Endocrinology Basic Principles Flashcards
What does the endocrine system regulate?
Growth
Appetite
Sexual Development etc.
What are the key steps in diagnosing endocrinological disorders?
Good history taking Clinical observation Attention to detail Understandng the physiology Multi-disciplinary working
What are the major endocrine glands?
Thyroid Pituitary and Hypothalamus Adrenal Calcium/Parathyroid Pancreas Reproductive
What are the basic hormone subtypes?
Protein and Peptide hormones
Amino acid hormones
Steroid hormones (Lipid derived)
Give examples of protein and peptide hormones…
Oxytocin
Growth hormone
FSH
Give examples of amino acid derived hormones…
Adrenaline - modified tyrosine
Melatonin - modified tryptophan
Give examples of lipid derived hormones…
Testosterone
Oestradiol
(These have a cholesterol backbone structure)
What are the different types of hormone receptors?
G-protein couples receptors
Receptor tyrosine kinases
Receptors associated with tyrosine kinase activity
Steroid hormon receptors
What are some features of g-protein coupled receptors?
7 transmembrane domain
Associated g-protein complex
Activate signalling cascades
What is the major role of g-protein coupled receptors within endocrinology?
Main sensors of the internal environment
What is the extracellular function of g-protein coupled receptors?
Associated with ligand binding
What is the intracellular function of g-protein coupled receptors?
Associated with intracellular signalling
What diseases can result from a loss of function of the g-protein coupled receptor - lutenizing hormone receptor?
Familial hypogonadism
Leydig cell hypoplasia (males)
Primary amenorrhoea
What diseases can result from a loss of function of the g-protein coupled receptor - thyrotropin-releasing hormone receptor?
Central hypothyroidism
What diseases can result from a loss of function of the g-protein coupled receptor - growth-hormone-releasing hormone receptor?
Short stature (growth hormone deficiency)
What diseases can result from a loss of function of the g-protein coupled receptor - calcium-sensing receptor?
Benign familial hypocalciuric hypercalcaemia (FHH)
Neonatal severe primary hyperparathyroidism
What are receptor tyrosine kinases?
These are single subunits with a hydrophobic, transmembrane domain
e.g. insulin receptor
What are tyrosine kinase activity linked receptors?
Cytokine Receptor
e.g. Prolactin receptor; growth hormone receptor
They have involved JAK-STAT signalling
Where are steroid hormone receptors?
These are typically intracellular - either in the cytoplasm or nucleus
Why are steroid hormone receptors intracellular?
Steroid hormones are lipids and are therefore able to diffuse across the plasma membrane more freely.
What is the process of steroid hormone receptor activation?
- The steroid hormone diffuses across the plasma membrane.
- This binds to a cytoplasmic receptor to form a steroid-receptor complex.
- This binds to DNA response elements.
- This results in a change in gene transcription
Why are G-protein receptors termed heterotrimeric?
They have three subunits: alpha, beta and gamma.
Why does dissociation of the alpha and beta-gamma units occur in G-protein receptors?
GDP is replaced by GTP
How do glucocorticoid receptors function?
With a similar mechanism to steroid receptors
What is the function of the hypothalmic-pituitary axis?
This is a key regulator of the majority of hormones.The hypothalamus controls the secretory activity of the anterior pituitary gland.
Wha are the major hormones of the anterior pituitary?
Growth hormone Prolactin Adrenocorticotrophic hormone (ACTH) Melanocyte stimulating hormone (MSH) Thyroid stimulating hormone (TSH) The gonadotrophins - FSH and LH
What is the mechanism of the hypothalmic-pituitary axis?
- In response to central input, the hypothalamic hormones are released from nerve endings into the hypophyseal portal blood and are carried down the pituitary stalk to the anterior lobe.
- Here, they act in specific pituitary cells to modify the rate of secretion of the anterior pituitary hormones.
- There is then a negative feedback loop to inhibit secretion
What is the major determinant of hormone concentration?
The rate of secretion. This is typically determined by highly refined feedback loops
What the thyroid axis rely on?
Highly regulated feedback control of TSH
What is the mechanism of the thyroid axis?
- The hypothalamus releases thyrotropin-releasing hormone.
- This stimulates the release of thyroid-stimulating hormone from the anterior pituitary. TSH acts as a negative feedback on the hypothalamus to reduce TRH secretion.
- This acts on the thyroid gland to produce thyroid hormones. The thyroid hormones can then either act on target tissues or work as negative feedback on the hypothalamus
What would the different values of TSH indicate in terms of thyroid pathology?
Normal TSH = Normal Thyroid
Raised TSH = Hypothyroid
Suppressed TSH = Hyperthyroid
Why does raised TSH indicate hypothyroidism?
If the thyroid gland secretes too little levels of thyroid hormones, this will cause the pituitary to secrete more TSH in response.
Why does low TSH indicate hyperthyroidism?
If the thyroid gland secretes levels of thyroid hormones that are too high, negative feedback means that the pituitary will produce less TSH
When would TSH not be a reliable marker of thyroid status?
Pituitary dysfunction
What is sick euthyroid syndrome?
Thyroid function will be disrupted in times of illness
What is the mechanism of the hypothalmic-pituitary-adrenal axis?
- The hypothalamus secretes corticotrophic-releasing hormone.
- This stimulates the anterior pituitary to secrete ACTH.
- This stimulated the adrenal cortex to release cortisol which has multiple physiological effects.
There is tight negative feedback loops
Describe the circadian cortisol secretion…
Peak cortisol is present in the morning and levels lower during the day. They begin to increase again overnight
What is the nature of growth hormone secretion?
It has a pulsatile nature
What term describe the rhythm of testosterone release?
Circadian
What factor stipulates hormone release in females?
Menstrual cycle
What is the mechanism for the hypothalmic-pituitary-gonodal axis?
- The hypothalamus releases gonadotropin releasing hormone in response to CNS stimuli.
- This causes the pituitary gland to release LH and FSH.
- This then stimulates the gonads to produce gametes.
What type of cells secrete prolactin?
Lactotroph cells
What type of cells secrete growth hormone?
Somatotroph cells
What type of cells secrete FSH and LH?
Gonadotroph cells
What type of cells secrete adrenocorticotrophic hormone (ACTH)?
Corticotroph cells
What type of cells secrete thyroid stimulating hormone (TSH)?
Thyroproph cells
What type of cells secrete melanocyte stimulating hormone?
Corticotroph cells
What are the principles of dynamic pituitary testing?
Hormone excess - do a suppression test
Hormone deficiency - do a stimulation test
What is the mechanism of the antidiuretic-vasopressin axis?
- The hypothalamus causes release of vasopressin from the posterior pituitary.
- This causes the constriction of blood vessels and fluid resorption fro, the kidneys to lead to an increase in arterial pressure.
What are the three major hormone groups produced from steroid hormone metabolism?
Aldosterone
Cortisol
Testosterone
What is the rate-limiting step in steroid hormone metabolism?
Cholesterol –> Pregnenolone
What disease would result from corticol excess?
Cushing Syndrome
What disease would result from cortisol deficiency?
Adrenal Insufficiency
