Adrenal cortex and adrenal causes of hypertension Flashcards by David Houghton

There are 3 main arteries that supply the adrenal glands. Label them on the image using the labels below:

Inferior adrenal artery
Superior adrenal artery
Middle adrenal artery

1 = Superior adrenal artery
2 = Middle adrenal artery
3 = Inferior adrenal artery

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There are 3 main arteries that supply the adrenal glands, the inferior, superior and middle adrenal artery. Where does the superior adrenal artery arise from?

inferior phrenic artery

- supplies the diaphragm

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There are 3 main arteries that supply the adrenal glands, the inferior, superior and middle adrenal artery. Where does the middle adrenal artery arise from?

abdominal aorta

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There are 3 main arteries that supply the adrenal glands, the inferior, superior and middle adrenal artery. Where does the inferior adrenal artery arise from?

renal arteries

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Where does all the blood from adrenal glands drain into?

left and right adrenal veins

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The adrenal gland is made up of 2 key parts, the adrenal cortex and medulla. The adrenal cortex can be further divided into 3 parts. Label the image below with the names provided:

zona glomerulosa
zona reticularis
zona fasciculata

1 = zona glomerulosa (outermost layer)
2 = zona fasciculata (middle layer) 
3 = zona reticularis (innermost layer)

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The adrenal gland is made up of 2 key parts, the adrenal cortex and medulla. Embryonically, where do the adrenal cortex and medulla originate from?

cortex = mesoderm

- medulla = neural crests

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What 2 key things does the medulla secrete?

catecholamines (adrenaline and noradrenaline)

- enkephalins (involved in pain inhibition)

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What are the key cells of the adrenal medulla that synthesis and secrete - catecholamines (adrenaline and noradrenaline) and enkephalins (involved in pain inhibition)?

chromaffin cells

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What are the key cells of the adrenal medulla that synthesis and secrete - catecholamines (adrenaline and noradrenaline) and enkephalins (involved in pain inhibition)?

chromaffin cells

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The cortex is stimulated by adrenocorticotropic hormone (released by the pituitary gland), stimulating what molecule that initiates the biosynthesis of the adrenal cortes secretions. What is this molecule?

cholesterol

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The cortex is stimulated by adrenocorticotropic hormone (released by the pituitary gland), stimulating cholesterol that initiates the biosynthesis of the adrenal cortes secretions. What are the 3 main secretions of the adrenal cortex?

1 - Glucocorticoids [e.g. cortisol]
2 - Mineralocorticoids [e.g. aldosterone]
3 - Adrenal androgens [e.g. dehydroepiandrosterone [DHEA] > converts to sex hormones].

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The image below shows how the adrenal gland is stimulated and and then the enzymes and reactions that take place to synthesise and secrete:

1 - Glucocorticoids [e.g. cortisol]
2 - Mineralocorticoids [e.g. aldosterone]
3 - Adrenal androgens [e.g. dehydroepiandrosterone [DHEA] > converts to sex hormones]

Why is it important to understand these pathways?

mutations/defects in any of these enzymes can lead to pathology

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There are 3 main hormones released by the adrenal gland, namely:

1 - Glucocorticoids [e.g. cortisol]
2 - Mineralocorticoids [e.g. aldosterone]
3 - Adrenal androgens [e.g. dehydroepiandrosterone [DHEA] > converts to sex hormones]

Which of these is key in the following:

Maintenance of homeostasis during stress (haemorrhage, infection, anxiety)
Anti-inflammatory
Energy balance / metabolism (increase and maintain glucose homeostasis)
Formation of bone and cartilage
Regulation of blood pressure
Cognitive function, memory, conditioning

glucocorticoids

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What colour do the adrenal medulla and cortex generally appear histology?

adrenal medulla = brown

- adrenal cortex = yellow

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What is essential hypertension?

no clear identifiable cause

- linked to genetics, poor diet, lack of exercise and obesity (most common form)

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What is hypertension caused by primary renal disease and artery stenosis?

primary renal disease = damage directly to the kidneys

- artery stenosis = narrowing of blood vessels to kidneys

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What is adrenal hypertension?

adrenal glands produce too much of the hormone aldosterone

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Specifically where in the adrenal gland is mineralocorticoid aldosterone produced?

outermost layer of the adrenal cortex

- zona glomerulosa.

