endocrine Flashcards
Describe the layers of the adrenal glands and what each layer produces?
Endogenous?
Exogenous?
Blockers?
Adrenal cortex - steroids hormones
- ZONA FACSCIULATA Glucocorticloids - cortisol - sugar control
- ZONA GLOMERULOSA Mineralocorticoids - aldosterone - salt and water
Mineralocorticoids are blocked by spironolactone and eplenerone
Exogenous glucocorticoids - dexamethasone, betamethasone
Exogenous mineralocorticloids -
fludrocortisone
ZONA RETICULARIS - androgens. primarily DHEA
Adrenal medulla
- Adrenaline, noradrenaline
How do you define delayed puberty in girls?
How about in boys?
What is precocious puberty?
No breast development by age 13 is amenorrhoeic. If. no breast development by 15 if have periods
No testicular development or <4ml by age 14
Precocious puberty - development of secondary sexual characteristics before age 8
What are the causes of raised prolactin?
Physical:
- Pituitary tumour
Drugs:
- Antipsychotics
- SSRIs
- opiates
- Ranitidine - H2 blockers
Endocrine:
- Hypothyroidism
- Lactation
- Pregnancy
- Acromegaly
Medical conditions:
- Liver failure
- Renal disease
- PCOS
Describe the cells present in the ovaries and their various functions
Theca cells
- Produce androgens but cant convert to oestradiol
- LH stimulates production of androgens
- LH also stimulates contraction of the smooth muscle layer of the theca externa which causes the mature oocyte to pop.
Granulosa cells
- FSH signals granulosal cells to produce aromatase which in turn converts the androgens to oestradiol.
- Produce progesteron
Where is glucagon produced?
What does it cause?What are the stimulants of glucagon?
What are the inhibitors of glucagon?
Alpha cells of pancreas
Increases blood glucose
Increases glycogenosysis
Increase gluconeogenesis
Stimulants
- Hypoglycaemia
- Adrenaline
- Acteylcholine
- Arginine/alanine
- Cholecystokinin - producted in small intesting and triggers release of enzymes to digest fat and protein
Inhibits:
- Insulin
- Raised urea
- Somatostatin
- keto-acids
What happens in pregnancy with:
- TSH
- T3/T4
Decreased TSH (remember the limits of normal go down in pregnancy)
Increase total T3/T4 but gradually go down a bit from 1-3 trimester.
Free T3/T4 is decreased
What is the typical finding on an FBC with addisons disease?
eiosinophilia - dont know why
Addisons disease.
What is it?
Causes?
Symptoms/signs?
Blood test results?
Treatment?
Primary adrenal insufficiency
Causes:
- Autoimmune adrenalitis (most common)
- Secondary - low ACTH from pituitary
- Tertiary - low CRH from hypothalamus
Symptoms:
- Fatigue
- Darkening of the skin
- Weight loss
- Hypotension
- Myalgia/arthralgia
Bloods:
- High K
- Low Na
- eiosinophilia
- Metabolic adicosis
- Hypoglyaemia
Treatment
- Hydrocortisone
- Fludrocortisone if BP low
Which hormones are structurally similar to TSH
What other group is similar?
FSH, HCG, LH
HAT - think HCG, androgen stimulating, TSH
Prolactin, GH, human placental lactogen
PHaG - prolactin, hpl, GH
What are the levels for:
- Osteopenia
- Ostoporosis
- Severe osteoporosis
Osteopnia -1 to -2.5
Osteoporosis <-2.5
Severe osteoporosis <-2.5 with fragility fracture
Fragility fracture: NOF, foosh, spine, proximal humerus
How does oxytocin stimulate the contraction of the uterus?
What inhibits contractions?
Activates phospholipase C –> producs IP3 –> Calcium release.
Ultimately needs to release intracellular calcium. Triggers this with activating phospholipase C to produce IP3 which then causes release of the calcium
Inhibitors of contractions:
- cAMP, which inhibits protein kinase A
- Hormones that inhibit - progesterone, inhibin, relaxin
What is the common precursor molecule for creation of androgens
cholesterol
What conditions lead to an increase in SHBG?
What is the function of SHBG
In general, conditions causing weight loss lead to an increased SHBG e.g.
- liver cirrhosis
- hyperthyroidism
- anorexia
In contrast, weight gain –> lower SHBG
- PCOS
- Hypothyroidism
- Cushings
- Anabolic steroids use
SHBG
- Binds 70% of testosterone
- Other 20-30% bound to albumin
- Approx 1% unbound
What is the first line investigation for addisons?
