1. By Dr.Mohamed Abd AlMoneim Attia
Thyroid gland By
Dr.Mohamed Abd AlMoneim Attia

2. Thyroid hormone synthesis
Uptake of iodide by thyroid gland
Oxidation of iodide to produce molecular iodine
Organification
Iodination of tyrosine residues on thyroglobulin
Monoiodotyrosine (MIT) and diiodotyrosine (DIT).
Coupling – formation of T4 and T3
Proteolysis of thyroglubulin and secretion of thyroid hormones
Conversion of T4 to T3 in peripheral tissues

3. Thyroid hormone synthesis
TBP T3
& Free T4 & T3
(Iodide Organification)
4. Coupling

4. Metabolism of thyroid hormones
Outer ring
Inner ring
(T4)
5’-deiodinase
(4X potent than T4)

5. General principles
T4 secretion is stimulated by thyroid-stimulating hormone (TSH). In turn, TSH secretion is inhibited by T4, forming a negative feedback loop.
The gland synthesizes T4 > T3 (20:1) but T3 is 4-times more potent than T4
Most of the circulating T3 is derived from peripheral deiodination of T4.
B-blockers and corticosteroids inhibit peripheral conversion of T4 into T3.

6. Thyroid hormones Mechanism of action
T4 and T3 must dissociate from thyroxine binding globulin (TBG) in plasma before entering into the cells.
In the cells, T4 is deiodinated to T3 that enters nucleus and attaches to specific receptors which promotes mRNA and protein synthesis.

7. Preparations of thyroid hormones
L-thyroxine: a synthetic sodium salt of T4 (t ½ is 7 days).
Liothyronine: a synthetic sodium salt of T3 (t ½ is 1 day).

8. Hypothyroidism (myxodema)
Hypothyroidism in infants leads to cretinism .
It is treated by replacement with L-thyroxin (T4).
Children require more T4 than adults due to rapid growth.
During pregnancy, hypothyroid woman require higher doses
T3 has a shorter t ½ than T4 and is therefore used for emergency treatment of myxoedema coma.

9. Management of myxedema coma
Hospitalization in intensive care unit (ICU).
All medications must be given intravenously .
Intravenous fluids should be given with caution (can aggravate hyponatremia commonly associated with hypothyroidism and avoid excessive water intake.
L-thyroxine (T4): 400 μg IV initially, followed by 50 μg daily͘ Intravenous .T3 can be used.
Hydrocortisone: 200 mg I.V. because the patient usually has associated adrenal insufficiency.
Treatment of associated diseases e.g. infection or heart failure.

10. Hyperthyroidism (thyrotoxicosis)
It is a clinical syndrome results from high levels of thyroid hormones. 
Clinical picture:.It resemble sympathetic over-activity because thyroxin increases sensitivity of B-receptors to circulating catecholamines.
There are tachycardia, arrhythmia, sweating, exophthalmos, etc.

11. Investigations:
Measuring serum T3, T4, and TSH: T4 is ↑ and TSH is decreased
Assay for positive thyroid antibodies: 90% +ve in Grave's disease.
Thyroid scan for tumors.
 Management:
Medical treatment: mainly for Grave’s disease
Surgical thyroidectomy: mainly for multiple nodular goiter

12. Antithyroid Drugs 1. Thiouracil drugs (thioamides):
(Carbimazole - Methimazole - Propylthiouracil)
Pharmacokinetics:
Methimazole is the active metabolite of Carbimazole.
The t1/2 of propylthiouracil is 1.5 hr while the t1/2 of methimazole is 6 hrs.
The short t½ of these drugs has little effect on their effect because they are selectively accumulated in the thyroid.
Propylthiouracil is preferable during pregnancy because it does not cross placental barrier (because it is strongly bound to plasma protein).

13. Mechanism of action:
They inhibit oxidation of iodides by inhibiting peroxidase enzyme.
Propylthiouracil also inhibits the peripheral conversion of T4 into T3.
They have slow onset of action (3-4 weeks) but propylthiouracil has faster effect (so it is used in thyrotoxic crisis).

