Directed Study Flashcards
What can lead to a secondary adrenocortical insufficiency (thus decreasing secretion of cortisol and adrenal androgens)?
ACTH Deficiency
What is ACTH excess?
Adrenal hyperfunction (Cushing Syndrome)
Is plasma ACTH a reliable indicator of pituitary function?
NO- It has a short plasma half life with episodic secretion
What does plasma ACTH have to be measured with to differentiate primary versus secondary adrenocortical insufficiency?
Simultaneous measurement of cortisol secretion
Why are basal cortisol levels generally unreliable?
They are low in the afternoon and evening (no value for diagnosis) and have a normal diurnal rhymthm
When should plasma cortisol be taken?
8AM
What is considered a deficiency of plasma cortisol?
Uner 5 ug/dL (lower it is, the more suggestive)
What level of plasma cortisol is not a deficiency and can virtually exclude diagnosis?
Over 20ug/dL
When should salivary coritsol be taken?
8AM
What is considered a deficiency for salivary cortisol?
Under 1.8 ng/mL
What level is considered not a deficiency of salivary cortisol and reduces the possibility of diagnosis?
Over 5.8 ng/mL
What is needed to diagnose secondary adrenal insufficiency (ACTH hyposecretion)?
Provacative testin (adrenal stimulation)
What is given in provactive testing to stimulate the adrenal?
Cosyntropin (a synthetic ACTH analogue)
After administration of cosyntopin, what is the normal cortisol response within 30 minutes?
Over 18-20 ug/dL
True or False: Stimulation of the adrenal gland with cosyntropin evaluates the ability of the HPA axis to respond to stress?
FALSE
What is considered a suboptimal response to cosyntopin, confirming adrenocortical insufficiency?
Under 20 ug/dL
When is evaluation of pituitary ACTH reserve unnecessary?
If cortisol response to rapid ACTH is subnormal (under 20 ug/dL) –> Adrenocortical insufficiency
What are 3 ways to evaluate pituitary ACTH reserve?
- Insulin-induced hypoglycemia
- Metyrapone Administration
- CRH stimulation
What must be achieved in insulin-induced hypoglycemia?
Blood glucose under 40 and patient should experience adrenergic symptoms like diaphoresis, tachycardia, weakness, and headache
In an insulin-induced hypoglycmiea test, what indicates normal ACTH reserve?
Plasma cortisol increases less than or equal to 20ug/dL
What are contraindictations to insulin-induced hypoglycemia test?
Elderly, cerebrovascular disease, cardiovascular disease, seizure disorder
If you suspect diminished adrenal reserve, waht would you prevede the insulin-induced hypoglycemia test with?
ACTH stimulation test
What 2 things does metyrapone administration do?
Inhibits P450c11 and interrupts negative feedback on HPA
What is p450c11?
11B-hydroxylase, which catalyzes the final step of cortisol synthesis
What does metyrapone administration result in?
Compensatory increase in ACTH
How is the compensatory increase in ACTH detected with metyrapone administration?
As increased precursor steroid, 11-deoxycortisol in plasma
What type of testing is preferred with metyrapone administration?
Overnight test (30mg/kg at midnight)
In a healthy individual, 11-deoxycortisol should raise to what the following morning after metyrapone administration?
Less than or equal to 7ug/dL
If there is suspected adrenal insufficiency, what should the metryapone administration test be preceded with?
ACTH stimulation test
What is given in the CRH stimulation test?
IV ovine CRH
True to False: CRH stimulation is less useful than insulin-induced hypoglycemia or metyrapone test for partial secondary adrenal insufficiency
TRUE- It overlaps with normal
In a health person when should peak ACTH and cortisol response be after CRH stimulation?
ACTH: 15 minutes
Cortisol: 60 minutes
In primary adrenal insufficiency, what is seen with CRH stimulation?
Elevated basal ACTH and exaggerated response to CRH
In secondary adrenal insufficiency with pituitary corticotroph destruction, what is seen after CRH stimulation?
Absent ACTH response
In secondary adrenal insufficiency with hypothalamic dysfunction, what is seen after CRH stimulation?
Prolonged and augmented ACTH response, delayed peak
What is the imaging procedure of choice for the hypothalamus and pituitary?
MRI
Why is MRI better than CT for imaging of the hypothalamus and pituitary?
Better definition of normal structures and hight resolution
What planes is MRI imaging of the hpothalamus and pituitary done in?
