THYROID AND ANTI THYROID

DRUGS

Dr.A.MADURAM
 Describe the anatomical position and
endocrine function of the thyroid gland.

 Explain the physiological effect of a

negative feedback mechanism.

 Describe the consequences of insufficient

circulating thyroid hormone.

 Describe the consequences of excessive

circulating thyroid hormone.

 Explain the management options

available to support an individual with
thyroid disease.
Effects of Thyroid Hormone
Increases metabolic rate of body tissues.
Gastro-intestinal function
 Increases appetite

 Increases digestive juice secretion

 Increases motility

 Increases absorption of food.

 Increases fat, carbohydrate, glucose

 metabolism & protein synthesis

 Relates inversely to body weight.

Effects of Thyroid Hormone
Central nervous system

 Speeds up mental processes.

 Cardio-vascular function

 Vasodilation

 Increases blood flow

 Increases heart rate and cardiac output

 Increases arterial pressure.

Respiratory function
 Increases rate and depth.
SYNTHESIS OF THYROID HORMONE

1. Iodide trapping
iodide Iodine
2.Oxidation of iodide
3. Iodination of tyrosine
4.Coupling of iodotyrosines
to form T3 or T4.
4.Iodide
6. Proteolysis of
organificatio thyroglobulin
n 7.Conversion of T4 or T3 in
tissues
8.
t1/2 = 5-7d

t1/2 = < 24 hrs

 Normal Daily Thyroid Secretion Rate:

T4 = 100 ug/day
T3 = 6 ug/day

( ratio T4:T3 = 5:1 )

T4 Protein binding + 0.04% free T4

85% (peripheral conversion)

T3 Protein binding + 0.4%

15%
free T3
(10-20x less than T4)
 T4 T3

Potency 1 10

Protein Bound 10-20 1

Half-Life 5-7d < 24h

Secreted by 100 ug/d 6 ug/d

thyroid
REGULATION OF THYROID
FUNCTION
Thyroid Function: blood
tests Thyroid Disease

TSH  Hypothyroidism
0.4 –5.0 mU/L  Hyperthyroidism
 Thyroid Nodules &
Free T4 (thyroxine) Cancer
9.1 – 23.8 pM

Free T3
(triiodothyronine)
2.23-5.3
pM
Hypothyroidism
 Definition:-

 "Decreased output of the thyroid hormone resulting

in an hypometabolic state.....onset is gradual and so
insidious that it may take
years for clinical manifestations to appear".
 Basal metabolic rate can fall as low as 40 %
 HYPOTHYROIDISM

