Primary Hypothyroidism: Management

Mathew John, MD, DM, DNB

Consultant Endocrinologist

Providence Endocrine & Diabetes Specialty Centre

www.endocrinologydiabetes.com

www.providence.co.in

Case

32 year old lady was evaluated for generalized

paraesthesias with aches and pains in different joints.

No arthritis was noted.

No fever/red eyes/ extraarticular

manifestations of collagen vascular diseases

Seen by a neurologist and investigated

Blood sugars : normal CPK: 300 U/L ( Normal < 200 )

Calcium parameters: normal

ANA/ dsDNA : negative RA factor : 86 ( Normal< 60 )

ESR: 26 mm / 1 hr Uric acid : 8.6 mg/dl (< 6 )

CBC: normal except for Hb: 9.8 gm/dl , MCV: 104

NCV: bilateral CTS

Think Thyroid

Vague symptoms

Mild anemia

Postpartumperiod

Multiple symptoms

Dimentia

Think Thyroidperiod

Elevated CPKAltered lipid profile

Carpal Tunnel Syndrome

Mild hyperuricemia

Hypothyroidism

• Diagnosis

• Etiology

• Treatment

What further to look before starting treatment ?

• Diagnosis

• Coexistent conditions

age of patient

severity of hypothyroidismseverity of hypothyroidism

coexistent drugs

coexistent medical conditions

The patient was seen by physician

Additional information generated

• Strong family history of hypothyroidism

• Delivered 6 months back and breast feeding • Delivered 6 months back and breast feeding

• Taking iron and calcium tablets

• Small firm goiter

• TSH > 100 IU/ml Free T4: 0.45 ng/dl

Diagnosis

Primary hypothyroidism Postpartum thyroiditis Postpartum thyroiditis

Etiology

PRIMARY HYPOTHYROIDISM

• Hashimoto’s thyroiditis-most commonPost partum thyroiditis

• Atrophic hypothyroidism• Atrophic hypothyroidism• Irradiation of thyroid• Surgical removal • Late stage invasive fibrous thyroiditis• Iodine deficiency• Drug therapy (Lithium, Interferon)• Infiltrative Diseases:Sarcoidosis, Amyloidosis

Scleroderma, Hemochromatosis

Diagnosis

Thyroid hormones feedback inhibit TSH

So So

If T3, T4 reducesTSH increases Primary hypothyroidism

The spectrum of diseaseEuthyroidFree T4/ T4: normal TSH : normal

Subclinical hypothyroidism Free T4/ T4 : normalTSH : elevated TSH : elevated

Overt HypothyroidismFree T4/ T4 : low

TSH : elevated

The spectrum of diseaseEuthyroidFree T4/ T4: normal TSH : normal

Subclinical hypothyroidism Free T4/ T4 : normalTSH : elevated TSH : elevated

Overt HypothyroidismFree T4/ T4 : low

TSH : elevated

The spectrum of diseaseEuthyroidFree T4/ T4: normal TSH : normal

Subclinical hypothyroidism Free T4/ T4 : normalTSH : elevated TSH : elevated

Overt HypothyroidismFree T4/ T4 : low

TSH : elevated

Further testing

• Anti TPO antibody (Thyroid Peroxidase)

• Anti Tg( Thyroglobulin) antibody

marker of autoimmunity

• Ultrasound thyroid : usually not needed

• FNAC thyroid:

usually not needed in autoimmune thyroiditis

needed in infiltrative diseases

Treatment

• Treated with thyroid replacement

• Normal thyroid produces both T4 and T3 , predominantly T4

• T3 is formed in periphery by deiodination of T4 • T3 is formed in periphery by deiodination of T4

• Commercial preparations are usually only L-thyroxine ( T4)

Dose

Thyroxine ( T4)

• Strengths: 25 mcg, 50 mcg, 75 mcg,88 mcg, 100 mcg and 125 mcg

• Adults require 1.6 mcg/kg/day

• Elderly : 1.0 mcg/kg/day• Elderly : 1.0 mcg/kg/day

T3 (Triodothyronine) : available as Tetroxin/ Cytomel

T3 as compare to T4 is

• 4 times more potent.

• Short duration of activity.

• Rapid onset of action

• Can be used for myxedema coma

Starting therapy

• Adults

50 to 100 mcg/day of thyroxine

• Elderly / Cardiac disease

25 mcg/day of thyroxine 25 mcg/day of thyroxine

• 80% bioavailability

• t1/2 1 week. Need 6 weeks for equilibration

Titrating therapy

• Call back after 6 –12 weeks with TSH

• Titrate 25-50 mcg/ day increments

• Repeat testing only by 3 months

• Only TSH is usually required for monitoring• Only TSH is usually required for monitoring

• Target TSH – lower half of the normal range (~2.5-3mU/L)

• Once TSH stable, repeat TFT annually. Ensure compliance

Changes with treatment

• Begin to feel better within 2 weeks

• Full symptom relief may take 3-6 months after TSH levels are normal

• Risk of over treatment • Risk of over treatment

– atrial fibrillation

– osteoporosis

Our patient

• Started on 100 mcg/day thyroxine in empty stomach

• Called back after 6 weeks

TSH : 63 mIU/L

• Patient reports good compliance

• Increased doses to 125 mcg/day

• Called back after 3 months

TSH : 38 mIU/L

Not controlled ?