Sagittal and coronal
What type of contrast is used for MRI of hypothalamus and pituitary?
Gadolinum (heavy-metal)
What is the most commong cause of hypothalamic-pituitary dysfunction?
Pituitary adenoma
Are most pituitary adenomas hyper or hypo secreting?
Hyper
Who do you see pituitary adenomas that secrete epinephrine?
Adults (rare in children)
What is the most common hormone secretion from a pituitary adenoma?
Prolactin
What is an intrasellar adenoma that is under 1cm in diameter with no sellar enlargment or extrasellar extension?
Microadenoma
What constitutes a macroadenoma?
Over 1cm in diameter and may extend suprasellar, into sphenoid sinus or lateral extension
What is the most frequent endrocrinologic abnormality and earliest symptom of a pituitary adenoma?
Hypogonadism
What causes hypogondadism?
Reduced GnRH
What does reduced GnRH result in?
Reduced FSH and LH
What causes primary gonadal failure?
Elevated FSH and LH
What things have a negative feedback on paraventricular neurons releasing GnRH?
Prolactin, GH, ACTH, and cortisol
What decreases anterior pituitary sensitivity to GnRH?
Prolactin
What causes acromegaly?
Hypersecretion of GH
Hypersecretion of ACTH results in what?
Cushing Syndrome
What are late manifestations of pituitary adenomas?
HA, visual loss (large tumors, due to suprasellar extension)
What visual defects are seen in pituitary adenomas?
Bitemporal hemianopsia (optic chiasm)
-If you see this, it is pituitary/hypothalamic disorder until proven otherwise)
If your patient has diplopia, what has happened?
Pituitary adenoma has extended into the cavernous sinus, affecting CN III, IV, VI
If a child has short stature, what might you suspect?
GH deficiency…. this is most frequent presentation of hypothalamic-pituitary dysfunction
That is treatment for pituitary adenoma?
Surgery, irradiation, or drugs to suppress hypersecretion or growth
What is the most common hypersecreting pituitary adenoma?
Prolactinoma
What does a prolactinoma cause in men?
Impotence, decreased libido
What does a prolactinoma cause in women?
Glactorrhea, amenorrhea
How do you diagnose prolactinoma?
MRI, PRL levels
Who do you measure PRL levels in?
Patients presenting with glacatorrhea, sellar enlargement, gonadal dysfuncion, amenorrhea, infertiliy, decreased libido, impotence
What is seen on histology with a prolactinoma?
Chromophobic, small and uniform, round/oval nuclei and scant cytoplasm, diffuse capillary network in stroma
What is done for treatment for prolactinoma?
- Dopamine agonist: Bromocriptine/Cabergoline
- Surgery: Transsphenoidal, microsurgery
- Radiotherapy: Persistent hypoerprolactinemia and not responded to surgery or dopamine agonists
What is the DOC for prolactinoma that is administeres 1-2 times/week and has a better SE profile than bromocriptine?
Cabergoline
What does cabergoline do?
Reduces microadenoma size and PRL levels
Who do you have to be careful in giving caergoline to?
Parkinsons disease patients receiving treatment- Risk of cardiac valve (need echo if long term treatment indicated)
Who do you see empty sella syndrome in?
Middle-aged obese women
What are some associations with empty sella syndrome?
Systemic HTN and benign intracranial HTN
What is the etiology of empty sella syndrome?
Subarachnoid space extends into the sella turcica (partial filling with CSF)
What does the subarachnoid space extending into the sella turcica lead to?
Remodeling and enlargement of sella with flattening of the pituitary
What causes primary empty sella?
Congential incompetence of diaphragma sellae
What are other causes of empty sella?
Pituitary surgery, radiation therapy, postpartum pituitary infarction (Sheehan syndrome), subclinical hemorrhagic infarction (PRL-/GH-secreting adenomas)
What is seen clinically with empty sella syndrome?
Uncommon.. but HA, CSH rhinorrhea, visual field impairment
How do you diagnose empty sella syndrome?
MRI
What is the % success for convential irradiation therapy for acromegaly?
60-80%
If supervoltage irradiation used for acromegaly?
NO…the GH levels take 10-15 years to normalize and there are severe consequences
What are the severe consequences of supervoltage irradiation?
Hypopituitarism, hypothyroidism, hypoadrenalism, hypogonadism
What is the success rate of gamma knife surgery for acromegaly?
