess only due to hyper functioning of the thyroid gland is hyperthyroidism.

Etiology/causes::

The major etiologies of thyrotoxicosis are hyperthyroidism caused by-

1. Graves' disease (76%)

2. Toxic Multinodular goiter

 (MNG) (14%)

3. Toxic adenomas (5%)

Thyrotoxicosis without hyperthyroidism ~

4. Subacute thyroiditis

5. Post partum

6. Other causes of thyroid destruction: amiodarone, radiation

7. Ingestion of excess thyroid hormone (Factitious thyrotoxicosis)

8. Extrathyroidal source of thyroid hormone (Struma ovarii)

9. TSH-secreting pituitary adenoma 

(Choriocarcinoma and hydatidiform mole)

Clinical features::

Symptoms:

Common:

1. Weight loss despite normal or increased appetite

2. Heat intolerance, sweating

3. Palpitations, tremor

4. Dyspnoea, fatigue

5. Irritability, emotional lability

Less common

6. Diarrhoea (even steatorrhoea)

7. Ankle swelling

8. Angina

9. Anxiety, psychosis

10. Muscle weakness

11. Periodic paralysis

12. Osteoporosis

13. Amenorrhoea /oligomenorrhoea

14. Infertility, spontaneous abortion

15. Loss of libido, impotence

Signs ::

Common:

1. Weight loss

2. Tremor

3. Sinus tachycardia

4. Lid retraction, lid lag

5. Palmar erythema

Less common

6. Goitre with bruit

7. Atrial fibrillation

8. Systolic hypertension

9. Cardiac failure

10. Hyper-reflexia + clonus

11. Proximal myopathy

• All causes of thyrotoxicosis can cause lid retraction (upper eyelids retracted above) and lid lag (Upper eyelids fail to come down) but Exophthalmos and Diplopia (double vision) are only due Graves' disease. Pretibial myxoedema are also specific to Graves' disease.

Investigations

1. T3, T4, TSH 

. (If abnormal values are found, the tests should be repeated)

         Mostly: T3 and T4, TSH

Occasionally- T4 is in the upper part of the reference range and ↑ T3 (T3 toxicosis)

When biochemical thyrotoxicosis confirmed -

Further investigations to determine the underlying cause include-

2. TSH receptor antibodies (TRAb)

- ↑ in Graves' disease

3. 

Thyroid scan(99mTechnetium scintigraphy scans]

a. Diffuse: Graves' disease

b. Multinodular: Toxic multinodular goitre

c. Solitary nodule : Toxicadenoma

d. Low uptake-Transient thyroiditis, Extrathyroidal T4 source

4. Radio-iodine uptake tests:

 largely superseded by Thyroid scan

{Low-uptake thyrotoxicosis in Thyroid scan/ Uptake test - the cause is usually a transient thyroiditis}

Other investigations: (some are non specific)

5. Altered LFT

GGT (gamma-glutamyl transferase)

GGT (gamma-glutamyl transferase)

↑ ALT , ↑ and ↑ ALP (Alkaline phosphatase) ↑bilirubin

6. Calcium

7. Blood Glucose :(IGT)

8. ECG

: may demonstrate sinus tachycardia or atrial fibrillation.

Problems interpretating of T3, T4, TSH

There may be three types of difficulty.

1. Serious acute or chronic illness

 (the 'sick euthyroid' syndrome)

• typically presents with a low serum TSH, raised T4 and normal or low T3 

[Seems like hyperthyroidism]

• The tests should be repeated after resolution of the underlying illness.

• During convalescence- ↑TSH (seems to be hypothyroidism)

2. Pregnancy and oral contraceptives

• (These lead to greatly increased TBG levels)

• High or high-normal total T4.

Free T4 is usually normal

 But 

• TSH is often slightly suppressed in the first trimester.

[So seems like hyperthyroidism.]

3. Drugs

• Amiodarone decreases T4 to T3 conversion

• Free T4 levels may be above normal 

 though euthyroid.

• Conversely amiodarone may induce both hyper- and hypothyroidism

• the TSH level is usually reliable.

Management

Symptoms of thyrotoxicosis respond to β-blockade but definitive treatment requires control of thyroid hormone secretion.

Treatment options for Hyperthyroidism:

A. Antithyroid drugs (Carbimazole & Propylthiouraci)

1. Carbimazole

     Advantage/Properties:

• Usually preferred in patients < 40 yrs for first episode.

• Also has an immunosuppressive action, leading to a reduction in serum TRAb concentrations.

    Caution:

• Hypersensitivity rash 2%

• 50% relapse rate usually within 2 yrs of stopping drug

• Cannot be used during breastfeeding & contraindicated atleast in 1st

 trimester of pregnancy (aplasia cutis) 

°Agranulocytosis 0.2%

[Agranulocytosis is a rare but potentially serious complication that cannot be predicted by routine measurement of white blood cell count. It occurs usually within 3 months of treatment.

