1. Thyroid gland
The thyroid gland consits of two lobes & is situated in the lower neck
The thyroid gland secretes three main hormones: thyroxine (T4), triiodothyronine (T3) and calcitonin
T4 and T3 are critically important for normal growth and development and for energy metabolism
Calcitonin is involved in the control of plasma Ca2+ .

2. 3,5,3’-Triiodothyronine (T3) Thyroxine (T4)
The principal hormones of the thyroid gland are the iodine-containing amino acid derivatives of thyronine (T4 and T3) O OH I
NH2 O OH I
NH2
3,5,3’-Triiodothyronine (T3)
Thyroxine (T4)

3. Synthesis, storage, release, and interconversion of thyroid hormones
Uptake of iodide ion (I-) by the gland by the sodium/iodide symporter (NIS)
Oxidation of iodide and the iodination of tyrosyl groups of thyroglobulin
Coupling of iodotyrosine residues to generate the iodothyronines
Resorption of the thyroglobulin colloid from the lumen into the cell
Proteolysis of thyroglobulin and the release of T4 and T3 into the blood

4. Na+ Extracellular space Follicle cell colloid space I- I- Io I- K+
T3, T4 I-
Na+ K+
Follicle cell
Extracellular space
colloid space
Exocytosis I-
T3, T4, DIT, MIT
Proteolysis T T T T Io
peroxidase I-
Thyroglobulin
Organification T T
DIT T4 T
MIT T4 T3
DIT T
Coupling T
MIT T
MIT
Thyroglobulin with monoiodotyrosines (MIT) & diiodotyrosines (DIT)

5. Synthesis, storage, release, and interconversion of thyroid hormones
More than 99% of the circulating thyroid hormones are protein bound, primarily thyroxin-binding globulin (TBG)
T4 is produced in the greatest amounts, but T3 is four times more potent in activity
T4 is converted into T3 in the tissues, especially in the liver, & this process may be an additional site for regulation

6. Summary of thyroid hormone kinetics
Variable T4 T3
Volume of distribution
10 L
40 L
Daily production
75 mcg
25 mcg
Metabolic clearance per day
1.1 L
24 L
Half-life (biologic)
7 days
1 day
Serum levels
Total
mcg/dL
nmol/L
ng/dL
nmol/L
Free
ng/dL
9-24 pmol/L
pg/dL
pmol/L
Amount bound
99.96%
99.6%
Biologic potency 1 4
Oral absorption
80%
95%

7. Control of thyroid function
Cold
Acute psychosis
Circardian & pulsatile rhythms + _
Stress
Hypothalamus +
TRH _
SST _ -
Dopamine
Corticoids
Anterior pitutary
gland - +
TSH _
I- (high)
Thyroid gland +
I- (low)
T3 & T4

8. Effects of Thyroid Hormones
Growth & development
Thyroid hormone is critical for the development and functioning of nervous, skeletal, and reproductive tissues during infancy and childhood
Thyroid hormone plays a critical role in brain development during the period of active neurogenesis (up to 6 months postpartum)
The absence of thyroid hormone during the period of active neurogenesis leads to irreversible mental retardation (cretinism)

9. Effects of Thyroid Hormones
Metabolic effects: increase in the metabolism of carbohydrates, fats and proteins
Calorigenic effect: increased O2 consumption & heat production
Cardiovascular effects: thyroid hormone influences cardiac function

10. Hypothyroidism
The most common cause of hypothyroidism is chronic antoimmune (Hashimoto’s thyroditis) resulting in thyroid atrophy or goiter

11. Thyroid preparations
Thyroid preparations may be synthetic (levothyroxine, liothyronine, liotrix) or of animal origin (desiccated thyroid, Thyroid (USP))
There is no significant difference in the qualitative response of the patient with hypothyroidism to triiodothyronine, thyroxine, or desiccated thyroid. However, there are obvious quantitative differences

12. Levothyroxine (T4)
It is the preparation of choice for maintenance of plasma T4 and T3 concentrations for thyroid hormone replacement therapy in hypothyroid patients
Its long half-life (7 days) allows for convenient once daily administration
Since much of the T4 is deiodinated to T3; thus, administration of T4 produces both hormones

13. Liothyronine (T3)
Has limited therapeutic applications and is not used for maintenance thyroid hormone replacement therapy because of:
shorter half-life and duration of action
Cost
Difficulty in monitoring by conventional lab methods
hormone activity and consequent greater risk of cardiotoxicity

14. Liotrix 4:1 mixture of levothyroxine sodium and liothyronine sodium
Based on the idea of combining T4 and T3 in replacement therapy so as to mimic the normal ratio secreted by the thyroid gland
It does not appear that liotrix offers any therapeutic advantage over levothyroxine alone

15. Adverse effects
The toxicity of thyroxine is directly related to the hormone level (i.e., symptoms of hyperthyroidism)
Careful monitoring of individual infants and dosage adjustment are necessary during early weeks and months of life to prevent prolonged hyperthyroxinemia
Premature synostosis with and without brain dysfunction: associated with T4 doses
In children: restlessness, insomnia, and accelerated bone maturation and growth

16. Hyperthyroidism
Hyperthyroidism refers to excess synthesis and secretion of thyroid hormones by the thyroid gland
Goal of treatment:
Inhibit synthesis of the hormone
Block the release of the hormone from the follicle

17. Inhibition of thyroid hormone synthesis Thioamides
Agents: propythiouracil (PTU) and methimazole (MMI)
Used in the management of hyperthyroidism and thyrotoxic crisis and in the preparation of patients for surgical subtotal thyroidectomy
Since the synthesis rather than the release of hormones is affected, the onset of these agents is slow (3-4 weeks) before stores of T4 are depleted

18. Thioamides
Prevent hormone synthesis by inhibiting the thyroid peroxidase-catalyzed reactions and blocking iodine organification
Block coupling of the iodotyrosines
Inhibit the peripheral deiodination of T4 and T3 (mainly propylthiouracil)
Pharmacodynamics

19. Thioamides- ADRs Maculopapular pruritic rash
Most serious: agranulocytosis ( % of patients
Rare: urticarial rash, vasculitis, a lupus-like reaction

20. Iodides The effects of iodide on the thyroid gland are complex:
Inhibit hormone release, possibly through inhibition of thyroglobulin proteolysis (major)
Inhibit organification
Decrease the size and vascularity of the hyperplastic gland
Improvement in symptoms occurs rapidly—within 2–7 days

21. Iodide
Iodide use is restricted to short term therapy and should not be used alone: thyroid gland will escape from the iodide block in 2–8 weeks, and its withdrawal may produce severe exacerbation of thyrotoxicosis

22. Iodides- ADRs Acute life threatening angioedema and laryngeal
Swollen salivary glands
Soreness of the teeth and gum
Mucous membrane ulcerations
Conjunctivitis
Rhinorrhea
Drug fever
Metallic taste
Bleeding disorders
Anaphylactoid reactions (rare)

23. Radioactive Iodine (131I)
131I is taken up and trapped in the same manner as I-: β- particle emissions, which destroy thyroid tissue
Advantages: easy administration, effectiveness, low expense, and absence of pain
Major disadvantage is the development of hypothyroidism