Lecture 12- Adrenal Disorders Flashcards
What are the 3 diff. zones of the adrenal glands and one example of the hormones it secretes?
(Go Find Racks, Makes Good Sex)
- Zona Glomerulosa: Mineralocorticoids (aldosterone)
- Zona Fasiculata: Glucocorticoids (cortisol)
- Zona Reticularis: Androgen (Sex hormones)
What is the adrenal gland seperated into?
- Cortex (all the zonas)
- Medulla (chromaffin cells that secrete adrenaline + noradrenaline)
What type of hormone is cortisol?
- Lipid sol, synthesised from cholesterol
How does corticosteroids affect target tissues?
- Readily diffuse across plasma membrane
- Bind to glucocorticoid receptor
- Causes dissociation of chaperone proteins
- Receptor ligand complex translocates to nuclues
- Bind with transcription factors / glucocorticoid response elements (GREs)
What type of hormone is aldosterone?
- Lipid sol.
- Mineralcorticoid, zona glomerulosa
How is aldo. transported?
- Mainly serum albumin
- Transcortin
What is the function of aldo.?
- Increases expression of Na/K+ pump
- Increases H2O + Na+ resabsorption & K+ secretion
- Increases BP + blood vol
When is renin released from the kidney? And what is it’s function?
- Released during hypotension or hypovolaemia (low blood vol)
Angiotensinogen (liver) –> angiotensin l –> angiotensin ll –> aldosterone/ADH
- Angiotensinogen cleaved by renin
What does angiotensinll (active form) cause?
- Vasoconstriction (increase BP)
- Secretion of aldosterone (increases expression of Na+/K+ pump, increase reabsorption of H2O and Na)
- ADH from PP (translocation of aquaporins, reabsorption)
What is the function of ACE inhibitors?
- Antihypertensive drugs
- Prevent ACE converting angiotensin l to ll
What is the diff. btw primary & secondary hyperaldosteronism?
- Primary:
(i) Defect in adrenal cortex
(ii) Bilateral idiopathic adrenal hyperplasia
(iii) Adrenal adenoma (Conn’s syndrome) - Secondary:
(i) Overactivity of RAAS
(ii) Renin producing tumour (rare)
(iii) Renal artery stenosis (no blood supply to kidney)
How do diff. btw 1 and 2 hyperaldosteronism?
1 (defect in adrenal cortex) has low renin, 2 (due to hyperactivity of RAAS) has high renin
Signs of hyperaldosteronism
- High BP
- Left ventricular hypertrophy
- Stroke
- Hypernatraemia (Na)
- Hypokalaemia (K)
Treatment of hyperaldosteronism
- Depends on type
- Surgically remove aldosterone secreting adenoma
- Spironolactone (mineralcorticoid receptor antagonist)
Function of cortisol
- Increase proteolysis, lipolysis and gluconeogensis
- Response to stress
- Anti-inflammatory effects
Desc the hypothalamic-pituitary-adrenal axis
CRH, Corticotropic Releasing Hormone (Hypothalamus) –> ACTH, Adrenocorticotropic Hormone (AP) –> Cortisol (Adrenal) –> Tissues
What is the effect of cortisol on metabolism?
- Increases gluconeogenesis, lipolysis and proteolysis
- Causes redistribution of fat
- Causes lipogenesis
- Inhibits insulin-induced GLUT 4 translocation in muscle (prevent glucose uptake glucose sparing effect)
What is Cushing’s syndrome? And what are its causes?
- Excessive cortisol
- Caused by exo factors (prescribed meds) or endo
- Endo:
(i) Pituitary adenoma secrete ACTH (Cushing’s disease)
(ii) Adrenal tumour secrete excess cortisol (adrenal cushing’s)
(iii) Non pituitary-adrenal tumours producing ACTH (small cell lung cancer) *very rare
Signs and symptoms of Cushing’s syndrome
- Plethoric (red) moon-shaped face
- Buffalo hump
- Abdominal obesity
- Purple striae
- Thin extremities
- Hyperglycaemia
- Hypertension
Give some examples of steroid drugs and their functions?
- Prednisolone, Dexamethasone
- Anti-inflammatory & immunomodulatory effects
- Treat:
(i) Asthma
(ii) Rheumatoid arthritis
(iii) Inflammatory bowel disease
Why should steroid drugs be reduced gradually & not stopped suddenly?
- Stopped sudd will induce Addisonian Crisis
What is Addison’s disease?
- Chronic adrenal insufficiency
- Used to be TB complication, now is autoimmune response
Signs & symptoms of Addison’s disease.
- Hypotension
- Increased skin pigmentation
- Lethargy
- Weight loss
- Anorexia
Explain why does hyperpigmentation occur in Addison’s disease?
- Decreased cortisol stimulates cleaving of POMC to form ACTH & aMSH
- Activates melanocytes to form more melanin (hyperpigmentation)
What is Addisonian Crisis?
- Life threatening med. emergency due to adrenal insufficiency
What are the symptoms & treatment of Addisonian Crisis?