50-70% at 2 years following therapy
What can radiotherapy cause in Cushing’s Syndrome?
Loss of pituitary function in over 50% of patients and visual defects (due to damage to the optic chiasm or cranial nerves)
What is the % success rate for conventional radiotherapy for Cushing’s?
55-70% remission at 1-3 years
What is the % remission seen with gamma knife therapy for Cushing’s?
65-75% remission at 1-3 years
Why is a single measurement of ACTH and adrenal hormones frequently unreliable?
ACTH and adrenal hormones
What is normal plasma ACTH?
9-52 pg/mL
In adrenal insufficiency (primary adrenal disease), what happens to ACTH levels?
ELEVATED
In Cushing’s syndrome (primary glucocorticoid-secreting adrenal tumor), what happens to ACTH levels?
LOW (under 5 pg/mL)
What happens to ACTH in congenital adrenal hyperplasia?
ELEVATED
What happens to ACTH in Cushing disease (pituitary ACTH hypersecretion)?
ACTH is inappropriately normal or elevated
What happens to ACTH in ectopic ACTH syndrome?
ACTH is markedly elevated
What happens to ACTH in pituitary ACTH deficiency and secondary hypoadrenalism?
ACTH is normal or under 10pg/mL
What 2 things can metyrapone testing do?
- Diagnose adrenal insufficiency
2. Assess pituitary-adrenal reserve
What does metyrapone do?
Blocks cortisol synthesis by inhibiting 11B=hydroxylase, resulting in a buildup of 11-deoxycortisol)
What does the reduction of cortisol syntehsis from metyrapone result in?
Increased ACTH (increases 11-deoxycortisol)
What is a normal response, indicating normal ACTH secretion and adrenal function in a metyrapone test?
11-deoxycortisol over 7ng/dL
Plasma ACTH over 100 pg/mL
What indicates adrenocorticol insufficiency with a metyrapone test?
11-deoxycortisol under 7ng/dL
What is the rapid ACTH stimulation test?
Acute adrenal response to ACTH
What does the rapid ACTH stimulation test diagnose?
Primary and secondary adrenal insufficiency
What agent is used for the rapid ACTH stimulation test?
Cosyntropin (synthetic ACTH)
-Also teracosactin
What are the steps in the procedure of the rapid ACTH stimulation test?
- Baseline cortisol obtained
- Cosyntropin administered (250 ug IM or IV)
- Plasma cortisol samples taken at 30/60 minutes
What is a normal response to ACTH stimulation test?
Peak corisol over 18ug/dL
With peak cortisol over 18ug/ML in the ACTH stimulation test, what does this exclude and what does it not rule out?
- Excludes primary and overt secondary adrenal insufficiency
- Doesn’t rule out partial ACTH deficiency (decreased pituitary reserve… need to test further with metyrapone, hypoglycemia, or CRH)
What indicates adrenal insufficiecny with the ACTH stimulation test?
Peak cortisol under 18ug/dL
What is seen in pituitary ACTH-dependent Cushing Syndrome?
Pituitary adenoma secreting ACTH with ELEVATED ACTH
What is seen in pituitary ACTH-independent Cushing Syndrome?
Adrenal tumor, LOW/UNDETECTABLE LEVELS OF ACTH
What does the overnight dexamethasone suppression test establish the presence of?
Cushing Syndrome
What is dexamethasone and how does it work?
Potent glucocorticoid
-Suppresses pituitary ACTH release, reducing plasma/urine cortisol, reducing feedback inhibition
What is done in the overnight dexamathasone suppression test?
1mg of dexamethason is given at 11PM, with plasma cortisol measured the folloing morning
What is a normal serum/plasma cortisol level with the overnight dexamethasone suppression test?
Uner 1.8ug/dL
If there is normal cortisol levels indicating that the dexamethasone suppression didn’t suppress cortisol, what is done?
High dose (8mg) test
With the high dose dexamathasone suppression test, what indicates Cushing’s?
Plasma cortisol uner 50% baseline values and a high ACTH
What is the diagnosis is the high dose dexamethasone suppression test fails to suppress cortisol levels (normal/elevated cortisol) and normal to elevated ACTH?
Ectopic ACTH syndrome
What is seen in the high dose dexamethasone suppression test in a cortisol-producing adrenal tumor
Fails to suppress (normal to elevated cortisol) and low/undetectable ACTH
