Adrenal cortex and cushing's syndrome Flashcards
Which steroids are produced by the adrenal cortex
Glucocorticoids
Mineralcorticoids
Androgens
Process of steroid hormone release
CRF–>ACTH–>steorid release, negative feedback
Definition cushing’s syndrome (3 aspects)
+Glucocorticoid excess
Loss of negative feedback
Loss of normal cyclical pattern of GC relese
Chief cause of cushing’s syndrome
Iatrogenic- oral steroids
80% of endogenous cushing’s caused by, commonest endogenous
ACTH excess
Pituitary adenoma- cushings disease
Broad categories of cushing’s
ACTH dependent
ACTH independent
ACTH dependent causes (2)
Cushings disease
Ectopic ACTH- Small cell lung, pancreatic, medullary thyroid
Rarely CRF tumor
ACTH independent causes (4)
Adrenal adenoma/cancer
Adrenal nodular hyperplasia
Iatrogenic
What is cushing’s disease
Bilateral adrenal hyperplasia, due to +ACTH from pituitary microadenoma
Epidemiology in cushings disease
30-50 yo
How does low dose and high dose dexamethasone test change cortisol levels in CD
Low dose, no effect High dose (>8mg) can halve morning cortisol levels
Specific features in ectopic ACTH production
Pigmentation
Hypokalemic metabolic alkalosis
Weight loss
Hyperglycemia
When ectopic ACTH, does high does dexamethasone suppress cortisol levels
No
Clinical features
Weakness Insomnia Mood disorders Impaired cognition Easy bruising Oligo/Amenorrhea Hirsutism and acne
Which symptoms are ACTH dependent
Hirsutism and acne
Signs
Central obesity Mood face Supraclabicular and dorsal fat pads Facial plethora Muscle wasting Purple abdominal striae Skin atrophy Acanthosis nigricans HTN Hyperglycemia Osteoporosis Pathalogical fractures Hyperpigmentation Hyperandrogenism
Key diagnostic factors
Risk factors Facial plethora SC fat pads Striae Absence of pregnancy Menstural irregularities Absence of malnutrition, alcoholism Absence of physiological stress Linear growth deceleration in children
Strong risk factors
Exogenous cortisol use
Pituitary adenoma
Adrenal adenoma
Adrenal carcinoma
History
Iatrogenic steroid use Features unusual for age->osteoporosis Unexplained psychiatric Nephrolithiasis Multiple/progressive symptoms PCOS Pituitary adenomas Adrenal adenomas
First line diagnostic test->use one of
Late night salivary cortisol >4nmol/L, at lease 2 readings
Overnight 1mg dex suppression testing >50nmol/L
24 hour urinary free cortisol-> >3 times upper limit of normal, at least 2 readings
48 hour 2mg dex suppression testing
Should repeat the diagnostic tests
Confirmed if any two are positive
Algorithm for cushing diagnosis
Cushings expected–>exclude exogenous–>Perform one of high sensitive tests
If negative->Cushings unlikely
If positive->exclude physiological causes->confirm positive test and perform 1 or 2 additional studies->referral to endocrinologist
If positive->cushings->measure plasma ACTH
If negative->cushings unlikely
Suppressed ACTH->independent of ACTH->imaging of adrenals
XSuppressed ACTH= ACTH-dependent–>MRI of pituitary
Physiological causes of cushing’s
Physical stress Malnutrition Alcoholism Depression Pregnancy Morbid obesity/metabolic syndrome
Other tests to perform
Glucose
Pregnancy
If a pituitary adenoma is found on MRI, at what size should you proceed to treatment
6mm
Management->ACTH secreting tumor
Transphenoidal pituitary adenomectomy
Adjunct:
Medical therapy prior to surgery–> mifepristone or pasiretide or ketoconazole
Post surgical cortisol replacement->hydrocortisone
Non-cortisol replacement->levothyroxine +/- testosterone, estrogen, medroxyprogesterone, somatotropin, desmopressin
What is pasireotide and how does it work
Somatostatin analogue->binds to receptor expressed by corticotrophs in adenomas->decreaseing cortisol
What tole does ketoconazole have
Steroidogenesis inhibitor
What is the role of mifepristone
Glucocorticoid receptor antagonist->blocks cortisol at receptor levels and attenuates effects of elevated cortisol
When treated with medical therapy before surgery, what must be monitored for
Adrenal insufficiency
Postoperatively what symptoms should be checked for
BP
Orthostatic hypotension
General sense of energy/fatigue
Which hormones may be needed (not including cortisol) post surgery
Levothyroxine Testosterone Estrogen + progestin (10 days/month) ?GH Desmopressin
Other options for management of ACTH tumor
Repeat surgery
Pituitary radiotherapy
Bilateral adrenalectomy
Management of ectopic ACTH or CRH syndrome
Surgical resection/ablation of tumor/metastasis
Medical therapy- mifepristone, pasireotide, ketoconazole
Chemo/radiotherapy for primary tumor
Management of ACTH independent->unilateral adrenal carcinoma or adenoma
Unilateral adrenalectomy/tumor resection
Medical therapy before surgery
Chemo/radiotherapy for adrenal carcinoma
Management of ACTH independent due to bilateral adrenal disease
Bilateral adrenalectomy
Permanent post surgical corticosteroid replacement therapy
Medical therapy before surgery
Which conditions are unlikely to having clinical features of cushings
Physical stress Malnutiriton Anorexia Intense chronic exercise Hypothalmic amenorrhea CBG excess
Interpreting high dose dexamethasone suppression test
8mg dexamethasone at 11pm- Next morning 8am cortisol Cushing syndrome of pituitary origin
What is the inferior petrosal sinus sampling for
Confirm side of hypersecretion
