Endocrinology Flashcards
Where would a paracrine hormone act?
in local ECF to neighbouring cells
What controls neuroendocrine cells?
synaptic transmission
Where embryologically do the
- ant pituitary
- post pituitary
develop from?
ant - from oralpharynx ectoderm - rathke’s pouch
post - from neural ectoderm, extension of infundibulum
In floor of 3rd ventricle
Where do the hypothalamic parvocellular neurosecretatory cells release hormones?
into the capillaries of the median eminence to ant pituitary
Where do the hypothalamic magnocellular nuclei project to?
post pituitary
Name 3 parameters that cause increased release of GH.
- Hypoglycaemia, starvation
- low FA
- excercise
- sleep
Name 2 parameters that cause decreased release of GH.
- hyperglycemia
- high FA
Outline GH action.
- stimulates liver IGF1 production
- increases lipolysis so increases FA
- increases gluconeogenesis
- stimulates chondrogenesis (more linear growth) up to 20yrs
- stimulates somatic/organ growth
Acromegaly symptoms in adults may include…
…insulin resistance, diabetes and hyperglycemia
-increased mass/thickness of bones
Name whats made in these adrenal cortex layers:
zona glomerulosa -
zona fasiculata -
zona reticularis -
z glomerulosa - mineralocorticoids
z fasiculata - cortisol
z reticularis - testosterone
Explain 2 steps in screening for Cushing’s?
- cortisol levels at night (loss of dinural rhythm)
- dexamethasone 11pm, measure cortisol in morning (los s of negative feedback)
What patient groups might be suspected to have Cushing’s, (but have pseudocushing’s)?
-depressed, alcoholics, anaorexics
baseline higher cortisol level individuals
How do you confirm a diagnosis of Cushing’s/rule out pseudocushings?
Low dose 48hr Dexamethasone Supression Test
should be <50 at end, if not it is true Cushings
How can you determine if Cushing’s is caused by excess ACTH from the pituitary/adrenal or an ectopic site?
High Dose 48hr Dexamethasone Supression Test
if pituitary/adrenal, ACTH should fall to 50% baseline-neg feedback, if ectopic will stay high
What metabolic results may you see in Cushing’s regarding:
- K+ levels
- Glucose
- pH
- hypokalemia
- hyperglycemia
- metabolic alkalosis
Why may you have the following in Cushing’s?
-hypokalemia
-metabolic alkalosis
The mineralocortidoid receptors in kidney respond normally to aldosterone, how does cortisol (usually inactivated as cortisone) have action here?
The enzyme 11BHSD2 which turns cortisol to cortisone can become saturated in cushings so cortisol can act in the same way as aldosterone…
- by retaining Na+ (and lose K+ in return)
- if K+ is depleted, when bringing in Na+ we lose H+ in return (–>low K+, high pH)
Which enzyme turns cortisol to cortisone?
11BHSD2 - 11 B Hydroxysteroid Dehydrogenase 2
Why can you have skin hyperpigmentation in Cushing’s?
-ACTH is a precursor of a-MSH which forms melanin.
Some of the ACTH forms this
How does the CRH test differentiate between all types of Cushing’s Syndrome?
(Results measure ACTH levels…)
- an exaggerated ACTH response will be die to a pituitary tumour. It is sensitive to CRH levels.
- an adrenal adenoma will be low. As its system is sensitive to ACTH levels, not CRH, so v low (no ACTH)
- ectopic will be high, no neg feedback
Give 5 symptoms of Addison’s disease?
- weight loss, hypoglycemia
- postural hypotension
- hyponatremia, salt craving
- hyperkalemia, acidosis
- nausea (steroids close pores that allow BBB to detect toxins, low steroids -> open pores -> more nausea)
Name 3 causes of Addison’s disease.
- autoimmune condition (e.g. from TB)
- steroid withdrawal (adrenal cortex had shrunk/reduced production)
- enzyme defect e.g. congenital adrenal hyperplasia
One way to test for Addison’s is to illicit a huge stress response and measure the cortisol response. What is used to illicit this?
