The Adrenal Gland Clinical Case & Discussion Flashcards
Describe the four layers of the adrenal gland
Capsule Zona glomerulosa Zona fasiculata Zona reticularis Adrenal medulla
Where is aldosterone synthesised?
In the zona glomerulosa of the adrenal cortex
Where is cortisol synthesised?
In the bona fasiculata of the adrenal cortex
Where are the sex steroids produced (adrenal)?
In the bona reticularis
What is synthesised in the adrenal medulla?
Norepinephrine, epinephrine
Describe the hypathalamo hypopituitary adrenal axis
Involves CRH synthesis in the hypothalamus and then synthesis of ACTH in the pituitary which then synthesises hormone production in the adrenal gland. As levels of cortisol increase, there is a negative feedback control on the system and the hypothalamic and subsequent secretions are reduced
What is the most common cause of primary adrenal insufficiency causing hyposecretion?
Addison’s Disease
What proportion of UK adrenal failure cases are caused by Addison’s disease?
> 85%
What is the basic autoimmune pathology of Addison’s?
In 70% of cases there is a production of positive adrenal autoantibodies to 21-OHase
There is then subsequent infiltration of the adrenal cortex and associated autoimmune conditions are common
Generally, does type 1 or type 2 diabetes present more acutely?
Type 1 - the gland has a reserve function which allows its actions be well preserves until a tipping point is reached and symptoms rapidly manifest
What is the location of the defect in the vast majority of Addison’s cases?
The adrenal glands
What are some symptoms commonly associated with primary adrenal failure?
Weakness, fatigue, anorexia, weight loss, skin pigmentation, vitiligo, hypotension, unexplained vomiting or diarrhoea
Why can hyper pigmentation be seen in Addison’s disease?
The hypothalamus detects the reduced cortisol in the plasma and stimulates further ACTH release from the pituitary, which in excess causes the stimulation melanocytes which cause the pigment change
What tests should be done for Addison’s?
Random cortisol - Nb that the tester must be aware of when the test was done in order to determine whether the results correlate with normal fluctuating daytime levels
Synacthen test and basal ACTH
Describe the basic investigative pathway where adrenal insufficiency is suspected
Rapid ACTH stimulation test/snynacthen test done on suspicion, if confirmed, a plasma ACTH level is measured and if suppressed the diagnosis points towards secondary adrenocortical insufficiency
If the plasma ACTH is shown to be elevated it is suggestive of primary adrenocortical insufficiency
What is the main drug used for glucocorticoid replacement?
Hydrocortisone (cortisol)
What is the main drug used for mineralocorticoid replacement?
Fludrocortisone - binds to mineralocorticoid receptors (aldosterone)
What is important to note regarding patients on long term steroids and their adrenal function?
They may be hypoadrenal even if the steroid treatment is for another condition. They will recover from this
What are the three self-care rules for patients on steroids?
- never miss steroid doses to maintain control
- double the medication dose in the event of illness
- If severe vomiting or diarrhoea, take emergency injection and call for help
What hormones are affected in Cushing’s syndrome?
Cortisol and androgens (sex hormones)
What is the effect of cortisol in with regard to sodium?
It causes sodium retention and may lead the HTN and HF
Why is cortisol diabetogenic and potentially damaging, (although essential)?
It is catabolic and will preserve BG at all costs, in order to protect the brain from hypoglycaemia. In doing so it may cause tissue breakdown and weakness of the skin, muscle and bone as well as HTN and HF due to sodium retention and is potentially causative of DM as it opposes the actions of isulin
What are some of the clinical signs of Cushing’s syndrome?
'Moon face' Muscle atrophy replaced with fat Pendulous breasts and abdomen Thin hands and feet Bruising Think skin ulcers Peripheral oedema 'Buffalo hump' Cardiac failure DM
What proportion of Cushing’s cases are ACTH-dependent?
80%
What are the two possible causes for ACTH-dependent Cushing’s syndrome?
75% cases: pituitary tumour
5% cases: ectopic ACTH secretion e.g. lung carcinoid
What are the causes of ACTH-independent Cushing’s syndrome?