U&E
AM cortisol
After this there is a place for the short synacthen test
Which are the X linked dominant conditions
3 Rs
Rickets, Retts, Rgile X
Fragile X
Rett syndrome
Vit D resistant rickets
What are the X linked recessive conditions
Ds:
DMD/BMD
Deficiency G6PD
Daemophilia
Dont see colour
DMD
G6PD deficiency
Haemophilia
Red-green colour blindness
What are the inheritence patterns of the PKDs
ADULT PKD - AD
Infantile PKD - recessive
Which conditions are associated with phaeochromocytoma
What is phaeochromocytoma?
What are the symptoms?
NOT MEN 1
MEN 2
Von hippel lindau
Neurofibromatosis 1
Paraganglioma syndromes 1,3,4
Neuroendocrine tumour of the medulla of the adrenal glands. Produces high levels of catecholamines
Symptoms:
- Sweating
- Headaches
- Palpitations
MEN 1 vs MEN 2
MEN 1 - PPP
- Pituitary
- Parathyroid hyperplasia
- Pancreas
MEN 2 - PMP
- Parathyroid hyperplasia
- Medullary thyroid carcinoma
- Pheochromocytoma
What do the islets in the pancreas secrete
Alpha cells - glucagon
Beta cells - Insulin
Delta cells - somatostatin
Gamma cells - Pancreatic polypeptide
Where does somatostatin come from?
What is it’s function?
Comes from the delta cells of the pancreas.
Function = THE MAIN INHIBITOR. Primarily prevents growth
Inhibits: pancreas/gastric/pituitary hormone release
- Both glucagon and insulin
- Growth hormone
- Prolactin
- TSH
We think it plays a role in preventing unnecessarily fast cell division
Which hormones are responsible for:
Ductal morphogenesis
Alveolar morphogenesis
Ductal - oestrogen and GH
DOM is resonsible for the ductal morphogenesis
- Ductal
- Oestrogen
- Morphogenesis
Alveolar - HPL, prolactin, progesterone
PAM is responsible for the alveolar morphogenesis
- Progesterone
- Alveolar
- Morphogenesis
What are the causes of cushing’s syndrome/disease
DISEASE - endogenous - pituitary adenoma.
SYNDROME - exogenous - steroids
How much testosterone is bound to SHBG
70%
What is the role of ALDOSTERONE?
Where is it released from?
What stimulates it?
What does it cause?
Na/water regulation
Released from the zona glomerulosa of the adrenal cortex.
Stimulated by:
- K+ being high
- Angiotensin 2
- ACTH and steroid hormones (minor)
It causes:
- Na resorption and therefore water resorption from the collecting duct in the kidneys
- Upregulates eNACs - epithelial sodium resorption - distal part of the nephron
- Vasoconstriction
What is the blood flow per minute through the uterine artery at term vs non pregnancy
Term = 750ml/minute. At term counts as 12% of full maternal circulation
Non pregnancy = 45ml/minute
What are the inhibitors of prolactin?
THERE ARE TWO OF THEM
Somatostatin
Dopamine
What is DHEA?
Where is it produced in the fetus?
Dihydroeipandosterone (DHEA) is a steroid hormone.
It is made from cholesterol (via pregnenarone). It is produced in the adrenals in the fetus which stimulates the placenta to produce oestrogen - keeps the pregnancy going.
The production of DHEA stops at birth and starts again around 6-8 before puberty
What is the main endogenous mineralocorticloid
Aldosterone
Progesterone is another example
In broad terms, what do mineralocorticoids do?
What do glucocorticoids do?
BOTH STEROIDS HORMONES
Mineralo - salt and water balance
Gluco - glucose balance
What are the types of haemoglobin and what are they made from?
What are the thalassaemias caused by in terms of genetic defect?
Adult Hb - 2x alpha, 2x beta (97% of HB)
HBa2 - 2x alpha, 2x delta (1-3% of HB)
HBF - 2x alpha, 2x gamma
Chromosome 16 codes for the alpha Hb - therefore alpha thalassaemia is a defect in chromosome 16
Chromosome 11 codes for the beta and delta hb - therefore beta/delta thalassaemia is a defect in chromosome 11
Give a summary of the homones that are released from the following areas:
Hypothalamus
Pituitary
Thyroid
Parathyroid
Pancreas
Adrenals
Ovary
Bowel
Placenta
Uterus
Adipose
Kidney
Liver
Hypothalamus
- TRH
- GRH
- CRH
- GHRH
- Oxytocin
- ADH/vasopressin
- Somatostatin
Pituitary
- ANTERIOR - prolactin, FSH, LH, TSH, GH, ACTH
- POSTERIOR - released but not synthesised - ADH, oxytocin
Thyroid
- T3/T4 (epithelial cells)
- Calcitonin (parafollicular cells)
Parathyroid
- Parathyroid hormone
Pancreas
- Insulin
- Glucagon
- Somatostatin
Adrenals (GETS SWEETER NEAR THE CENTRE)
- Zona glomerulosa CORTEX - mineralocorticoids - aldosterone
- Zona fasicularis CORTEX - glucocorticoids - cortisol
- Zona reticulata CORTEX - androgens
- Chromaffin cells MEDULLA - adrenaline
- Chromaffin cells MEDULLA - dopamine
- Chromaffin cells MEDULLA - noradrenaline
Ovary
- AMH (granulosa cells)
- Androgens (theca cells)
- Oestrogen
- Progesterone
GIT
- Stomach - Gastrin (g cells), Somatostatin (D cells)z, Histamine (StomachECL cells)
- Duodenum - Secretin (S cells), Cholecystokinin (I cells)
Placenta
- Human placental lactogen
- Progresterone
- HCG
Uterus
- Prolactin (decidual cells)
- Relaxin (decidual cells)
Adipose
- Leptin
- Estrone
- Small amount of progesterone
Kidney
- Renin
- EPO
- Thrombopoetin
Liver
- Insulin like growth factor
- Angiotensinogen, angiotensin
- Thrombopoetin
Summary of Addisons:
What is it?
