Adrenocorticotropic hormone Flashcards
How is ACTH hormone released? (5)
- Hypothalamus - releases Corticotropic releasing hormone
- Anterior pituitary gland - ACTH release into blood stream
- Adrenal cortex (zone fasciculata) - ACTH bind to adrencortical cells stimulates increase in cortisol level
- High cortisol level inhibits hypothalamic release of CRH
- Reduced CRH decreases ACTH
Which other cells have ACTH receptors?
Melanocytes - also have ACTH receptors and cause hyperpigmentation
What is cushing’s syndrome vs cushing’s disease?
Cushing’s syndrome : disease caused by excess secretion of glucocorticoids from the adrenal cortex
Cushing’s disease : Excess cortisol secondary to pituitary adenoma releasing ACTH which stimulates adrenal cortisol release
Which hormones are released by the Adrenal Cortex? (2)
- Mineralcorticosteroids : Aldosterone
- Glucocorticoids : Cortisol
What is the function of Aldosterone hormone? (3)
- acts on kidneys to provide active reabsorption of sodium
- active secretion of potassium
- in the principle cell of the collecting tubules
What are the primary causes of Cushing’s syndrome? (2)
- Endogenous
- Tumor/adenocarcinoma in adrenal gland secretes cortisol - Exogenous -
- Primary - Glucocorticoid steroid medication to treat inflammatory, autoimmune disorder
What are the secondary causes of Cushing’s syndrome? (3)
- Cushing’s disease - Pituitary adenoma - excess ACTH
- Ectopic ACTH - released from bronchial/lung paraneoplatic cancers
What are the 5 main clinical features of Cushing’s syndrome?
- Hyperglycaemia - Diabetes
cortisol stimulate gluconeogenesis which triggers beta cells - Central obesity, Buffalo hump, moon face, skin straie
* high glucose triggers beta cells of the pancreas to release insulin which triggers increase adipose tissue to accumulate - Sexual dysfunction - Amenorrhea
high cortisol inhibits gonadotropin release hormone which - Hypertension - high levels of corticosteroids reacting with mineralocorticoid receptors
- Immunosupression - Ulcers, infection
cortisol dampens inflammatory and immune response by inhibits cytokine and T cell activity - Osteoporosis
What are the common blood test results seen in Cushing’s syndrome? (3)
- Hypokalaemia
- Metabolic acidosis
AKA ‘Hypokalaemic metabolic alkalosis’ - Raised blood glucose
What is the first line test to confirm the diagnosis of Cushing’s syndrome?
Overnight (low-dose) dexamethasone suppression test
- Low dose dexamethsone given before bed
- Cortisol levels checked in the morning
- Low : normal
cortisol levels should be supressed in response to Dex. - High : Abnormal
Lack of Cortisol supression - Adrenal glands continue to produce cortisol
What is the first line localisation test for Cushing’s syndrome
- What is used for?
- 9am and midnight plasma ACTH (and cortisol) levels
* Assess function of the hypothalamic-pituitary-adrenal (HPA) axis. -
9 a.m. Plasma ACTH and Cortisol Test:
* Cortisol levels expected to be at their highest in the morning
* If ACTH is supressed - then non ACTH dependant cause such as adrenal adenoma -
Midnight Plasma ACTH and Cortisol
* Cortisol expected to be at its lowest
What is the test used to localise pathology of Cushing’s syndrome?
high-dose dexamethasone suppression
used to identify whether excessive cortisol production is due to
* an adrenal tumor (ACTH-independent)
* overactive pituitary gland producing excess ACTH (ACTH-dependent).
Describe and explain the steps in the ‘High dose - dexamethasone test’
- Dexamethosone is administered to suppress ACTH production in the pituitary gland - normally this should decrease in serum cortisol levels
- Cortisol and ACTH levels are checked
Interpret results of Dexamethasone supression test;
Cortisol : not supression
ACTH : Supression
Adrenal adenomas producing Cortisol
Interpret results of Dexamethasone supression test;
Cortisol : Supression
ACTH : Supression
Cushing’s disease (i.e. pituitary adenoma → ACTH secretion)
Interpret results of Dexamethasone supression test;
Cortisol : Raised
ACTH : Raised
Ectopic ACTH syndrome
What are the different causes of ‘Cushing’s syndrome’?