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Aldosterone is part of the Renin-angiotensin-aldosterone system. What stimulates the - outermost layer of the adrenal cortex, the zona glomerulosa and thus aldosterone release?

angiotensin II

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Aldosterone is part of the Renin-angiotensin-aldosterone system. Once angiotensin II has stimulated the outermost layer of the adrenal cortex, the zona glomerulosa aldosterone is release. What is aldosterone then able to do?

binds to receptors in the distal and collecting tubes of the nephron
increases gene up-regulation of Na+/K+ ATPase
NA+ and H2O are drawn into blood increasing blood volume and blood pressure
K+ is excreted

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What is primary hyperaldosteronism?

excessive production of the hormone aldosterone from the adrenal glands

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Primary hyperaldosteronism, a rare condition causing excessive production of the hormone aldosterone from the adrenal glands. What are the 2 most common causes of this?

1 - adenoma called conns syndrome

2 - hyperplasia

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Primary hyperaldosteronism, a rare condition causing excessive production of the hormone aldosterone from the adrenal glands and can lead to hypertension and hypokalaemia. What % of all hypertension patients does this account for?

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- metabolic alkalosis - aldosterone helps retain Na+ and H2O - BUT also retains HCO3- whilst excreting H+

- cardiac events

If we suspect primary hyperaldosteronism, how would this present in a younger adult, <40 years of age?

- hypertension (especially severe - systolic BP > 160 and/or a diastolic BP > 100mmHg. - hypokalaemia (K+ not reabsorbed in place of Na+) - metabolic alkalosis (HCO3- absorbed but H+ excreted) - adrenal incidentoloma (nodular growth on adrenal gland) - family history

In relation to the renin-angiotensin-aldosterone system, how can we investigate for hyperaldosteronism?

- renin/aldosterone ratio | - low renin and high aldosterone

What dynamic test can we use to investigate for hyperaldosteronism?

- saline suppression test - patient is infused with H2O and Na+ to attempt to suppress renin and aldosterone - measure aldosterone and if not suppressed (>140 pmol/L) confirms hyperaldosteronism - MUST correct for K+ - ensure other medication is stopped

In addition to static and dynamic testing, how else can we test for hyperaldosteronism?

- imaging CT first - MRI - last test should be Metomidate PET CT

In the following conditions that can cause hypertension, would we expect to find high or low levels of renin and aldosterone? - hyperaldosteronism - renovascular - cushings

- hyperaldosteronism = HIGH aldosterone and LOW renin - renovascular = HIGH aldosterone and HIGH renin - cushings = LOW aldosterone and LOW renin

What is adrenal venous sampling (AVS)?

- blood samples are taken from the veins of the adrenal glands - cannula is passed into veins and samples taken

Adrenal venous sampling (AVS) is blood sampling from the veins of the adrenal glands. What is this used for?

- if imaging is unsuccessful this is the gold standard for diagnosing hyperaldosteronism - AVS is used to identify a nodule (s) on adrenal glands - high failure rate (especially on right) - elevated aldosterone will be present in one or both sides depending on pathology

Treatment of hyperaldosteronism is dependent in the cause. If the problem is an adenoma or nodule, what is the most likely treatment?

- surgery to remove the adenoma/nodule

Treatment of hyperaldosteronism is dependent in the cause. If the problem can not be isolated to a specific gland or surgery is not an option, what are the treatment options for the following: - hyperaldosterone - hypokalaemia - hypertension

- Aldosterone Antagonists (diuretics spironolactone or amiloride) - Hypokalaemia - restore K+ levels - Hypertension - reduce blood volume and therefore blood pressure

Cushings syndrome is when patients have excessive cortisol levels. This can lead to cushings hypertension. What % of all hypertensive patients is caused by cushings?

