Thyroid Physiology Flashcards
What is the HPA axis?
Hypothalamic-Pituitary-Adrenal axis
Structure of the thyroid gland?
2 lobes connected by an isthmus; the 2 lobes have 4 parathyroid glands attached to their posterior surfaces (2 each)
Occasionally, the isthmus is absent and the 2 lobes are separate
Hormones secreted by the thyroid gland?
Thyroxine (T4)
Tri-iodothyronine (T3)
Calcitonin
Hormone secreted by the parathyroid glands?
Parathyroid hormone (PTH)
Effect of pregnancy and menstruation on the size of the thyroid gland?
Increases in size
Innervation of the thyroid gland?
Autonomic nerve supply:
• Parasympathetic from vagus nerve
• Sympathetic fibres from superior, middle and inferior ganglia of the sympathetic trunk
Blood supply of the thyroid gland?
Superior and inferior thyroid arteries (branch of the thyroid gland)
+/-
Thyroid ima artery (variant that is present in a minority of the population)
Venous drainage of the thyroid gland?
Three pairs of veins:
• Superior and middle thyroid veins drain to the internal jugular
• Inferior thyroid vein drains to the brachiocephalic vein
Support of the thyroid gland?
Ligament and strap muscles
Posteromedial aspect is attached by the posterior suspensory ligament (Berry ligament)
Importance of the Berry ligament?
Recurrent laryngeal nerve runs within/close to it; this has surgical importance
Implications the thyroid gland has for a tracheostomy?
Isthmus encountered during routine tracheostomy and it must be retracted
Histological structure of the thyroid gland?
Follicle is lined by follicular cells
Parafollicular C cells secrete calcitonin
Contained within the follicle is a colloid (tyrosine-containing thyroglobulin filled sphere that is enclosed by the follicular cells; it stores thyroid hormones)
Storage and release of thyroid hormones?
Colloid thyroglobulin contains T3 and T4
This enters the follicular cell via pinocytosis and lysosomes bind to the vesicle to digest thyroglobulin and leave thyroid hormones
T3 and T4 are released into the bloodstream
Synthesis of T3 and T4?
- Iodine uptaken by follicle cells
- Iodine attached to tyrosine residues on thyroglobulin to form:
• Monoiodotyrosine unit (MIT)
• Di-iodotyrosine unit (DIT) - These couple to form the hormones:
• MIT + DIT = T3
• 2 DITs = T4 - Stored in the colloid thyroglobulin till required
Mechanism of action of Carbimazole?
Inhibits iodine attachment to MIT and DIT do thyroid hormone production decreases
Amount of thyroid hormone produced?
90% is T4 and 10% is T3
Which of the thyroid hormones is more potent?
T3 is more potent whereas T4 is converted to T3 by the liver and kidney
Which is the major biologically active thyroid hormone?
T3
Main regulator of thyroid hormones?
Thyroid Stimulating Hormone (TSH), which is produced by the piuitary gland
Binding of T3 and T4 in blood?
T3 and T4 re hydrophobic/lipophilic and bind to plasma proteins:
• Thyroxine Binding Globulin (TBG) binds 70%
• Thyroxine Binding Prealbumin (TBPA) binds 20%
• Albumin binds 10%
UNBOUND/FREE FORM IS BIOLOGICALLY ACTIVE and is available to tissues
Differences in the binding strength of T3 and T4?
T3 is is bound more weakly to TBG than T4 is and it is not significantly bound by TTR
This is because T3 has a more rapid onset and offset of actions
Difference between free and total concentration of thyroid hormone in the plasma?
Metabolis state correlates more closely with free than with total conc.
Conc. of total hormone does not necessarily vary directly with that of the free hormones
Lab measurements of T3 and T4?
In Ninewells, FREE T3 and T4 are measured
When does total T4 increase but not free T4?
Pregnancy
Newborn state
Hep A & chronic active hepatitis
Biliary cirrhosis
Acute intermittent porphyria
Genetically determined
Drugs that increase total T4 but not free T4?
Tamoxifen
Clofibrate
Heroin
Oral contraceptive pill and other sources of oestrogen
When does total T4 decreased but not free T4?
Androgens
Active acromegaly
Severe systemic illness
Chronic liver disease
Nephrotic syndrome
Genetically determined
Drugs that decrease total T4 but not free T4?
Large doses of glucocorticoids, e.g: in Cushing’s syndrome
Phenytoin
Carbamazepine
Which systems of the body does thyroxine affect?
