Adrenal cortex and cushing's syndrome

Question 1

Which steroids are produced by the adrenal cortex

Answer 1

Glucocorticoids
Mineralcorticoids
Androgens

Question 2

Process of steroid hormone release

Answer 2

CRF–>ACTH–>steorid release, negative feedback

Question 3

Definition cushing’s syndrome (3 aspects)

Answer 3

+Glucocorticoid excess
Loss of negative feedback
Loss of normal cyclical pattern of GC relese

Question 4

Chief cause of cushing’s syndrome

Answer 4

Iatrogenic- oral steroids

Question 5

80% of endogenous cushing’s caused by, commonest endogenous

Answer 5

ACTH excess

Pituitary adenoma- cushings disease

Question 6

Broad categories of cushing’s

Answer 6

ACTH dependent

ACTH independent

Question 7

ACTH dependent causes (2)

Answer 7

Cushings disease
Ectopic ACTH- Small cell lung, pancreatic, medullary thyroid
Rarely CRF tumor

Question 8

ACTH independent causes (4)

Answer 8

Adrenal adenoma/cancer
Adrenal nodular hyperplasia
Iatrogenic

Question 9

What is cushing’s disease

Answer 9

Bilateral adrenal hyperplasia, due to +ACTH from pituitary microadenoma

Question 10

Epidemiology in cushings disease

Answer 10

30-50 yo

Question 11

How does low dose and high dose dexamethasone test change cortisol levels in CD

Answer 11

Low dose, no effect
High dose (>8mg) can halve morning cortisol levels

Question 12

Specific features in ectopic ACTH production

Answer 12

Pigmentation
Hypokalemic metabolic alkalosis
Weight loss
Hyperglycemia

Question 13

When ectopic ACTH, does high does dexamethasone suppress cortisol levels

Answer 13

No

Question 14

Clinical features

Answer 14

Weakness
Insomnia
Mood disorders
Impaired cognition
Easy bruising
Oligo/Amenorrhea
Hirsutism and acne

Question 15

Which symptoms are ACTH dependent

Answer 15

Hirsutism and acne

Question 16

Signs

Answer 16

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

Question 17

Key diagnostic factors

Answer 17

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

Question 18

Strong risk factors

Answer 18

Exogenous cortisol use
Pituitary adenoma
Adrenal adenoma
Adrenal carcinoma

Question 19

History

Answer 19

Iatrogenic steroid use
Features unusual for age->osteoporosis
Unexplained psychiatric
Nephrolithiasis
Multiple/progressive symptoms
PCOS
Pituitary adenomas
Adrenal adenomas

Question 20

First line diagnostic test->use one of

Answer 20

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

Question 21

Algorithm for cushing diagnosis

Answer 21

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

Question 22

Physiological causes of cushing’s

Answer 22

Physical stress
Malnutrition
Alcoholism
Depression
Pregnancy
Morbid obesity/metabolic syndrome

Question 23

Other tests to perform

Answer 23

Glucose

Pregnancy

Question 24

If a pituitary adenoma is found on MRI, at what size should you proceed to treatment

Answer 24

6mm

Question 25

Management->ACTH secreting tumor

Answer 25

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

Question 26

What is pasireotide and how does it work

Answer 26

Somatostatin analogue->binds to receptor expressed by corticotrophs in adenomas->decreaseing cortisol

Question 27

What tole does ketoconazole have

Answer 27

Steroidogenesis inhibitor

Question 28

What is the role of mifepristone

Answer 28

Glucocorticoid receptor antagonist->blocks cortisol at receptor levels and attenuates effects of elevated cortisol

Question 29

When treated with medical therapy before surgery, what must be monitored for

Answer 29

Adrenal insufficiency

Question 30

Postoperatively what symptoms should be checked for

Answer 30

BP Orthostatic hypotension General sense of energy/fatigue

Question 31

Which hormones may be needed (not including cortisol) post surgery

Answer 31

``` Levothyroxine Testosterone Estrogen + progestin (10 days/month) ?GH Desmopressin ```

Question 32

Other options for management of ACTH tumor

Answer 32

Repeat surgery Pituitary radiotherapy Bilateral adrenalectomy

Question 33

Management of ectopic ACTH or CRH syndrome

Answer 33

Surgical resection/ablation of tumor/metastasis Medical therapy- mifepristone, pasireotide, ketoconazole Chemo/radiotherapy for primary tumor

Question 34

Management of ACTH independent->unilateral adrenal carcinoma or adenoma

Answer 34

Unilateral adrenalectomy/tumor resection Medical therapy before surgery Chemo/radiotherapy for adrenal carcinoma

Question 35

Management of ACTH independent due to bilateral adrenal disease

Answer 35

Bilateral adrenalectomy Permanent post surgical corticosteroid replacement therapy Medical therapy before surgery

Question 36

Which conditions are unlikely to having clinical features of cushings

Answer 36

``` Physical stress Malnutiriton Anorexia Intense chronic exercise Hypothalmic amenorrhea CBG excess ```

Question 37

Interpreting high dose dexamethasone suppression test

Answer 37

8mg dexamethasone at 11pm- Next morning 8am cortisol Cushing syndrome of pituitary origin

Question 38

What is the inferior petrosal sinus sampling for

Answer 38

Confirm side of hypersecretion