• Patients should be warned 

to stop the druga and seek medical advice immediately if a severe Sore throat or fever

 develop whilst on treatment.]

CBC should be performed to see ↑Neutrophil count. This is reversible on stopping treatment.

Carbimazole dosing guideline

■ Start carbimazole 20-40 mg daily. 8-hourly, or in single dose

■ Start concomitant 

Propranolol Hydrochloride

Propranolol Hydrochloride

 40-80 mg every 6-8 h. [to provide rapid partial symptomatic control]

■ Review after 4-6 weeks and reduce the dose of carbimazole, 

depending on clinical state and FT4/FT3

 (TSH levels are unhelpful at this stage).

■ Usually, results in subjective improvement within 10-14 days and leads to clinical and biochemical euthyroid at 3-4 weeks.

■ When clinically and biochemically euthyroid, stop propranolol.

■ In most patients, carbimazole is continued at 5-20 mg per day for 12-18 months.

■ Reduce carbimazole if FT4 ↓ or TSH ↑.

■ Increase carbimazole if FT4 or FT3 are above normal (and TSH ↓ even after several months with a normal FT4).

■ Stop treatment at end of course, if the patient is euthyroid on 5 mg daily carbimazole.

☞Rarely, T4 and TSH levels fluctuate between those of thyrotoxicosis and hypothyroidism at successive review

Appointments. In this case a 'block and replace' regime is required with carbimazole 30-40 mg daily and adding levothyroxine 100-150 µg daily as replacement therapy.

2. Propylthiouracil:

Starting dose 100-200 mg 8-hourly. Indication: First episode in patients < 40 yrs Advantage:

• Ideal drug for 1

 trimester of pregnancy.

• Can be used in breastfeeding woman.

   Caution:

  

• Hepatotoxicity- very rare but potentially fatal

• Rash, nausea, vomiting, agranulocytosis

• 50% relapse within 2 yrs of stopping drug

B. Surgery (Subtotal Thyroidectomy)

   Advantage/Indication:

• Large goitre

• Poor drug compliance, especially in young patients

• Recurrence after course of antithyroid drugs in young patients

   Conventional practice is -

■ Stop the antithyroid drug 10-14 days before operation and

■ Give Potassium Iodide

 (60 mg three times daily), which reduces the vascularity of the gland.

■ The operation should be performed only by experienced surgeons to reduce the chance of complications:

    Caution: 

■ Thyroidectomy should be performed only in euthyroid patients.

■ It is best avoided in professional singers, lecturer.

■ Adverse effects include-

• Hypothyroidism (~25%)

• Transient hypocalcaemia (10%)

• Permanent hypoparathyroidism (1%)

• Recurrent laryngeal nerve palsy (1%)

C. Radio-iodine

   Indication:

• Patients > 40 yrs

• Recurrence following surgery irrespective of age

• Other serious comorbidity

   Advantage

• Single or a few session required.

• Non invasive.

• No need to continue drug for long time.

   Caution

• Pregnancy or planned pregnancy within 6 mths of treatment 

Pregnancy or planned pregnancy within 6 mths of treatment

• Active Graves' ophthalmopathy

• Can develop Hypothyroidism, ~40% in first year, 80% after 15 yrs

• Can exacerbate ophthalmopathy

■ Patients must be rendered euthyroid before treatment

■ Antithyroid drugs should be stopped at least 4 days before

 not reintroduced until 3 days after radioiodine

And

 Patients on propylthiouracil should stop earlier because of its radioprotective action.

Hyperthyroidism in Pregnancy:

Antithyroid drugs are the treatment of choice for thyrotoxicosis in pregnancy.

In 1st trimester:

Propylthiouracil

- (as carbimazole is associated with rare cases of skin defect known as aplasia cutis)

Caution:

• It is important to use the smallest dose of antithyroid drug (optimally, 

<150 mg)

• Should switched to Carbimazole from

 2nd &3rd trimester:

Carbimazole

• Should be used instead of 

Propylthiouracil

. (because the later one is having potential hepatotoxicity).

• Lowest possible dose like 

15 mg/day

.Monitoring:

Frequent review is important .

Fetus

(heart rate and growth).

Mother-

• Free T4, T3 and TSH in each trimester.

• TRAb levels in the third trimester (to predict the likelihood of neonatal thyrotoxicosis) .

TRAb levels in the third trimester (to predict the likelihood of neonatal thyrotoxicosis) .

➣If TRAb levels are not elevated -

The antithyroid drug can be discontinued 4 weeks before the EDD

(to minimize the risk of fetal hypothyroidism at the time of maximum brain development).

After delivery-

if antithyroid drug is required and the patient wishes to breastfeed, then- 

Propylthiouracil

Propylthiouracil

is the drug of choice (as least excretion in the milk)

➣Thyroid function should be monitored periodically in the breastfed child.

Surgery

If poor drug compliance or drug hypersensitivity-

Thyroidectomy can be safely performed in the second trimester.