Cushings clinical features
Centripetal obesity, limb wasting
Thin skin, easy bruising, livid wide striae
Proximal myopathy
HTN, osteoporosis, glucose intolerance/DM
Hyperpigmentation in Cushings
Indicates ACTH excess -hence pituitary/ectopic ACTH
Causes of ACTH dependent Cushings syndrome
Cushings disease, Ectopic ACTH, ectopic CRH
Causes of ACTH independent Cushings
Adrenal adenoma, carcinoma
Micronodular hyperplasia
Macronodular hyperplasia
Causes of pseudo-Cushings
Major depressive disorder, alcoholism related
Diagnosis of Cushings
First demonstrate hypercortisolism -
-24hr urinary free cortisol, retest if less than 3 fold
-Late evening plasma cortisol <50-not CS,>207-CS
-Overnight low dose dexamethasone 1mg Dex, check morning plasma cortisol
N<140nmol/l,<50nmol/L -Excludes Cushings
Check plasma ACTH -ACTH indep if ACTH<5mcg/l
ACTH depen if ACTH>15mcg/l
Diagnosis of Cushings disease vs Ectopic ACTH
High dose Dex suppression test 2mg 6hrly x 8doses
UFC suppression by>90% -highly spf for Cushings disease
MRI pituitary
Petrosal sinus sampling for ACTH after injecting CRH
Management of Cushings
Transsphenoidal selective microadenomectomy
Total hypophysectomy if macroadenoma
Pituitary irradiation, radio Sx
Bilateral adrenelectomy in refractory disease
Pre op medical Mx of Cushings
Metyrapone, ketoconazole, mifepristone
Pasireotide -if failed other Rx-s/e hyperglycemia
Rare causes of Cushings
Factitious - exogenous intake of steroid
Anomalous R expression on adrenal cells
GIP-dependent (low fasting cortisol,PP rise,low ACTH)
Vasopressin dependent -orthostatic hypo, AVP increases cortisol
Beta adrenergic dependent- postural increases in catechols increases cortisol
Clinical presentation of hyperprolactinemia
Amenorrhoea, galactorrhoea, hypogonadism/sexual dysfunction
Drugs and non pituitary causes of hyperprolactinemia
Drugs -phenothiazine, olanzapine, risperidone, metoclopramide
Other causes -post partum, CKD, seizure
Pituitary/hypothalamic causes of hyperprolactinemia
Pituitary tumour -micro/macro
Macroadenoma with stalk disruption
Stalk trauma
Management of hyperprolactinemia
Microprolactinoma -Medical- dopamine agonist-bromocriptine/cabergoline
Macroprolactinoma -Medical Rx initially
Sx if needed after medical Rx
Adjunctive RT
Etiology of panhypopituitarism
Pituitary or hypothalamic tumour(craniopharyngioma)
Trauma
Sheehans syndrome
Autoimmune hypophysitis/empty sella syndrome
Clinical presentation of panhypopituitarism
Fatigue, pale (ACTH def), poor response to intercurrent illness, postural hypotension, loss of body hair, fine facial wrinkling, cold intolerance, amenorrhoea, infertility, failed lactation, impotence/reduced libido
Hypopituitarism investigations
Visual assessment
MRI/CT brain for tumour
Basal hormone assay:cortisol, TFT, FSH,LH,E2,T
Dynamic testing: Synacthen test
Management of hypopituitarism
Treat underlying cause
Steroid replacement first followed by thyroxine
Males -testosterone , females -oestrogen,progesterone
fertility requires gonadotropin therapy
Diabetes insipidus
Central DI - Vasopressin/ADH insufficiency
Presence suggets hypothalamic damage
Investigations for DI
Water deprivation test:
DI :Failure to concentrate urine, failure of volume to decrease
Central DI: Responds to DDAVP
Nephrogenic DI: No response to DDAVP
Treatment of DI
Temporary or mild: Fluids to thirst
Severe/permanent: Desmopressin nasal spray/tabs