Adrenal gland (hyper) Flashcards
What are the clinical features of Cushing’s disease?
1) Excess cortisol
2) Centripetal obesity
3) Moon face and buffalo hump
4) Proximal myopathy
5) Hypertension and hypokalaemia
6) Red striae, thin skin, and bruising
7) Osteoporosis and diabetes
What are the main causes of Cushings?
- Overdose of oral corticosteroids
- Pituitary dependent Cushing’s disease
- Ectopic ACTH from lung cancer
- Adrenal adenoma secreting cortisol
What are the investigations that are conducted to determine the cause of Cushing’s syndrome?
-24H urine collection for urinary free cortisol
-Blood diurnal cortisol levels
(Cortisol usually highest at 9am and lowest at midnight, if asleep)
-Low dose dexamethasone suppression test
In patient’s with Cushing’s, the cortisol level remains elevated throughout the day
What type of rhythm is exhibited by cortisol secretion?
Diurnal rhythm
What is a positive result for a low dose dexamethasone suppression test?
There is a failure of cortisol ACTH suppression, therefore morning cortisol remains elevated >50nanomol/L.
What suppressive investigation is done to identify a patient with potential Cushing’s disease?
Low dose dexamethasone suppression test.
What pharmacological interventions are implemented for patients with hypersecretion of cortisol from the adrenal cortex?
Metryapone
Ketoconazole
Which adrenal cortex structure is affected in a patient with Conn’s syndrome?
Tumour of the zona glomerulosa, therefore leading to excess aldosterone
Which enzyme is inhibited by metyrapone?
11B-hydroxylase
What is the mechanism of action of metryapone?
Inhibition of 11B-Hydroxylase, this arrests steroid synthesis within the zona fasciculata at the 11-deoxycortisol stage
Does 11-deoxycortisol exert negative feedback on the hypothalamus?
There is no negative feedback effect on the hypothalamus and pituitary gland.
What are the advantages of using metryapone preoperatively?
Improves patient’s symptoms and promotes better post-operative recovery (better wound healing, less infection).
How should cortisol be controlled and regulated in patients taking metryapone?
Adjust oral dose according to cortisol level (aim for mean serum cortisol 150-300nmol/L).
What are the side effects of using metryapone on aldosterone synthesis?
Deoxycorticosterone accumulates within the zona glomerulosa, exhibiting aldosterone-like (mineralocorticoid) activity, leading to salt retention and hypertension.
What type of effects are exerted by deoxycoticosterone?
Mineralocorticoid activity
Where does deoxycorticosterone accumulate in patients taking metryapone?
Accumulates in the zona glomerulosa.
What are the unwanted actions of metryapone?
Hypertension on long-term administration
Hirsutism (increased adrenal androgen production in women)
What toxic risk is associated with ketoconazole?
Hepatotoxicity
Therefore monitor liver function weekly, clinically and biochemically
Which enzyme is inhibited by ketoconazole?
17-alpha hydroxylase
What follow up investigations should be conducted in patients prescribed with ketoconazole?
Weekly liver function tests due to hepatotoxicity risks (P450 poison)
What is the 1st line of treatment for a patient with an ACTH-secreting pituitary adenoma?
Pituitary surgery (transsphenoidal hypophysectomy)
What are the surgical interventions for the treatment of Cushing’s?
1) Transsphenoidal hypophysectomy
2) Bilateral adrenalectomy
3) Unilateral adrenalectomy for adrenal mass.
What is the main cause of Conn’s syndrome?
Benign adrenal cortical tumour of the zona glomerulosa
Resulting in an excess production of aldosterone
What are the associated clinical features of Conn’s syndrome?
Hypertension
Hypokalaemia
Hypernatremia
What type of hyperaldosteronism is Conn’s syndrome?
Priamry hyperaldosteronism
What impact does Conn’s syndrome have on the Renin-angiotensin system?
RAAS should be suppressed (exclude secondary hyperaldosteronism)
What two main drugs are prescribed in patients with Conn’s syndrome?
Spironolactone
Epleronone
What is the mechanism of action of spironolactone?
Converted to several active metabolites, including canrenone, a competitive antagonist of mineralocorticoid receptors (MR)
- Blocks sodium reabsorption and potassium excretion in the kidney tubules (potassium sparing diuretic)
- antihypertensive
Which metabolite is formed through the conversion of spironolactone?
Canrenone
Which receptors are antagonised by spironolactone metabolites?
Mineralocorticoid receptors
Describe the pharmacokinetics of spironolactone?
Orally active
Highly protein bound and metabolised in the liver.
What are the unwanted actions of spironolactone?
Menstrual irregularities (+progesterone receptor)
Gynaecomastia (inhibits androgen receptors)
What type of antagonist is epleronone?
A mineralocorticoid receptor antagonist
Which conn’s syndrome drug is better tolerated?
Epleronone
Why is epleronone better tolerated than spironolactone?
Less binding to androgen and progesterone receptors compared to spironolactone
What is a phaechromocytoma?
Tumours of the adrenal medulla which secrete catecholamines
How are catecholamines secreted from the adrenal medulla?
Secreted in response to sympathetic stimulation
What type of receptors does cortisol bind onto?
Mineralocorticoid and glucocorticoid receptors
Which enzyme is secreted by the kidney to convert bioactive cortisol to cortisone?
11B-hydroxysteroid dehydrogenase 2
What is the purpose of 11b-hydroxysteroid dehydrogenase 2?
Converts bioactive cortisol to cortisone, constantly removing cortisol to reduce interference with mineralocorticoid receptors
What are the catecholamine producing cells of the adrenal medulla?
Chromaffin cells
What are the potential risks with a phaeochromocytoma?
Elevations in adrenaline typically manifest as severe hypertension causing potential myocardial infarctions or strokes, as well as ventricular fibrillation within patients becoming a medical emergency.
How are catecholamines released from the adrenal medulla in patients with a phaeocromocytoma?
Released upon sympathetic activation leading to an adrenaline storm.
Which hormone can be measured in urine and blood as a marker for phaeochromocytoma associated release of adrenaline?
metanephrine (has a long half life)
What is the classic triad of symptoms for patients with a phaeocromocytoma?
Palpitations
Headaches
Diaphoresis (excessive sweating)
What is the main clinical feature of a phaeochromocytoma?
Sustained or paroxysmal hypertension
Cases of hypertension may proceed after abdominal pain episodically, in comparison to Conn’s syndrome (smooth secretion of aldosterone)
What are the associated risks with a phaeochromocytoma?
Family history of endocrine disorders
MEN, Von-Hippel-Lindau syndrome, germline mutations in the succinate dehydrogenase
What is the first line of treatment of a phaeochromocytoma?
Anti-hypertensive agents: phentolamine IV and sodium nitroprusside
What are the precautions required for patients with a phaeochromocytoma surgical excision?
Careful preparation as anaesthetic can precipitate a hypertensive crisis
Why is an alpha-blockade administered in the management of a phaeochromocytoma?
Inhibition of alpha-receptors minimises the impact of vasoconstriction induced by noradrenaline/adrenaline, therefore reducing blood pressure.
-IV fluids to compensate for potential hypotensive crisis
Why is a beta-blockade administered in the management of a phaeochromocytoma?
Administer atenolol/metoprolol/propanolol to prevent tachycardia and arrhythmia.