Follow up

• What are the cause for high dose requiremts ?

• Is thyroxine treatment during breast feeding harmful to baby ?

• How long to continue treatment ? • How long to continue treatment ?

High dose requirement of thyroxine

• Medications

– Estrogen – Aluminium hydroxide

• Malabsorption (celiac disease, small bowel surgery)

• Compliance

– Estrogen

– Cholestyramine

– Ferrous sulfate

– Calcium

– Lovastatin

– Colsevelam

– Lanthanum carbonate

– PPI ( ?)

– Aluminium hydroxide

– Rifampicin

– Amiodarone

–Carbamazepine

– Phenytoin

–Magnesium containing laxatives

–Bulk laxatives with fiber

What to do ?

• Space out tablets of thyroxine from other offending drugs

• Can be converted to night dosing

• Empty stomach : 30-60 minutes before breakfast • Empty stomach : 30-60 minutes before breakfast

• To minimize interference with food

• No dose adjustment for kidney and liver disease

Hashimoto’s thyroiditis Chronic lymphocytic thyroiditis

• Most common cause of hypothyroidism

• Can be goitrous or non goitrous

• Anti TPO antibody positive

• Euthyroid Hashimoto’s : no treatment/ LT4 to reduce • Euthyroid Hashimoto’s : no treatment/ LT4 to reduce goiter size and antibody levels

• Very rarely associated with thyroid lymphoma

• Can have co-existent papillary carcinoma

Postpartum thyroiditis

• Usually 2-6 months after delivery

• Transient thyrotoxicosis followed by hypothyroidism /hypothyroidism

• Silent thyroiditis in postpartum period • Silent thyroiditis in postpartum period

• 23 % progress to permanent hypothyroidism

• More common with

severe hypothyroidism

higher Anti TPO antibody titre

Postpartum thyroiditisClinical course

Case continued

• Patient evaluated after spacing out the iron/calcium tablets

• TSH : reduced to 2.8 mU/L

• Continued same dose of LT4 125 mcg/day• Continued same dose of LT4 125 mcg/day

• Asked to come back after 3 months

TSH: < 0.01 mU/L

Next ?

Reversibility of primary hypothyroidism

• Reversible hypothyroidism: Post partum

Drug induced( alfa interferon, Li )

Infectious ( Whipple’s disease, Sub acute thyroiditis) )

• 20 % of autoimmune hypothyroidism has been • 20 % of autoimmune hypothyroidism has been found to be reversible

• Spontaneous disappearance of blocking antibodies

Do you need to treat subclinical

hypothyroidism

• 3-8 % of individuals have subclinical thyroid disease

•

• Most common cause is autoimmune thyroid disease

• 4.3 % progress to hypothyroidism is anti TPO • 4.3 % progress to hypothyroidism is anti TPO

antibody present

• Therapy indicated if

1. TSH > 10 mU/ml

2. Anti TPO positive

3. Goiter present

4. Menstrual irregularities/ infertility

5. Childhood

6. Bipolar disease/ depression

7. Increasing TSH

Hypothyroid symptoms and normal TFT (functional hypothyroidism)

• Many patients, especially in internet era

• Wilson's syndrome ( not Wilson’s disease) refers to the presence of common and nonspecific symptoms, relatively low body temperature, and normal levels of relatively low body temperature, and normal levels of thyroid hormones in blood.

American Thyroid Association Statement on "Wilson's Syndrome" , Updated May 24, 2005

ATA : no scientific basis for Wilson Syndrome

http://www.wilsonssyndrome.com/Assets/ebooks/WTSchecklistScore.pdf

Functional somatic syndromes.

• More than 20% of adults report significant fatigue

• 30% have current musculoskeletal symptoms

• Typical adult has one of the symptoms every 4 to 6

days

• More than 80% of the general population has one of these symptoms during any 2 to 4 week period.

Barsky AJ, Borus JF. Functional somatic syndromes Ann Intern Med 1999;130:910-21

Deja vu

• A lady with weight gain

• A lady with lowish resting heart rates

• Lady with tiredness

• Lady with memory loss• Lady with memory loss

• Lady with “ low” pressure

• A lazy boy with poor school performance

Have you ever started thyroxine for these people ?

Messages

• Suspect hypothyroidism

• Thyroxine is the treatment for primary hypothyroidism

• Dose changes in thyroxine according to TSH • Dose changes in thyroxine according to TSH

• Some causes of primary hypothyroidism are reversible

• Treat patients only with abnormal thyroid functions

Thank you

www.providence.co.in: for patient information materials

twitter.com/providenceendo : for slide presentations

Diagnosis

2.0 ng/dl

Normal range of population

Normal range for patient

TSH

Fre

e T

4

0.8 ng/dl4 mIU/L

0.3 mIU/L

Euthyroid Subclinical hypothyroidism

Not drawn to scale

Free T4

Disclaimer

The material for these slides were derived from various sources includingpictures and cartoons from the world wide web. I have tried my best toacknowledge all possible sources and references. However, if I have overlookedany particular reference, it is not done intentionally. Anyone reproducingmaterials from this presentations should acknowledge the author of the originalwork. The case given is imaginary and is given only to support the purpose ofwork. The case given is imaginary and is given only to support the purpose ofthis talk. Any similarity to published case report/ patient is unintentional.