A CASE PROFILE OF THYROID DISEASE

- Dr.Mohammed Siraj

- Dr.Parvez Khan
- Dr.Mohammed Sadiq Azam - Dr.Praneetha Gayathri

HORMONOGENESIS
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THYROID GLAND

Thyroid Regulation
HYPOTHALAMUS - TRH ANT. PITUITARY - TSH TSH -R THYROID T4 and T3 PLASMA T4 + FT4 PLASMA T3 + FT3 TISSUES FT4 to FT3, rT3

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In the Thyroid Gland

There the following 5 steps in the hormonogenesis 1. 2. Trapping of inorganic Iodine from dietary Iodides Activation of Iodine to high valance I2

3.
4. 5.

Incorporation of I2 into Tyrosine of Thyroid Globulin

Coupling of formed MIT and DIT to form T4 & T3 Proteolysis of Thyroglobulin to release T4 & T3
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The Thyronines
Mono Iodo Tyrosine MIT Di Iodo Tyrosine DIT Tri Iodo Thyronine T3 half life 6 hours Tetra Iodo Thyronine T4 half life 7 days Reverse T3 - metabolically inactive T4 is 99.9% protein bound to TBG, TPA, TA T3 is 99.5% protein bound to TBG, TPA, TA Bound hormones are inactive should not be measured Only Free T4 and Free T3 are metabolically active 6

The Thyroxines
Tri Iodo Thyronine T3 - 10% is from thyroid gland - 90% derived from conversion of T4 to T3 Tetra Iodo Thyronine T4 - Is exclusively from thyroid gland From the thyroid gland - 80% of hormone secreted is T4 - 20% of hormone secreted is T3

Throid hormones in peripheral tissues

Plasma transport by thyroxine binding globulin TBG -75 -80%bound Transthyretin 10-15% Albumin 5-10%

Thyroid Function Tests

1. TSH 2. Free T4 3. Free T3 4. Anti-Thyroid Antibodies 5. Nuclear Scintigraphy 6. FNAC of nodule
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BASIC THYROID EVALUATION

FREE THYROXINE or FT4

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

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BASIC THYROID EVALUATION

FREE THYROXINE or FT4

EUTHYROID

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

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BASIC THYROID EVALUATION

FREE THYROXINE or FT4

PRIMARY HYPOTHYROID

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

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BASIC THYROID EVALUATION

FREE THYROXINE or FT4 PRIMARY HYPERTHYROID

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

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BASIC THYROID EVALUATION

FREE THYROXINE or FT4

SECONDARY HYPOTHYROID

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

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BASIC THYROID EVALUATION

FREE THYROXINE or FT4

SECONDARY HYPERTHYROID

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

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BASIC THYROID EVALUATION

FREE THYROXINE or FT4

SUB-CLINICAL HYPERTHYROID

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

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BASIC THYROID EVALUATION

FREE THYROXINE or FT4

SUB-CLINICAL HYPOTHYROID

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

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BASIC THYROID EVALUATION

FREE THYROXINE or FT4

NON THYROID ILLNESS or NTI LOW NORMAL HIGH

THYROID STIMULATING HORMONE - TSH

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BASIC THYROID EVALUATION

FREE THYROXINE or FT4

NTI or Pt. on ELTROXIN

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

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BASIC THYROID EVALUATION

FREE THYROXINE or FT4

PRIMARY NTI or Pt. SECONDARY HYPERTHYROID on ELTROXIN HYPERTHYROID

SUB-CLINICAL EUTHYROID HYPERTHYROID

SUB-CLINICAL HYPOTHYROID

SECONDARY NON THYROID PRIMARY HYPOTHYROID ILLNESS - NTI HYPOTHYROID LOW NORMAL HIGH

THYROID STIMULATING HORMONE - TSH

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THYROID HORMONES

TEST TSH

REFERENCE RANGE Normal Range 0.3 - 4.0 mU/L

Free T4 Normal Range 0.7-2.1 ng/dL TSH upper limit will soon be revised to 2.5 mU/L
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Thyroid Antibodies

Anti Microsomal (TM ) Antibodies Anti Thyroglobulin (TG) Antibodies Anti Thyroxine Per Oxidase (TPO) Ab. Anti Thyroxine antibodies Thyroid Stimulating (TSA) Antibodies
High titres TPO Ab in Hashimotos & Reidles thyroiditis Anti thyroxine Ab in peripheral resistance to Thyroxine 23 TSA (TSI) in Graves Hyperthyroidism

hypothyroidism

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Hypothyroidism

Epidemiology Presentation
Most common endocrine disease Females > Males 8 : 1 Often unsuspected and grossly under diagnosed 90 % of the cases are Primary Hypothyroidism Menstrual irregularities, miscarriages, growth retard. Vague pains, anaemia, lethargy, gain in weight
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Disease Burden
1. 2. 3.

4.

