Cushing’s syndrome & disease

Circadian rhythms & stress 🡪  CNS higher centres (NA, ACH, 5HT) 🡪 Hypothalamus (CRH) 🡪 Anterior pituitary (ACTH) 🡪 Adrenal cortex fasciculata (cortisol)

• Circadian rhythm – most secretion occurs in the morning & the secretion is PULSATILE. 
• Most at time of waking up (light stimulation & also stimulus of ‘waking up’). 
• Food intake also causes an increase, vigorous exercise, stress, etc

• Cushing syndrome =  set of symptoms that results when there is a surplus of cortisol in the body.
• Cushing disease = when Cushing syndrome is caused by an ACTH-producing pituitary tumor, 
• Exogenous Cushing’s syndrome (most common cause of Cushing’s syndrome)
  • Glucocorticoid treatment (eg for asthma, RA, SLE, etc)

• Endogenous Cushing’s Syndrome
  • Central Cause: ACTH-producing pituitary tumor = Cushing Disease
  • Adrenal Cause
    • Adrenal Adenoma
    • Adrenal Hyperplasia
    • Adrenal Malignancy (15%)
  • Ectopic Source
    • Malignancy (Small Cell Carcinoma of the lung: 15%)

Symptoms

• Mood changes (depression and euphoria)
• Easy Bruising
• Weakness
• Weight gain
• Amenorrhea
• Back pain

Clinical Features of Cushing’s Syndrome:

1. central obesity (94%)
2. Hypertension (82%)
3. glucose intolerance or DM
4. Hirsutism 
5. amenorrhoea or impotency in men (cortisol inhibits the HP-gonadal axis)
6. purple or dark striae
7. plethoric face (because cortisol ↑ RBC production + thin skin so see capillaries)
8. easy bruising (weak skin due to fibroblast inhibition)
9. osteoporosis
10. proximal myopathy – so get flattened buttocks (60%)
11. personality change (euphoria/ bipolar)   (55%)
12. acne (excess adrenal androgens DHEA from reticularis is concomitant usually) (50%)
13. oedema
14. headache
15. poor wound healing (cortisol inhibits the immune system & inhibits fibroblasts too)
16. polyuria, polydipsia (due to ↑ BGL)

• clinical manifestations of Cushing’s syndrome overlap with those of metabolic syndrome, including hypertension, obesity, diabetes, depression and menstrual irregularity. 
• Cushing’s syndrome presenting as hypertension is usually overt, with characteristic features such as proximal myopathy, truncal obesity including intrascapular (Buffalo hump) and supraclavicular fat pads, facial plethora and violaceous abdominal striae or easy bruising

DIAGNOSIS:

• overnight dexamethasone suppression test

• 1 mg dexamethasone tablet is taken at midnight followed by an 8.00 am cortisol estimation
• In most people, this high dose will rapidly lead to suppression of ACTH/cortisol
  • cortisol levels <50 nM rules out Cushing’s syndrome
  • cortisol levels <70 nM likely to be normal
  • cortisol levels 51 nmol/L – 138 nmol/L possible autonomous cortisol secretion’
  • cortisol levels   >138 nmol/L = ‘autonomous cortisol secretion’

• 24-hour urinary free cortisol
• midnight salivary cortisol estimation
• Radiology

• CT or MRI – Pituitary Adenoma
• CT Abdomen- Adrenal Adenoma

Management

• Exogenous Cushing Syndrome (Iatrogenic Cushing Syndrome, most common cause)
  • Stop Corticosteroids or decrease dose
  • Change steroid dosing to every other day with drug holiday
• Endogenous Cushing Syndrome
  • Surgically excise adenoma (in pituitary or adrenal)