Disorders of cortisol regulation

Question 1

Name the disease/s involved in Primary & secondary cause of hypocortisolism

Answer 1

1: Addison’s disease from Autoimmune, bacterial/Viral Infections, tumours (that affect the adrenal cortex)
2: Hypothalamic disease pituitary disease (other structures affected, not adrenal cortex)

Question 2

Briefly describe the pathophysiological process involved in Primary & secondary cause of hypocortisolism

Answer 2

1: Low cortisol => inc ACTH
2: Low ACTH => low cortisol

Question 3

Expected signs & symptoms involved in hypocortisolism

Answer 3

(aldosterone> reabsorb Na & release K & H)
• Lo aldosterone = Inc K+ (&H+), Dec Na+, pH & HCO3- [DC notes]
• Hypovolemic & Hypotension
• Hypoglycemia
• ACTH: Hi in 1º (Inc pigmentation)& Lo in 2º

Question 4

Laboratory investigation of hypocortisolism

Answer 4

1st collection: U/E, gkucose, plasma cortisol
Synacthen stimulation test > test responsiveness to adrenal glands (Synthetic ACTH)
2nd collection at 30 min
=> Normal: plasma cortisol inc by 200-500+ nmol/L

Question 5

Name the disease/s involved in Primary & secondary cause of hypercortisolism

Answer 5

1: Cushing’s syndrome from adrenal adenoma/carcinoma
2: Pituitary adenoma (=> Cushing’s disease)

Question 6

Briefly describe the pathophysiological process involved in Primary & secondary cause of hypercortisolism

Answer 6

1: Inc Cortisol => dec ACTH
2: Inc ACTH => inc cortisol

Question 7

Expected signs & symptoms involved in hypercortisolism

Answer 7

• Hi aldosterone = Lo K (& H), Hi Na, pH, HCO3
• Hypertension
• Hyperglycemia (diabetes)
• Hyperlipidemia
• Buffalo hump from fat distributed in back & torso

Question 8

Laboratory investigation of hypercortisolism

Answer 8

Low dose suppression test w/ Dexamethasone (synthetic glucocorticoid > suppress ACTH). Normal = Cortisol <190nmol/L
24hr Urinary Free cortisol. Normal = cortisol <300 nmol/24hr
*If ≥1 test not normal do further test

Question 9

Role of cortisol hormones

Answer 9

• Enhances Renin-angiotensin system (stimulates mineralcorticoid synthesis = aldosterone) so works closely w/ aldosterone
• Stimulates gluconeogenesis

Question 10

Pitfalls in interpretation of cortisol (4)

Answer 10

• Variability: e.g. single blood samples may be misleading
• Drug effects e.g. Oestrogens inc CBG (cortisol binding globulin)
• Stress: dexamethasone may not be able to supress inc cortisol (from the stress)
• Obesity bc dec resp. to dexamethasone

Question 11

What’s the Regulatory control mechanisms of cortisol

Answer 11

Hypothalamic pituitary Adrenal Axis: Cortisol => metabolic affects

Question 12

What may it mean if results ACTH doesn’t increase even after the suppression test?

Answer 12

atrophy can occur to receptors/signals in hypothalamus since they’ve been switched off for a long time

Question 13

Describe the regulation of cortisol

Answer 13

S: Low cortisol?
1.	Cortico Release Hormone (CRH) released by Hypothalamus
2.	Ant. Pituitary secrete ACTH
3.	Adrenal cortex release Cortisol
F: High cortisol = -ve FB to CRH & ACTH

Question 14

Give examples when CRH is strongly influenced in CNS (2-3) & overrides inhibitory influences of cortisol

Answer 14

• Stress
• Injury/trauma
  Hypoglycemia

Question 15

Methods for measuring cortisol

Answer 15

• Serum, Urine, Saliva samples: Immunoassay (competitive, heterogenous, chemiluminescence labels)
• Mass spectro

Question 16

Methods for measuring ACTH

Answer 16

Chemiluminescent (non-competitive sandwich, heterogenous assays)

Question 17

dexamehtasone is a synthetic ____

Answer 17

Glucocorticoid