pathophys adrenal

Question 2

What increases ACTH drive?(5)

Answer 2

 Chronic stress (increased CRH) CRH-independent secretion of ACTH frompituitary (corticotroph) tumour Glucocorticoid resistance - loss of negative feedback Ectopic ACTH secretion (e.g. small cell lung tumour) Defect in cortisol synthesis(e.g. CAH or Addison’s disease)

Question 3

differentiate between Cushing’s disease and Cushing’s syndrome:

Answer 3

Cushing’s disease - pituitary defect Cushing’s syndrome - increased cortisolaction NOT due to a pituitary tumour Chronic stress Ectopic ACTH secretion Functional ZF tumour NOT Glucocorticoid resistance

Question 4

Cushing’s syndrome: causes

Answer 4

•Long-term use of corticosteroids e.g. cortisone or prednisone•A tumour /abnormality of adrenal gland, –> excess cortisol•Tumours of the lungs, thyroid, pancreas or thymus gland, rarely can produce hormones that trigger the syndrome

Question 5

Cushing’s syndrome: symptoms

Answer 5

central adiposity: moon face, buffalo hump. lipolysis at extremities–> thin limbs •hyperpigmentation, easy bruising and abdominal striae• Hirsutism and acne in women•Menstrual disorders, esp infrequent or absent periods•Fatigue and muscle weakness•Personality changes or mood swings• predisposed to gastric ulceration•thin osteoporotic bones that # easily

Question 6

Cushing’s syndrome: diagnosis (3)

Answer 6

1. 24 hour urine collection to test cortisol levels2. dexamethasone suppression test: synthetic cortisol taken overnight, measure cortisol in intervals3. X-rays, scans to detect any pituitary/adrenal tumour

Question 7

Cushing’s syndrome: treatment (2)

Answer 7

1. tumours: laparoscopic surgery2. gradual withdrawal of cortisone like drugs, drugs to suppress adrenal function

Question 8

ACTH testinghighest in early morning: btw 6am and 8amlowest in the evening btw 6pm and 11pm 1. high ACTH and low cortisol (or vv) could be a problem with the _________ _____2. Low levels of ACTH and cortisol could be a problem with the ______3. Overproduction of ACTH. This may be caused by an overactive pituitary gland.

Answer 8

1. adrenal glands2. pituitary glandACTH tests also to check the correct dose of corticosteroid medicine.

Question 9

ACTH ResultsNormal: 6 - 8 am: <less than 11 pmol/Lhigh levels may be due to :low levels may be due to:

Answer 9

1. •Emotional or physical stress (e.g. recent surgery /severe pain).•Diseases such as Addison’s, Cushing’s disease, or a tumour in adrenal or pituitary glands2. •Damage to the pituitary gland from surgery, radiation, stroke, head injury, or a tumour.•increased cortisol from an adrenal tumour in (Cushing’s syndrome).•Corticosteroid medicines

Question 10

Tests to distinguish between diseases:CRH Test•distinguish between Cushing’s Disease and an ectopic source of ACTH. CRH is given IV and the cortisol response monitored. Normally there is a rise in both ____and ____. In Cushing’s Disease patients the response is _________, in ectopic ACTH syndrome there will be ___ response.

Answer 10

1. ACTH and Cortisol2. exaggerated3. no

Question 11

Inferior petrosal sinus sampling: distinguish pituitary and ectopic sources of ACTH causing Cushing’s syndrome. A petrosal:peripheral ratio of >___, indicating excess ACTH from the pituitary, is necessary to diagnose Cushing’s disease with confidence. Accuracy can be improved using _____stimulation to exaggerate the difference

Answer 11

1. 22. CRH

Question 12

Addison’s disease: causes

Answer 12

• autoimmune destruction•Infections, such as tuberculosis, HIV, and other bacterial /fungal infections.•Cancer that has spread to the adrenal glands. esp lung cancer.•Bleeding into the adrenal glands as a side effect of using anticoagulants.• surgery or radiation treatments.• high doses of ketoconazole, sudden cessation after long term steroid use•Injury to the adrenal glands

Question 13

How can a defect in ACTH drive to the adrenal cortex be differentiated from Addison’s disease?

