adrenal glands Flashcards
describe how the adrenal glands develop?
- urogenital ridge has the adrenogonadal primordium
- primordial germ cells invade the adrenogonadal primordium
- splits off into adrenal and gonadal primordium
- Adrenal part gets invaded with neural crest cells which develop into nervous tissue
- gets surrounded by capsule of mesenchymal cells
- Starts to differentiate the cortex in the embryo into the definitive and fetal zone
what are the 3 cortical zones of the adrenal glands? what do they each make?
- ZG – make aldosterone. Not a continuous layer
- ZF – makes glucocorticoids. Main one is cortisol
- ZR – makes adrenal androgens
where is the adrenal artery?
on the outside of the adrenal glands
what layer of the adrenals are closest to the blood vessels?
ZF
describe the passage of blood through the adrenal glands
- Delivers blood to the plexus of blood vessels under the capsule
- Blood flows through the capsule, ZG, ZF, ZR to the medulla
what kind of blood does the medulla receive?
blood with high levels of hormones
why does the adrenal gland have a lot of fat?
bc it makes cortisol which is fat
what are the types of stress?
starvation, infection and severe volume loss
what enzyme is found in the ZG and what gene is associated with this?
ZG is characterised by aldosterone synthase
CYP11B2 is the gene for the aldosterone synthase enzyme
what enzyme is found in the ZF?what gene is associated with this?
• ZF is characterised by CY11B1 (beta hydroxylase)
what is aldosterone release stimulated by?
potassium and low BP
what stimulates renin release?
sodium loss, haemorrhage, upright posture and decreased renal perfusion
describe how the RAA system works?
renin release is stimulated
• Increases AT1 AT2
• Angiotensin 2 causes vasoconstriction. Also increases aldosterone production
• AT2 binds to AT receptors on the ZG cells to increase aldosterone secretion
• Aldosterone causes vasoconstriction increased BP
• Affects kidney to increase total body fluid volume reduces K+
what effect do aldosterone and cortisol have on inflammation?
- Aldosterone = pro-inflammatory
* Cortisol = anti-inflammatory
what binds to the mineralcorticoid receptor? which binds more
aldosterone and cortisol
cortisol binds more
what stops only cortisol binding to the MCR?
cortisol –> cortisone by an enzyme called 11BHSD-2– stops cortisol binding to receptor instead of aldosterone
what are the 2 main cells involved in the renal effects of aldosterone?
o Principal cell (DCT) – needed in salt and water balance
o intercalated cell – acid-base balance
what is the effect of high aldosterone in principal cells?
- If aldosterone binds to the MCR, it activates all processes for reabsorbing Na+ and secreting K+
- Upregulates the sodium/potassium pump for energy and inserts more ENAC channels into the luminal membrane for Na+ absorption.
- For electroneutrality you have to secrete K+ and absorb Cl- along w the Na+
- High aldosterone = loss of K+ and Na+ reabsorption
what is the effect of aldosterone on the intercalated cell?
- Aldosterone upregulates;
- H+/K+ exchanger and a H+ ATPase –> loss of H+ ions fall in acid levels alkalotic state
- High BP Aldosterone = loss potassium = metabolic alkalosis
what happens in Conn’s syndrome?
o Hypertension
o Suppressed plasma renin activity
o Increased aldosterone secretion
what causes primary hyperaldosteronism?
- conn’s syndrome
- aldosterone producing adenoma
- bilateral adrenal hyperplasia
how do you diagnose hyperaldosteronism?
aldosterone:renin ratio saline suppression test CT adrenal adrenal venous sampling metomidate PET
what are symptoms of syndrome of apparent mineralocorticoid excess and what causes it?
• Glycorisic acid inhibits 11BHSD-2 – increases cortisol levels in contact with the MCR low K+, metabolic alkalosis and high BP from liquorice toxicity
what happens in Liddle syndrome?
- Import more ENAC channels into the luminal membrane of the collecting duct increased Na+ absorption
- Leads to: hypertension, hypokalaemia and metabolic alkalosis
what effect does POMC have and how?
In the anterior pituitary, cleavage of POMC produces ACTH - binds to the melanocortin-2 receptor on ZF cells which tell them to produce cortisol
• Also stimulates MC1R – also on melanocyte cells which cause it to produce melanin
how does too much ACTH stimulate hyperpigmentation?
• When you break down ACTH to aMSH, MC1R is stimulated.
• Local aMSH binds to MC1R produces a tan
MC1R – also on melanocyte cells which cause it to produce melanin
what sits on the same gene as aldosterone synthase?
11-B hydroxylase
what happens when ACTH binds to ZF?
it upregulates production of 11-beta hydroxylase by activating the promoter
how does glucocorticoid remediable aldosteronism occur?
