Thyroid Physiology Flashcards
Hypothalamic Pituitary Thyroid Axis
Thyrotropin releasing hormone (TRH) released by hypothalamus –> Thyroid stimulating hormone (TSH) released by anterior pituitary –> Stimulate thyroid to release T3 and T4
Negative Regulators -> somatostatin, dopamine, high glucocorticoids all decrease TSH release
Thyrotropin releasing hormone
translated as preprohormone -> mature is tripeptide
- stimulates release of TSH from thyrotrophs in anterior pituitary
- regulates energy homeostasis, feeding, thermogenesis, autonomic regulation
- bind to TRH receptors in anterior pituitary -> promote release of TSH
Thyroid Stimulating Hormone
alpha and beta chains –> beta is specific to TSH and confers hormonal specificity
- receptor is GPCR -> stimulates many aspects of thyroid hormone synthesis and release
7 Steps of Thyroid Hormone Synthesis
- Dietary Iodine is required, active transport of I into thyroid follicular cell
- Oxidation of I to I2 = organification
- Iodination of tyrosines make MIT, DIT
- Conjugation of MIT and DIT to T3, T4 (thyroid peroxidase dependent)
- Endocytosis of conjugates
- Proteolysis of conjugates into mature T3 and T4
- Movement of T3 and T4 out of cell
Comparison of T3 and T4
T3 is more active, shorter circulating half-life
T4 us converted to T3 intracellularly
- they both bind thyroid hormone receptors
Thyroid Hormone Carrier Proteins
- Thyroxine binding globulin (TBG) -> binds 75% of T4 and T3, 1 binding site for 1 thyroid hormone
- Transthyretin -> binds 20% of T4, 5% of T3, 2 binding sites for hormones
- Albumin -> binds 5% of T4 and 20% of T3, several binding sites
Carrier proteins and thyroid hormones
99% of T4 and T3 bound
- serum proteins increase during pregnancy, estrogen/androgen treatment
- serum proteins decrease during hyperthyroidism, malnutrition, and nephritic syndrome
Intracellular Metabolism
Deiodinase I and II activate T4 to T3
Deiodinase I and III deactivate T4 to rT3
Deiodinase I
highly prevalent in kidney/liver
- converts T4 -> T3, or T4 -> rT3
- drugable target
Deiodinase II
present in brain, pituitary, muscle
- converts T4 -> T3
Deiodinase III
present in brain, skin, placenta
- deactivates T4 -> rT3
TSH stimulation of thyroid
- secretion of mature thyroid hormones
- production of new thyroid hormone batch
- thyroid peroxidase, thyroglobulin transcription, Na/I transport activity
Thyroid Hormone Actions
- normal growth, development, and metabolism
- promotes oxygen consumption, heat productions, free radical formation
- regulates BMR, increase glucose utilization, permissive to sympathetic effects (increase HR and contractility)
- if replacement therapy started a few days after birth in deficiency patient, growth is normal
Hypothyroid in Infants
Congenital or maternal causes
- profound mental retardation
- short stature
- delay motor development
- coarse hair
- protuberant abdomen
Maternal Etiology of Hypothyroidism
lack of iodine in diet –> RARE
- Hasimoto’s thyroiditis -> blocking anti-TSH receptor antibodies
Cretinism
hypothyroidism in infants
- respiratory difficulty, cyanosis, jaundice, poor feeding, harsh cry, umbilical hernia
- proximal tibial and distal femur epiphysis have certain lengths –> if shorter it suggests hypothyroidism
Physiological Effects of Low Thyroid Hormone in Adults
- Lethargy
- somnolence
- slowed intellectual and speech
- stiffness and muscle aches
- cold intolerance
- delayed deep tendon reflex
- anovulation/amenorrhea
Physiological Effects of Excess Thyroid Hormone in Adults
- increased HR and contractility (increased sensitivity to catecholamines) –> increased O2 demand –> increased EPO
- promotes GI motility and hyperdefecation
- promotes bone turnover -> net loss and hypercalcuria
- promotes protein turnover -> muscle loss and myopathy
- increase muscle contraction and relaxation
- increased gluconeogenesis and glycogenolysis -> diabetes
- increase LDL receptor #
- early bone closure -> precocious puberty
- impairs GnRH -> infertility
Thyrotoxicosis
ANY cause of excessive thyroid hormone [ ]
- specturm –> thyroid storm is WORSE
- treat immediately with beta-blocker, thioamides, corticosteroids (cover functional hypoadrenalism)
Etiology of Hypothyroidism
Primary
- congenital, gland destruction, iodine deficiency, autoimmune (Hashimoto)
Secondary
- associated with other pituitary deficiencies
Etiology of Hyperthyroidism
Graves’ disease -> production of thyroid stimulating immunoglobulins (TSI)
- T cells become sensitive to thyroid antigen –> B-cells produce antibodies that mimic TSH –> hyperstimulation of thyroid hormone production
Goiter
enlarged thyroid gland
Hypothyroidism –> thyroid is stimulated to grow and produce by can’t so there is no negative feedback and the thyroid enlarges
Hyperthyroidism -> Graves’ (TSI is unregulated and causes thyroid hypertrophy)
Diagnostic Tests
- TSH test -> most accurate measure of thyroid activity
- T3 and T4 -> levels of free T3 and T4 in blood
- TSI test -> measures TSI levels –> Graves’ disease
- Radioactive iodine uptake -> measures amount of iodine thyroid collects from bloodstream
- Thyroid Scan -> how and where iodine is distributed in thyroid (nodules/irregularities)
Hypothyroidism replacement
- Levothyroxine (T4) –> narrow therapeutic index, AlOH, Fe, Ca decrease absorption
- Liothyronine (T3) -> shorter onset and half-life, greater potency because of T3 action
S.E. = hyperthyroidism
Thioamides
treat hyperthyroidism (Graves’) and prepare for thyroid surgery
- Methimazole & Carbimazole - inhibit thyroid peroxidase
- Prophylthiouracil (PTU) - inhibis thyroid peroxidase and deiodinase I
- Potassium Iodide (KI) -> block radiation uptake
Radioactive Iodine
- 131-I –> thyroid ablation
- 123-I –> thyroid imaging
S.E. = allergic rxns, sore teeth and gums, excess salivation
