thyroid

What you need to know about thyroid?

Dr. JOHAN

ASST PROF

MGMCRI

Grave and Basedow

THYROXINE was the first hormone to be synthesised in the laboratory

THYROID HORMONES• Thyroid gland secretes 3 hormones: 1.Thyroxine(t4) 2.Triiodothyronine(t3) 3.Calcitonin

• Out of this calcitonin is produced by parafollicular C cells and concerned with the Ca2+ balance

• Other two is produced by thyroid follicles

HYPOTHALAMIC PITUTARY THYROID HORMONE AXIS

SYNTHESIS OF T4 & T3 FOLLOWS 5 STEPS:1. Iodide uptake2. Oxidation and iodination3. Coupling4. Storage and release5. Peripheral conversion of t4 to t3

Thyroid Hormone synthesis

Numerical Facts• Daily req of iodine – 1-2 mcg/kg• Iodised salt – 100 mcg/gm of salt• Normal blood iodide – 0.2-0.4 mcg/dl• Daily production of T4 –

70-90mcg/day• T3 60-80 mcg/day• Normal bound T4 – 4.5-11mcg/dl• T3 – 60-180ng/dl or 0.1-0.2 mcg/dl• Free T4 – 0.03-0.08% • Free T3 – 0.2-0.5%

TRANSPORT• Thyroid hormones bind to plasma

proteins-

1.Thyroxine binding globulin (TBG)

2.Thyroxine binding prealbumin (transthyretin)

3.Albumin

Increased Ty binding Decreased

• Estrogen• Tamoxifen• 5FU• clofibrate

• Androgens• Mefenamic acid• Phenytoin• Carbamazepine• glucocorticoids

T4 T3• 15 times more protein

bound• T1/2 6-8 days• Secretion more than

T3• Mainly a transport

form• Prohormone of T3• Converted to T3 in

periphery

• Less bound• 1-2 days• 5 times more potent

than T4• Active form, act faster

METABOLISM AND EXCRETION• Metabolic inactivation occurs by

deiodination, glucoronide/sulfate conjugation.

• Liver is the primary site, also take place in salivary glands and kidneys

• Conjugates excreted in bile undergo enterohepatic circulation

• Excreted in urine

DRUGS THAT INHIBIT PERIPHERAL CONVERSION OF T4 TO T3

• Propranolol• Propylthiouracil• Amiodarone• Corticosteroids• Ipodate

THYROID PREPARATIONS

• LEVOTHYROXINE(T4)• LIOTHYRONINE(T3)• LIOTRIX 4:1 mixture of t4 and t3• DESSICATED OR ARMOUR THYROID – derived

from dried and defatted bovine or porcine thyroid glands

ACTIONS• Growth and development: Essential for

normal growth and development.

• Intermediary metabolism: Marked effect on lipid, carbohydrate and protein metabolism.

• Calorigenesis: BMR is maintained.

• CVS: Heart rate, contractility and output are maintained.

• GIT: Propulsive activity.

• Nervous system: maturation of nervous system. Deficiency leads to mental retardation and cretinism.

• Skeletal muscle: needed for normal muscle contour. Muscles bcom flabby and weak in myxoedema.

• Kidney: Rate of urine flow is maintained

• Haemopoiesis: Facilitatory to erythropoiesis.

• Reproduction: Indirect effect on reproduction.

Pathology• Hypothyroidism• Cretinism• Hashimoto• Myxedema coma

• Hyperthyroidism• Grave disease• Thyroid storm• Thyrotoxicosis in pregnancy

USES OF T4 & T3• The most important uses of thyroid hormone is

in the replacement therapy namely in:1. Cretinism2. Adult hypothyroidism3. Myxoedema coma4. Nontoxic goiter5. Thyroid nodule6. Papillary carcinoma of thyroid 7. Some empirical uses

CRETINISMSPORADIC CRETINISM – defect in thyroid hormone synthesisENDEMIC CRETINISM – due to extreme iodine deficiency

TREATED WITH THYROXINE 8-12mcg/kg DAILY MENTAL RETARDATION ONLY PARTIALLY REVERSIBLE

CRETIN FACIES

Adult hypothyroidism• Commonest endocrine disorder due to

thyroiditis, thyroidectomy• I131, lithium, iodide, amiodarone cause

hypothyroidism• Treat with low dose of levo thyroxine daily

and increase every 2-3 wks to 100-200mcg/day

• Subclinical hypothyroidism – euthyroid status, raised TSH levels to be treated with T4

