HPA Flashcards
Hormones released by anterior pituitary
Thyroid Stimulating Hormone (TSH) Adrenocorticotropic Hormone (ACTH) Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH) Growth Hormone (GH) Prolactin
Hormones released by posterior pituitary
Oxytocin
ADH
How does the thyroid axis function
Hypothalamus releases thyrotropin-releasing hormone (TRH).
This stimulates the anterior pituitary to release thyroid stimulating hormone (TSH).
This in turn stimulates the thyroid gland to release triiodothyronine (T3) and thyroxine (T4).
What is cortisol released by
Secreted by the two adrenal glands, which sit above each kidney. The release of cortisol is controlled by the hypothalamus.
Pattern of cortisol release
Released in pulses and in response to a stressful stimulus
Diurnal variation
How does hypothalamus control cortisol release
Hypothalamus –> CRH –> Anterior pituitary –> ACTH –> Cortisol
Actions of cortisol within the body
Inhibits the immune system Inhibits bone formation Raises blood glucose Increases metabolism Increases alertness
How does the hypothalamus control release of growth hormone
GHRH is released from hypothalamus which stimulates growth hormone release from anterior pituitary
Growth hormone stimulates release of insulin-like growth factor 1(IGF-1) from liver
Effects of growth hormone
Stimulates muscle growth
Increases bone density and strength
Stimulates cell regeneration and reproduction
Stimulates growth of internal organs
What is parathyroid hormone released in response to
Low serum calcium
Also released in response to low magnesium and high serum phosphate
Action of PTH
Increases the activity and number of osteoclasts in bone, causing reabsorption of calcium from the bone into the blood thereby increasing serum calcium concentration.
PTH also stimulates an increase in calcium reabsorption in the kidneys meaning that less calcium is excreted in the urine.
Also stimulates the kidneys to convert vitamin D3 into calcitriol, which is the active form of vitamin D that promotes calcium absorption from food in the small intestine.
Where is renin secreted
Renin is a hormone secreted by the juxtaglomerular cells that sit in the afferent (and some in the efferent) arterioles in the kidney.
What causes secretion of renin
JG cells sense low blood pressure and secrete more renin
Renin is an enzyme that acts to convert angiotensinogen (released by the liver) into angiotensin I. Angiotensin I converts to angiotensin II in the lungs with the help of an enzyme called angiotensin-converting enzyme (ACE).
Angiotensin II acts on blood vessels to cause vasoconstriction. This results in an increase in blood pressure. Angiotensin II also stimulates the release of aldosterone from the adrenal glands.
What is aldosterone
Mineralocorticoid steroid hormone
actions of aldosterone
Increase sodium reabsorption from the distal tubule
Increase potassium secretion from the distal tubule
Increase hydrogen secretion from the collecting ducts
What is cushing’s syndrome
Used to refer to signs and symptoms that develop after prolonged abnormal elevation of cortisol
What is cushing’s disease
Refers to the specific condition where a pituitary adenoma (tumour) secretes excessive ACTH. Cushing’s Disease causes a Cushing’s syndrome, but Cushing’s Syndrome is not always caused by Cushing’s Disease.
Physical features of Cushing’s syndrome
Round “moon” face Central Obesity Abdominal striae Buffalo Hump (fat pad on upper back) Proximal limb muscle wasting
Effects of cushing’s syndrome due to high levels of stress hormone
Hypertension Cardiac hypertrophy Hyperglycaemia (Type 2 Diabetes) Depression Insomnia
Osteoporosis
Easy bruising and poor skin healing
Causes of cushing’s syndrome
Exogenous steroids (in patients on long term high dose steroid medications)
Cushing’s Disease (a pituitary adenoma releasing excessive ACTH)
Adrenal Adenoma (a hormone secreting adrenal tumour)
Paraneoplastic Cushing’s
What is paraneoplastic cushing’s
Is when excess ACTH is released from a cancer (not of the pituitary) and stimulates excessive cortisol release. ACTH from somewhere other than the pituitary is called “ectopic ACTH”.