- iatrogenic: corticosteroid therapy
- ACTH-dependent causes
* Cushing’s disease (a pituitary adenoma → ACTH secretion)
* ectopic ACTH secretion secondary to a malignancy - ACTH-independent causes
adrenal adenoma
What is the definition of ‘Adrenal insufficiency’
- Endocrine disorder characterised by primary adrenal insufficiency due to bilateral adrenal cortex destruction
- Reduced production of glucocorticoids, mineralcorrticoids, androgen deficiency - adrenals are the only source of androgens in female
Addision’sdisease : Autoimmune destruction of the adrenal glands is the most common cause of primary hypoadrenalism
reduced cortisol and aldosterone being produced.
Other causes of adrenal insufficiency
Primary causes
tuberculosis
metastases (e.g. bronchial carcinoma)
meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
HIV
antiphospholipid syndrome
Where is aldosterone produced?
A mineralcorticoid hormone produced in the zona glomerulosa of the adrenal cortex
What is the function of the Adrenal cortex?
-
Zona Glomerulosa:
* Produces mineralocorticoids, primarily aldosterone,
* MOA : regulates electrolyte balance, sodium retention, and potassium excretion in the kidneys.
2 . Zona Fasciculata:
* Produces glucocorticoids, primarily cortisol.
MOA : Cortisol is involved in the regulation of metabolism, immune response, and the body’s response to stress.
3 . Zona Reticularis:
* Produces androgens, including dehydroepiandrosterone (DHEA) and androstenedione.
Contributing to the development of secondary sexual characteristics and influencing sexual function.
What are the causes of Adrenal Insufficiency?
- Autoimmune destruction - Addison’s disease
- Infection - tuberculosis
- Adrenal haemorrhage - WFS
What are the clinical features of Adrenal Insufficiency? (4)
Fatigue, weakness, weightloss
- Low cortisol levels -
Hypotension - low vascular responsiveness to angiotensin II and norepinephrine
Hypoglycaemia - reduced gluconeogenesis - Low aldosterone levels -
Hyponatremia and excess thirst - due to increased excretion of sodium, excess water loss
Hyperkalaemia - Low androgen levels - low libido, low pubic/axillary hair in females
- High ACTH levels
Hyperpigmentation - due to ACTH stimulation of melanocyte activity
What are the investigations of adrenal insufficiency? (2)
- Short syacthen test(ACTH stimulation test) - plasma cortisol is measured before and 30 mins after giving synacthen 250ug IM
9 am serum cortisol can be useful:
> 500 nmol/l makes Addison’s very unlikely
< 100 nmol/l is definitely abnormal
100-500 nmol/l s
What are the blood test results for Adrenal insufficiency? (2)
- Lab results -
* low serum cortisol (100-500 - consider short synacthen test)
* raised serum ACTH
* raise plasma renin due to low aldosterone,
* Low Na+, raised K+
What is the management of Adrenal insufficiency?
- IV hydrocortisone and IV dextrose - no fludrocortisone required because high cortisol exerts weak mineralocorticoid action, carry on with oral replacement over 3-4 days
Longterm
1. Hydrocrotisone and Fludrocortisone PO - during illness double hydrocortisone dose
What is the definition of hyperaldosteronism?
Excess aldosterone - increased sodium and water retention - raised blood voume - raised BP
What are the causes of Hyperaldosteronism? (2)
Primary
* Con’s syndrome - Adrenal adenoma - excess aldosterone production- unilaterally
* Bilateral idiopathic adrenal hyperplasia - most common cause - bilaterally
Secondary
* Hypotension - activates RAAS - leading to hyperaldosteronisms
What are the clinical features of ‘Hyperaldosteronism’ (2)
- Hypertension (increases water retention) often treatment resistant - headaches, facial flushing
- Hypokalaemia - constipation, muscle weakness, arrhythmia
- Metabolic alkalosis
What is the first line investigation of Hyperaldosteronism?