- 2-5%

What is Phaeochromocytoma?

- phios = greek for means dusky - chroma greek for color - cytoma means tumuor - a type of neuroendocrine tumor that grows from chromaffin cells in medulla, that acquires a dusky colour when stained on histology

Phaeochromocytoma is a type of neuroendocrine tumour that grows from chromaffin cells in medulla, that acquires a dusky colour when stained on histology. What does phaeochromocytoma cause the over secretion of?

- catecholamines | - adrenalin and noradrenaline

What is the catecholamine synthesis pathway that occurs in the adrenal medulla?

- tyrosine is converted in L-DOPA - L-DOPA is converted into dopamine and can be released - dopamine can also be converted into adrenaline and noradrenaline and released

What are the 2 key effects of noradrenaline?

1 - vasoconstriction | 2 - glycogenolysis (glycogen turned into glucose)

What are the 3 key effects of adrenaline?

1 - vasocontriction 2 - increased HR 3 - sweating

What are the clinical features of Phaeochromocytoma?

- headache, sweating and palpitations - hypertension and tachycardia - chest or abdominal pain - pallor/flush - sense of impending doom - episodic - precipitating factors

There is one proto-oncogene that has been linked with causing phaeochromocytoma, what is this?

- re-arranged during transfection (RET) MEN-2

There are two tumour suppressor genes that has been linked with causing phaeochromocytoma, what are they?

- von Hippel-Lindau disease tumor suppressor gene = VHL | - neurofibromatosis type 1 tumor suppressor gene = NF-1

There are two succinate dehydrogenase complex (SDH) (complex 2 in mitochondria) subunits that has been linked with causing phaeochromocytoma, what are they?

- PGL-1 | - PGL-4

As there is a genetic risk for phaeochromocytoma, when would genetic testing be conducted?

- <20 years old - family history - clinical features of genetic syndrome - paraganglioma (neuroendocrine tumour affecting sympathetic system)

What basic biochemistry measurements would we want to make in an attempt to diagnose Phaeochromocytoma?

- 24 hour urinary catecholamines (adrenaline, noradrenaline and dopamine) - 24 hour urinary metanephrines (unfractionated catecholamines) - plasma free metanephrines

What is the gold standard biochemistry measurements we want to make in an attempt to diagnose Phaeochromocytoma?

- plasma free metanephrines

What imaging techniques can we use in an attempt to diagnose Phaeochromocytoma?

- CT - MRI - Meta-iodobenzylguanidine (MIBG)

When a patient has been diagnosed with Phaeochromocytoma, what is the most curative form of treatment?

- surgery to remove the lesion called laparoscopic adrenalectomy - only if surgery is safe though

If surgery is unsafe, what medical treatment can be used in a patient with Phaeochromocytoma?

- alpha 1 receptor blockers (phenoxybenzamine and doxazocin) - beta blockers (propranolol) - radiotherapy

What is adrenal incidentalomas?

- a tumour discovered incidentally | - in one or both of the adrenal glands

Adrenal Incidentalomas are an unsuspected tumuors in one or both of the adrenal glands, that are picked up during a scan for something else. What % of adrenal Incidentalomas are non-secreting lesions?

- 75%

If an adrenal Incidentalomas, an unsuspected tumuors in one or both of the adrenal glands, is detected, it must be assessed whether it is pathological. To test we can use the triple testing. This includes testing for: - glucorticoids - mineralcorticoids - catecholamines How would we test for the above 3 things?