Corticosteroid therapy induced Cushing’s
Adrenal tumour
What is the most common cause of Cushing’s syndrome?
Over production of ACTH in the pituitary - tumour
What are the very first tests to do for suspected hypercortisolism?
Overnight dexamethasone test
24 hour urine free cortisol test
What are the two tests done to confirm suspected hypercortisolism?
24 hour urine free cortisol
Low dose dexamethasone test
What test can be done to determine between ACTH-dependent and ACTH-independent hypercorticolism once confirmed?
Paired morning-midnight ACTH cortisol test
What test can be done to determine whether ACTH dependent hypercortisolism is caused by a pituitary pathology?
High dose dexamethasone test
What tests can be done to localise a hypercorticolising pathology?
MRI Sella turcica
CT adrenals
BIPSS
CT chest
What are the two screening tests for Cushings syndrome?
24 hour urinary free cortisol
1mg dexamethasone supression test
Explain the physiology and interpretation of low and high dose dexamethasone testing
Dexamethasone is an exogenous steroid that provides negative feedback to the pituitary gland to suppress the secretion of adrenocorticotropic hormone (ACTH). Specifically, dexamethasone binds to glucocorticoid receptors in the anterior pituitary gland, which lie outside the blood brain barrier, resulting in regulatory modulation
Interpretation
Low-dose and high-dose variations of the test exist. The test is given at low (usually 1–2 mg) and high (8 mg) doses of dexamethasone and the levels of cortisol are measured to obtain the results
A low dose of dexamethasone suppresses cortisol in individuals with no pathology in endogenous cortisol production. A high dose of dexamethasone exerts negative feedback on pituitary ACTH-producing cells, but not on ectopic ACTH-producing cells or adrenal adenoma.
In Cushing’s caused by adrenal carcinoma, what would you expect cortisol levels to be elevated or depressed? What about ACTH levels?
Cortisol levels would be increased as it is a hypersecreting condition. The ACTH levels would be low, as although there is no pituitary pathology the negative feedback from the high levels of cortisol will suppress the CRH hypothalamic secretion and therefore the pituitary ACTH secretion
Is congenital adrenal hyperplasia a hypersecreting or hyposecreting disorder?
Hyposecreting
What hormone is affected in Conn’s syndrome? Is this a hypo or hypersecreting condition?
Aldosterone
Hypersecreting
What are the two most common causes of Conn’s syndrome (hyperaldosteronism)
Are these primary or secondary causes?
Adrenal adenoma
Bilateral adrenal hyperplasia
Primary causes
What is the effect of an aldosterone producing tumour in the adrenal gland(s)?
The increase in aldosterone results in increased urine K+, increased Na+ and H20 retention => increased blood volume and BP
What screening tests can be done for aldosterone -producing adrenal adenomas?
Plasma Renin Activity (PRA)
Plasma Aldosterone concentration (PA(C))
A plasma aldosterone : plasma renin activity ratio test
What does a PA:PRA ratio of >20 indicate?
Primary hyperaldosteronism
What does a PA:PRA ratio of 20?
Secondary hyperaldosternoism or essential hypertension
Less reliable
What does a high PRA with high PAC indicate?
Secondary hyperaldosteronism - requires investigation
What does a low pRA with high PAC indicate?
Primary hyperaldosteronism - requires investigation
When hypertension and hypokalaemia are seen in a patient what condition should be suspected?
Conn’s syndrome
What hyper secretive disorder affects the adrenal medulla?
Phaeochromocytoma
What type of hormones are affected in phaeochromocytoma?
Catecholamines
What is the most common symptom of pheochromocytoma? What other set of symptoms may present?
Hypertension (70% of cases) Paroxysmal attacks -headache -sweating -palpitations
What are the two major causes of hypertension (endocrine)? Why?
Unilateral adrenal adenoma
Bilateral hyperplasia
What is a key difference between congenital adrenal hyperplasia and bilateral hyperplasia?
Congenital adrenal hyperplasia is hyposecreting
Bilateral hyperplasia is hypersecreting
What genetic defect is the cause of over 90% of congenital adrenal hyperplasia cases?
21-hydroxylase deficiency
