Endocrine Flashcards
What do the cells of pancreatic islets secrete
alpha - glucagon
beta - insulin
gamma - somatostatin
PP - pancreatic polypeptide
Where is insulin synthesised and describe the structure of it before it is cleaved
RER of beta cells
called prepoinsulin
alpha and beta chain with C peptide - sulphide bonds
C peptide where does it come from and what does it do
prepoinsulin is cleaved and C peptide is a by product of insulin
no known physiological function
how many phases does insulin have? describe them
biphasic
rapid phase (5%) lasts 5-10mins
slow phase - lasts 1-2 hours
what is the insulin receptor called
tyrosin kinase
what happens when insulin binds to its receptor
beta chains of the receptor are phosphorylated which caused insulin substrates to phosphorylate
PK13 -> PKB -> glycogen synthesis
Ras -> MAP kinase activity -> gene expression
PKB -> GLUT4 - allows glucose entry into cells
what is leprechaunism
also known as donohue syndrome
autosomal recessive
genetic mutation in the insulin receptor causing severe insulin resistance
what are the symptoms and signs of leprechaunism (4)
elfin facial appearance
growth retardation
absence of fat
decrease in muscle mass
What is rabson mendenhall syndrome
defect in insulin binding
autosomal recessive
insulin resistance, hyperglycaemia and compensatory hyperinsulinaemia
symtoms and signs of rabson mendenhall syndrome (5)
development abnormalities
hyper pigmentation
acanthuses nigricans
DKA
How are amines released
how are peptides and proteins released
how are steroids released
pre synthesised and released in response to stimuli by ca dependant exocytosis. hydrophilic
synthesised and released on demand. hydrophobic. transported bound to plasma proteins
Whats is DIDMOAD (wolfram syndrome)
diabetes insipidus diabetes mellitus optic atrophy deafness neurological abnormalities
Thyroid pathology - draw it out
what does the centre contain
what do C cells secrete
draw
What happens when the TSH binds with the TSH receptor on thyroid epithelial cells
GTP->GDP which causes cAMP to produced which then further releases T3 and T4
what HLA is involved in hypothyroidism
HLA DR3 and DR5
What antibodies are released in hashimotos and other things are released
anti thyroid antibodies
CD8 T cells which cause destruction of thyroid epithelium
cytokine mediated cell death
What thyroid carcinoma leads to amyloid deposition
medullary (calcitonin)
what two cells is the parathyroid composed off
describe what the first set of cells do and what they look like
chief cells - secrete PTH, act on calcium homeostasis, they are round cells with moderate cytoplasm and bland round nuclei
supported by oxyphil cells
subclinical hypothyroidism
secondary hypothyroidism
subclinical hyperthyroidism
increase in TSH, normal T3/T4
normal or decrease in TSH, decrease in T3/T4
decrease in TSH and normal T3/T4
Nodular thyroid disease who does it happen in what kind of onset does it have what are the thyroid hormone levels what antibodies are present exams and ix
elder population insidious onset low TSH high T3/T4 AB negative assym goitre high uptake on scintigraphy
what are the screening tests and the definitive tests for cushings
overnight 1mg dex tests 100 abnormal
24 hour urinary cortisol free test
what are the drug treatments for cushings
metyprane if treatment failed or waiting for radiotherapy to start working
ketocondzone
pasicreatide (somatostatin analogue)
water deprivation test
check 8 hours before and 4 hours after giving IMDDAVP
Ur/serum osmolality ration >2 normal
which of the thyroid homorones is most secreted
T4 90%
T3 10%
what is T4 converted to and where
T3
liver and kidneys
which thyroid hormone is the more biologically active
T3
how do the thyroid hormones travel
hydrophobic/lipophillic
bound to plasma proteins
zona glomerular
zona fasciculate
zona reticularis
mineralocorticoids - aldosterone
glucocosteroids - cortisol
adrenal androgens
investigation for Conns
measure aldosterone: rennin if raised (abnormal) do a 2L saline suppression test failure to suppress by 50% diagnostic for Conns
what is CAH (recessive/dom)
what is the investigation for it
treatment
21 alpha hydroxyls deficiency
autosomal recessive
base 17 hydroxyprogesterone (17 OH progesterone) levels checked
