L20: Adrenal disorders

Question 1

What is the clinical presentation of cortisol deficiency?

Answer 1

Weakness, tiredness, weight loss, hypoglycaemic, nausea

Question 2

What is the clinical presentation of mineralocorticoid deficiency?

Answer 2

Dizziness, low Na and high K, hypotension

Question 3

What is the clinical presentation of androgen deficiency?

Answer 3

Mostly testosterone
No symptoms in men as not major testoterone producing organ
Women–> Hair loss, loss of libido

Question 4

What is the clinical presentation of cortisol excess?

Answer 4

Weight gain

Features of Cushing syndrome

Question 5

What is the clinical presentation of mineralocorticoid excess?

Answer 5

High BP and low K+

Question 6

What is the clinical presentation of ACTH excess from pituitary?

Answer 6

Skin pigmentation–> Melanocyte stimulaton

Question 7

What is the clinical presentation of adrenal medulla disease?

Answer 7

Excess adrenaline and NA
Acute episodes
Sweating
Anxiety 
Palpitations
High or low BP
Collapse
Can lead to sudden death

Question 8

What biochemical assessment (tests) would you do for suspected adrenal hormone deficiency?

Answer 8

Electrolytes–> Na+ low, K+ high (low BP)
Basal cortisol (0900)–> low (should be high)
Stimulation test–> Inject synthestic ATCH (synatchen)–> see if cortisol levels increase

Question 9

What biochemical assessment (tests) would you do for suspected adrenal hormone excess?

Answer 9

Electrolytes–> Na+ high, K+ low (high BP)
Midnight cortisol–> high (should be low)
24hr urine–> cortisol high
Suppression test–> failure to suppress cortisol
Androgens and derivatives high

Question 10

What biochemical assessment (tests) would you do for the adrenal medualla?

Answer 10

24hr urine catecholamines –> adrenaline, NA, dopamine, 3-Methoxy-Tyramine
24hr urine metanephrines–> metabolites of adrenaline and NA–> metadrenaline and normetadrenaline
Plasma metanephrines–> more sensitive than 24hr urine

Question 11

Before doing a biochemical assessment of adrenal medulla function what should be avoided?

Answer 11

Coffee, cake, bananas, chocolate and vanilla

Question 12

What is Cushing’s syndrome?

Answer 12

Excess secretion of cortisol caused by hyperactivity of the adrenal cortex

Question 13

What causes Cushing’s syndrome?

Answer 13

Adrenal adenoma–> tumour of the adrenal cortex
Pituitary adenoma–> Cushing’s disease–> tumour of the anterior pituitary–> increase ACTH secretion
Ectopic tumours secreting ACTH or CRH
Glucocorticoid treatment

Question 14

What are the signs and symptoms of excess cortisol?

Answer 14

1) Thin arms and legs and muscle weakness–> muscle proteolysis
2) Abdominal fat, dorso-cervical fat pad, moon shaped face–> increased lipogenesis
3) Purple striae–> lower abdomen, upper arms and thighs–> catabolic effects–> protein breakdown–> easy bruising due to thinning of skin and subcutaneous tissue
4) High blood pressure and diabetes
- -> hyperglycaemia–> increased muscle proteolysis and hepatic gluconeogenesis–> polyuria and polydipsia
- -> mineralocorticoid effect of excess cortisol–> increased sodium and fluid retention
5) Osteoporosis–> thin bones –> disturbance in calcium metabolism
6) Plethoric (flushed) face

Question 15

How is a suspected Cushing’s syndrome diagnosed?

Answer 15

Low dose dexamethasone test

Slight decrease in ACTH or Cortisol indicates Cushing’s syndrome

Question 16

How can you differentiate between the causes of Cushing’s syndrome?

Answer 16

ACTH test

• -> Supressed= adrenal adenoma or glucocorticoid treatment
• -> Elevated= Cushing disease (pituitary tumour) or ectopic tumour

Differentiate between ACTH supressed–> Are they on glucocorticoids? –> yes glucocorticoid fault, no then adrenal ademona

High dose Dexamethosome test

• -> ACTH (therefore cortisol) levels decreased –> Pituitary tumour (Cushing’s disease)–> relatively insensitive to cortisol but a huge amount will have an effect
• -> ACTH level remains the same–> Ectopic tumour

Question 17

How are adrenal adenomas treated?

Answer 17

Adrenalectomy Laproscopic ‘key hole surgery’

Question 18

What do we call the disease that cause primary hyperaldosteronism?

Answer 18

Conn’s syndrome–> aldosterone-secreting adrenal adenoma
OR
Bilateral (idiopathetic) adrenal hyperplasia–> no discrete adenoma, increase in cell number

Question 19

What does hyperaldosteronism lead to (signs and symptoms)?

Answer 19

Endocrine hypertension and hypokalaemia (low K+)
Elevated aldosterone despite the renin-angiotensin aldosterone system
Occasional muscular weakness and spasms
Tingling sensations
Excessive urination

(high BP, LV hypertrophy, stroke, hypernatraemia, hypokalaemia)

Question 20

How is primary hyperaldosteronism diagnosed?

Answer 20

Clinical suspicion
Increase aldosterone with decreased renin
Scan–> confirm adrenal adenoma or bilateral hyperplasia

Question 21

How does hyperaldosteronism lead to increased blood pressure?

