Pharmacotherapy Thyroid Disorders

Edy Junaidi

Regulation of thyroid hormone secretionGoodmann & Gillman, 2008

Biosynthesis

Talbert, R.L, 2005Iodide Uptake.Active transport via Na-I symporter (NIS)thyroid/plasma Iodide concentration usually 20 50, it can exceed 100 when thyroid is stimulatedThyrotropin stimulate NISOxidation & IodinationOxidation of iodide to its active form & iodination of thyrosine is catalyzed by thyroid peroxidase which is abundant in apical siteFormation of thyroxine & triiodothyronine from thyrosineResorption, proteolisis of colloidSecretion of thyroid hormonePeripheral convertion of T4 into T3

Thyroid hormone synthesis & secretion inhibitorsThyroid hormone transported by binding mainly to TBG, small proportion to thyroxine-binding prealbumin (TBPA), and albumin99.95% of T4 & 99.5% of T3 are bound to proteinsMajority of T3 is from breakdown of T4 catalyzed by monodeiodenase, less than 20% are produced by thyroidMonodeiodenase :Type I in peripheral tissuesType II in CNS, pituitary, & thyroidType III in placenta, skin, & developing brain inactivate T4 & T3Thyroid hormone transported by binding mainly to TBG, small proportion to thyroxine-binding prealbumin (TBPA), and albumin99.95% of T4 & 99.5% of T3 are bound to proteinsMajority of T3 is from breakdown of T4 catalyzed by monodeiodenase, less than 20% are produced by thyroidMonodeiodenase :Type I in peripheral tissuesType II in CNS, pituitary, & thyroidType III in placenta, skin, & developing brain inactivate T4 & T3

Properties of 5`-monodeiodinase IsoformsAction of thyroid hormoneExert its effect by binding to nuclear thyroid receptor (TR) modulate gene transcription protein synthesis. Unliganded TR bind TRE (thyroid respons elements) & repressing gene transcriptionTwo distinct gene encode 2 family of TR, TR & TREffect of thyroid hormone:Growth & developmentCalorigenic effectsCardiovascular effectsMetabolic effectsClinical Aspects of THExcessive thyroid hormoneDeficient thyroid hormoneDisorders of thyroid growth

ThyrotoxicosisThe term applied to any conditions caused by elevated level of circulating free thyroid hormones, Hyperthyroidism is restricted to those of gland hyperfunction

Differential Diagnosis of ThyrotoxicosisTherapeutics objectivesEliminate excess of hormonesControl symptomsControl long-term consequences of disordersAntithyroid & other thyroid inhibitorsClassified into 4 categories :Antithyroid drugs; directly inhibit synthesis of thyroid hormonesIonic inhibitors, blocks iodide transport mechanismsHigh concentration of Iodine, decrease release of hormon & synthesisRadioactive Iodine, damage the gland by ionizing radiation

HypothyroidismClinical & biochemical syndrome result from decreased thyroid hormone production

Causes of hypothyroidismGoal of therapyRestore normal thyroid hormone in tissueProvide symptomatic reliefPrevent neurologic deficit in newborn & childrenReverse biochemical abnormalities caused by hypothyroidismTherapeutic Use of Thyroid HormonesHormone replacement therapyThyroid hormone replacement during pregnancyTreatment of myxedema comaTreatment of critinismThyroid nodulesThyroid cancerTherapeutic Use of Thyroid HormonesHormone replacement therapyThyroid hormone replacement during pregnancyTreatment of myxedema comaTreatment of critinismThyroid nodulesThyroid cancerLipiodol (iodized oil)