Adrenal gland disorders

Question 1

which hormones are produced by the adrenal cortex

Answer 1

Mineralocorticoids: (aldosterone)
glucocorticoids: cortisol
androgens (testosterone)

Question 2

which hormones are produced by the adrenal medula

Answer 2

epinephrine and norepinephrine (activated by ACh through the muscarinic receptor)

Question 3

what’s the function of mineralocorticoids

Answer 3

most important is aldosterone which causes Na/water reabsorption
and K/H excretion

other mineralocorticoids are corticosterone and 11deoxycorticosterone

Question 4

name the androgens and their function

Answer 4

Testosterone, DHEA(dehydroepiandrosterone), androstenedione

help with sexual development

Question 5

whats the function of ACTH

Answer 5

stimulates androgen and cortisol release

Question 6

where are the receptors for cortisol (plasma membrane or intracellular)

Answer 6

since they are lipid soluble (steroids), they diffuse though the membrane and bind to intracellular receptors

Question 7

which hormones control cortisol secretion

Answer 7

pituitary-adrenal axis
hypothalamus (paraventricular nucleus) releases CRH=> induces the release of ACTH=> induces cortisol release (though cAMP/PKA)

ACTH activates desmolase which converts cholesterol into pregnenolone=> the rest of the steps

Question 8

when is physiologic cortisol secretion at its highest levels

Answer 8

6AM, its released cyclically (as a rhythm)

Question 9

Is cortisol transported freely in plasma ?

Answer 9

its poorly soluble so its bound to Cortisol binding globulin (CBG) 90%

CBG levels increases with increase estrogen (same as TBG)

Question 10

what are the functions of cortisol

Answer 10

increases sensitivity of blood vessels to nor/epinephrine = hypertension

sequesters lymphocytes to the, inhibit NF-KB, spleen/nodes, block neutrophil migration, blocks histamine release from mast cells = immunosuppression

increase gluconeogenesis, less glucose uptake by fat and muscle, more glycogen storage but enhanced glucagon, increased lipolysis= increase serum glucose levels and increase triglycerides

blunted epidermal cell division= skin striae (stretch marks), thing skin, easy bruising

inhibits osteoblasts= osteoporosis, osteopenia

Question 11

what are the layers of adrenal cortex and what’s their function

Answer 11

GFR =>ACE
Glomerulosa =>aldosterone
Fasciculata =>cortisol/corticosterone/cortisone
Reticularis =>epinephrine/norepinephrine

Question 12

what are the causes of Cushing’s syndrome

Answer 12

ACTH independent :
adrenal adenomas, glucocorticoid therapy

ACTH dependent:
ectopic secretion
Cushing’s disease (pituitary ACTH secreting tumor)

Question 13

what’s the cause of hyperpigmentation in ACTH dependent Cushing’s syndrome

Answer 13

ACTH and MSH (melanocyte stimulating hormone) share the same precursor which is proopiomelanocortin, when you need more ACTH then MSH will also be synthesized which will cause hyperpigmentation

Question 14

how do you test for Cushing’s syndrome

Answer 14

since cortisol secretion is rhythmic, we have to do either:

• 24h urine free cortisol
• saliva test, measured at night
• low dose dexamethasone suppression test

(normally low dose dexamethasone will depress ACTH, so you take it at night and in the morning you measure it and ACTH will be decreased, if we have cushings syndrome, this low does has no effect and no inhibition of ACTH will be seen)

Question 15

high dose vs low dose Dexamethasone suppression test

Answer 15

low dose is used to detect if we have cushing’s syndrome or not, if we have suppressed ACTH then there is no cushings syndrome (this does not tell us the cause of cushings syndrome if it exists )

adenomas on the other hand will RESPOND to high dose dexamethasone, while ACTH secreting tumors (ectopic ACTH secretions) will not. so this will give us the cause of the cushings syndrome

Question 16

how do you treat cushings syndrome

Answer 16

surgery

ketoconazole:(antifungal) inhibits desmolase which converts cholesterol into pregnenolone. this leads to lower cortisol synth. this also lowers androgen synthesis which causes gynecomastia

Question 17

what are the types of adrenal insufficiency

Answer 17

PRIMARY: adrenal insufficiency, low Cortisol and aldosterone but high ACTH

SECONDARY: low ACTH and low cortisol but aldosterone is normal

Question 18

adrenal insufficiency symptoms

Answer 18

Loss of cortisol:
weight loss
abdominal pain
postural hypotension
weakness
hypoglycemia 

Loss of aldosterone:
potassium retention => hyperkalemia
Na loss =>hypovolemia
H retention => acidosis

Question 19

skin hyperpigmentation in primary adrenal insufficiency

Answer 19

when there is primary adrenal insufficiency, ACTH will raise to compensate.

