Survey of Some Human Endocrine Glands

Endocrine organs

Central Roles of the Hypothalamus and Pituitary

Pituitary Dwarfism

Gigantism and Acromegaly

Action of Steroid Hormones

Action of Peptide Hormones

Thyroid Gland P618-623located over tracheainferior to larynx

Hormones:Thyroid hormoneCalcitoninF16.7

anterior pituitaryparaventricular nucleusThyroid

Synthesis and secretion

Oxidization and organification

Clinical uses of thyroid hormoneLevothyroxine (synthetic T4) Drug of choice for routine replacement therapyIdentical to endogenous T4 and converted to T3Long half-life allows once daily oral administrationLiothyronine (synthetic T3) Rapid absorption, shorter T1/2 spiking, uneven blood levels, transient actionFrequent dosing requiredUse limited to situations requiring rapid response

Hyperthyroidism (thyrotoxicosis)Characterized by: Increased cardiac outputNervousness Muscle weaknessIncreased BMRHyperglycemiaHypocholesterolemiaWeight lossGraves' disease:Most common form of hyperthyroidismThyroid-stimulating immunoglobulins (TSIg) interact with the TSH receptor, activate the thyroidSymptoms: Diffuse goiterExophthalmus - protruding eyes, mucopolysaccharide infiltration of the extraocular tissueOther signs of hyperthyroidism (above)

HypothyroidismCharacterized by: decreased cardiac output slow mental functionmuscle fatiguehypoglycemiadecreased body temperature

Causes:Primary hypothyroidism:Hashimoto's autoimmune thyroiditisradiation damagethyroidectomyiodine deficiencyautosomal defects in hormone synthesisidiopathicSecondary hypothyroidism

HypothyroidismMyxedema: Onset of hypothyroidism in the adultNamed for characteristic thickening of subcutaneous tissue caused by deposition of mucopolysaccharides Once thought to be due to increased mucus ("myx") formation

Cretinism:Onset in infancyUsually due to thyroid dysgenesisImpaired physical growthImpaired brain growth and myelinationMental retardation

Adverse effectsNervousnessHypertensionVomiting and diarrheaIncreased sensitivity to heatImpaired reproductive functionCardiotoxicityIatrogenic hyperthyroidism Especially in the elderlyArrhythmiasShortness of breath

Contraindications to T4 therapyUse with caution in presence of:Adrenal insufficiency: increases cortisol turnoverCoumarin anticoagulants: increases catabolism of clotting factorsDiabetes mellitus: increases insulin requirementStimulates gluconeogenesis and glycogenolysisCardiovascular disease: initiate therapy slowly, monitor closely because of effects on the heart

Thionamides: Clinical usesGraves' hyperthyroidism:

100 to 600 mg propylthiouracil/day in divided doses or 10 to 40 mg methimazole /day as single doseReduce dose for maintenanceContinue for 6 months or longer, until remissionPropylthiouracil: also partially inhibits T4 T3 May be used when fast action is desiredMethimazole: longer duration of actionSuitable for once daily dosingPropylthiouracil indicated for hyperthyroidism during pregnancyUse minimum dose that controls symptoms

Thionamides: Clinical usesFollowing radioiodine treatment:To achieve euthyroid status until effects of radiation are observedPrior to subtotal thyroidectomy:Euthyroid status improves response to surgical stress

Thionamides: Adverse effectsSkin rashesAgranulocytosis (in 0.3 % of patients) -reversible upon discontinuationArthralgia and myalgiaHepatic abnormalitiesnecrosis (propylthiouracil)cholestatic jaundice (methimazole)

Radioactive iodine (131I)Most common treatment in U.S.Radioactive T1/2: 8 daysRapidly and efficiently trapped by the thyroidDose is determined by preliminary uptake testAdjusted for complete or partial destruction of thyroid with no injury to adjacent tissueAdjunctive therapy:-adrenergic blocking agents (propanolol) orCa2+ channel antagonists (verapamil)For relief of symptoms (tachycardia, hypertension, arrhythmias) until euthyroid