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Thyroid Gland
Thyroid Gland
Thyroid cells are the only cells in the body which can absorb iodine. These cells combine iodine and the amino acid tyrosine to make triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine) Every cell in the body depends upon thyroid hormones for regulation of their metabolism.
Levothyroxine
Dosage
Infants : 16 months of age is 1015 mcg/kg/d Adult is about 1.7 mcg/kg/d. Adults
Pharmacokinetics
Should be taken 30min before or 1 hour after meals (delayed absorption for soy, other foods and drugs) Takes 6-8 weeks to reach steady state levels Labs should be repeated after 2 months
Antithyroid Agents
Reduction of thyroid activity and hormone effects can be accomplished by
agents that interfere with the production of thyroid hormones agents that modify the tissue response to thyroid hormones glandular destruction with radiation or surgery.
Thioamides
The major action is to prevent hormone synthesis by inhibiting the thyroid peroxidasecatalyzed reactions and blocking iodine organification. blocking coupling of the iodotyrosines.
Thioamides
The thioamides methimazole and propylthiouracil are major drugs for treatment of thyrotoxicosis Pharmacokinetics:
almost completely absorbed in the GIT serum half life: 90mins propylthiouracil (PTU) ; 6 hours (methimazole) excretion: kidney 24 hours (PTU) ; 48 hours (Methimazole) can cross placental barrier (lesser with PTU) Methimazole 10x more potent than PTU PTU more protein-bound
Thioamides
Adverse Effects:
maculopapular rash benign transient leukopenia agranulocytosis hepatitis (PTU) ; cholestatic jaundice (Methimazole) vasculitis lupus-like syndrome
Anion Inhibitors
Monovalent anions such as (ClO4), pertechnetate (TcO4), and thiocyanate (SCN) can block uptake of iodide by the gland by competitive inhibition of the iodide transport mechanism can be overcome by large doses of iodides ? useful for iodide-induced hyperthyroidism (amiodarone-induced hyperthyroidism) rarely used due to its association with aplastic anemia
Iodine131
preparations: sodium iodide 131 MOA: trapped within the gland and enter intracellularly and delivers strong beta radiations destroying follicular cells Penetration range-400-2000m Clinical uses: Graves, primary inoperable thyroid CA Contraindication: pregnancy
Iodine131
Advantages
Easy administration Effectiveness Low expense Absence of pain
Iodine131
Thioamides should be given initially and stop 5-7 days before radioactive iodine administration in elderly or patients with heart disease 131I dosage generally ranges between 185 MBq to 555 MBq repeated after 6 months Adverse effects permanent hypothyroidism potential for genetic damage may precipitate thyroid crisis
Inorganic Iodines
major anti-thyroids before the introduction of thioamides (1950s) preparations:
strong iodine solution (Lugols) potassium iodide iodone
Inorganic Iodines
MOA:
acutely blocks release of thyroid hormone from the gland by inhibiting thyroglobulin proteolysis
Caution:
it may delay onset of thioamide effects; should be given after initiation of thioamides
Beta Blockers
Drugs: Propranolol, Metoprolol, Atenolol MOA:
Membrane-stabilizing action: inhibits T4 to T3 (propranolol at high dose) Ameliorate many disturbing s/sxs of hyperthyroidism secondary to increased circulating catecholamines by blocking beta receptors
Corticosteroids
Prednisone is given for patients with Graves ophthalmopathy 1mg/kg/day (60mg/day 3 divided doses); if it should be given for more than 4 weeks, taper to decrease risk of adrenal crisis
Hypothyroidism
Hypothyroidism is a syndrome resulting from deficiency of thyroid hormones and is manifested largely by a reversible slowing down of all body functions . In infants and children, there is striking retardation of growth and development that results in dwarfism and irreversible mental retardation.
Hypothyroidism
Primary infant born without a thyroid gland Secondary throiditis, tumor, destruction of thyroid tissue from radiation .
Hashimoto's thyroiditis, an immunologic disorder in genetically predisposed individuals
Hypothyroidism
All newborns are tested at birth for thyroid function. If untreated can lead to retardation due to effects on brain development. Treatment is life-long replacment of the hormone.
Hypothyroidism - Adults
Presenting clinical manifestations
Weight gain Constipation Fatigue Irregular menstrual cycle in women Edema More common in females than males
Hypothyroidism
Laboratory value to look at: TSH thyroid stimulating hormone will be increased - it is working hard to stimulate the production of T3 and T4. T3 and T4 levels would be low.
Hyperthyroidism
Excessive secretion of thyroid hormone and usually involves an enlarged thyroid gland. TSH levels would be low and the T3 and T4 high.
Clinical Presentation
Skin: sweating; heat intolerance Eyes: diplopia (Graves' disease) Cardio: increased heart rate, stroke volume, cardiac output, pulse pressure; high-output heart failure GI: increased appetite; increased frequency of bowel movements CNS:Nervousness; hyperkinesia; emotional lability Menstrual irregularities; decreased fertility; increased gonadal steroid metabolism
Graves Disease
The most common form of hyperthyroidism is Graves' disease, or diffuse toxic goiter. Graves' disease is an autoimmune disorder Management of Graves' Disease
antithyroid drug therapy surgical thyroidectomy destruction of the gland with radioactive iodine.