ACTH and MSH have the same precursor, so when ACTH increase, MSH will increase too and cause hyperpigmentation

Question 20

whats adrenal crisis

Answer 20

acute adrenal insufficiency

manifestation is SHOCK, hypoglycemia, nausea and vomiting, fatigue

Question 21

definition of Addison’s disease, which parts of the adrenal gland is affected and what are its causes

Answer 21

definition: primary adrenal insufficiency

autoimmune adrenalitis: antibody and cell mediated disorder caused by antibodies to 21-hydroxylase, this will result in atrophy of adrenal gland and loss of cortex ONLY, medulla is spared

infections: fungal, CMV, tuberculosis

Question 22

whats waterhouse-friderichsen syndrome

Answer 22

acute adrenal insufficiency caused by a hemorrhage into the adrenals. it is associated with meningococcemia

e.g. patient with meningitis with acute onset of shock

Question 23

what are common causes of secondary adrenal insufficiency

Answer 23

glucocorticoid therapy: exogenous steroids causes adrenal to hypo function which will on the long term causes atrophy

P.S no skin findings since ACTH isn’t elevated
and no hyperkalemia since aldosterone is not affected

Question 24

primary aldosteronism, definition, causes, diagnosis and treatment

Answer 24

high aldosterone which causes
hypertension (high water and NA)
hypokalemia (loss of K)
alkalosis (loss of H)

common causes bilateral idiopathic hyperaldosteronism

diagnosis:
high plasma aldosterone
low renin activity since hypervolemia is caused by aldosteronism, renin-angiotensin will undercompensate

if we have high renin activity and high plasma aldosteron => renal artery stenosis, CHF, low volume

treat with spironolactone. aldosterone antagonist

Question 25

what’s pheochromocytoma and how does it present

Answer 25

catecholamine secreting tumor that arises from the adrenal medulla (chromaffin cells).

presentation: the secretion happens in an episodic manner therefore the symptoms come and go accordingly, those include:
hypertension
headache
palpitation
sweating 
pallor

Question 26

how do you diagnose pheochromocytoma

Answer 26

since the hormone levels fluctuate, we cant detect their levels well, plus most of the catecholamines are metabolized by the tumor itself, for the diagnosis we look for the metabolites for catecholamines which are metanephrine thought a 24h urine collection.

Question 27

how do you treat pheochromocytoma and what special precautions should be made

Answer 27

treat with surgery but with IMPORTANT preoperative management.
during surgery the patients could be exposed to high levels of catecholamines, thus we give them phenoxybenzamine which is an irreversible alpha blocker

(Beta blocker increases alpha receptor effect, this is why we must block alpha receptors first)

Question 28

what are NON-cushing causes of hypercortisolemia

Answer 28

Stress: 
surgery
malnutrition
mental stress
drug and alcohol abuse and withdrawal
estrogen (causes more cortisol to bind to CBG)
glucocorticoid resistance
complicated diabetes

Question 29

characteristics of cushing syndrome

Answer 29

truncal obesity 
moon face
buffalo hump
acne, hirsutism
striae
hypertension 
osteoporosis
amenorrhea
diabetes (causes insulin resistance)

Question 30

things to consider after cushing syndrome treatment (outpatient management)

Answer 30

long term follow up because relapses happen in a big number of patients

after removal of tumor, the HPaxis will remain suppressed (for months to years) thus hydrocortisone replacement needs to take place

Question 31

what’s conn’s syndrome

Answer 31

Primary aldosteronism

aldosterone producing adrenal adenoma

Question 32

causes of primary hyperaldosteronism and its treatment

Answer 32

Conns syndrome
primary idiopathic hyperplasia
primary adrenal hyperplasia
aldosterone producing carcinoma 
ectopic aldosterone producing adenoma/carcenoma
glucocorticoid remediable aldosteronism

treated surgically for adenomas

for bilateral hyperplasia we use spironolactone (K sparing diuretic that is aldosterone antagonist)

Question 33

whats glucocorticoid remediable aldosteronism

Answer 33

mutation in 11B hydroxylase which results in mineralocorticoid secretion control under ACTH => treat with glucocorticoid therapy

Question 34

effects of cortisol on the WBC counts

Answer 34

neutrophils are increased (neutrophilia)because of inhibition of migration