- If there’s a mistake in cell division, promoter region for 11BH is attached to the coding region of aldosterone synthase
- What normally stimulates cortisol production will produce aldosterone production
- Causes high BP
- Can treat by reducing ACTH levels – quickest way to do this is with steroids (have negative effects on the pituitary)
what is the response to starvation?
tissue breakdown for fuel
what is the response to infection?
immunosuppression
what is the response to hypotension?
increase BP
what is the fat distribution in Cushing’s syndrome?
High visceral fat but low subcutaneous fat
what are causes of Cushing’s syndrome?
- Iatrogenic
- Corticotroph adenoma of the pituitary
- Ectopic ACTH secreting neuroendocrine tumour
- Cortisol secreting adrenal adenoma
- Bilateral adrenal hyperplasia
how do you diagnose Cushing’s?
- Overnight dexamethasone suppression test
- 24-hour urine free cortisol
- LDDST: 0.5mg dexamethasone every 6 hours for 48 hours
- Cortisol day curve plus midnight sleeping cortisol
what imaging do you do in Cushings?
- MRI Pituitary
- CT Adrenals
- Inferior petrosal sinus sampling
- NM: Octreotide uptake scan
how is inferior petrosal sinus sampling done and why?
o Blood taken from inferior petrosal sinuses (just under pituitary) to see where the ACTH is from. If its high from here then its from the pituitary. No point doing this test unless you’ve confirmed Cushings
how is Cushing’s syndrome treated?
• Pituitary tumour o Transsphenoidal surgery o External beam radiotherapy o Stereotactic radiosurgery (gamma knife) • Adrenal o Adrenalectomy • Metyrapone/Ketoconazole/Etomidate
what is Addison’s disease?
• Primary adrenal failure
o Autoimmune
o Tuberculosis
what symptoms does Addison’s present with?
• Vague symptoms initially
o Fatigue, weakness, myalgia
o Anorexia, weight loss
o Hyperpigmentation
what is Addisonian crisis and how does it present?
failure to respond to stress
o Low BP, low glucose, low Na+ and high K+
how do you diagnose Addison’s?
- Low 9am cortisol
- High ACTH
- Short Synacthen Test
how is Addison’s treated?
Replacement steroid
• Hydrocortisone (glucocorticoid)
• Fludrocortisone (mineralocorticoid)
Addisonian crisis;
• IV fluid resuscitation
• IM hydrocortisone
what causes congenital adrenal hyperplasia?
• Caused by 21-hydroxylase deficiency
o Decreased cortisol increased ACTH more androgens produced
what does congenital adrenal hyperplasia lead to?
o Salt-losing
o Adrenal Insufficiency
o Virilisation – new born baby girls develop male external genitalia
o Adrenal hyperplasia
what are congenital adrenal hyperplasia symptoms similar to?
PCOS
how do you screen for congenital adrenal hyperplasia?
Screen for this condition by measuring 17(OH)-progesterone – high in this condition
what type of hormones are catecholamines?
• Catecholamines are amine hormones made from tyrosine
what cells make catecholamines?
chromaffin cells
name locations of chromaffin cells
o Adrenal medulla o Para-aortic sympathetic chain o Organ of Zuckerkandl o Wall of urinary bladder o Neck and mediastinal sympathetic chain
name chromaffin cell tumours
o Phaeochromocytoma - Arising from within the adrenal medulla
o Paraganglioma - Extra-adrenal tumours
what do a1 adrenoreceptors do?
vascular and smooth muscle contraction
what do a2 adrenoreceptors do?
presynaptic, inhibitory to noradrenaline release - suppresses BP
what do b1 adrenoreceptors do?
positive inotropic and chronotropic in the heart; increased renin; lipolysis
what do b2 adrenoreceptors do?
bronchial, vascular, uterine smooth muscle relaxation; glycogenolysis
what do b3 adrenoreceptors do?
Lipolysis, energy expenditure, eg at brown fat tissue
what do d1 adrenoreceptors do?
cerebral, renal, mesenteric, coronary vasculature dilatation
what do d2 adrenoreceptors do?
presynaptic inhibition of noradrenaline and prolactin release
what are symptoms of catecholamine excess?
- Impending doom
- Diaphoresis
- Dyspnea
- Headache
- Hypertension
- Palpitation
- Tremor
- Nausea and vomiting
how do you diagnose a catecholamine excess?
- 24 hour urine metanephrines
- Plasma metanephrines
- CT/MRI adrenals and abdomen
- 123I-MIBG scintigraphy
what is MIBG?
a tracer taken up by neuroendocrine cells. Localised in granules where we store catecholamines and chromogranin
how is a catecholamine excess treated?
• Surgical resection
• Pre-operative alpha and beta-blockade
o Phenoxybenzamine 10mg bd and titrate
o Propranolol 10mg qds and titrate
• Acute crisis: IV phentolamine or nicardipine
• Avoid opiates
• 131I-MIBG therapy for malignant disease