Myxedema comaLio thyronine acts faster but high risk of arrythmias, 10 mcg 8 hrlyL- thyroxine 200-500mcgiv followed by 100 mcg iv OD till oral therapy substituted

Corticosteroids, ventilatory support, correction of hyponatremia and hypoglycemia

Non toxic goitreSPORADIC- DEFECT IN HORMONE SYNTHESISENDEMIC – IODINE DEFICIENCY

ENDEMIC GOITRE AND CRETINISM DUE TO IODINE DEFICIENCY IN PREGNANT MOTHERS IS PREVENTED BY 150-200MCG ORAL IODINE DAILY

IODISED SALT- 100MCG IODINE/ GM OF SALT

Empirical Uses

Refractory anemiasMental depressionMenstrual disordersInfertilityChronic non healing ulcersConstipation

THYROID INHIBITORS

Chernobyl disaster The worst manmade disaster in human history

UKRAINE, 25TH APRIL 1986

The Chernobyl Nuclear Disaster25th April 1986:The accident at reactor 4 occurred during an experiment to test a potential safety emergency core cooling feature.• 115,000 people evacuated and 220,000 people relocated

• 6,000 cases of thyroid cancer

• 5.5 million people still live in contaminated areas

• 31 people died in 3 months of radiation poisoning

• 134 emergency workers suffered from acute radiation sickness

• 25,000 rescue workers died since then of diseases caused by radiation

Cancer afflicts many othersIncreased birth defects, miscarriages, and stillbirths

High number of suicide and violent death among Firemen, policemen, and other recovery workers

PATHOLOGIES• Grave’s disease – autoimmune disorder,

antibodies to TSH receptor- bind and stimulate thyroid cells producing TSH like effects, but TSH levels are low due to feedback inhibition

• Toxic nodular goitre

• Endemic goitre – in iodine deficient regions, intake of GOITRINS – cabbage, turnip, mustard, cauliflower, radish

Inhibit thyroid hormone synthesis (ANTITHYROID DRUGS)PropylthiouracilCarbimazolemethimazole

Inhibit Iodide Trapping(IONIC INHIBITORS)ThiocynatesPerchloratesNitrates

Inhibit thyroid hormone releaseLugol’s iodineIodides of Na and KOrganic Iodide

Destroy thyroid tissue

I131, I123, I125

CLASSIFICATION

GOITROGENS = Antithyroid drugs + Ionic inhibitors

CLASSIFICATION

ANTI THYROID DRUGS(THIOAMIDES)

PROPYL THIO URACILCARBIMAZOLEMETHIMAZOLE

MECHANISM OF ACTION

Inhibit iodination of tyrosine residues in thyroglobulin

Inhibit coupling to form T4 and T3

Inhibit peripheral conversion of T4 to T3 only with

propylthiouracil

PROPYLTHIOURACIL CARBIMAZOLE

Less potent Highly plasma protein

bound Less transfer across

placenta, preferred in pregnant and nursing women

T1/2 1-2 hrs Single dose for 4-8hrs No active metabolite 2-3 daily doses needed Inhibit peripheral

conversion of T4 to T3

5 times more potent Less bound Not used in pregnant

and nursing women T1/26-10 hrs Single dose for 12-24 hrs Active metabolite -

methimazole Single daily dose needed Does not Inhibit

peripheral conversion of T4 to T3

ADVERSE EFFECTS Reversible hypothyroidism and goitreSkin rashesReversible agranulocytosisCholestatic jaundiceLupus like reactionJoint painPeriodic leukocyte counts