5% of the general population are Sub-clinically Hypothyroid 15 % of all women > 65 yrs. are hypothyroid Detecting sub-clinical hypothyroidism in pregnancy is highly essential order for TSH and FT4 routinely in all pregnant women at the beginning of each trimester All persons aged above 60 years Order for TSH 26

 Primary hypothyroidism with Goitre Aquired Hashimotos thyroiditis Iodine deficiency Drugs blocking synthesis or release of T4 Goitrogens Cytokines Thyroid infiltration Congenital Iodide transport or utilization defect Iodotyrosine dehalogenase deficiency TPO deficiencyn\ nd dysfunction Defects in thyroglobulin synthesis

Causes of Hypothyroidism

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 ATROPHIC HYPOTHYROIDISM Acquired HASHIMOTOS DISEASE Postablative due to 131 Iodine surgery Congenital Thyroid agenesis or dysplasia TSH receptor defects Thyroidal Gs protein abnormalities Idiopathic TSH unresponsiveness TRANSIENT HYPOTHYROIDISM following subacute painless or postpartum thyroiditis

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 CONSUMPTIVE HYPOTHYROIDISM hemangiomas ,hemangioendoheliomas CENTRAL HYPOTHYROIDISM Acquired pituatary origin hypothalamic disorders dopamine & or severe stress Congenital TSH deficiency/structural abnormality TSH receptor defect RESISTANCE TO THYROID HARMONE generalised or pituatary dominant

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Multi system effects - Hypothyroidism

General Lethargy, Somnalence Weight gain, Goitre Cold Intolerence Cardiovascular Bradycardia, Angina CHF, Pericardial Effusion HyperlipIdemia, Xanthelsma Haematological Iron def. Anaemia, Normo cytic /chromic Anaemia Reproductive system Infertility, Menorrhagia Impotence, Inc. Prolactin Neuromuscular Aches and pains Muscle stiffness Carpel tunnel syndrome Deafness, Hoarseness Cerebellar ataxia Delayed DTR, Myotonia Depression, Psychosis Gastro-intestinal Constipation, Ileus, Ascites Dermatological Dry flaky skin and hair Myxoedema, Malar flushes 30 Vitiligo, Carotenimia, Alopecia

Clinical Signs of Hypothyroidism

Coarse Hair; Dry cool and pale skin

Goitre (not in all cases), Hoarseness of voice

Non-pitting oedema (myxoedema)

Puffiness of eyes and face

Delayed relaxation of DTR Slow hoarse speech and slow movements Thinning of lateral 1/3 of eye brows Bradycardia, pericardial effusion

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Thyroid Failure - Organ Systems

Cardiovascular

Decreased ventricular contractility Increased diastolic blood pressure Decreased heart rate
Central Nervous

Decreased concentration General lack of interest Depression

Gastro-instestinal

Decreased GI motility Constipation

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Thyroid Failure - Organ Systems

Musculoskeletal
Muscle stiffness, cramps, pain, weakness, myalgia Slow muscle-stretch reflexes, muscle enlargement, atrophy

Renal

Fluid retention and oedema

Decreased glomerular filtration

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Thyroid Failure - Organ Systems

Reproductive

Arrest of pubertal development Reduced growth velocity Menorrhagia, Amenorrhea Anovulation, Infertility

Hepatic

Increased LDL / TC Elevated LDL + triglycerides

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Thyroid Failure - Organ Systems

Skin and Hair

Thickening and dryness of skin Dry, coarse hair, Alopecia Loss of scalp hair and / or lateral eyebrow hair

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HORMONAL EFFECTS ON THYROID FUNCTION

Glucocorticoid Excess-decreased TSH,TBG,TTR

Decreased serum T3/T4 and increase Rt3 production Decreased T4 and increased T3 in graves disease Deficiency-Increased TSH Estrogen-Increased TBG sialylation and half life in serum Increased TSH in post menopausal women Increased T4 requirement in hypothyroid patients Androgen-Decreased TBG Decreased T4 requirment in hypothyroid patient 36 Growthhormone-Decreased D3 activity

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Cassava Plant

Topiaco - Sago (Javva Arisi)

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Tapioca Root - Sago

Tapioca (tubers)

Dried Tapioca - Sago

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Myxedema

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Myxedema
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Co-morbidity
Hypercholosterolemia

Depression
Infertility Menstrual Irregularities Diabetes mellitus

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Hypothyroidism and Hypercholesterolemia

14% of patients with elevated cholesterol have hypothyroidism

Approximately 90% of patients with overt hypothyroidism have increased cholesterol and / or triglycerides
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Lipids in Patient with Hypothyroidism

Hypercholesterolemia (>200 mg/dL) Hypertriglyceridemia (>150 mg/dL) Hypercholesterolemia and mild Hyper TG N= 268

Normal Lipids
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Effect of Thyroxine therapy on Hypercholesterolemia in Patients with mild Thyroid failure

The decrease in total cholesterol achieved with [Thyroxine replacement] substitution therapy in patients with subclinical hypothyroidism [mild thyroid failure] may be considered as an important decrease in cardiovascular risk favouring treatment.