14. Doses and duration:
Carbimazole (Neomercazole): start with 30 mg/d till reach euthyroid state (after 4-8 weeks) then maintain on 15 mg /d for 1-2 years (until the gland undergo spontaneous remission).
Propylthiouracil: start with 300 mg/d for 4-8 weeks then 150 mg/d for 1-2 years.

15.  Adverse effects:
Agranulocytosis & bone marrow depression.
Hypothyroidism with increased size and vascularity of the gland due to ↑ TSH͘
Hypothyroidism of the infant (fetal goiter) if given during pregnancy.
Cholestatic jaundice.
Hypersensitivity reactions: may require stopping of the drugs.
There is 50-68% incidence of relapse.

16. Follow up with WBC count.
Precautions during thiouracil (thioamides)treatment:
Therapy with thiouracil drugs should continue for 1-2 years and should be stopped gradually (to prevent relapse).
Follow up with WBC count.
If used during pregnancy, propylthiouracil is the drug of choice.

17. 2. β-blockers Propranolol
It controls sympathetic over activity e.g. tachycardia and arrhythmia.
It ↓ insomnia, and tremors
It inhibits peripheral conversion of T4 to T3.
If propranolol is contraindicated give diltiazem (calcium channel blocker).

18. 3. Radioactive iodine
It is an effective oral treatment for thyrotoxicosis caused by Graves’ disease or by toxic nodular goiter.
Delayed hypothyroidism is the main adverse effect so; replacement therapy with T4 is required after functional ablation.
Contraindication:
Pregnancy and lactation: I131 crosses placental barrier and excreted in milk.
Age < 16 years for fear of delayed malignant changes.

19. 4. Iodides
Potassium iodides or Lugol’s iodine: (10% KI + 5% iodine) is given 1-2 weeks before surgery in order to:
Inhibit synthesis and release of T4 & T3.
Inhibit release of TSH leading to ↓↓ size and vascularity of the gland.
Improvement in thyrotoxic symptoms occurs within 2-7 days, but if therapy with iodides is continued (>2-4 weeks), the beneficial effects disappear and manifestations of hyperthyroidism reappear (iodine escape).

20. Therapeutic uses:
Preparation of the patient before operation to decrease size and vascularity of the gland.
Treatment of thyroid storm .
Adverse effects:
Metallic taste.
Swollen salivary glands, mucous membrane ulceration and gastric irritation.
Increased lacrimal and nasal secretions (rhinorrhea).
Allergic reactions: skin rash, drug fever, etc.
Iodine escape if used > 2-4 weeks.

21. Preparation of patient before operation:
Carbimazole: 10 mg t.d.s weeks before operation to reach euthyroid state.
Potassium iodide: 1-2 weeks before operation to ↓ size and vascularity of the gland (see below).
Propranolol: to control HR and cardiac arrhythmia.
Sedatives (phenobarbitone or diazepam): to ↓ anxiety͘

22. Thyrotoxic crisis (thyroid storm)
It is a sudden severe exacerbation of the manifestations of thyrotoxicosis due to sudden release of T3&T4 (medical emergency).
It is a common postoperative complication if the patient was not well-prepared.
Manifestations:
High fever with vomiting and sweating
Tachycardia and arrhythmia, occasionally heart failure and shock.
Convulsions, coma, and even death from heart failure.

23. Management:
Intravenous fluids and antipyretics to control dehydration and fever. Aspirin must be avoided because it displaces thyroid hormones binding from thyroid binding globulin (TBG)
Propranolol: 1-2 mg slowly I.V. or 40 mg oral /6 hrs. It controls excessive adrenergic response (tachycardia, arrhythmia, tremors, etc.).
Esmolol is short-acting β-blocker can be also given.
If β-blockers are contraindicated give diltiazem orally or by I.V. infusion.

24. Potassium iodides: 10 drops orally/day to block hormone release and peripheral conversion of T4 to T3.
Propylthiouracil: 250 mg/6 hrs orally to block hormone synthesis. It acts more rapidly than other thiouracil drugs.
Hydrocortisone: 50 mg I.V./6h to elevates BP and reduces toxemia. It also blocks peripheral conversion of T4 to T3.

25. GOOD LUCK