Thyroid_2013_gyogyszer_e_student

Thyroid hormones
Structures of the major circulating thyroid
hormones
Dynamics of Thyroid Hormone Production
Thyroid hormone metabolism
Type1 (D1)
Type2 (D2)
Type3 (D3)
5’-deiodinase I
5’-deiodinase II
5-deiodinase
certain beta blockerscorticosteroids starvation, amiodarone All family members contain the novel amino acid selenocysteine (SeC) in their catalytic center.
The Hypothalamic-Pitutary Gland-
Thyroid Gland Axis
The Effects of TSH
Ca2+ + PLC
Immediate effects
Long term effects (trophic effects)
Hormone synthesis
Endocythosis of colloidProteolysis of thyreoglobulinGlucose oxidationNADPH generation Circadian rhythm: peak serum TSH at night, usually between 0.00 and 4.00 AM Antithyroid Drugs
II. Block of organic binding of iodine IV. The effect of large doses of iodides V. Naturally occurring thyroid inhibitor Effects of Antith
n and Coupling
thiocarbamides
methimazole
propylthiouracil
lithium ion
Alteration of iodide trapping
chlorate
perchlorate
pertechnetate
periodate
biiodate
nitrate
propylthiouracil
thyocyanate acids
dinitrotyro T
propylthiouracil
Antithyroid Drugs IV
Wolff-Chaikoff effect
Increasing doses of Iodine increase hormone synthesis initially Large dose of Iodide inhibits the hormone production.
– inhibits the organic binding of iodide – inhibits proteolysis of thyroglobulin – decreases the vascularity of the hyperplastic gland – this inhibitory effect can be explained by the down-regulation of the Antithyroid Drugs
II. Block of organic binding of iodine IV. The effect of large doses of iodides V. Naturally occurring thyroid inhibitor - Thiocyanates are sometimes ingested with food - It occurs as progoitrin in vegetables of Brassicaceae family (cabbage, turnips, kale, kohlrabi, rutabaga) - there are progoitrin activators in the intestine - Goitrin intake on a normal mixed diet is usually not harmful Mechanism of Thyroid Hormone Action I
- T3 and T4 enter target cells by carrier mediated energy-dependent, Na+ coupled transport - Unliganded high-affinity nuclear T3 receptors are bound to The receptor function requires zinc ions.
- Because thyroid hormones act trough gene transcription the hormone effects become evident several hours later and lasts more days.
- Elevated serum thyroid hormone level and fasting decrease the number and binding capacity of thyroid hormone receptors.
Mechanism of Thyroid Hormone Action II
- increase the number of “pump units” - stimulate oxygen consumption (except in brain) - increase the basal metabolic rate (calorigenic action) except in brain, gonads and spleen (low concentration of T receptors) Effects on intermediary metabolism
Carbohydrate metabolism
blood glucose level is slightly increased
Lipid metabolism
Protein metabolism
- low doses of thyroid hormone stimulate protein synthesis- large doses of thyroid hormone accelerate protein catabolism Effects of Thyroid hormones
Thermoregulation
- extra heat production- slight rise in body temperature- activation of heat dissipating mechanisms (sweating, cutaneous vasodilation) Effects on cardiovascular system
- ↑ number of βAR- ↑ heart rate- ↑ force of contraction- ↑ stroke volume- ↑ cardiac output- ↑ P Effects on respiration
Effects of Thyroid hormones
Effects on blood
- Increased production of erythropoietin- The need for all vitamin is increased due to the increased Effects on the nervous system
- Thyroid transport across the blood-brain barrier- Thyroid hormone excess causes rapid mentation, - reaction time of stretch reflexes shortened Effects on skeletal muscle
- large doses of thyroid hormone causes myopathy Effects on the gonads
- to the normal process of sperm production- to the ovarian cycle of follicular development- to the maintenance of healthy pregnancy Effects of Thyroid hormones
- thyroid hormones promote skeletal maturation cartilage ossification, maturation of epiphyses - thyroid hormones change the process of bone remodelling Effects on growth and development
- it requires the presence of thyroid hormone, GH and insulin - thyroid hormone potentiates the effects of GH on the tissues- thyroid hormone stimulates linear growth and maturation of bone - growth of cerebral and cerebellar cortex - proliferation of axons- branching of dendrites- myelinization Alteration of thyroid gland function Thyroid gland enlargement (goiter) - dietary deficiency of Iodide- thyroiditis- excess Iodide- malignancy Thyroid Hormone Deficiency
In infancy
- cretenism, mental and growth retardation
- dwarfism, limbs are disproportionately short compared
- neurologic signs of pyramidal and extrapyramidal tract In childhood
- less prominent mental retardation
- impairment of linear growth
- child who appears younger than his or her chronological age
- epiphyseal development is delayed
Thyroid Hormone Deficiency
nonspecific symptoms and signs appear over month or years-cold intolerance- hair loss, -dry, coarse skin accumulation of mucopolisacharids in subcutaneous tissues - delayed muscle contraction and relaxation - SV and heart rate are reduced - altered mental function impaired memory, slow speech, decreased initiative, somnolencelethargy Thyroid Hormone Excess
nervousnessirritabilityemotional instability - weight loss despite normal or increased food intake - heat intolerance, increased sweting, increased ventillation , tachycardia, atrial arrhythmias may develop - fatigue, muscle weakness, osteoporosis - women have decreased or absent menstrual flow Measurement of TSH level
"Full thyroid function tests"
Measurement of total T4 levels
Measurement of antithyroglobulin antibodies
TRH stimulation test

Source: http://physiology.med.unideb.hu/files/oktatas/gyogyszeresz/human_elettan_ii/eloadasanyagok/Thyroid_hormones.pdf