The Thyroid Gland Flashcards
Describe the structure of the thyroid gland?
Butterfly shaped, lies across trachea at base of larynx
Not visible or palpable in health
One of the larger endocrine glands
What are the 2 active forms of thyroid hormones?
T3 - triiodothyronine
T4 - thyroxine
What are the 2 cells in thyroid gland?
C (clear) cells
Follicular cells
What are C cells?
Secrete calcitonin - Ca regulating hormone
What are follicular cells?
Support thyroid hormone synthesis and surround hollow follicles
What are thyroid follicles?
Spherical structures which walls are made of follicular cells
Centre of follicle filled with colloid - sticky glycoprotein matrix
How much TH does the colloid contain?
2-3mnths supply
What do follicular cells produce?
Enzymes which make thyroid hormones as well as thyroglobulin - protein rich in tyrosine residues
These are secreted into colloid
Explain iodide and follicular cells
These cells actively concentrate iodide from plasma and transport it into colloid where it combines with tyrosine residues to form TH
How does iodide enter follicular cells?
From plasma via Na/I symport transporter
Allows iodide to be transported against conc. gradient
Into colloid by pendrin transporter
What is the role of thyroid peroxidase?
Enzymes exocytose into colloid with thyroglobulin
Catalyses the oxidation of iodide to iodine
Addition of iodine to tyrosine residues on thyroglobulin molecule
What is the addition of one iodine and a second iodine to thyroglobulin?
MIT - monoiodotyrosine
DIT - diiodotyrosine
What does conjugation of MIT and DIT form?
MIT + DIT - T3 triiodothyronine
DIT + DIT - T4 thyroxine
Conjugation by thyroid peroxidase
What happens in response to TSH?
Portions of colloid undergo endocytosis and within these cells they are packaged into vesicles containing proteolytic enzymes that cut thyroglobulin to release TH
How do TH travel in plasma?
They are lipophilic so pass across follicular cell membrane and bind to plasma proteins - mainly thyroxine binding globulin
Where is TSH released from?
Anterior pituitary
Describe circulating TH
More than 99.8% of T3 and 4 circulates in plasma bound to plasma protein - T4 higher affinity so longer half life
Only free hormone exerts an inhibitor effect on TSH and TRH
Explain negative feedback control on TH
Free hormone in plasma exerts effects on TSH (anterior pituitary) and TRF (hypothalamus)
Can lower at both these points if too much TH
Is T3 or T4 more physiologically active?
T3 as TH receptor has higher affinity for T3 than T4 so 3-5 x more active
90% of TH binding to receptor is T3
What happens to T4?
De-iodinated to T3 by deiodinase enzymes
Half de-iodinated in plasma and half inside target cells as TH receptors are in cell
What are hypothyroid patients supplemented with?
T4 but have normal T3 levels
What can increase tonic release of TRH?
Cold, pregnancy and exercise
What hormones are inhibitory for TSH?
Glucocorticoids - inhibits TSH and conversion of T4 to 3
Somatostatin (GHIH) - inhibits TSH
What does thyroid hormone bind to and what does this do?
Nuclear receptors in target cells - change transcription and translation to alter protein synthesis
What is the function of TH?
Raises metabolic rate and promotes thermogenesis
Increases hepatic gluconeogenesis
Net increase in proteolysis
Net increase in lipolysis
Critical in growth and brain development in utero
How does TH promote thermogenesis?
Through promoting futile cycles of simultaneous catabolism and anabolism - produces heat and not ATP
What are some causes of hyperthyroidism?
Graves Disease
Thyroid adenoma - hormone secreting thyroid tumour
How does Graves disease cause hyperthyroidism?
Antibodies produced mimic TSH and continually activate thyroid gland
Increased release turns off TSH from pituitary so low TSH in plasma
Hyperplasia of gland and hyperactivity
What are the symptoms of hyperthyroidism?
Weight loss/heat intolerance
Muscle weakness/weight loss
Hyper excitable reflexes and physiological disturbances
Increased HR/contractile force as TH is permissive to epinephrine B receptors
What are some causes of hypothyroidism?
Hashimoto’s disease - autoimmune attack on thyroid gland
Deficiency in dietary iodine
Idiopathic
What are the symptoms of hypothyroidism?
Weight gain/ cold intolerance
Brittle nails and thin skin
Slow speech/ reflexes and fatigue
Slow heart rate and weaker pulse
What is goitre?
Significant of thyroid gland in both hypo or hyperthyroidism
Increased trophic action of TSH on thyroid follicular cells in hypo and over activity in graves disease
Describe hypothyroidism due to low iodine
Low iodine in diet so T3 and T4 remain low so no negative feedback so increased TRH and TSH released
Describe hyperthyroidism due to Graves disease
Thyroid stimulating immunoglobulins make gland enlarge and increase T3 and T4 so strong negative feedback which decreases TSH and TRH but does not effect thyroid