glucocorticoid and mineralocorticoid replacement
treatment of phaemochromocytoma
A before B
alpha blocker phenylbenzamine
BBs propranolol, atenolol
what is anterior pit called and where is it derived from
what is the posterior pit called and where is it derived from
adenohypophyisus - derived from rathkes pouch
neurohypophisus - extension of neural tissue
what is a craniopharyngioma derived from
give three symptoms/signs of it
who does it occur in
symptoms
remnants of rathkes pouch
slow growing, cystic, may calcify
5-15s, 60s, 70s
headaches, visual disturbances, growth retardation in children
How much do adrenal glands weigh and what are the cells called and what do they secrete
4-5g each neuroendocrine cells (chromaffin) secrete catecholamines
Causes of pit hyper function
hypofunction
adenoma/carcinoma
surgery. haemorrhage. ischaemic necrosis (sheegans syndrome)
Autocrine
Parocrine
Endocrine
releases hormones - acts on itself
releases hormone - acts on cells nearby
releases hormone - enters blood and travels
what are the three different types of hormones
glycoproteins and peptides - oxytocin, insulin
steroids - cortisol, testosterone
tyrosine and tryptophan derivatives
what are the three types of hormone receptors
G coupled - activated by amines and peptides
receptor kinases - activated by proteins (insulin)
nuclear receptors - class 1 activated by steroids - move from cytoplasm to nucleus
-class 2 activated by lipids in nucleus
-class 3 activated by T3
what are acinar cells
functional unit of the exocrine pancreas
what kind of a receptor do KATP channels have
a sulphylurea receptor
what are the 4 effects of insulin
lipolysis and glucagonesis in liver
glucose uptake into adipose and muscles
lipogenesis in adipose and liver
glycogen synthesis in liver and muscle
how are ketones formed
derived from acetyl coA
how are ketone bodies in DM
oxaloacetate is low in the liver due to gluconeogenesis excess acetyl CoA enters the krebs cycle leading to ketone body formation
give an example of alpha glucose inhibitors
arcarbose
what do alpha glucose work on and how
effect
side effects
alpha glucosidase is a brush border enzyme that breaks down starch to form glucose
inhibitors delay absorption of glucose
prevent post prandial rise in glucose
GI symptoms
DPP4 inhibitors - how do they work
inhibits DPP4 allowing prolongation of GLP and GLP-1 action
what is MODY treated with
SU
give rapid acting insulins short acting insulins intermediate insulins long lasting insulins rapid acting - intermediate mix short acting - intermediate mix
humolag, apidra, novarapid humalin S, actrapid, insumen rapid insulatard, humulin, insumen basal lantus, levemir humalog mis 25/50, novomix 30 humulin M3, insumen comb 15, 25, 50
HbA1c diabetes and pre diabetes
target
48 (6.5%) - diabetes
42-47 (6-6.4%) - pre diabetes
48 but 53 is okay
levels of DM foot
low - pulses and sensation present
medium - loss of pulse or sensation
high - loss of both or previous ulcers/amputation
BP control in DM - when to treat and what is the target
lifestyle unless >140/90
target 130/80
what is charcots foot and what is the treatment
disarticulation of bone and collapse of mid foot
immobilise and cast
adrenal hyperplasia diffuse enlargement is ACTH what
adrenal hyperplasia nodular enlargement is ACTH what
diffuse ACTH driven
nodular ECTH independent
describe an adrenal adenoma
well circumsised, encapsulated, small nuclei, yellow, non functional
Describe an adrenal carcinoma
local invasion to retroperonium and kidney
large haemorrhage and necrosis
frequent and atypical mitosis
lack of clear cells and capsular or vascular invasion
what are the two types adrenal medullary tumours and describe the second one
pheochromocytoma
neuroblastoma - 40% are in medulla, rest are along the sympathetic chain, might differentiate towards ganglion cells
causes of goitrous hypothyroidism
causes of non goitre hypothyroidism
causes of secondary hypothyroidism
hashimotos, iodine deficiency, drug induced (amiodarone)
congenital atrophic thyroiditis, post ablative, post radiation
hypothalamic (infection, congenital, malignancy) or pituitary (trauma)
MEN1 autosomal what what gene what does the gene do how is it activated where is the mutation
