3.Kuliah Endokrin I UWK

7/28/2019 3.Kuliah Endokrin I UWK

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Survey of Some Human

Endocrine Glands


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Endocrine organs


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Central Roles of the

Hypothalamus and Pituitary


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Pituitary Dwarfism


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Gigantism and Acromegaly


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Action of Steroid Hormones


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Action of Peptide Hormones


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Thyroid Gland P618-623

located over trachea

inferior to larynx

Hormones:

Thyroid hormoneCalcitonin

F16.7


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anterior

pituitary

paraventricular

nucleus

Hypothalamus

Anterior Pituitary

Thyroid gland

TRH+

+

TSH

Thyroid

-

T4, T3

-

SRIF


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Follicle epithelial cell

Thyroidfollicle Thyroidfollicle

Thyroidfollicle

Synthesis and secretion

EC Space Follicle Lumen


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Oxidization and organification

TPO

TPO

I-

apical membrane

Thyroid peroxidase:Oxidation

Incorporation into thyroglobulin

Monoiodotyrosine

Diiodotyrosine

Coupling of MIT and DIT

within TG to form T3 and T4

Reabsorption of TG into follicle cellProteolysis: release of T3, T4

SecretionPeripheral conversion of T

4to T

3

Regulated by TSH


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Cli i l f th id


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Clinical uses of thyroid

hormoneLevothyroxine (synthetic T

4

)

Drug of choice for routine replacement therapy

Identical to endogenous T4 and converted to T3

Long half-life allows once daily oral administration

Liothyronine (synthetic T3)

Rapid absorption, shorter T1/2

spiking, uneven blood levels, transient action

Frequent dosing required

Use limited to situations requiring rapid response


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Hyperthyroidism (thyrotoxicosis)

Characterized by: Increased cardiac output Nervousness

Muscle weakness Increased BMR

Hyperglycemia Hypocholesterolemia

Weight loss

Graves' disease:

Most common form of hyperthyroidism

Thyroid-stimulating immunoglobulins (TSIg) interact with theTSH receptor, activate the thyroid

Symptoms: Diffuse goiter

Exophthalmus - protruding eyes, mucopolysaccharideinfiltration of the extraocular tissue

Other signs of hyperthyroidism (above)


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Hypothyroidism

Characterized by:

decreased cardiac output slow mental function muscle fatigue hypoglycemia decreased body temperature

Causes: Primary hypothyroidism: Hashimoto's autoimmune thyroiditis radiation damage thyroidectomy iodine deficiency autosomal defects in hormone synthesis idiopathic

Secondary hypothyroidism


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HypothyroidismMyxedema:

Onset of hypothyroidism in the adult Named for characteristic thickening of subcutaneous tissue

caused by deposition of mucopolysaccharides

Once thought to be due to increased mucus ("myx")formation

Cretinism: Onset in infancy

Usually due to thyroid dysgenesis

Impaired physical growth Impaired brain growth and myelination

Mental retardation


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Adverse effects

Nervousness Hypertension

Vomiting and diarrhea

Increased sensitivity to heat Impaired reproductive function

Cardiotoxicity

Iatrogenic hyperthyroidism

Especially in the elderly

Arrhythmias

Shortness of breath


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Contraindications to T4

therapyUse with caution in presence of:

Adrenal insufficiency: increases cortisol turnover

Coumarin anticoagulants: increases catabolism of

clotting factors

Diabetes mellitus: increases insulin requirement

Stimulates gluconeogenesis and glycogenolysis

Cardiovascular disease: initiate therapy slowly, monitor

closely because of effects on the heart


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Thionamides: Clinical usesGraves' hyperthyroidism:

100 to 600 mg propylthiouracil/day in divided doses or10 to 40 mg methimazole /day as single dose

Reduce dose for maintenance

Continue for 6 months or longer, until remission

Propylthiouracil: also partially inhibits T4 T3 May be used when fast action is desired

Methimazole: longer duration of action

Suitable for once daily dosing

Propylthiouracil indicated for hyperthyroidism duringpregnancy

Use minimum dose that controls symptoms


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Thionamides: Clinical uses

Following radioiodine treatment:

To achieve euthyroid status until effects ofradiation are observed

Prior to subtotal thyroidectomy:

Euthyroid status improves response tosurgical stress


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Thionamides: Adverse effects

Skin rashes Agranulocytosis (in 0.3 % of patients) -

reversible upon discontinuation

Arthralgia and myalgia Hepatic abnormalities

necrosis (propylthiouracil)

cholestatic jaundice (methimazole)


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Most common treatment in U.S. Radioactive T1/2: 8 days

Rapidly and efficiently trapped by the thyroid

Dose is determined by preliminary uptake test

Adjusted for complete or partial destruction ofthyroid with no injury to adjacent tissue

Adjunctive therapy:

-adrenergic blocking agents (propanolol) or

Ca2+ channel antagonists (verapamil)

For relief of symptoms (tachycardia, hypertension,arrhythmias) until euthyroid

Radioactive iodine (131I)

3.Kuliah Endokrin I UWK

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