Endocrinology - Basic Principles

Question 1

what are the 3 types of hormone?

Answer 1

proteins and peptides - insulin, GH, prolactin
steroids - cortisol, testosterone
tyrosine and tryptophan derivatives (amino acids) - adrenaline, thyroid hormones, melatonin

Question 2

what type of receptor is the insulin receptor?

Answer 2

tyrosine kinase

Question 3

what are the 4 types of hormone receptor?

Answer 3

tyrosine kinase
nuclear/steroid?
GPCR
steroid/nuclear?) receptor (can be in nucleus or cytoplasm and move to the nucleus)
receptors associated with tyrosine kinase activity

Question 4

which receptor causes change in transcription?

Answer 4

steroid/nuclear

Question 5

what are the key features of GPCR?

Answer 5

extracellular domain and intracellular domain
transmembrane (crosses membrane 7 times)
associated G protein (alpha, beta, gamma subunits)
activates regulatory signalling cascades (cAMP, IP3)

Question 6

give 2 examples of cytokine receptors (linked to tyrosine kinase activity)?

Answer 6

prolactin receptor
growth hormone receptor
- works via same principle as tyrosine kinase

Question 7

how do steroid/nuclear receptors work?

Answer 7

intracellular - either cytoplasm or nucleus
steroid/receptor complex binds to DNA response elements
results in change in gene transcription

Question 8

how do glucocorticoid receptors work?

Answer 8

corticosteroids enter the cells and bind to the glucocorticoid receptor (GR) in the cytoplasm and translocate to the nucleus where the transcription of target genes is initiated/inhibited

Question 9

what hormones are secreted by anterior pituitary?

Answer 9

GH
LH/FSH
ACTH
TSH
PRL

Question 10

what hormones are secreted by the posterior pituitary?

Answer 10

ADH

oxytocin

Question 11

what is the major determinant of hormone concentration?

Answer 11

rate of secretion

- determined by highly refined feedback loops

Question 12

when might TSH not be a reliable marker of thyroid status?

Answer 12

in pituitary dysfunction

Question 13

why shouldn’t you check thyroid function when sick/in hospital?

Answer 13

hormones can be irregular in illness

Question 14

what tests are done to assess pituitary function?

Answer 14

9am cortisol
T3/T4
TSH
Prolactin
IGF1
LH, FSH, E2/testosterone
Us&Es, plasma/urine osmolality
imagine MRI
synacthen test

Question 15

what is the synacthen test?

Answer 15

where you give synthetic ACTH and test cortisol response

synACTHen

Question 16

what is released from the hypothalamus to stimulate the anterior pituitary?

Answer 16

corticotropin releasing hormone (CRH)
gonadrtrophin
TRH

Question 17

how do you measure cortisol and why?

Answer 17

9am cortisol
circadian/diurinal secretion of cortisol through day so will be at different levels
- random cortisol therefore not useful

Question 18

how is growth hormone measured?

Answer 18

random measurement is useless

measuring IGF1 can give a good indication of GH hypersecretion

Question 19

when should sex hormones be measured?

Answer 19

testosterone = at 9am
female = depends on timing in menstrual cycle

Question 20

what is prolactin?

Answer 20

secreted by lactotroph cells of the anterior pituitary

Question 21

what regulates prolactin secretion?

Answer 21

tonic inhibition by hypothalamic dopamine
secretion regulated by a short-loop negative feedback
effects of prolactin mediated by prolactin receptor

Question 22

which hormone released from the posterior pituitary regulates thirst and water balance?

Answer 22

vasopressin
V1 causes vasoconstriction
V2 causes fluid reabsorption

Question 23

what are the principles of dynamic pituitary testing?

Answer 23

biochem tests before imaging (usually)
to test hormone excess = suppression test (e.g dexamethasone suppression test)
if testing if hormone deficiency = stimulation test (e.g synacthen)
imaging then used to localise/characterise disease after biochemical diagnosis
combined biochem/imaging diagnosis might be needed

Question 24

what can cause a cortisol deficiency?

Answer 24

adrenal insufficiency

- adrenal failure (addisons disease), pituitary disease etc

Question 25

what can cause cortisol excess?

Answer 25

cushings syndrome

Question 26

what causes Chushing's syndrome?

Answer 26

``` pituitary origin - tumour arising from corticotroph cells in anterior pituitary - most common cause adrenal origin - ACTH independent - adrenal hyperplasia/adenoma/carcinoma ectopic ACTH - malignancy exogenous steroids ```

Question 27

what are the features of Cushing's disease?

Answer 27

``` acne hirsutism abdominal striae and central obesity interscapular and supraclavicular fat pads proximal myopathy osteoporosis hypertension impaired glucose tolerance cushingoid facies (moon face) ```

Question 28

name 2 ACTH dependant and 2 ACTH independent causes of Cushing's syndrome/

Answer 28

``` dependant - excess ACTH production in pituitary - ectopic ACTH independent - adrenal problem producing excess cortisol - exogenous steroids ```

Question 29

how is cushing's syndrome diagnosed?

Answer 29

low dose dexamethasone suppression test | - failure to suppress = cushings syndrome diagnosis

Question 30

other investigations in cushing's disease?

Answer 30

measure of ACTH - low ACTH = adrenal origin is likely - high ACTH = could be cushings disease or ectopic ACTH high cortisol and ACTH indicates pituitary origin

Question 31

cushings disease vs syndrome?

Answer 31

``` disease = pituitary tumour causing the symptoms syndrome = the general term for the symptoms of any cause ```

Question 32

what are the 3 screening tests for cushings syndrome?

Answer 32

1mg overnight dexamethasone suppression test 24 urinary free cortisol midnight cortisol