- S: Nausea, vomitting, pyrexia, vascular collapse, hypotension
- T: Fluid replacement, Steroid hormone therapy
What is Addisonian Crisis caused by?
- Severe stress
- Salt depravation
- Infection
- Abrupt steroid drug withdrawal
Function of androgen
- Promote secondary sexual characteristics in male n female
- Converted to testosterone & oestrogen
Tests to diagnose Cushing Syndrome?
- Measure free cortisol: 24 hr urine sample
- Dexamethasone suppression test: low dose of D given, should decrease cortisol if normal
- Check plasma ACTH levels: Low (adrenal carcinoma/adenoma), High: Cushing disease/ectopic production
- Imaging
Treatment of Cushing
- Exo: gradually decrease drug
- Pituitary adenoma: surgical exicision
- Adrenal carcinoma/ectopic ACTH: adrenal steroid inhibitors
What enzyme catalyses conversion of noradrenaline to adrenaline?
Methyl Transferase
Which diagnostic test would typically be used to confirm Addison’s disease?
Short Synacthen test:
- Synacthen is a synthetic ACTH analogue used to test adrenal function. The administration of Synacthen intramuscularly, would increase plasma cortisol by >200 nmol/L in a normal patient.
- As steroid deficiency needs long-term (often lifelong) treatment, a Synacthen test is typically used to make a definitive diagnosis of Addison’s.
A 26 year old woman is diagnosed with iatrogenic Addison’s disease.
What could have caused this disease in this patient?
- Adrenalectomy (removal of 1 or 2 adrenal glands)
- Iatrogenic= caused by med. treatment
Investigations show a patient has an elevated ACTH and a high cortisol, neither of which are suppressed by high dose dexamethasone.
What condition is this patient most likely suffering from and why?
- Ectopic ACTH syndrome
- Production of ACTH by the cancer cells cannot be supressed by a high dose dexamethasone test so ACTH and cortisol remain high.
- Very rare
At what time of the day should cortisol levels be measured for a patient that is suspected of Cushing’s Syndrome?
- Midnight. Cortisol is at its lowest
N.B Addison’s 9am, cortisol highest
Why for a patient with Cushing’s giving them low dose dexamethasone at 12am X lower ACTH/cortisol levels?
- Both ACTH and cortisol would be high in a midnight blood sample (you would expect cortisol to be at its lowest at midnight due to diurnal rythmn).
- A low dose dexamethasone supression test would not be sufficient to decrease ACTH or cortisol in Cushing’s disease but a higher dose would be enough to supress ACTH from the pituitary adenoma so you would see both cortisol and ACTH suppressed in the high dose test with Cushing’s disease.
What is phaeochromocytoma?
- A rare tumour of chromaffin cells in the adrenal medulla that results in increased secretion of adrenaline and noradrenaline
Symptoms of pheochromocytoma
- headaches, palpitations, diaphoresis, anxiety and weight loss
What is the best method of diagnosis of phaeochromocytoma?
measurement of urine metanephrine
What is the percentage of saline for rehydration?
- 0.9%
What is symptoms of Addison’s disease?
- Fatigue
- Weakness
- Anorexia
- Weight loss
- Dizziness
- Skin pigmentation
What is signs of Addison’s disease?
- Underweight
- Vitiligo
- Hypotension
- Skin pigmentation
What are some causes of primary adrenal failure?
- Auto-immune disease
- Infection (TB, AIDS)
- Malignancy
- Genetic
- Iatrogenic (drugs, adrenalectomy)
What are clinical features and treatment of Addisonian Crisis?
- Collapse
- Hypotension
- Dehydration
- Pigmentation
- Coma
- Treatment: Rapid rehydration with fluids, intravenous hydrocortisone, correction of hypoglycaemia
What is maintanence treatment of Addison’s disease?
- Lifelong treatment of glucocorticoid (hydrocortisone, prednisolone) and mineralocorticoid (fludrocortisone)
- Education to prevent crises
(Steroid card and bracelet, double dose glucocorticoid in times of illness)
What and when does ACTH deficiency cause/occur?
- Occurs in hypopituitarism
- No pigmentation = ACTH X increase
- No hyperkalaemia
- Hyponatraemia = cortisol ⬆️
What is primary aldosteronism associated with and what confirms it?
- Hypertension and hypokalemia
- Confirmed with high aldosterone and suppressed renin
What does Congenital Adrenal Hyperplasia (CAH) result in and what is it caused by?
- Caused by block in adrenal cortex pathway: presentation depends on enzyme defect
- Cause adrenal defect and ambiguous genitalia
- Autosomal recessive
- Results in: Low cortisol and aldosterone
How is congenital adrenal hyperplasia treated and presented in clinic?
- Presentation:
(i) Hypotension
(ii) Hyponatraemia
(iii) Hyperkalaemia
(iv) Hypoglycaemia - Treatment:
(i) Treat adrenal crisis
(ii) Long term GC and MC
(iii) Corrective surgery