Aetiology

Primary
Secondary
(90%) Tertiary
(<10%)
(Rare)
Thyroid Tissue Dysfunction of
Loss or Atrophy Pituitary Gland Dysfunction of
Hypothalamus
Autoimmune Tumor or
Post Surgery surgery Decreased TRH
Production
Post Irradiation Decreased TSH
Infiltration Production
Decreased Hormone
Synthesis
Decreased Thyroxin
Production
Hypothyroidism
 Decreased thyroid hormone levels
Low T4
Possibly Low T3 too.
Raised TSH (unless pituitary problem!)
Reproduction Fertility is impaired oligomenrrhoea
 HYPOTHYROIDISM
Signs & Symptoms
Tiredness / malaise
 Mental slowness
 Headaches
 Reduced appetite
 Constipation
 Sensitivity to drugs
 Change in appearance
 Anemia
 Heart failure
 Hypertension
 Bradycardia
 Dyspnoea
 Cold intolerance / Hypothermia
CONDITIONS THAT IMPAIR THYROID
Function: Hypothyroidism
Insufficient amount of thyroid hormone
synthesized causing lethargy and weight gain,
among other symptoms.
Primary hypothyroidism is typically caused by
Hashimoto’s Disease, an auto-immune disorder
in which the thyroid is destroyed by antibodies.
Impaired hypothalamus and pituitary function,
typically due to a tumor, can inhibit the secretion
of THS, causing secondary hypothyroidism.
A diet insufficient in iodine causes
hypothyroidism as well.
Symptoms of Thyroid Disfunction:
Goiter
 Enlarged thyroid, symptom of hypothyroidism.
 Goiters form for different reasons depending on
the cause of hypothyroidism
Hashimoto’s disease, also known as chronic lymphocytic
thyroiditis, causes goiters due to the accumulation of
lymphocytes.
The decreased amount of thyroid hormones in the body,
due to Hashimoto’s or other thyroid disorders including
infection, signals the increased production of TSH which
accumulates in the thyroid causing a characteristic goiter.
 Goiters form due to an insufficient amount of ingested
iodine and serve to increase the surface area of the thyroid
and aid in its absorption of iodine.
Treatment for Hypothyroidism
♣ Hormone replacement therapy
♣ Thyroid hormones
♣ Chemistry naturally are levo isomers.
♣ Kinetics.
♣ It is best absorbed in the duodenum and ileum
♣ Modified by intra luminal factors such as food, drugs and
intestinal flora.
♣ Oral bioavailability -80%
♣ Drugs that induce heptic microsomal enzymes the
metabolism of both T4 and T3.
♣ MOA : T3 penetrate cells and combine with a nuclear
receptor .It binds to a specific thyroid hormone response
element to which T3 receptor complex binds
Thyroid preparations
§ Synthetic :
1. Levothyroxine ,(T4)
2. Liothyronine,(T3)
3. Liptrix
Animal origin (desiccated thyroid)
 Synthetic levothyroxine : Its stability
 content uniformity
 low cost
 lack of allergenic foreign protein
 long half life(7daya)
 In addition T4 is converted to T3
so it produces both hormones
 Liothyronine : I
 Is 3 to 4 times more potent not used – short half life
multiple dosing and its higher cost
 more greater risk of cardiotoxicity

MANAGEMENT OF HYPOTHYROIDISM
 Infants and children –require more T4 per kg of
body weight than adult. Average dosage for an
infant 1-6 months is 10-15 mcg/kg/d,
 Adult is about 1.7 mcg/kg/d
 Thyroxine given in empty stomach
 Toxicity of thyroxine is directly related to the
hormone level.
 In children – restlessness, insomnia, accelerated
bone maturation and growth signs of toxicity.
 In Adult - nervousness, heat intolerance,
episodes of palpitation and tachycardia and
unexplained weight loss.
Uses
 Absence of thyroxine in children-as cretinism
or juvenile myxedema.
 In adult myxedema
 1. thyroxine 12.5-50µg daily started early.
 Adult hypothyroidism – due to thyroiditis,

thyroidectomy, treatment of goitrogens low dose -

50µg of thyroxine daily upto 100-200 µg/day
 Simple Goitre and Hashimoto’s thyoiditisDose

of 100-200 µg/day .
 Hypothyroidism and pregnancy –
 HYPOTHYROIDISM

DIAGNOSIS

Serum T4 or fT4

Below Normal

? Primary Hypothyroidism

? Secondary Hypothyroidism

? Tertiary Hypothyroidism
HYPOTHYROIDISM

DIAGNOSIS
TRH Stimulation Test

TSH Response

No Excessive Delayed
Response Response Response

Secondary Primary Tertiary

Hypothyroid Hypothyroid Hypothyroid
ThankYou
HYPERTHYROIDISM

 Definition:-

 "Excessive secretion of the thyroid hormone

 resulting in an hypermetabolic state.....".