-Insulin
insulin tolerance test
2 Treatments for Addison’s disease
- Hydrocortisone
- Fludrocortisone (also increases aldosterone)
What is the common enzyme deficiency in CAH-congenital adrenal hyperplasia? What is the result?
21-Hydroxylase
- so cant convert progesterone-deoxycorticosterone-corticosterone to aldosterone
- cant convert 17OH progesterone to 11-deoxycortisol-cortisol
- so only pathway that can be maintained is testosterone production
What does excess sex steroids in 21OH deficiency of CAH lead to?
- virilisation
- hirsuitism
- infertility
Without aldosterone in CAH Addison’s what happens to:
- Na
- K
- BP
- you lose salt (Na)
- hyperkalemia
- hypotension
The less common enzyme deficiency of CAH is 11BOH so deoxycorticosterone rises and has partial aldosterone action. How do these children present?
What is the synacthen test result?
- Present with hypertension and hypokalaemia
- no cortisol rise with synacthen but 17OH progesterone rises (cholesterol precursor)
Which layer of the adrenal cortex makes aldosterone?
zona glomerulosa
What stimulates aldosterone release?
Where is this sensed?
-low BP
-low Na+
Macula densa of kidney
What is Conn’s syndrome?
Give 2 symptoms
1ry aldosterone excess due to adrenal adenoma producing it.
- hypertension
- hypocalcemia
What may be the cause of 2ndry Aldosterone Excess (driven by kidney) with hypertension?
- renal disease/renin releasing tumour
- renal artery stenosis (low BP sensed)
What may be the cause of 2ndry Aldosterone Excess (driven by kidney) with normal BP?
May be due to oedema in the tissues (kidney only senses low intravasular volume) caused by e.g. cirrhosis, dehydration, nephrotic syndrome…
What is phaechromocytoma a “yellow” tumour of?
What does the tumour produce?
Tumour of the enterochromaffin cells of adrenal medulla
Produces catecholamines e.g. A, NA, DA
How does a phaechromocytoma patient present?
-sweaty, paroxysmal HT (shoots up/down), palpitations, constipation, headache…
How do we test for phaechromocytoma?
Look for metanephrines in urine (breakdown of catechols)
A phaechromocytoma is a medical emergency how is it treated?
- First a-adrenergic blockade, e.g. phentolamine
- then B-adrenergic blockade
- fluid resusitation and surgery
Why is it contraindicated/dangerous to give B-blocker before a-blocker in treatment of a phaechromocytoma?
- If B-blocker is given first, you cancel out the vasodilatory effect of peripheral B2 adrenoceptors
- leading to unopposed alpha-adrenoceptor stimulation, causing vasoconstriction and ultimately hypertensive crisis
What does lipoprotien lipase (LPL) hydrolise triglycerides from the blood into?
Which hormone favours this action?
Free fatty acids (in the adipocyte)
Insulin
What does hormone sensitive lipase’s (HSL) hydrolise?
Which hormone favours this action?
Fat stored as triacylglycerol
Adrenaline
Name 2 ways fat acts as an endocrine gland.
- Amomatase enzymes in adipose act on androgens and oestrogens
- leptin (secreted in response to adipose mass)
What does the hormone adiponectin released from adipocytes do?
(this hormone is lower in obesity)
Increased insulin sensitivity
Explain why you get cytokines, chemokines and macrophages raised in obesity.
As adipose cells increase and grow, they become further from capillaries so become hypoxic.
This triggers the inflammatory mediators.
Give 3 effects of cholecystokinin’s (CCK).
- supress appetite
- stimulate secretion of pancreatic enzymes
- empty gall bladder
What type of hormones are gastric inhibitory peptide (GIP) and GLP-1?
What are their actions?
Incretin hormones
GIP-potentiates insulin release, inhibits gastrin release
GLP-1-potentiates insulin release, reduces appetite
The lateral hypothalamus is the feeding centre. What 2 neurones are stimulated from here?
AGRP & NPY
The ventromedial hypothalamus is the satiety centre. What neurones 2 are stimulated from here?
POMC & CART
When is erythropoetin secreted by the kidney?
Where does it act?
In response to low partial pressure of O2 in circulation
Acts on bone marrow
The SCN acts via the pineal gland to mediate release of….