1 - overnight dexamethasone suppression test (ONDST) 2 - plasma or urine metanephrines 3 - renin:aldstonerone ratio

If an adrenal Incidentalomas, an unsuspected tumuors in one or both of the adrenal glands, is detected, it must be assessed whether it is pathological. In addition to the triple testing, detailed below, what else can be used to monitor patients? 1 - overnight dexamethasone suppression test (ONDST) 2 - plasma or urine metanephrines 3 - renin:aldstonerone ratio

- imaging | - assess if adenoma is increasing in size

When trying to determine a nodule on the adrenal gland is benign there are some tests with cut offs that we need to be aware of. What is the cut off in hounsfield units (HU)on a CT scan?

- <10 HU | - associated with the density of the nodule

When trying to determine a nodule on the adrenal gland is benign there are some tests with cut offs that we need to be aware of. What information can we use on an MRI scan of a nodule?

- loss of signal intensity on out phasing | - benign nodules are lipid rich tissue

When trying to determine a nodule on the adrenal gland is benign there are some tests with cut offs that we need to be aware of. What cut offs can we use on CT with delayed contrast media washout?

- absolute washout = 60% | - relative washout = 40%

When trying to determine a nodule on the adrenal gland is benign there are some tests with cut offs that we need to be aware of. In a nuclear scan what can tell us that the nodule is benign?

- benign tumours are lipid rich and have a low metabolism | - therefore they have lo absorption of FDG, or less than the liver

What is Congenital Adrenal Hyperplasia?

- group of genetic disorders that affect the adrenal glands - metabolic disorder impairing biosynthesis of cortical steroid - causes low cortisol and aldosterone

Congenital Adrenal Hyperplasia is group of genetic disorders that affect the adrenal glands. It is a metabolic disorder impairing biosynthesis of cortical steroids. What type of inheritance is the disease?

- autosomal recessive (non sex chromosome is affected) - both parents would need to pass on the mutated gene - typically autosomal recessive inheritance

Congenital Adrenal Hyperplasia is group of genetic disorders that affect the adrenal glands. It is a metabolic disorder impairing biosynthesis of cortical steroids. How does this affect cortisol and aldosterone levels?

- both can decrease, causing an increase in ACTH | - excessive ACTH causes adrenocorticol hyperplasia

- 21-hydroxylase deficiency | - accounts for aprox 95%

Congenital Adrenal Hyperplasia is group of genetic disorders that affect the adrenal glands. It is a metabolic disorder impairing biosynthesis of cortical steroids. There are multiple clinical syndromes, but the most common is 21-hydroxylase deficiency, accounting for aprox 95% of cases. What is this characterised by in relation to the adrenal glands?

- cortisol and aldosterone are low | - androgen excess

Congenital Adrenal Hyperplasia is group of genetic disorders that affect the adrenal glands. It is a metabolic disorder impairing biosynthesis of cortical steroids. There are multiple clinical syndromes, but the most common is 21-hydroxylase deficiency, accounting for aprox 95% of cases and is this characterised by cortisol and aldosterone deficiency and androgen excess. Where is this gene located?

- chromosome 6p21 within the major histocompatibility complex

Congenital Adrenal Hyperplasia is group of genetic disorders that affect the adrenal glands. It is a metabolic disorder impairing biosynthesis of cortical steroids. There are multiple clinical syndromes, but the most common is 21-hydroxylase deficiency, accounting for aprox 95% of cases and is this characterised by cortisol and aldosterone deficiency and androgen excess. The clinical phenotype has been classified as what 2 classifications?

1 - classic (severe) = salt losing (aldosterone deficiency) and non salt losing (simple virilising) 2 - non-classic = mild or late onset

What is the mnemonic that helps remember what each zone in the cortex secretes? - Most superficial cortical layer: zona glomerulosa - Deepest cortical layer: zona reticularis - Middle cortical layer: zona fasciculata

Another mnemonic is "Salt, Sugar, Sex: The deeper you go, the sweeter it gets." As one moves layers into the adrenal cortex, compounds that control salt (mineralcorticoids), sugar (glucocorticoids), and sex (weak androgens) are produced