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Suspect Hypothyroidism
1. 2. 3. 4. 5. 6. 7. 8. 9. Amenorrhea Oligomenorrhea Menorrhogia Galactorrhea Premature ovarian failure Infertility Decreased libido Precocious / delayed puberty Chronic urticaria

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Algorithm for Hypothyroidism

Measure TSH
Elevated TSH Measure FT4 Normal Sub-clinical hypo TPO + T4 repl TPO Annual FU Normal TSH Considering Pituitary

Low Primary hypothyroid

TPO + Hashimoto Others TPO -

No No tests
Low Evaluate Pituitary Sick Euthyroid Drugs effect

Yes
Measure FT4

Normal

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Hormone replacement

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Treatment
Goal : Normalize TSH level regardless of cause of hypothyroidism
Treatment : Once daily dosing with Levothyroxine sodium (1.6g/kg/day-1.8ug/kg/day) Monitor TSH levels at 6 to 8 weeks, after initiation of therapy or dosage change

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Treatment
Treatment of choice is levothyroxin Not recommended for use :
Desiccated thyroid extract
Combination of thyroid hormones T3 replacement except in Myxedema coma

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Dosage Adjustments
Age (in elderly start with half dose) Severity and duration of hypothyroidism ( dose) Weight (0.5g/kg/day upto 3.0g/kg/day) Malabsorption (requires dose) Concomitant drug therapy (only on empty stomach)

Pregnancy ( 25% -50% in dose), safe in lactating mother

Presence of cardiac disease (start alt. day Rx)
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Start Low and Go Slow

Goal : normalize TSH level 25, 50 and 100 mcg tablets avail. Starting dose for healthy patients < 50 years at 1.0 g/kg/day Starting dose for healthy patients > 50 years should be < 50 g/day. Dose by 25 g, if needed, at 6 to 8 weeks intervals.

Starting dose for patients with heart disease should be 12.5 to 25 g/day and increase by 12.5 to 25 g/day, if needed, at 6 to 8 weeks intervals
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How the patient improves

Feels better in 2 3 weeks

Reduction in weight is the first improvement

Facial puffiness then starts coming down Skin changes, hair changes take long time to regress TSH starts showing decrements from the high values TSH returns to normal eventually
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Drug Interactions
Malabsorption Syndromes Reduced Absorption

Drugs that affect metabolism

Rifampin
Carbamazepine Phenytoin Phenobarbitol Amiodarone
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Cholestyramine resin
Sucralfate Ferrous sulfate

Soybean formula
Aluminum hydroxide Colestipol hydrochloride

Inappropriate Dosage
Over-replacement risks

Reduced bone density / osteoporosis

Tachycardia, arrhythmia. atrial fibrillation In elderly or patients with heart disease, angina, arrhythmia, or myocardial infarction2 Under-replacement risks Continued hypothyroid state Long-term end-organ effects of hypothyroidism Increased risk of hyperlipidemia
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20.2.98

Massive Pericardial Effusion in Hypo

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26.7.98

Clearing of Pericardial Effusion with Rx.

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14.9.99

Reappearance of Pericardial Effusion after treatment is discontinued

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 CENTRAL HYPOTHROIDISM AFTER SURGERY

FT4 evaluation

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Diet in Iodine deficiency

Iodized salt Selenium supplementation Avoid Cassava Avoid cabbage (goitrogens) Avoid formula milk Fish, meat, milk & eggs
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Special situations

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Myxedema Coma
Precipitating factors :

Infection, trauma, stroke, cardiovascular, hemorrhage drug overdose, diuretics Mental confusion, hypothermia, bradycardia, older age, Na, glucose, CO2, WBC, Hct, CPK

Signs and Symptoms :

EKG voltage, myxedema, b-carotnenemia

Treatment
Initial IV THYROXINE 500-800 mcg/day ,followed by daily dose of I.V thyroxine 100 mcg thereafter ,alt I.V leothyronine 25mcg b.d

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Sick Euthyroid Syndrome

Total T3 reduced
FT3 reduced Total T4 reduced FT4 Normal TSH Normal

Clinically Euthyroid
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 T3 -0.04nmo/l T4-59.70nmol/l TSH-2.52IU/ml

0.93-2.33nmol/lit 60-120 nmol/lit >7.0-hypothyroid <0.2 hyperthyroid

Case-1

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 T3 -1.42nmol/l T4-106.96nmol/l TSH-<0.05IU/ml

Case 2

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The Commandments

Highly suspect hypothyroidism All obese patients TSH a must Growth and pubertal delay Unexplained depression TSH is the test in Hypothy.

For all pregnant -test TSH, FT4 Postmenopausal 15% Hypothy

Start low and go slow

Use Levothyroxine only Always on empty stomach

TSH, FT4 to confirm Dx.

Nine square magic Test cord blood for TSH

Thyroxine - avoid empirical use

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Thank you

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