Answer 21

Excess aldosterone
Increased Na+ reabsorption and K+ secretion
Increased blood volume and pressure
↑ BP–> increased renal perfusion–> ↓ renin
Normal ↓ renin–> ↓ aldosterone
However Conn’s syndrome–> ↑ aldosterone despite renin↓

Question 22

What is congenital adrenal hyperplasia (CAH)?

Answer 22

Inherited disorder–> autosomal recessive
Deficiency in enzyme needed to synthesis corticosteroids from cholesterol
Lack of cortisol–> no negative feedback so ↑ACTH secretion–> enlargement of adrenal cortex (hyperplasia)

Question 23

What is the most common enzyme deficiency in CAD? What does this deficiency result in?

Answer 23

Deficiency in 21-hydroxylase
Position means inhibits production of glucocorticoids and mineralocorticoid
No affect on adrogen synthesis
Therefore 17α hydroxylase precursor–> diverted to produce more androgens

Question 24

What does increased androgen production result in in CAH?

Answer 24

Genital ambiguity in female infants–> look like boys–> clitoromegaly
Salt wasting crises–> high rate of Na+ loss in urine
Hypotension, hyponatraemia, hyperkalaemia, hypoglycaemia and virilisation (male characterisitcs)

Question 25

How is CAH treated?

Answer 25

Long term glucocorticoids and mineralocorticoids
Determine sex of baby
Corrective surgery
Treat adrenal crisis

Question 26

What is Addison’s disease?

Answer 26

Chronic adrenal insufficiency
Decreased activity of the adrenal cortex
Leading to decrease glucocorticoids (cortisol), mineralocorticoids (aldosterone)

Question 27

What can cause Addison’s disease?

Answer 27

Auto immune destruction of adrenal cortex
Disorders of pituitary or hypothalamus–> decreased secretion of ACTH and CRF–> glucocorticoid secretion reduced
Infection
Infiltration
Malignancy
Genetic
Vascular
Iatrogenic –> caused by medical treatment

Question 28

What are the symptoms of Addison’s disease?

Answer 28

Fatigue
Weakness
Anorexia
Weight loss
Nausea
Abdominal pain 
Dizziness and pigmentation

(postural hypotension, lethargy, weight loss, anorexia, increased skin pigmentation, hypoglycaemia)

Question 29

What are the signs of Addison’s disease?

Answer 29

Underweight 
Signs of weight loss
General Malaise
Other autoimmune disease
--> Vitiligo
--> Thyroid
Postural hypotension 
Pigmentation

Question 30

What causes increased skin pigmentation?

Answer 30

Increase in ACTH from POMC and α-MSH and γ-MSH
Melanocyte stimulating hormone
Stimulate meloncytes to produce more melanin

Question 31

What is Addisonian crisis?

Answer 31

Clinical emergency of Addison’s disease
Caused by trauma, severe infections, abrupt withdrawal of steroids, salt deprevation, cold exposure, severe stress, over exertion
Leads to collapse, hypotension, dehydration, pigmentation and coma

Question 32

How is Addisonian crisis treated?

Answer 32

Rapid rehydration–> fluid replacement dextrose in normal saline
Intraventous hydrocortisone–> replace cortisol
Fludrocortisone –> aldosterone replacement

Question 33

What other adrenal insufficencies are there?

Answer 33

Secondary adrenal failure–> ACTH deficiency from hypopituitrism
Steroid-induced hypoadrenalism–> ACTH suppression

Question 34

How can steroid cause mineralocorticoid effects?

Answer 34

Steroid receptor–> nuclear DNA binding proteins
Three main domain–> DNA binding region rich in cysteine and basic AA, hydrophobic hormone-binding region and variable region
Hormone binding region sequence homology with mineralocorticoid receptor and androgens meaning excess cortisol will bind–> Na+ retention and water retention etc…

Question 35

What does excessive secretion of male androgens in females do?

Answer 35

Stimulate growth and development of male genital tract and male secondary characteristics (heigh, body shape, facial and body hair, muscle protein etc)
Over production in female–> male characteristics

Question 36

What does the female androgen oestrogen do?

Answer 36

Stimulate growth and development of female genital tract, breasts and female secondary characteristics
Fat in breast and buttocks, broad hips, body hair distribution
Weakly anabolic and decrease circulating cholesterol levels

Question 37

What is phaeochromocytoma?

Answer 37

Tumour of the adrenal medulla

Dusty, coloured, cell tumour

Question 38

What is paraganglioma?

Answer 38

Extra-adrenal tumour

Chromaffin tissue origin

Question 39

What are the symptoms associated with phaeochromocytoma and paraganglioma? What happens in acute crisis?

Answer 39

Acute episode
Sweating
Panic attacks 
Palpitations 
High or low BP
Collapse

(severe hypertension. headaches, palpitation, diaphoresis (excessive sweating), anxiety, weight loss, elevated blood glucose)

Acute crisis--> hypertensive crisis
Encephalopathy
Hyperglycaemia
Cardiac arrythmias
Sudden death

Question 40

How is phaeochromocytoma and paraganglioma managed?

Answer 40

Alpha blockade (phenoxybenzamine) and beta blockade (bisoprolol) and surgical incision 
Important to alpha blockade before beta blockade--> unapposed alpha stimulation--> hypertensive crisis

Question 41

What are the causes of phaeochromocytoma and paraganglioma?

Answer 41

Genetic causes

Especially if malignant, extra-adrenal and bilateral