Cushings Flashcards
cushings
prolonged exposure to high levels of cortisol - hormone produed by adrenals
causes of excess cortisol
therapeutic administration of synthetic steroids - iatrogenic
cushings disease v cushings syndrome
disease is when the increased cortisol levels are caused by a functioning pituitary adenoma all others are referred to as cushings syndrome
ACTH dependant cushings
- Pituitary adenoma (68%) → Cushing’s disease
- Ectopic ACTH (12%) - carcinoid/carcinoma e.g. lung, pancreas
Ectopic CRH (<1%)
- Ectopic ACTH (12%) - carcinoid/carcinoma e.g. lung, pancreas
ACTH independant
- (Exogenous steroids)
- Adrenal adenoma (10%) or carcinoma (8%)
- Adrenal cortical nodular hyperplasia (1%)
False positive (pseudo) - severe depression, severe alcoholism
pathophysiology of ACTH independant
autonomous over production of cortisol by the adrenal gland due to neoplasia / nodular hyperplasia
ACTH dependant pathophysiology
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
consequences of increased cortisol levels
- Protein loss
- Altered carbohydrate and lipid metabolism
- Excess mineralocorticoid
Excess androgen
general clincial presentation of cushings
- 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
skin conditions in cushings
- Bruising
- Striae (purple or red)
- Pigmentation (only occurs with ACTH-dependent causes)
- Thin skin
- Hirsutism
Acne
MSK presentations in cushings
proximal myopathy
wasting
oteoporosis
fractures
reproductive presentations in cushings
oligo / amenorrhoea
characterisations of cushings
- Thin skin
- Proximal myopathy
- Frontal balding in women
- Conjunctival oedema (chemosis)
Osteoporosi
investigations in cuhshings
- 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
- 24hr urine free cortisol (24hr urine collection)
diagnostic criteria for cushings
- 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
What suggests non ACTH dependant disease
if serum acth levels are low
adrenal imaging should be planned
what suggetss acth dependant disease
if serum acth levels are high
management of adrenal adenoma
adrenalectomy
maangement of pituitary
- Hypophysectomy (transsphenoidal route)
- External radiotherapy if recurs
Last line: bilateral adrenalectomy
- External radiotherapy if recurs
drug management
- 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)
what to measure once cushings is diagnosed
ACTH
pituitary apoplexy
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
what does a pitiutary apoplexy cause
rapid expansion of the gland and compression of surrounding structures, causing acute symptoms
clinical features of pituitary apoplexy
Severe headache
* Nausea & vomiting
* Vision – visual acuity and visual field defects
* Ocular palsy (cranial nerve compression)
* Hypopituitarism
* Reduced GCS
management of pituitary apoplexy
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
hypohysitis
inflammation of pituitary gland
management of hypophysitis
treat underlying cause
hormone deficit replacement
