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The thyroid gland in intermediary metabolismThe thyroid axis and thyroid gland anatomy Synthesis of thyroid hormones T3 and T4Stimuli for hormone secretionActions of thyroid hormonesFacilitation of catecholamine activityBMR (basal metabolic rate) and BMI (body mass index)Hypo- and hyper-thyroidism signs & symptoms myxedema vs Graves disease Immune modulation of thyroid gland & diseasesSynergism in growthTH radioimmunoassay & Ab measurements

Figure 23-7 - Overview

Figure 23-8

Steps in synthesis of THsIodide trap concentrates I- Iodide oxidation to iodine by peroxidaseIodination of tyrosines on thyroglobulin Coupling reaction:MIT + DIT T3 DIT + DIT T45.Pinocytosis of TG with all these attached6.Phagolysosome release of T3, T4, etc.T3 and T4 secretion into blood when TSH/thyrotropinPlasma proteins transport variable %s

Figure 23-9 Overview

Figure 23-10

Comparison of T4 to T3Larger for T4:amount secreted by thyroid glandtotal and free plasma hormone concentration% bound to plasma pre-albuminhalf-life in circulationSmaller for T4:volume of distribution - T3 additionally in cellsamount active in peripheral tissues after conversion T4 thus pro-hormone for T3

Table 23-2

Actions of thyroid hormonesStimulate metabolismNet effect on carb, fat & protein may be anabolic or catabolic depending on levelsIncrease calorigenesis/heat productionPromote normal growthPromote development and maturation of nervous systemIncrease cardiac functionIncrease respiration & red cell productionIncrease sympathetic/adrenaline actionsProduce typical patient signs & symptoms

Figure 23-12

Figure 23-14 - Overview

Hypothyroidism e.g. myxedemaLow oxygen consumption and slow metabolic rate feel coldDecreased protein synthesisSlowed reflexes, slow speech and thought processes, and feelings of fatigueBradycardiaEffects on gastrointestinal and female reproductive systems (opposite to hyper)Less FB TSH goitreCretinism in infants can result if born hypothyroid but TH treatment delayed

Hyperthyroidism (e.g. Graves disease)Increased oxygen consumption and metabolic heat production feel hotIncreased protein and fat catabolism and possible muscle weaknessHyperexcitable reflexes and psychological disturbances (e.g. anxiety)Increased cardiac 1-adrenergic receptor and myosin expression tachycardia & palpitations Increased muscle 2-adrenergic receptors: vascular smooth muscle relaxationvasodilatationtotal peripheral resistance pulse pressure (systolic diastolic) & bounding pulseskeletal muscle contraction tremor Abnormal Igsgoitre, exophthalmos (not all hyperthyroidism)

Treatments for hyperthyroidismPropylthiouracil (PTU) inhibits TH production by blocking iodination & the coupling reaction, and interfering with conversion of T4 to T3Beta-blockers prevent adrenergic side-effects of excess THImmunosuppressive drugs inhibit auto-immune antibodies targeting the thyroidNote that there are many auto-immune thyroid diseases, some of which cause hypothyroidism, where treatment would be hormone replacement therapy with TH

BMR and BMIBasal Metabolic Rate occurs when energy use is at its lowest levelBMR is increased by THBody Mass Index = weight (kg)/height(m)2When excess TH increases BMR, it would be expected to decrease BMI, unless there is an increase in calorie intake greater than the increased energy outputWhen lack of TH decreases BMR, it would be expected to increase BMI, unless there is a decrease in calorie intake greater than the decreased energy outputThis is the reason why it is important to take a detailed history of a thyroid patient, as food (& exercise) also weight change

Clinical measurementsTHs are measured by radioimmunoassay(see The Human Endocrine System practical)First test in patients is for TSH, which is simplerIf raised, most likely due to low TH and less FBIf lowered, most likely due to high TH and more FBTreatment to reduce excess TH results in TH and TSH levels recovering at different ratesAntibodies can also be measured in those thyroid diseases which are auto-immune These are clustered with other auto-immune diseases, so having one increases probability of having another e.g. coeliac disease

Growth promotion