When darkness falls, this hormone’s level..
MELATONIN
increases…promoting sleep
Which thyroid hormone is responsible for the negative feedback? How?
T4
Intravascular T4 is de-iodinated into T3 which enters cells, so T4 is what decreases/runs out hence gives the negative feedback
When a cell needs active T3, how does it get the intravascularly stored inactive T4 to enter and be active?
- it expresses a de-iodinase on its cell surface
- so passing T4–>T3
- T3 enters cell
The following are problems where?
Primary hyperthyroidism…
Secondary hyperthyroidism…
Sick Euthyroid…
Primary hyperthyroidism - thyroid gland (organ)
Secondary hyperthyroidism - ant pituitary
Sick Euthyroid - stress response (decreased TRH)
What happens to LH/FSH with tumours of the ant pituitary?
They stop secretion as the secretion is so complex
When/at what time does GH release peak?
during REM sleep
Give 3 signs of acromegaly
- acral enlargement (bigger fingers, feet, tongue, arthritis)
- greasy sweat
- diabetes and increased nitrogen retention (protein)
- cardiomyopathy, bowel cancer (as fast turnover)
Why is acromegaly described as “insiduous”
It takes 5yrs to notice symptoms such as coarsening of facial features
Give 4 features of a Cushing’s Syndrome appearence
- lemon on stick body shape (central obesity)
- moon face
- buffalo hump (temporal fat pad)
- thin skin, bruises easily, sub-dermal cracks as purple striae
- diabetes..osteoporosis
What sex hormone changes occur in Cushing’s syndrome?
- excess hair growth or hirtuism (as high testosterone)
- irregular periods
- problems conceiving (virulised)
- impotence
How does the hypothalamus inhibit prolactin (PRL) release?
Releases dopamine
Name 3 things that may occur with a prolactinoma.
- infertility as PRL inhibits LH&FSH (like contraception)
- irregular periods, decreased sex drive
- production of breast-milk even without a baby
How can you treat prolactinomas pharmalogically?
Dopamine agonists
e.g. bromocriptine, cabergoline
As LH and FSH pituitary tumours are “non-functioning” (dont cause a massive excess) how are they picked up?
Symptoms arise due to the space occupying lesion.
E.g. headache, visual field defect, nerve palsys
The optic chiasm sits on top of the pituitary.
A pituitary tumour affects the nasal retina fibres that cross at the chiasm. Describe the visual defect?
Start as bitemporal upper quadrantopia as the bottom of the retina looks at the top of your visual field, and the tumour is growing from under the chiasm
-then bitemporal hemianopia
In what order are the pituitary hormones lost with an expanding tumour?
In order of biological importance
- LH/FSH (remember PRL increases as DA cant inhibit)
- GH
- TSH
- ACTH last as important for survival
What can treat GH excess pharmacologically?
Octreotide (biologically active somatostatin)
Name a pharm. agent to correct deficiencies of:
- thyroid hormones
- sex steroids
- cortisol
- GH
thyroxine
testosterone/oestrogen
hydrocortisone
GH
What is Vasopressin’s action and when is it released?
- retains water, causes vasoconstriction
- released in response to increased plasma osmolality or decreased PaO2, or low BP
How does Vasopressin retain water?
Increases CD permeability for H20
Vasoconstriction
Name 3 causes of Syndrome of Inappropriate ADH (SIADH)
- brain injury
- infection esp pneumonia
- lung cancer
- asthma
How is SIADH diagnosed?
- low plasma Na+, dilute plasma
- urine Na+ high, and concentrated urine
What are the 2 causes of underproduction of ADH also known as Diabetes Insipidus?
- Cranial (lack of production)
- Nephrogenic (receptor resistance)
Diabetes Insipidus is characterised by:
Plasma-
Urine-
Plasma-high Na+, high osmolality
Urine-low Na+, low osmolality (dilute)
Diabetes insipidus categorisation as cranial/nephrogenic is via the water deprivation test. Explain this.
- measure blood and urine concentration upon water deprivation
- at end of dehydration phase give a shot of ADH
- if body responds its cranial, if no change-nephrogenic