 Incidence:-

 2 - 5% of all females between age of 30-50 yrs

 Male / female 1 : 7

 Can be precipitated by a life 'crisis'

Hyperthyroidism
 Increased thyroid hormone levels
 High T4 +/- High T3
 Low (suppressed) TSH

 Graves’ Disease
 Most common cause of hyperthyroidism
 Goitre, Orbitopathy, Dermopathy
 TSH-R antibody (stimulating)
Hyperthyroidism S&S
 Heat intolerance
 Weight loss (normal to increased appetite)
 Hyperdefecation (diarrhea)
 Tremor, Palpitations
 Diaphoresis (sweating)
 Lid retraction & Lid Lag (thyroid stare)
 Decreased menstrual flow
 HYPERTHYROIDISM
Aetiology
Primary Secondary
(99%) (Rare)
Thyroid Tissue Over Secretion
Disease by Pituitary

Autoimmune Pituitary
(Graves Disease) Tumour
Thyroid Stimulating
Antibodies Increased TSH
Production
Increased
Stimulation of
TSH Receptors
Increased Thyroxin
Production
 HYPERTHYROIDISM

DIAGNOSIS

Serum TSH

Below Normal Above Normal

? Primary ? Secondary
Hyperthyroidism Hyperthyroidism
THYROID INHIBITORS
 These are drugs used to lower the functional capacity of the
hyperactive thyroid gland
 HYPERTHYROIDISM : Excessive secertion of thyroid

hormones1. Graves’s disease

2.Toxic nodular goiter
Classification : -
1.Inhibit hormone synthesis :propythiouracil, methimazole ,
Carbimazole
2.Inhibit iodide trapping: Thiocyanates, perchlorates,
Nitrates.
3.Inhibit hormone release: Iodine, Iodides of Na and K,
Organic iodide.
4.Destory thyroid tissue: Radioactive iodine (131I 125I, 123I.)
ANTI THYROID DRUGS(hormone synthesis Inhibitors )

 The most commonly used drugs in hyperthyroidism

 MOA: They bind to thyroid peroxidase and prevent
oxidation of iodide or iodotyrosyl residues
 Inhibit iodination of tyrosine residues in
thyroglobulin
 Inhibit coupling of iodotyrosine residues to form T3
AND T4.
 Propylthiouracil inhibits the peripheral
deiodination ofT4 toT3 so preferred drug for
thyroid strom.
 Methimazole is 10 times more active .
Pharmacokinetics
 Well absorbed orally ,enter milk and cross placenta,
except –propylthiouracil
 Metabolized in liver and excreted in urine primarily
Carbimazole is metabolized to methimazole in the
body.
 ADR: Hypothyroidism due to overtreatment
 G.i intolerance, skin rashes and joint pain .
 Rare-loss or graying of hair , loss of taste, fever and
liver damage.
 A less common but serious adverse effect 0.5% of
patients develop rapidly during the first few weeks of
therapy. Is agrnoulocytosis .
 A dose therapy in pregnancy can cause fetal goitre .
THERAPEUTIC USES
 Propylthiouracil: 50mg -150mg TDS followed by25-
50mg BD or TDS for maintenance.
 Carbimazole :15-20 mg TDS daily followed by 2.5 -
25 mg daily TDS. Only
 Methimazole :5-10mg TDS followed by 5-15mg daily
TDS.
 INDICATIONS: 1.Juvenile thyrotoxicosis
2. Before subtotal thyroidectomy to
make the patient euthyroid.
3.Hyperthyroidism of
pregnancy
4.Toxic nodular goitre.
 CONTRAINDICATIONS: 1.severe adverse effects.
2. repeated relapses.
IONIC INHIBITORS
 Thiocyanates and potassium perchlorate ,
NITRATES inhibit the iodide trapping in the
gland.
 They are toxic and not used now
 Agrnoulocytosis and aplastic anemia
 NITRATES –Induce methemoglobinaemia and

