Cushings

Question 1

cushings

Answer 1

prolonged exposure to high levels of cortisol - hormone produed by adrenals

Question 2

causes of excess cortisol

Answer 2

therapeutic administration of synthetic steroids - iatrogenic

Question 3

cushings disease v cushings syndrome

Answer 3

disease is when the increased cortisol levels are caused by a functioning pituitary adenoma all others are referred to as cushings syndrome

Question 4

ACTH dependant cushings

Answer 4

• Pituitary adenoma (68%) → Cushing’s disease
  
  • Ectopic ACTH (12%) - carcinoid/carcinoma e.g. lung, pancreas
    Ectopic CRH (<1%)

Question 5

ACTH independant

Answer 5

• (Exogenous steroids)
  
  • Adrenal adenoma (10%) or carcinoma (8%)
  • Adrenal cortical nodular hyperplasia (1%)
    False positive (pseudo) - severe depression, severe alcoholism

Question 6

pathophysiology of ACTH independant

Answer 6

autonomous over production of cortisol by the adrenal gland due to neoplasia / nodular hyperplasia

Question 7

ACTH dependant pathophysiology

Answer 7

Pituitary adenomas (Cushing’s disease)
* Pituitary secretes increased ACTH → increased cortisol production by adrenal gland

Ectopic ACTH
* Carcinoma e.g. small cell lung cancer secretes ACTH → increased cortisol production by adrenal gland

Ectopic CRH
Carcinoma e.g. medullary thyroid carcinoma secretes CRH → increased ACTH by pituitary → increased cortisol by adrenal gland

Question 8

consequences of increased cortisol levels

Answer 8

• Protein loss
  
  • Altered carbohydrate and lipid metabolism
  • Excess mineralocorticoid
    Excess androgen

Question 9

general clincial presentation of cushings

Answer 9

• Plethora (redness of the face)
  
  • Moon face
  • Hypertension
  • Central obesity
  • Depression/psychosis
  • Glycosuria/diabetes mellitus
  • Oedema
  • ‘Buffalo hump’
    Virilism
    recent weight gain
    plethora
    oligomenorrhea
    hypertension
    easy brusing
    thin skin

Question 10

skin conditions in cushings

Answer 10

• Bruising
  
  • Striae (purple or red)
  • Pigmentation (only occurs with ACTH-dependent causes)
  • Thin skin
  • Hirsutism
    Acne

Question 11

MSK presentations in cushings

Answer 11

proximal myopathy
wasting
oteoporosis
fractures

Question 12

reproductive presentations in cushings

Answer 12

oligo / amenorrhoea

Question 13

characterisations of cushings

Answer 13

• Thin skin
  
  • Proximal myopathy
  • Frontal balding in women
  • Conjunctival oedema (chemosis)
    Osteoporosi

Question 14

investigations in cuhshings

Answer 14

• Overnight 1mg dexamethasone suppression test (oral) - first line
  ○ Normal: cortisol <50 nmol/l next morning
  ○ Abnormal: cortisol >130 nmol/l
  
  • 24hr urine free cortisol (24hr urine collection)
    ○ Total <250 is normal
    ○ Cortisol/creatinene ratio of<25 is normal
  • Diurnal cortisol variation (midnight/8am)
    ○ Loss of diurnal variation suspicious of Cushings
    Serum/saliva/spot urine collection

Question 15

diagnostic criteria for cushings

Answer 15

• Low dose dexamethasone suppression test
  ○ 2 day 2mg/day dexamethasone
  ○ Normal: cortisol <50 nmol/l 6 hours after last dose
  ○ Cushing’s: cortisol >130 nmol/l
  Repeat to confirm

Question 16

What suggests non ACTH dependant disease

Answer 16

if serum acth levels are low
adrenal imaging should be planned

Question 17

what suggetss acth dependant disease

Answer 17

if serum acth levels are high

Question 18

management of adrenal adenoma

Answer 18

adrenalectomy

Question 19

maangement of pituitary

Answer 19

• Hypophysectomy (transsphenoidal route)
  
  • External radiotherapy if recurs
    Last line: bilateral adrenalectomy

Question 20

drug management

Answer 20

• Metyrapone given when other treatments fail or while waiting for radiotherapy to work
  ○ Side effects e.g. N+V common
  Other options include ketoconazole (hepatotoxic) and pasireotide LAR (somatostatin analogue)

Question 21

what to measure once cushings is diagnosed

Answer 21

ACTH

Question 22

pituitary apoplexy

Answer 22

clinical syndrome resulting from the rapid expansion of a pituitary tumour due to either haemorrhage or infarction

sudden bleeding into or sudden blood loss to pituitary gland typically due to a pituitary adenoma

Question 23

what does a pitiutary apoplexy cause

Answer 23

rapid expansion of the gland and compression of surrounding structures, causing acute symptoms

Question 24

clinical features of pituitary apoplexy

Answer 24

Severe headache
* Nausea & vomiting
* Vision – visual acuity and visual field defects
* Ocular palsy (cranial nerve compression)
* Hypopituitarism
* Reduced GCS

Question 25

management of pituitary apoplexy

Answer 25

Pituitary function
* MRI
* Formal visual field/ophthalmic assessment
* Treat acute hormone deficits (e.g. emergency steroid dosing)
* Conservative vs surgical management dependent on clinical features

Question 26

hypohysitis

Answer 26

inflammation of pituitary gland

Question 27

management of hypophysitis

Answer 27

treat underlying cause
hormone deficit replacement