Flashcards in Adrenal cortex and cushing's syndrome Deck (38)
1
Which steroids are produced by the adrenal cortex
Glucocorticoids
Mineralcorticoids
Androgens
2
Process of steroid hormone release
CRF-->ACTH-->steorid release, negative feedback
3
Definition cushing's syndrome (3 aspects)
+Glucocorticoid excess
Loss of negative feedback
Loss of normal cyclical pattern of GC relese
4
Chief cause of cushing's syndrome
Iatrogenic- oral steroids
5
80% of endogenous cushing's caused by, commonest endogenous
ACTH excess
Pituitary adenoma- cushings disease
6
Broad categories of cushing's
ACTH dependent
ACTH independent
7
ACTH dependent causes (2)
Cushings disease
Ectopic ACTH- Small cell lung, pancreatic, medullary thyroid
Rarely CRF tumor
8
ACTH independent causes (4)
Adrenal adenoma/cancer
Adrenal nodular hyperplasia
Iatrogenic
9
What is cushing's disease
Bilateral adrenal hyperplasia, due to +ACTH from pituitary microadenoma
10
Epidemiology in cushings disease
30-50 yo
11
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
12
Specific features in ectopic ACTH production
Pigmentation
Hypokalemic metabolic alkalosis
Weight loss
Hyperglycemia
13
When ectopic ACTH, does high does dexamethasone suppress cortisol levels
No
14
Clinical features
Weakness
Insomnia
Mood disorders
Impaired cognition
Easy bruising
Oligo/Amenorrhea
Hirsutism and acne
15
Which symptoms are ACTH dependent
Hirsutism and acne
16
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
17
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
18
Strong risk factors
Exogenous cortisol use
Pituitary adenoma
Adrenal adenoma
Adrenal carcinoma
19
History
Iatrogenic steroid use
Features unusual for age->osteoporosis
Unexplained psychiatric
Nephrolithiasis
Multiple/progressive symptoms
PCOS
Pituitary adenomas
Adrenal adenomas
20
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
21
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
22
Physiological causes of cushing's
Physical stress
Malnutrition
Alcoholism
Depression
Pregnancy
Morbid obesity/metabolic syndrome
23
Other tests to perform
Glucose
Pregnancy
24
If a pituitary adenoma is found on MRI, at what size should you proceed to treatment
6mm
25
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
26
What is pasireotide and how does it work
Somatostatin analogue->binds to receptor expressed by corticotrophs in adenomas->decreaseing cortisol
27
What tole does ketoconazole have
Steroidogenesis inhibitor
28
What is the role of mifepristone
Glucocorticoid receptor antagonist->blocks cortisol at receptor levels and attenuates effects of elevated cortisol
29
When treated with medical therapy before surgery, what must be monitored for
Adrenal insufficiency
30
Postoperatively what symptoms should be checked for
BP
Orthostatic hypotension
General sense of energy/fatigue
31
Which hormones may be needed (not including cortisol) post surgery
Levothyroxine
Testosterone
Estrogen + progestin (10 days/month)
?GH
Desmopressin
32
Other options for management of ACTH tumor
Repeat surgery
Pituitary radiotherapy
Bilateral adrenalectomy
33
Management of ectopic ACTH or CRH syndrome
Surgical resection/ablation of tumor/metastasis
Medical therapy- mifepristone, pasireotide, ketoconazole
Chemo/radiotherapy for primary tumor
34
Management of ACTH independent->unilateral adrenal carcinoma or adenoma
Unilateral adrenalectomy/tumor resection
Medical therapy before surgery
Chemo/radiotherapy for adrenal carcinoma
35
Management of ACTH independent due to bilateral adrenal disease
Bilateral adrenalectomy
Permanent post surgical corticosteroid replacement therapy
Medical therapy before surgery
36
Which conditions are unlikely to having clinical features of cushings
Physical stress
Malnutiriton
Anorexia
Intense chronic exercise
Hypothalmic amenorrhea
CBG excess
37
Interpreting high dose dexamethasone suppression test
8mg dexamethasone at 11pm- Next morning 8am cortisol Cushing syndrome of pituitary origin
38