Adrenal Flashcards
(32 cards)
What are the areas of the adrenal glands?
Capsule
Cortex -
zona glomerulosa - mineralocorticoids (e.g.aldosterone)
zona fasiculata - glucocorticoids (e.g. cortisol)
zona reticularis - androgens (e.g.DHEA+androtenedione)
Medulla - catecholamine (Adrenaline + NA) +enkephalins
Where are corticosteroids produced?
cortex
What are corticosteroids?
Cholesterol derivative (3 6-ring, 1 5-ring) Lipid soluble (can diffuse through membranes) Alter gene transcription directly/indirectly Exact action depend on structure, ability to bind genes and recruit co-factors
How does ACTH stimulate synthesis acutely?
Bind to GPCR > increase STAR production > increase cholesterol uptake by mitochondria
Effect on adrenal size - Increase ACTH > hyperplasia, Decrease ACTH > atrophy
How are corticosteroid classified?
Pregnane derivatives (21C) - progesterone and corticoids Androstane derivative (19C) - Androgens Estrane derivative (18C) - e.g. oestrogen
Glucocorticoids e.g. cortisol
Not water soluble, synth in z.f and z.r, permissive actions (effect only apparent in deficiency), diurnal rhythm, increase in stress
Actions: Increase lipolysis & gluconeogenesis, maintain circulation, immunomodulation (dampen immune response)
Cortisol - binds to mineralocorticoid receptor as well glucocorticoid receptor but system isn’t swamped as 11beta-HSD2 inhibits (cortisol>cortisone) by reducing affinity
Mineralocorticoids e.g. aldosterone
Imp in salt and water balance, aldosterone increases Na reabsorption and K excretion
What is congenital adrenal hyperplasia(CAH)?
Block in adrenal steroidogenesis that affects the synthesis of glucocorticoids, and occasionally mineralocorticoids.
What is the commonest cause of CAH?
21-hydroxylase deficiency- usually due to autosomal recessive mutation in the CYP21 gene
Enzyme converts: 17OHP > deoxycortisol & Progesterone > deoxycorticosterone
What will 21-hydroxylase deficiency do?
Loss of cortisol > stimulate increase in ACTH (due to -ve feedback)
> increased 17 OHP and progesterone and other precursors
> hyperplasia of adrenal glands > generate more cholesterol
Glucocorticoid cannot be produced therefore some steroid precursors e.g. 17-OHP are shunted to androgen synthesis (however increase in androgen production mainly due to ACTH stimulation of hyperplasia)
How is CAH diagnosed and what are the symptoms & Signs?
Diagnosis: High levels of 17-OHP
Symptoms & signs: Androgen excess
Female - > virilisation of females infants (appearance of male genitalia with scrotum not containing testes - measure via Prader stage I - V)
Male - > more difficult to spot, salt wasting crisis due to lack of mineralocorticoids, and effects of lack of cortisol (Addison’s like symptoms)
Can pick up decreased linear growth in children
Treatment of CAH?
Exogenous cortisol and aldosterone replacement -> decrease ACTH drive and lowers androgen excess
Excessive use of cortisol -> Cushing’s symptoms e.g. central obesity, moon face, striae, suppression of LH and FSH (->amenorrhea)
Lack of GC -> adrenal crisis and androgen excess (-> anovulation and oligiomenorrhea)
What is a 46XX male?
When a female has androgen excess and develops a male appearance despite female anatomy
What is an adrenal incidentaloma?
An incidentally discovered adrenal mass - commonly found in normal CT investigation. Usually benign endocrine inactive tumours but some may cause hormone excess or be a malignant growth or metastases.
What is the difference between an adrenal carinoma and an adrenal adenoma?
Adenoma - benign fat based
Carcinoma - malignant, larger (usually >4cm), higher density, irregular edges
How do you determine if there is hormone excess in an adrenal incidentaloma?
Cushing’s - excluded by 24-h urinary free cortisol followed by dexamethasone overnight test (should suppress ACTH release > lowering endogenous cortisol secretion below clinical detection i.e. high cortisol if secreting tumour)
Phaeochromocytoma - excluded with a 24-h urinary free catecholamines/ metanephrines (metabolite of catecholamines), or by measuring plasma metinephrine levels (high in phaeochromocytoma)
Primary hyperaldosteronism - Measurement of blood pressure and plasma K+ levels & renin (in primary hyperaldosteronism would have high BP, low plasma K+ and low renin despite high aldosterone)
CAH - excluded via measurement of DHEAs and 17-OHP
Why is it important to rule out a hormone secreting tumour before operating on a patient with an adrenal incidentaloma?
If patient has phaeochromocytoma (overproducing catecholamines) > high intra-operative BP (potentially life threatening
What is phaeochromocytoma?
Tumour of chromaffin tissue > increase in catecholamine production
Present in adrenal medulla/sympathetic ganglia (phaeoganglioma)
Symptoms of phaeochromocytoma?
Headache, sweating, palpitations, nausea, tremor, pallor, hypertension, postural hypotension (due to low plasma volume), supraventricular tachycardia, myocardial ischaemia, cardiomyopathy (-> irreversible heart failure)
What are the genes associated with phaeochromocytoma?
RET protooncogene Von Hippel Lindau syndrome (VHL) NF-1 SDHC & SDHB tumour genes Genetic causes account for 25% of phaeochromacytoma
RET protooncogene
Will cause multiple endocrine neoplasia (MEN) type 2
- > phaeochromocytoma
- > medullary thyroid carcinoma,
- > parathyroid hyperplasia (MEN2A) / mucocutaneous neuroma (MEN2B) [present with multiple nodules on the tongue]
Von Hippel Lindau syndrome (VHL)
Patients at risk of:
Haemangioblastoma (malignant tumours of cerebellum, retina or spinal cord cancer), phaeochromocytoma, renal angioma & renal cancer
NF-1
- > neurofibromatosis type 1
- present with café au lait spots on the skin + benign tumours of the nerve endings (neuromas)
SDHC & SDHB tumour genes
-> familial head and neck paragangliomas
SDHB -> phaeochromocytoma + extra-adrenal paragangliomas (frequently malignant)