Sore throat and fever not ignored

THERAPEUTIC USES

THYROTOXICOSIS •Grave’s disease. Clinical improvement after 1-2 wks

•Toxic nodular goitre

PREOPERATIVELY •Render euthyroid before subtotal thyroidectomy

ALONG WITH RADIO IODINE

•Till radio iodine acts•To prevent initial hyperthyroidism when radio

iodine given due to release of stored t4

ANTI THYROID DRUGS

ADVANTAGES No surgical risk No injury to

parathyroid and recurrent laryngeal nerve

Hypothyroidism-reversible

Used in children and young adults

DISADVANTAGES Life long treatment High relapse rate Not used in

uncooperative patient Drug toxicity Fetal hpothyroidism

and goitre

IODINE AND IODIDES

FASTEST ACTING THYROID INHIBITOR ,WITH PEAK AT 10-15 DAYS

• LUGOL’S IODINE – 5% IODINE IN 10% POT IODIDE

Inhibits iodide trapping, oxidation, coupling, endocytosis, proteolysis, hormone release – THYROID CONSTIPATION/WOLF-CHAIKOFF EFFECT• ON STOPPING THYROID ESCAPE OCCURS-

THYROTOXICOSIS RETURN WITH GREATER SEVERITY

THERAPEUTIC USES

PRE OPERATIVE PREPARATION –

TO MAKE GLAND FIRM,

LESS VASCULAR

THYROID STORM

PROPHYLAXIS OF ENDEMIC

GOITREANTISEPTIC

ADVERSE EFFECTS

ALLERGIC TO IODINE

PETECHIAL HEMORRHAGES

ACUTEIODISM- SALIVATION, LACIMATION ETC

FETAL GOITRE- CI IN PREGNANCY

CHRONIC

IONIC INHIBITORS

• They inhibit iodide trapping by the thyroid

• Toxic and not used now

• Thiocyanates cause liver, kidney, brain and bone marrow toxicity

• Perchlorates cause fever, aplastic anemia and agranulocytosis

• Nitrates – weak drugs, cause methhemoglobinemia

RADIOACTIVE IODINE I131

Xrays Beta particles

MOA- concentrated by the thyroid colloid, emits radiation from within the follicles, half life of 8 days

ADMINISTERED AS SODIUM SALT, DISSOLVED IN WATER AND TAKEN ORALLY

For diagnostic purposes 25-

100 microcurie used

For treatmentPenetrate 0.5-2mm of tissue

So no damage to neighbouring tissue3-6millicurie in grave’s disease and toxic

nodular goitre

RADIOACTIVE IODINE

ADVANTAGES No surgical risk No injury to

parathyroid and recurrent laryngeal nerve

Permanent cure As OP procedure and

inexpensive

DISADVANTAGES hypothyroidism Long latent priyan Not used in

uncooperative patient Drug toxicity Fetal hpothyroidism

and goitre

• Emergency due to acute hyperthyroidism precipitated by trauma, surgery, diabetic ketoacidosis, toxemia of pregnancy

• Not rendered euthyroid before surgery are at risk. GA or stress of procedure precipitates it

THYROID STORM / THYROTOXIC CRISIS


• SUPPORTIVE MEASURES:Maintain airway and breathing with ventilatory

supportMaintain circulation with iv fluids and rehydrateExternal cooling by wet spongingControl fever with paracetamolCorrect electrolytic disturbancesAnxiolytic – to suppress anxietyAntibiotics if necessaryPlasmapheresis – to remove large amounts of

hormone

• PHARMACOLOGICAL MEASURES:

1. Non selective beta blocker – propranolol Rapid control of sympathetic symptoms-palpitations, sweating,

myopathy

Peripheral conversion of T4 to T3

Inhibit adrenergically evoked tremor by direct action on beta2 receptors and inhibit increase in blood flow to skeletal muscles, also inhibiting glycogenolysis and lipolysis that provide fuel to skeletal muscles

DOSE – 1-2 MG SLOW IV FOLLOWED BY 40-80MG ORAL 6TH HOURLY


2. Propylthiouracil – 200-300mg 6th hrly orally• Inhibit thyroid hormone synthesis• Inhibit peripheral conversion of T4 to T3

3. Iopanoic acid – 0.5-1gm oral OD• Inhibit thyroid hormone release• Inhibit peripheral conversion of T4 to T3

4. Corticosteroids- hydrocortisone 100mg iv 8th hrly followed by oral prednisolone

• Treat adrenal insufficiency• Inhibit peripheral conversion of T4 to T3

5. Diltiazem – 60-120mg 0ral BD in asthmatic pts with thyroid storm and if tachycardia not controled by propranolol


Czech Technical University in Prague 4523 May 2007

thyroid

Health & Medicine