Almost all tissues in the body throughout life to alter gene transcription and protein synthesis
Effect of thyroxine?
Metabolism, growth, development, reproduction and behaviour
How do thyroid hormones affect basal metabolic rate (BMR)?
Increase BMR to:
• Increase no. and size of mitochondria
• Increase oxygen use and rates of ATP hydrolysis
• Increase synthesis of respiratory chain enzymes
How do thyroid hormones affect thermogenesis?
30% of temp regulation is due to thyroid hormone thermogenesis
How do thyroid hormones affect carb, lipid and protein metabolism?
Carb metabolism:
• Increase BG, due to stimulation of glycogenolysis and gluconeogenesis
• Increase insulin-dependent glucose uptake into cells
Lipid metabolism:
• Mobilise fats from adipose tissue
• Increase fatty acid oxidation in tissues
Protein metabolism:
• Increase protein synthesis
How do thyroid hormones affect growth?
Growth hormone releasing hormone (GHRH) production and secretion requires thyroid hormones
Glucocorticoid-induced GHRH release also depends on thyroid hormones (permissive action)
GH/somatomedins require thyroid hormone for activity (permissive action)
How do thyroid hormones affect development of the foetal and neonatal brain?
Myelinogenesis and axonal growth require thyroid hormones
If the fetus is deprived of thyroid hormones, results in poor brain development
How do hypo and hyperthyroidism affect normal CNS activity?
Hypothyroidism:
• Slow intellectual function
Hyperthyroidism:
• Nervousness
• Hyperkinesis
• Emotional lability
Describe the permissive sympathomimetic action of thyroid hormones
Increased responsiveness to adrenaline & sympathetic NS neurotransmitter, noradrenaline, by increasing no. of receptors
Cardiovascular responsiveness also increase due to this effect, i.e: increased force and rate of contraction of heart
How are the cardiovascular symptoms treated in hyperthyroidism?
β-blocker, e.g: propranolol, is used to treat symptoms in the initial stages
Regulation of thyroid hormone release?
- Negative feedback system
- Low temperatures - in babies and young children, exposure to cold environments stimulates TRH release, which stimulates TSH release and so increases T3 & T4 release from thyroid
- Stress - inhibits TRH & TSH release
- Circadian rhythm - thyroid hormones are higher late at night and lowest in the morning
Describe the -ve feedback system that regulates thyroid hormone release
Thyrotrophin releasing hormone (TRH), from the hypothalamus, stimulates TSH release from the anterior pituitary
TSH stimulates release of T3 and T4 from thyroid gland
T3 and T4 exert negative feedback control of release of TRH and TSH
Describe how thyroid hormones are regulated at the tissue level
Delodinase enzymes are a sub-family of 3 enzymes that are important in the activation and deactivation of thyroid hormone
They add/remove an iodine atom in the outer ring to convert T4 to T3
Types of de-iodinase enzymes?
- Type 1 (D1)
- Type 2 (D2) - this is the one that controls the interplay between T4 and T3
- Type 3 (D3)
Locations of the different de-iodinase types?
Type 1 - commonly found in the liver and kidneys
Type 2 - found in the heart and skeletal muscle, CNS, fat, thyroid and pituitary
Type 3 - found in fetal tissue, placenta and brain (except the pituitary)
Causes of thyroid hormone deficiency?
Primary gland failure may be assoc. with an enlarged thyroid (AKA goitre)
May occur secondary to TRH or TSH (no goitre)
Lack of iodine in the diet (may also be assoc. with a goitre)
Symptoms of hypothyroidism?
- Reduced BMR
- Slow pulse rate
- Fatigue, lethargy, slow response times and mental sluggishness
- Cold intolerance
- Easy weight gain
Symptoms of myxoedema?
Occurs in adults and causes puffy face, hands and feet
Symptoms of cretinism?
In utero, low thyroid hormone results in dwarfism and limited mental functioning
What is Grave’s disease?
An autoimmune disease that causes hyperthyroidism; thyroid-stimulating Ig acts like TSH but is unchecked by T3 and T4
Signs of Grave’s disease?
Exophthalmos - bulging eyes due to water retaining carbohydrate build-up behind eyes
Goitre
Symptoms of hyperthyroidism?
Increased BMR
Very fast pulse rate
Excessively emotional and nervous
Insomnia
Sweating and heat intolerance
Easy weight loss