autosomal dominant MEN1 gene 11q tumour suppressor bi-allelic activation mutations throughout gene
MEN2 autosomal what
what gene
what does the gene do
where is the mutation
autosomal dominant
RET gene 10q
proto oncogene
mutation in one specific codon
what is MEN2 associated with
medullary thyroid carcinoma
parathyroid hyperplasia
bilateral phaemochromocytoma
give the process of bone remodelling
takes place at remodelling sites
osteoclasts absorb old bone
osteoblasts replace them - fill gap with osteoid
osteoid mineralises to form new bone
what is oogenesis and when does it restart and end
creation of ovum
restarts at puberty and end at menopause
what is the earliest female germ cell
primordial cell
what are oocytes and when are they formed
immature ovum and are formed after completion of ion and pre meiotic division
what do two polar bodies indicate
sperm entry and completion of second meiotic division
what is the follicular phase
what is the primary follicle and secondary follicle
how does the follicular phase end and what is it the main hormone
maturation of egg
primary oocyte surrounded by single layers of granulosa cells is the primary follicle
oocyte grows and follicle expands and becomes differentiated - secondary follicle
ends with ovulation
main hormone - oestrogen
Luteal phase - what happens
main hormone
life span of the copeus leutum - what happens after it died
what happens if fertilised
follicular cells undergo luetinisation and transform into CL and reproductive tract
progesterone
14 days - degeneration - new follicular phase
if fertilised CL persists and produces progesterone and oestrogen
what are the hormone changes in pregnancy
embryo produces hCG to maintain CL
progesterone to support pregnancy and suppress ovulation
Kallmans syndrome - what is it
genetics
symptoms/signs
loss of GnRH secretion and anosmia
X linked - just males - autosomal dominant
cleft lip palate, missing tooth, delayed puberty
male hypogonadism
primary - causes
secondary - causes
primary - decreased testosterone increased FSH/LH
klinefines syndrome, undescendent testcles, haemachromatosis
secondary - hypothalamic/pit dysfunction
kallmans, pit dysfunction, sarcoid, HIV/AIDS, meds, obesity, ageing
Klinefelters syndrome - how symptoms what gene hormone levels treatment
congenital decreased testosterone volume, gynacamastea, azoosprenia, infertility K7XXY decreased testosterone, increased FSH/LH testosterone therapy
rubella syndrome - signs
rash at birth small head low birth weight bulging forehead visual problems patent ductus arteriosis
what changes in the endometrium could lead to infertility
anatomical change
dyspareunia
altered peritoneum environment
why are there eye changes in Graves
fibroblasts etc. express TSH receptors
when is octeotride used in acromegaly and why
1st line
used post op resolves in 1 hour improves outcome
Why are phaemachromocytoma tumours brown/red
brown due to catecholamines
red- due to haemorrhagic/necrosis
What is MODY
defective glucose sensing in pancreas or loss of insulin secretion
Normal ion gap
10-18
What is the normal osmolality
285-295
How long is the normal menstrual cycle last
28-35 days
What kind of drug is clementine citrate and why is it given
anti androgen
to stimulate FSH
What cells in the anterior pit release prolactin
lactotroph cells
Structure of T3
T4
DIT + MIT
DIT + DIT
Where is the defect in pseudo hypoparathyroidism
GNAS1
ACTH level in adrenal cushings
ectopic cushings
pit cushings
low
high
high on in between
low dose dex suppression test how much over how many hours
2mg/24 hours
CRH test in cushings
increase in cortisol and ACTH - pit not ectopic
test done in addisons
250mg synching at 0 and 30 mins
30 minute level of 580 diagnostic
What is secreted in phaeos
catecholamines (metanpehrines)
MEN1 (3Ps)
pituitary, parathyroid, pancreatic endocrine tumours
Conns tests
Aldosterone:rennin ratio high >750 then
2L saline suppression test - if fail to suppress over 50%
adrenal CT to confirm adenoma
Adrenal vein sampling in elderly
Thyroid uptake scans cold nodule graves toxic multi nodular hot nodule autonomous thyroiditis
cyst, cancer butterfly hot and cold one bit high uptake only one side loads no uptake
what is hyperemesis rabidarcom
picture of thyrotoxicosis but no symptoms
usually after pregnancy or during preg