vascular effect.
 3.Inhibit hormone release
 IODINE : It affects all the steps in hormone synthesis
except iodide uptake .
 Preparations and uses Lugol’s Iodine or strong iodine
solution (5% iodine and 10%potassium iodide) in dose of
0.5 ml (65mg iodine) BD for 10 days before sub total
thyroidectomy to make the gland shrink, firmer and less
friable and less vascular .
 Saturated solution of potassium iodide 40mg of iodine
per drop -6-12 drops Bd for 10 days preceeding
operation and after the glands becomes euthyroid by anti
thyroid drugs.
 INDICATION
 1. Before subtotal thyroidectomy.
 2.Thyrotoxic crisis in conjunction with anti thyroid
drugs and Beta blocker.
 INDICATION
 1. Before subtotal thyroidectomy.
 2.Thyrotoxic crisis in conjunction with

antithyroid drugs and Beta blocker.

 ADR: I Hypersensitivity reactions- anaphylaxis,

serum sickness type of hypersensitivity ,

thrombocytopenia and periarteritis nodosa
 Chronic intoxication – unpleasant taste,

burning sensation in mouth and throat

 Lacrimation, pulmonary edema. All symptoms

disappear after stopping the therapy.

Radioactive iodine
 IODINE 131 IS USED CLINICALLY-The radioiodine is taken
up by the glands and is deposited in the follicles from where
it is slowly liberated .
 Emitted exclusively affect the parenchymal cell without
damaging the surrounding tissues.
 The cellular changes include pyknosis, necrosis, followed by
disappearance of colloid and ultimately fibrosis of the gland.
 The half life is 8 days and over 99% of its radiant energy
is lost within 56 days.

 IODINE 123- Is used for screening the thyroid functions.

 The half life is 13 hours
PREPARATIONS AND USES.
 Sodium iodide 131 is available as solution or capsule for
oral use as a single dose.- hyperthyroidism. – dose of iodine
varies from 80-150µci with total dose of 4-10mci . The response
is seen over a period of 2-3 months
 The antithyroid drugs are withheld for a week before and
after radioiodine therapy and symptoms may be controlled by
beta blocker during this period.
 INDICATION AND ADVANTAGES OF RADIOACTIVE IODINE
THERAPY
 1.Old patients with heart disease
 2.Failed surgery or antithyroid drug therapy
 3.Nodular goitre
 4.Metastatic thyroid cancer
 5.Diagnostic use of the tracer dose.
 ADVANTAGES: low cost, least mortality, sparing of risks of
surgery and no need of hospitalization.
Adverse effect and disadvantages
 Delayed onset of action
 Delayed hypothyroidism in majority of

patients.
 Can not be administered during childhood,

pregnancy and lactation

 Risk of mutagenic effect.
DRUGS FOR ADJUNCTIVE THERAPY
 β BLOCKER –Non selective and cardioselective are
useful in controlling signs and symptoms of
hyperthyroidism.
 The heart rate, tremors, stare and anxiety are rapidly

controlled.
 Oral dose 20-80mg every six hours.
 INDICATIONS:

1. Thyroid strom- life saving

2. Before thyroidectomy.
3. With thioamides.
4. While awaiting the response to radioactive iodine.
5. Post partum hyperthyroidism and hyperthyroid
state of thyroiditis.
Thyroid strom (thyroid crisis).
TREATMENT-
1. Injection propranolol 5-10mg i.v. at rate of
1mg/min or 20-40mg 4th hourly orally.
2. Sodium iodide – 1-2g/day i.v. infusion or
potassium iodide 40mg/drop orally in dose
of 5drops every 4th hourly.
3. Hydrocortisone sodium succinate 100mg
i.v. every 8 hourly .
4. Propylthiouracil 200mg orally every 4-6
hours
 DRUGS CAUSING HYPOTHYROID:
 1.Lithium carbonate
 2.Amiodarone
 3.Sulfonly urea group of drugs
 4.Phenylbutazone
 5.Paraminosailcyclic acid
 6.iodinated contrast agents
 NATURAL GOITROGENS
 Cabbage.
 Soyabeans,resorcinol, phloroglucinol
ThankYou