Main symptoms?
Main tests?
Primary adrenal insufficiency
Cortisol and adrenal insufficiency
Clinical features: hypotension, hyponatraemia, hyperkalaemia
Testing: cortisol/ short synacthen
Summary of Cushings:
What is it?
Main symptoms?
Main tests?
Increase in cortisol
Symptoms: hypertension, weight gain, moon face, diabetes, buffalo neck lump
Test: dexamethasone suppression test, 24h cortisol
Summary of Conn’s:
What is it?
Main symptoms?
Main tests?
Primary hyperaldosteroneism
Symptoms: hypokalaemia, hypernatraemia, weight loss, tanned skin, hypertension
Test: Renin:aldosterone, salt suppression or fludrocortisone suppression
What is the role of aromatase?
Where is aromatase produced?
Causes conversion of androgens produced by the theca cells into oestrogen (happens in the granulosa cells)
Aromatase is produced in the granulosa cells
What is the major oestrogen of pregnancy and where is it produced
Estriol. Produced by the placenta
What are the types of oestrogen and what are their functions?
E1 - Estrone (produced in adipose tissue)
E2 - Estradiol (predominant in reproductive years)
E3 - Estriol (predominant during pregnancy - produced by the placenta)
What is the definition of primary ovarian insuffficiency
Menopause before the age of 40
How do you diagnose perimenopause/menopause?
> 45 by perimenopausal symptoms or no periods for 12 months
<45 can use FSH
Give examples of prolactin antagonists?
What receptors do they act on?
Bromocriptine
Cabergoline
They act on D2 receptors
They are dopamine AGONISTS.
They are therefore prolactin antagonists.
Most common cause of acromegaly
Pituitary adenoma
What is Conn’s syndrome?
Bloods?
Causes?
Primary hyperaldosteroneism
HYPERTENSION - water retention
Tests:
- Aldosterone:renin ratio is useful first test
- Diagnosis - saline suppression test/fludrocortisone suppression test
Bloods:
- Hypernatraemia
- Alklaemia
- Sometimes low K but often normal
Causes:
- Adrenal hyperplasia (60%)
- Adrenal adenoma (technically Conns)
Define endocrine/autocrine/exocrine/paracrine
Endo - secrete hormone into circultion to act elsewhere
Auto - acts within a cell
Exo - secrete into ducts
Paracrine - near by cells
What is the definition of puberty in girls
Stage 2 breast development
In relation to ovulation when does the LH surge occur
24-36h prior to ovulation
What is the classification system for puberty?
what is the first sign in girls?
Tanner classification
Breast development is first sign in girls
What are the test results for:
- Primary hyperparathyroidism
- Secondary hyperparathyroidism
- Tertiary hyperparathyroidism
Primary - high PTH, high Ca
Secondary - high PTH, low Ca (usually due to renal failure)
Tertiary - High PTH, high Ca (usually after prolonged period of secondary, there will be a history of renal failure)
What happens to T3/T4 levels in pregnancy
FREE T3/4 - drop
Total T3/4 - increase
Cause of hypothyroidism WITH antibodies
Hashimotos
De Quervains - not autoimmune. Get hyperT then hypoT. Wont have abs
Commonest cause of hypothyroidism worldwide?
In UK?
Worldwide - iodine deficiency
UK - hashimotos
Phaeochromocytoma
How much HTN is caused by this?
How much is familial?
0.1%
20% familial
What is the drug of choice to promote lactation?
What inhibits it?
Promote - domperidone
Inhibit - cabergoline, bromocriptine
What is the cause of the hyperpigmentation in hypoadrenalism
The high ACTH. Therefore in secondary adrenal insufficiency the skin is not discoloured
What causes angiotensinogen to turn into angiotensin 1
renin