Answer 13

 Addison’s disease - ALL adrenal steroidssuppressed ACTH defect - only ACTH-dependent steroids are decreasedaldosterone unaltered by ACTH defect- [ aldosterone ] decreased in Addison’s–> polyuria; polydipsia; increased Na+ intake

Question 14

Congenital Adrenal HyperplasiaWhat causes the hyperplasia?

Answer 14

elevated ACTH as there is no negative feedback to suppress CRH–> increase trophic action

Question 15

Congenital Adrenal Hyperplasia“Salt-wasting” CAH: due to gene mutation in ______increase DHEA due to increased______ drive which leads to female ___________HYPONATRAEMIA, HYPERKALAEMIA

Answer 15

1. CYP21, encoding P450 C21. progesterone X–> DOC. 17OHprogesterone X–> 11-deoxycortisol2. ACTH3. pseudohermaphroditism (Cliteromegaly, labial fusion)

Question 16

Congenital Adrenal HyperplasiaSalt-sparing” CAH = simple-virilising CAH – sufficient ___________to stimulate Na+ resorption2. loss of function mutation in gene______increase DHEA, NO natriuresis, K+ only slightly inc3. excess________ –> malignant hypertension . no -ve f/b, does not respond to RAS

Answer 16

1. mineralocorticoid 2. CYP11B1DOC X–> Corticosterone. can bind to MR and act as a mineralocorticoid11-deoxycortisol X–> cortisol3. DOC

Question 17

Iatrogenic Cushing’s (4)

Answer 17

Plethoric, moon Face NO HIRSUTISM (not stimulated by endogenous adrenal gland)BruisingCentral adipositybuffalo hump

Question 18

Treatment for Cushingoid patients:disease?syndrome?

Answer 18

Cushings disease:•transphenoidal surgery Cushing’s syndrome:•resect ectopic site of ACTH secretion•adrenalectomy (& steroid replacement)•anti-glucocorticoids (e.g. RU486) & anti-androgens (e.g. flutamide)

Question 19

Why do glucocorticoids increase gastric ulceration?1. acid attack on gastric mucosa normally inhibited by__________2. Prostaglandin synthesis inhibited byglucocorticoids (via increased _______,________)

Answer 19

1. prostaglandins2. lipocortin/Annexin

Question 20

Conn’s syndrome1. primary hyperaldosteronism is due to_____2. secondary hyperaldosteronism :

Answer 20

1. benign tumor of the adrenal gland2. excess aldosterone is caused by something outside the adrenal gland that mimics the primary condition Generally related to high blood pressure.Related disorders : Cirrhosis of the liver, Heart failure, /over-activity of the RAS- i.e. a renin producing tumour.

Question 21

Conn’s syndrome: symptoms

Answer 21

• Fatigue• Headache• High blood pressure• Intermittent paralysis• Muscle weakness• Numbness

Question 22

Conn’s syndrome: signs and tests

Answer 22

• Abdominal CT scan that shows adrenal mass• ECG shows heart rhythm abnormalities due to with low potassium levels• Elevated plasma aldosterone level• Elevated urinary aldosterone• Low plasma renin activity• Low serum potassium level

Question 23

Conn’s syndrome: diagnosis and treatmentadrenal CT scanunilateral adenoma of adrenal gland –> hyperaldosteronism.•both adrenal glands : called ____ _____ _______•Most cases occur in people between 30-50 years of age.•__________acts as an anti-androgen, aldosterone antagonist and mild potassium-sparing diuretic.

Answer 23

1. bilateral adrenal hyperplasia.2. Spironolactone Generally, patients are referred for an adrenalectomy after an abdominal CT scan reveals an enlarged adrenal gland. can be done laparoscopically

Question 24

Nelson’s syndromeiatrogenic condition that occurs as a result of bilateral adrenalectomy Treatment involves ______surgery to remove the pituitary tumour.•The common signs and symptoms include muscle weakness and skin hyperpigmentation due to excess __.

Answer 24

1. trans-sphenoidal 2. MSHNelson’s syndrome is now rare because bilateral adrenalectomy is now only used in extreme circumstances.