Adrenal Glands Flashcards
Left adrenal gland
Crescent shaped
Arterial supply to adrenal glands
Superior adrenal –> inferior phrenic artery –> Abdominal aorta
Middle Adrenal –> abdominal aorta
Inferior adrenal –> renal artery –> abdominal aorta
Venous supply adrenal glands
Right adrenal vein drains directly into the IVC
Left adrenal vein drains into the renal vein then into the IVC
Lymphatic supply to adrenal glands
Para-aortic nodes
Development of adrenal glands
Cortex –> derived from mesoderm
Medulla –> derived from renal crest/ ectodermal tissue
Nervous supply to adrenal glands
Cortex –> hormonal control
Medulla –> sympathetic stimulation from splanchnic nerve from thoracic segment
Adrenal gland consists of two parts
- Outer adrenal cortex (90%)
2. Inner adrenal medulla (10%)
Three zones of the adrenal cortex and what it secretes?
- Zona glomerulosa –> mineralocorticoids
- Zona fasciculata –> glucocorticoids
- Zona reticularis –> androgens
Glomerulosa –> clusters
Fasciculata –> arranged in cords
Reticularis –> networks around blood sinusoids
Types of cells in the adrenal medulla?
Two cell types:
- Nor-epinephrine producing cells 20%
- Epinephrine producing cells 80%
Produces catecholamines
3 hormones secreted by the cortex
Mineralocorticoids –> aldosterone
Glucocorticoids –> cortisol
Androgens –> DHEA
Aldosterone production
Produced by zona glomerulosa Sodium/BP homeostasis Release is stimulated by three factors - angiotensin II - high plasma potassium - ACTH
Regulation of aldosterone production
Blood pressure falls/ low plasma sodium
Detected by juxtagkomerular cells of the kidney
Secrete renin in response
Plasma renin carries out the conversion of angiotensinogen produced by the liver to active angiotensin I
Angiotensin I is subsequently converted to angiotensin II by angiotensin converting enzyme found in the lungs
Angiotensin II is a potent vasoconstrictor that constricts the blood vessels
Angiotensin II also stimulates the secretion of the hormone aldosterone from the adrenal cortex
Aldosterone causes the tubules of the kidney to increase the reabsorption of sodium and water into the blood to raise blood pressure . At the same time potassium is excreted and potassium levels fall in the blood.
Hypo-pituitary-adrenal axis
- CRH is secreted by the hypothalamus
- Stimulates the anterior pituitary to release ACTH
- This hormone acts on the zona fasciculata and reticularis of the adrenal cortex which secretes cortisol
- Cortisol has a negative feedback system on the hypothalamus and AP to inhibit CRH & ACTH release
Affected by stress, illness and time of day
Cortisol release is in what rhythm?
Circadian rhythm
- rate of secretion changes throughout a 24 hr period
- highest levels of cortisol are released earliest in the morning -6am
- falls through the day
Right adrenal
Pyramidal in shape
Anterior to diaphragm
Definition of Adrenal insufficiency
Inadequate adreno cortical function
Causes of primary insufficiency
Addisons disease
Congenital adrenal hyperplasia
Adrenal TB malignancy
Causes of secondary adrenal insufficiency
Lack of ACTH stimulation
Iatrogenic (excess steroid use)
Pituitary or hypothalamic disorders
Definition of addisons disease
Autoimmune destruction of adrenal cortex causes decreased cortisol production and aldosterone deficiency
Clinical features of addisons disease
Tanned Tired Weight loss Dizziness Low BP Suspect addisons in all with unexplained abdominal pain or vomiting
Diagnosis of addisons disease
Suspicious biochemistry
- decreased sodium and increase potassium
-hypoglycaemia due to decreased cortisol
Short synACTHen test
“if you think a gland is deficient you stimulate it”
- measure plasma cortisol before and 30 minutes after an IV injection of ACTH
- cortisol normally would increase in addisons there is no increase
ACTH levels
- should be increased
- causes skin pigmentation
- High ACTH levels POMC also produces melanin
Treatment for addisons disease
Do not delay treatment to confirm diagnosis
- hydrocortisone as cortisol replacement (15-25mg in 2-3 doses)
- If unwell then IV first, then tablets, try to mimic diurnal variation “twice daily, higher dose in the morning, smaller dose in the afternoon”
- fludrocortisone as aldosterone replacement (50-200ug PO)
What do patients need to know about steroid replacement
- Sick day rules “double your dose” in febrile illness, stress or injury
- Prescribing doctors/dentists/surgeons must now about steroid use (Need to wear identification e.g card and wrist band)
- Can’t stop steroids suddenly
- Add 5-10mg of hydrocortisone to daily intake before strenous activity/exercise
Exogenous steroid use causing secondary adrenal insufficiency mechanism
Exogenous steroids also feedback to the HPA axis and switch off own production of cortisol
Gradually wear of steroids to re sensitise the pituitary and adrenal cortex
Clinical features of exogenous steroid use
Similar to addisons except
- skin pale (no increased ACTH)
- aldosterone production intact (regulated by RAAS)
Treatment if exogenous steroid use
Treat with hydrocortisone as fludrocortisone (aldosterone replacement) is unnecessary
Definition of Cushings syndrome
Clinical state produced by chronic glucocorticoid excess + loss of the normal feedback mechanisms of the HPA axis and loss of circadian rhythm of cortisol secretion
Causes of Cushings
ACTH dependent causes: - Cushings disease (bilateral adrenal hyperplasia from an ACTH secreting tumour) - ectopic ACTH production - rarely - ectopic CRH production ACTH independent causes: - adrenal adenoma/cancer -adrenal nodular hyperplasia - iatrogenic -pharmacological doses of steroids