First line
1. Plasma aldosterone/renin ratio - indicates primary hyperaldosteronism
* High aldosterone levels : low renin levels due to negative feedback due to sodium retention from aldosterone
What is the second investigation of Hyperaldosteronism?
Second line.
High resolution CT abdomen
What is the third line investigation of Hyperaldosteronism?
Adrenal venous sampling - used to distinguish between unilateral adenoma and bilateral hyperplasia.
What is the management of hyperaldosteronism?
Conn’s tumor - Adrenectomy
Bilateral adrenal hyperplasia - Spirnolactone
What is the mechanism of action of aldosterone?
- Aldosterone acts late distal tubule and collecting duct
- Acts on channels to favour;
- Sodium and thus water reasborption
- Potassium excretion
Which channels does Aldosterone influence in the kidneys?
Within the late distal tubule and collecting duct, Aldosterone acts upon
- Sodium channels
- N+/K+ exchange pumps
- H+ ion atpases
- Bicarbonate-Chloride transporters
State the ways in which Aldosterone impacts electrolyte balance in the body?
- Increases sodium reabsorption
- Increases water retention
- K+ and H+ ion excretion
- HCO3- excretion and Cl- reabsorption
Describe the steps which lead to Aldosterone release?
(4)
- Low BP
- Renin is released from the juxtaglomerular cells of the kidneys
- Angiotensin cleaving enzyme
- Converts Angiotensinogen into Angiotensin I - Angiotensin converting enzyme from the lungs;
- Converts Angiotensin 1 into Angiotensin 2
—> Triggers Aldosterone release
What is the management of Hyperaldosteronism?
- Laparoscopic adrenalectomy of adrenal ademona
- Spirnalactone - aldosterone antagonist
What is the steroid activity of : Fludrocortisone
mineralocorticoid activity
What is the steroid activity of : Hydrocortisone
glucocorticoid and high mineralocorticoid activity
What is the steroid activity of : Prednisolone
predominant glucocorticoid activity, low mineralocorticoid activity
What is the steroid activity of : Dexamethasone
very high glucocorticoid activity
What are the main side effects of long term steroid use? (4)
- Endocrine - impaired glucose regulation, increased appetite, hypertipidaemia, hirsuitisim
- MSK - osteoporosis, avascular necrosis of the femoral head
- Immunosupression
- Psychiatric - isomnia, mania, depression
GI - peptic ulceration, acute pancreatitis
Adrenal medulla : Function
Anatomy : Chromaffin Cells:
* The adrenal medulla contains chromaffin cells, which are modified sympathetic nervous system neurons.
Function
1. Release of Catecholamines:
The adrenal medulla releases catecholamines, primarily epinephrine (adrenaline) and norepinephrine (noradrenaline), into the bloodstream in response to stress or the “fight or flight” response.
Phaeochromocytoma : Associations
Phaeochromocytoma is a rare catecholamine secreting tumour
develops in the adrenal glands, which are located on top of each kidney. These tumors arise from chromaffin cells and produce excess catecholamines, such as adrenaline and noradrenaline
MEN type II, neurofibromatosis and von Hippel-Lindau syndrome.
Phaeochromocytoma : Clinical features
Features are typically episodic
* hypertension (around 90% of cases, may be sustained)
* headaches
* palpitations
* sweating
* anxiety
Phaeochromocytoma : Investigations
24 hr urinary collection of metanephrines
Phaeochromocytoma : Mx
- Initial medical mx
- alpha-blocker (e.g. phenoxybenzamine), given before a
beta-blocker (e.g. propranolol) - Surgery is definitive mx