Small Cell Lung Cancer is the most common cause of paraneoplastic Cushing’s.
IX of choice for diagnosing Cushing’s syndrome
Dexamethasone suppression test
Involves initially giving the patient the “low dose” test. If the low dose test is normal, Cushing’s can be excluded. If the low dose test is abnormal, then a high dose test is performed to differentiate between the underlying causes.
How is the dexamethasone suppression test carried out
To perform the test the patient takes a dose of dexamethasone (a synthetic glucocorticoid steroid) at night (i.e. 10pm) and their cortisol and ACTH is measured in the morning (i.e. 9am). The intention is to find out whether the dexamethasone suppresses their normal morning spike of cortisol.
Cortisol and ACTH findings after DST in pituitary adenoma
Cortisol not suppressed by low doses but is suppressed by high doses
ACTH normal to elevated
Cortisol and ACTH findings after DST in adrenal adenoma
Cortisol not suppressed buy low or high doses
ACTH undetectable or low
Cortisol and ACTH findings after DST in ectopic ACTH
Cortisol not suppressed by high or low doses
ACTH elevated
Alternative to DST for diagnosis of Cushing’s syndrome
24 hour urinary free cortisol
Management of Cushing’s syndrome
Trans-sphenoidal (through the nose) removal of pituitary adenoma
Surgical removal of adrenal tumour
Surgical removal of tumour producing ectopic ACTH
What does Addison’s disease refer to
Refers to the specific condition where the adrenal glands have been damaged, resulting in a reduction in the secretion of cortisol and aldosterone. This is also called Primary Adrenal Insufficiency.
Most common cause of primary adrenal insufficiency
The most common cause is autoimmune.
What is secondary adrenal insufficiency due to
inadequate ACTH stimulating the adrenal glands, resulting in low cortisol release. This is the result of loss or damage to the pituitary gland.
What can cause secondary adrenal insufficiency
Can be due to surgery to remove a pituitary tumour, infection, loss of blood flow or radiotherapy. There is also a condition called Sheehan’s syndrome where massive blood loss during childbirth leads to pituitary gland necrosis.
What is tertiary adrenal insufficiency and what is usually due to
result of inadequate CRH release by the hypothalamus. This is usually the result of patients being on long term oral steroids (for more than 3 weeks) causing suppression of the hypothalamus.
When the exogenous steroids are suddenly withdrawn the hypothalamus does not “wake up” fast enough and endogenous steroids are not adequately produced. Therefore long term steroids should be tapered slowly to allow time for the adrenal axis to regain normal function.
Symptoms of adrenal insufficiency
Fatigue Nausea Cramps Abdominal pain Reduced libido
Signs of adrenal insufficiency
Bronze hyper pigmentation to skin
(ACTH stimulates melanocytes to produce melanin)
Hypotension (particularly postural hypotension)
IX for adrenal insufficiency
Short synacthen test Hyponatraemia Hyperkalaemia Early morning cortisol ACTH Adrenal autoantibodies CT/MRI
ACTH in primary adrenal failure
In primary adrenal failure the ACTH level is high as the pituitary is trying very hard to stimulate the adrenal glands without any negative feedback in the absence of cortisol.
ACTH in secondary adrenal failure
ACTH level is low as the reason the adrenal glands are not producing cortisol is that they are not being stimulated by ACTH.
Which antibodies may be present in autoimmune adrenal insufficiency
adrenal cortex antibodies and 21-hydroxylase antibodies
Purpose of long synacthen test
used to distinguish between primary adrenal insufficiency and adrenal atrophy secondary to prolonged under stimulation in secondary adrenal insufficiency
In primary adrenal failure there is no cortisol response as the adrenals no longer function.
In adrenal atrophy (secondary adrenal insufficiency), the prolonged ACTH eventually gets the adrenals going again and cortisol rises.
Now we can simply measure ACTH and this indicates the underlying cause.
