Cushings, hypopituitarism and DI Flashcards
What is cushings due to ?
- Excess cortisol
- Excess mineralocorticoid
- Excess androgen
What are the consequences of excess cortisol ?
Protein loss:
- Myopathy; wasting
- Osteoporosis; fractures
- Thin skin; striae, bruising
Altered Carbohydrate/Lipid metabolism; DM, Obesity
Altered psyche; psychosis, depression
What are the consequences of excess mineralocorticoid?
Hypertension, oedema
What is the consequences of excess androgen ?
- Virilism
- Hirsutism
- Acne
- oligo/amenorrhoea
Describe the clinical presentation of cushings syndrome
- Thinning of skin - stretch marks
- Increased Abdominal fat, buffalo hump
- Muscle wasting causing thin arms and legs
- Poor wound healing/ easy bruising
- AVN
- Moon face
- Cataracts
How is cushings diagnosed ?
Definite test = low dose dexamethasone suppression test
What are the screening tests for cushings ?
- Overnight dexamethasone suppression test
- Urine free cortisol
- Diurnal cortisol variation
What are the different causes of cushings syndrome ?
ACTH dependent causes:
- Pituitary tumour secreting ACTH producing adrenal hyperplasia - most common cause
- Ectopic ACTH production (5-10%): e.g. SCLC
ACTH independent causes:
- Iatrogenic: steroids
- adrenal adenoma (5-10%)
- adrenal carcinoma (rare)
- micronodular adrenal dysplasia (very rare)
(note ACTH is what indirectly stimulates cortisol so if its not something in the adrenal gland or an exogenous source then it needs to be producing ACTH to stimulate its production)
What are the causes of pseudo-cushings (mimics of cushings) ?
- Often due to alcohol excess or severe depression
- causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
- insulin stress test may be used to differentiate
How is the cause of cushings localised once confirmation of cushings disease is made?
Measure midnight plasma ACTH (and cortisol) levels:
- Pituitary < 300
- Adrenal < 1
- Ectopic > 300
What is the treatment of cushings syndrome?
- Pituitary = transsphenodial pituitary appendectomy
- Adnreal = adrenelectomy
- Ectopic = surgical ressection or ablation of the tumour and metastases
If not suitable for surgery then give Metyrapone or ketaconazole. And if steroid use causing it then taper off the steroids
What are the 2 main types of hypopituitarism ?
Anterior and posterior (Diabetes insipidus)
Define what panhypopituitarism is ?
A rare condition in which the pituitary gland stops making most or all hormones. (anterior & posterior pituitary signs would be seen)
What are the causes of hypopituitarism ?
- Pituitary tumours/ metastatic lesions
- Local brain tumours
- Granulomatous disease - e.g. TB, sarcoidosis
- Trauma
What are the signs/symptoms of anterior hypopituitarism ?
Depends on the hormones which are lacking in secretion:
- Growth Hormone; growth failure
- TSH; hypothyroidism
- LH/FSH; Hypogonadism
- ACTH; hypoadrenal
- Prolactin; none known
The general signs/symptoms of anterior hypopituitarism
- Menstrual irregularities (F)
- Infertility, impotence
- Gynaecomastia (M)
- Abdominal obesity
- Loss of facial hair (M)
- Loss of axillary and pubic hair (M&F)
- Dry skin and hair
- Hypothyroid faces
- Growth retardation (children)
How is hypopituitarism diganosed ?
By measuring anterior pituitary hormones
What is the treatment of hypopituitarism ?
- Replacement therapy:
- Thyroxine - for TSH
- Hydrocortisone - for cortisol
- ADH - desomspray or tablets
- GH
- Sex steroids - HRT/Oest/prog pill for female, Testosterone for males
What is the effect of GH replacememt therapy ?
- Improves well being and Quality of life
- Decreases abdominal fat
- Increases muscle mass, strength, exercise capacity and stamina
- Improves cardiac function
- Decreases cholesterol and increases LDL
- Increases bone density
What are the risk of testosterone replacement ?
- Prostate Enlargement.
- Polycythaemia - increased blood cells
- Hepatitis
What are the 2 main types of diabetes insipidus ?
Central and nephrogenic
- Central = problem with the production/secretion of ADH
- Nephrogenic = no problem with production/secretion but cells not responsive to ADH
What are the causes of central diabetes insipidus ?
Familial:
- Isolated in most cases
- DIDMOAD (DI, DM, optic atrophy, deaf) also known as wolfmans syndrome
Acquired:
- Idiopathic in 50%
- Trauma; road accidents, surgery (pituitary), skull fracture
RARE:
- Tumour (e.g. craniopharyngiomas), sarcoid, ext irradiation, meningitis
What are the causes of nephrogenic DI?
- Genetic: the more common form affects the vasopression (ADH) receptor, the less common form results from a mutation in the gene that encodes the aquaporin 2 channel
- Electrolytes: hypercalcaemia, hypokalaemia
- Drugs: demeclocycline, lithium
- Tubulo-interstitial disease: obstruction, sickle-cell, pyelonephritis
What are the clinical features of DI ?
- Polyuria
- Polydipsia
- High plasma osmolality, low urine osmolality
How is diabetes insipidus diagnosed ?
Water deprivation test
What can be used to exclude DI?
A urine osmolality of >700 mOsm/kg
What is the treatment of central diabets insipidus ?
- Desmospray or Desmopressin injections or tablets
Essentially giving ADH
What is the treatment of nephrogenic DI?
Thiazides, low salt/protein diet