Symptoms of Cushings
- Weight gain
- Mood change (depression, lethargy, irritability
- Proximal weakness
- Gonadal dysfunction (irregular menses)
- Acne
Signs of Cushings
- Central obesity
- Plethoric, moon face
- Buffalo neck hump
- Supraclavicular fat distribution
- Skin and muscle atrophy
- Bruises easily
- Purple abdominal striae
- Osteoporosis
Diagnosis of Cushings
Step 1: Establish cortisol excess: “too much, so suppress” -Dexamethasone suppression testing -24 hour urinary free cortisol -Late night salivary cortisol
Step 2:
Establish source of cortisol excess:
- meausure ACTH
a) If normal or High then do a CRH stimulation test
ii. If no change in ACTH do a CT chest/abdo/pelvis (ectopic ACTH)
ii If exagerated rise in ACTH do a pituitary MRI (pituitary ACTH source)
b) If undetecable do an adrenal CT scan
Management of Cushings
Surgical
- transphenoidal pituitary surgery
- laparoscopic adrenalectomy- adrenal source
- removal of ACTH source
Medical
- Metyrapone/ketoconazole (inhibts cortisol production)
- short term measure
Iatrogenic Cushings syndrome mechanism
- commenest cause of cortisol excess
- prolonged steroid use
- chronic suppression of piuitary ACTH production and results in adrenal atrophy
Implications of cushings SYNDROME
- Unable to respond to stress
- need exra doses when ill/surgical procedure
- cannot stop suddenly
- gradual withdrawl of steroid therapy if>4-6 weeks
Definition of primary hyperaldosteronism
-Autonomous production of aldosterone independent of its regulators (angiotensin II/potassium) causes increased sodium and water retention
Causes of primary hyperaldosteronism
- Single aldosterone adrenal adenoma (Conn’s syndrome)40% or
- bilateral adrenalcorticol hyperplasia 60%
Clinical features of primary hyperaldosteronism
- Significant hypertension
- Hypokaelaemia (in up to 50%)
- Alkalosis (urinary secretion of H+)
Diagnosis of primary hyperaldosteronism
Think Conns if:
- Hypertension associated with hypokaelamia
- Refractory hypertension e.g despite >3 hypertensive drugs
- Hypertension occurring before 40 years of age
U&E’s ( for hypokaelamia, alkalosis)
Renin and aldosterone ration – best screening tool
- Before screening stop medications if possible (definitely stop beta blocker and MR antagonists)
- Elevated aldosterone and decreased renin
Saline suppression test (“if you think a gland is excessive then suppress it”)
o Volume expansion should suppress renin and aldosterone
o 2L saline over 4 hours
o 4h aldosterone >270pmol/l highly suspicious
o Aldosterone will still be high!!
CT or MRI of the adrenals to localise the cause
- If CT/ MRi shows a unilateral adenoma adrenal vein sampling from both adrenals. If one side shows >3 fold increase in aldosterone production and adenoma is likely and surgical excision is indicated
Management of Primary hyperaldosteronism
Surgical
- Unilateral laproscopic adrenalectomy
- Only if adrenal adenoma
- Cure of hypokalaemia
- Cures hypertension in 30-70% cases
Medical
- In bilateral adrenal hyperplasia
- Use MR antagonists (spironolactone or eplerenone- newer selective antagonist which doesn’t cause gynaecomastia)
- Or amiloride (blocks Na reabsorption by kidney)
Secondary hyperaldosteronism cause
Due to a high renin and high aldosteronism from decreased renal perfusion e.g renal artery stenosis, accelerated hypertension, diuretics or hepatic failure
Phaechromocytoma definition
Catecholamine secreting tumour of the adrenal medulla or extra-adrenal neural crest cells such as sympathetic ganglua (paraganglioma)
Causes of phaechromocytoma
Rule of tens
- 10% malignant
- 10% extra-adrenal
- 10% bilateral
- 10% familial - Von Hippel-Lindau syndrome, Men II, Neurofibromatosis I
Clinical features of pheochromocytoma
- Hypertension (intermittent in 50%, persists in 25%)
- Episodes of headache, palpitations, pallor and sweating
- THINK if pale AND sweaty as also vasoconstriction
- Also tremor, anxiety, nausea, vomiting, chest or abdo pain
- Crises last 15 minutes
- Often well in between crises
Diagnosis of Phaechromocytoma
- Measure 24 urinary catecholamines o At least twice - Plasma catecholamines o Only if high index of suspicion - Imaging o CT abdomen o MIBG scan (chromaffin seeking analogue) –uptake scan
Management of phaechromocyoma
- Pre-operative treatment “patient prepped for surgery then surgeon handles pheo then catecholamines bind to receptors and patient dies” therefore:
- Alpha-blockade
- Phenoxygenzaine or doxazosin
Adrenal incidentaloma definition
True incidentaloma is an incidentally detected lesion with no pathophysiological significance, and needs to be differentiated from incidentally detect but clinically relevant masses
Importance of incidentaloma
Important to determine whether the incidentally discovered adrenal mass is:
- malignant
- functioning and associated with excess hormonal secretion
Differential diagnosis of incidentaloma
- cortisol secreting adrenal adenoma (cushings)
- mineralocorticoid-secreting adrenal adeoma
- androgen secreting adenoma
- CAH
Investigations of adrenal incidentaloma
- Clinical assessment for symptoms and signs of excess hormone secretion
- urinary free cortisol and overnight dexamethasone suppresion
- urinary free catecholamines
- aldosterone/renin ratio
Management of incidentaloma
- up to 20% may develop hormonal excess during follow up
- unlikely if 4cm (likely malignant)
- imaging features suggestive of malignancy (lack of clearly defined borders)
Non surgical
- repeat MRI at 6 and 12 months
- repeat biochemical screening annualy
