Cushing's Disease

Question 1

What is Cushing’s disease?

Answer 1

• It is a disorder caused by excess cortisol (hormone)
• Can become serious if not treated

Question 2

What are important questions to ask someone with suspected Cushing’s disease?

Answer 2

• Past medical history e.g. diabetes (increased in T2DM), obesity
• Medication e.g. long term/frequent STEROIDS
  
  • e.g. prednisolone, hydrocortisone, methyl-prednisolone

Question 3

What are differential diagnosis of Cushing’s disease?

Answer 3

• Hypothyroidism
• Depression
• PCOS
• T2DM

Question 4

What are symptoms & signs of Cushing’s disease?

Answer 4

• Moon face (build up of fat around neck)
• ‘Buffalo hump’ - fat accumulation at the back of the neck
• Truncal obesity with striae
• Facial plethora
• Buccal hyperpigmentation (increased melanocyte stimulating hormone as a by-product of ACTH synthesis)
• Weight gain
• Acne
• Thin skin
• Easy bruising
• Insomnia
• Skin pigmentation
• Headaches and visual defects
• Weakness in arms + legs
• Decreased libido
• Fertility problems
• Depression
• Mood swings

Question 5

What is this sign?

Answer 5

Moon face

Question 6

What sign is this?

Answer 6

‘Buffalo hump’

Question 7

What sign is this?

Answer 7

Truncal obesity with striae

Question 8

What sign is this?

Answer 8

Facial Plethora

Question 9

What sign is this?

Answer 9

Buccal Hyperpigmentation

Question 10

What is the main role of the hypothalamus?

Answer 10

• Key role in homeostasis
  
  • Heart rate + BP
  • Body Temperature
  • Fluid and Electrolyte balance – including thirst
  • Appetite and Body weight
  • Sleep cycle
  • GI secretion
• Regulates the anterior pituitary gland
  
  • Via releasing hormone
  • Secretes dopamine (Inhibits prolactin)
• Synthesises hormones that are released from posterior pituitary

Question 11

What hormones does the pituitary gland make and from where?

Answer 11

Anterior pituitary

• Adrenocorticotropic hormone (ACTH)
• Thyroid stimulating hormone (TSH)
• Growth Hormone (GH)
• Luteinizing Hormone (LH)
• Follicle stimulating hormone (FSH)
• Prolactin (in milk production)

Posterior pituitary

• Oxytocin (in reproductive cycle, breast feeding and child birth)
• Anti-diuretic Hormone (ADH)

Question 12

Draw the cortisol axis

Answer 12

Raised cortisol levels inhibit the production of ACTH and CRH

Question 13

What do the different areas and zones in the adrenal gland make?

Answer 13

Adrenal cortex - 3 main steroid hormones

• Zona glomerulosa → mineralocorticoids
  
  • e.g. aldosterone → controls BP (regulation of water & electrolytes)
• Zona fasciculata → glucocorticoids
  
  • e.g. cortisol (in controlling metabolism, immune response and impacts sugar levels)
• Zona reticularis → Androgens
  
  • e.g. sex hormones

Adrenal medulla → ‘fight or flight’ response

• Secretes epinephrine/ norepinephrine (adrenaline → spikes HR, increase bloof

Question 14

What is Cushing’s syndrome & types?

Answer 14

Caused by prolonged exposure to either endogenous or exogenous glucocorticoids

ACTH Dependent

• Excessive ACTH from pituitary gland (Cushing’s disease)
• Ectopic ACTH secretion

ACTH Independent

• Adrenal Cortisol Excess (Adrenal Tumours/Adenomas (more common in females)
• Exogenous steroids

Question 15

How can you confirm someone has Cushing’s syndrome?

Answer 15

• 24 hour urinary cortisol
• Late night salivary cortisol (Elevated due to loss of diurnal variation)
• Overnight dexamethasone suppression test
  
  • 9 AM (morning)LOW cortisol = (Normal result) → as diurnal variation

HELPS identify excess hypercortisolaemia but NOT the cause

Question 16

How can you identify the cause of Cushing’s syndrome?

Answer 16

• Plasma ACTH
  
  • Raised ACTH compatible with ATCH dependent Cushing’s syndrom
    
    • e.g. Pituitary adenoma, ectopic ACTH secretion
    • Low ACTH compatible with ATCH independent Cushing’s syndrome
      
      • e.g. Primary cortisol producing adrenal adenoma or carcinoma, exogenous glucocorticoid use
• High dose dexamethasone suppression test
  
  • Can help distinguish between pituitary and ectopic ACTH secretion
  • Will suppress pituitary ACTH but not ectopic ACTH
• Inferior petrosal sinus sampling
  
  • ACTH levels measured from veins draining pituitary gland and these are compared to peripheral ACTH levels

Question 17

What scans can be done for someone with Cushing’s disease?

Answer 17

• CT chest (Ectopic ACTH) or abdomen
• MRI adrenals
• MRI pituitary

Question 18

What is the management of Cushing’s disease?

Answer 18

Definitive management is surgical resection

• Medical (these inhibit glucocorticoid synthesis) → done when awaiting surgery + unknown site of lesion, unsuitable for surgery/ persistent raised glucocorticoids despite surgery
  
  • Metyrapone and ketoconazole (Fast acting but not effective long term)
  • Mitotane (Slow onset of action but more effective long term)
  • Reduce steroid dose SLOWLY
• Surgical
  
  • Trans-sphenoidal surgery
  • Laparoscopic surgery
  • Bilateral adrenalectomy
• Radiotherapy

Post treatment patients will have adrenal insufficiency

Question 19

What is Pseudo-Cushing’s?

Answer 19

• Clinical features and biochemical evidence of cortisol excess but NOT caused by hypothalamic-pituitary axis
  
  • Depression
  • Alcohol excess
  • Obesity

Question 20

What are the complications of Cushing’s disease?

Answer 20

• Hypertension (as has some mineralocorticoid activity thus can cause high Na+ and low K+)
• Diabetes (cortisol will increase blood glucose through gluconeogenesis)
• Osteoporosis (decreases bone formation)
• Prone to infections (suppresses the immune system)