Treatment of adrenal insufficiency
Hydrocortisone to replace cortisol as it is a glucocorticoid hormone
Fludrocortisone is a mineralocorticoid used to replace aldosterone if insufficient
Patients given steroid card and emergency ID tag
What does addisonian crisis refer to
acute presentation of severe Addisons, where the absence of steroid hormones leads to a life threatening presentation.
Features of addisonian crisis
Reduced consciousness
Hypotension
Hypoglycaemia, hyponatraemia, hyperkaemia
What can trigger addisonian crisis
Triggered by infection, trauma or other acute illness in someone with established Addisons.
It can present in someone on long term steroids suddenly withdrawing those steroids.
Management of addisonian crisis
Intensive monitoring if unwell
Parenteral steroids (i.e. IV hydrocortisone 100mg stat then 100mg every 6 hours)
IV fluid resuscitation
Correct hypoglycaemia
Careful monitoring of electrolytes and fluid balance
VBG abnormality seen in cushion’s
Hypokalaemic metabolic alkalosis - due to excess aldosterone which increases acid and potassium excretion in the kidney
Also impaired glucose tolerance
Ectopic ACTH secretion is characteristically associated with very low potassium levels
How can pituitary and ectopic ACTH secretion be differentiated
Petrosal sinus sampling of ACTH
How can true cushing’s and pseudo-cushing’s be differentiated
Insulin stress test
Which cells produce adrenaline
Chromaffin cells in the adrenal medulla
What is a phaechromocytoma
phaeochromocytoma is a tumour of the chromaffin cells that secretes unregulated and excessive amounts of adrenaline.
In patients with a phaeochromocytoma the adrenaline tends to be secreted in bursts giving periods of worse symptoms followed by more settled periods.
Aetiology of phaechromocytoma
25% are familial and associated with multiple endocrine neoplasia type 2 (MEN 2).
There is a 10% rule to describe the patterns of tumour:
10% bilateral
10% cancerous
10% outside the adrenal gland
Diagnosis of phaeochromocytoma
24 hour urine catecholamines
Plasma free metanephrines
Presentation of pheochromocytoma
Anxiety Sweating Headache Hypertension Palpitations, tachycardia and paroxysmal atrial fibrillation
Mx of pheochromocytoma
Alpha blockers (i.e. phenoxybenzamine) Beta blockers once established on alpha blockers Adrenalectomy to remove tumour is the definitive management
Patients should have symptoms controlled medically prior to surgery to reduce the risk of the anaesthetic and surgery.
Classification of pituitary adenomas
size (a microadenoma is <1cm and a macroadenoma is >1cm)
hormonal status (a secretory/functioning adenoma produces and excess of a particular hormone and a non-secretory/functioning adenoma does not produce a hormone to excess)
Most common type of pituitary adenomas
Prolactinomas
Symptoms of pituitary adenomas
Dependent on excess/depletion of hormone
Stretching of the dura within/around pituitary fossa(causing headaches)
Compression of the optic chasm(bitemporal hemianopia)
Mx of pituitary tumours
hormonal therapy (e.g. bromocriptine is the first line treatment for prolactinomas)
surgery (e.g. transsphenoidal transnasal hypophysectomy)
e.g. if progression in size
radiotherapy
What is nelson’s syndrome
Nelson’s syndrome occurs due to rapid enlargement of a pituitary corticotroph adenoma (ACTH producing adenoma) that occurs after the removal of both adrenal glands (bilateral adrenalectomy) which is an operation used for Cushing’s syndrome
What is conn’s syndrome
Primary hyperaldosteronism - bilateral idiopathic adrenal hyperplasia or adrenal adenoma
Features of conn’s syndrome
hypertension hypokalaemia e.g. muscle weakness this is a classical feature in exams alkalosis
IX for conn’s syndrome
plasma aldosterone/renin ratio is the first-line investigation in suspected primary hyperaldosteronism
HRCT abdo and adrenal vein sampling to differentiate between unilateral and a bilateral sources
Mx of conn’s syndrome
adrenal adenoma: surgery
bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone
Mx of hirsutism
Weight loss
Cosmetic techniques
COCP
Eflornithine for facial hirsutism
