THYROID & ANTITHYROID DRUGS

I.

T3: triiodothyronine
T4: thyroxine
II. Calcitonin
Regulation of Thyroid Hormone Synthesis
Hypothalamus>>>>Ant Pituitary>>>Thyroid

Thyroid Function Tests

Free T4 - direct measurement of free T4.

Total T4 - free and protein-bound T4.
Total T3 - free and protein-bound T3.
TSH test
T3RU (T3 Resin Uptake) measures % of total T3 bound to
resins. (T3 NOT bound to protein).
Low in hypothyroidism & high TBG states
High in hyperthyroidism & low TBG states
ESTROGEN RAISES TBG
STEROIDS REDUCE TBG

Thyroid Hormone Synthesis

1. Uptake of Iodide (iodide trapping)
2. Iodide organification
(oxidation and iodination)
3. Coupling of MIT and DIT
4. Secretion of thyroid hormones
5. Conversion of T4 to T3

It is all about Free hormone

T4 99.97% bound and 0.03% Free
T3 99.70% bound and 0.3% Free
T3 has 3 times metabolic activity than T4
100% T4 made in the Thyroid gland
20% of T3 made in the thyroid 80% peripherally

Preparations
Levothyroxine (T4) **most preferred because long
duration of action
Liothyronine (T3) **can be cardiotoxic
Liotrix
Use:
Hypothyroidism
Infancy cretinism
Childhood hypothyroidism
Adult hypothyroidism
- Hashimoto's thyroiditis
- autoimmune destruction of the thyroid gland
- Rx: Levothyroxine
Note: The list of hypothyroidism signs and symptoms also includes
anemia; hyponatremia, or deficiency of sodium in the blood;
galactorrhea, or excessive or spontaneous flow of breast milk; goiter;
hard, pitting edema of the lower extremities; and delayed return of
deep tendon reflexes. Any combination of a few or many signs and
symptoms may occur at any given time. Some signs and symptoms,
such as galactorrhea, anemia, and skin changes are seen in individuals
in later stages of hypothyroidism.

Myxedema Coma
- end state of untreated hypothyroidism.
- progressive weakness, stupor, hypothermia, hypoventilation,
hypoglycemia, hyponatremia, water intoxication, shock, and
death. **medical emergency
Treatment:
Intubation and mechanical ventilation
Control hypothermia
infection or heart failure must be treated by appropriate
therapy
Levothyroxine i.v
Liothyronine i.v

Antithyroid drugs:
Thioamides

Propylthiouracil (PTU)
Methimazole
Carbimazole
Mechanism:
Inhibit thyroid peroxidase
Block iodine oxidation
Coupling of MIT and DIT
Propylthiouracil - Inhibit peripheral conversion of T4 to T3
Block synthesis T3 and T4 not release, therefore slow onset
of action
Toxicity
maculopapular pruritic rash
agranulocytosis (granulocyte count < 500 cells/mm3) **small
subset
cross the placental barrier and are concentrated by the fetal
thyroid. Be sure to choose PTU in pregnancy b/c this does not
cross placenta as much.
Anion Inhibitors
perchlorate (ClO4),
pertechnetate (TcO4)
thiocyanate (SCN)
block uptake of iodide by the gland through competitive
inhibition of the iodide transport mechanism
Causes aplastic anemia
Iodine and Iodides
Mechanism:
inhibit hormone release (in high doses) ** WolffChaikoff effect
decrease the vascularity, size, and fragility of a hyperplastic
gland, making the drugs valuable as preoperative preparation for
surgery
Improvement in thyrotoxic symptoms occurs rapidlywithin 27
days
Preparations:
Lugols Iodine, Na Iodide, K Iodide
Thyroid escape: gland escapes from the iodide block in 28 weeks
Toxicity

 acneiform rash
swollen salivary glands
mucous membrane ulcerations
Conjunctivitis
rhinorrhea,
rarely, anaphylactoid reactions
The iodinated contrast media
diatrizoate
iohexol
Radioactive Iodine (131I) Rapidly absorbed (orally)
Concentrated in thyroid
Emits radiation destruction of thyroid gland
Advantage:
Inexpensive, simple, outpatient basis
No surgical risk
Permanent cure
Disadvantage:
response slow
Hypothyroidism
CI-pregnancy, young patients
Adrenoceptor-Blocking Agents
metoprolol, propranolol, atenolol
Inhibit many symptoms of thyrotoxicosis - sympathetic
stimulation- palpitation, nervousness, tremors
Uses of Antithyroid drugs
HYPERTHYROIDISM
1.Graves' Disease (diffuse toxic goiter)
Most common form of hyperthyroidism
Autoimmune disorder : antibodies against the TSH Receptor
Antithyroid drug therapy:
Methimazole
Propylthiouracil
Radioactive iodine
- preferred treatment for most patients over 21 years of age.
- In patients without heart disease
2.Toxic Adenoma
3.Toxic Multinodular Goiter

Thyroid Storm
- sudden acute exacerbation of all of the symptoms of thyrotoxicosis
Propranolol
Diltiazem
Potassium iodide or iodinated contrast media
Propylthiouracil or Methimazole
Hydrocortisone
Supportive therapy - fever, heart failure, and any underlying
disease process that may have precipitated the acute storm.
Amiodarone induced thyrotoxicosis
Type I: Iodine induced - PTU
Type II: Inflammatory Steroids
Radiation exposure and the thyroid