Lecture 5 - Pituitary Disorders Flashcards
What is the best imaging modality for looking at pituitary?
MRI
at T1
What are common disorders of the anterior pituitary?
pituitary tumors
hypofunction
hyperfunction
What are the common disorders of the posterior pituitary?
Diabetes insipidus
SIADH
What hormones are synthesized and stored in the anterior pituitary?
FSH LH TSH ACTH PRL GH
What hormones are stored in the posterior pituitary and where are they produced?
AVP
Oxytocin
produced in the hypothalamus
The 7 I’s
causes of hypopituitarism
Invasive (adenomas) Infarction Infiltrative Injury Immunologic Iatrogenic Isolated
Sheehan’s syndrome
infarction hypopiutitarism
seen in pregnancy MC
mechanism for ischemia uncertain - believed to be hypotension and vasospasm of the hypophysial arteries
extent of pituitary damage determines speed of onset of hypopituitarism: days to weeks to months
failure to lactate, post-partum menstrual irregularities
What infiltrating diseases can cause hypopituitarism?
sarcoidosis
hemochromatosis
Langerhan’s Histiocytosis
Lymphocytic hypophysitis
immunologic cause for hypopituitarism
seen during pregnancy and post-partum period
infiltration of pituitary by lymphocytes and plasma cells that destroys anterior pituitary
may result in isolated hormone deficiencies - ACTH most common
Gonadotropin deficiency
hypogonadotropic hypogonadism
Kallman’s syndrome:
defect in GnRH secretion and maldevelopment of olfactory center
List the hormones from early to late that become deficient in hypopiutitarism.
GH LH and FSH TSH ACTH PRL
What signs and sxs do you see in GH deficiency?
decreased muscle mass
increased fat mass
What signs and sxs do you see in LH and FSH deficiency?
amenorrhea
ED
decreased libido
Pituitary failure vs primary gland failure
pituitary failure = low levels of pituitary hormones
primary gland failure = high levels of pituitary hormones
Stimulation testing
not often used for thyroid or gonadotropin
used for GH or ACTH to determine if there is a true deficiency
ACTH stimulation test
draw baseline labs for ACTH and Cortsiol levels
inject cosyntropin (synthetic ACTH)
check cortisol levels 30 - 60 minutes later
If a person at baseline has low ACTH, after cosyntropin they have low cortisol and normal aldosterone, what does this mean?
this means central adrenal insufficiency
pituitary or hypothalamic failure
If a person at baseline has high ACTH, after cosyntropin they have low cortisol and low aldosterone, what does this mean?
primary adrenal insufficiency
adrenal gland failure
How do you dx isolated growth hormone deficiency in children?
typically noticed clinically vis length/height growth charts
then explore the possibility of systemic disease, hypothyroidism, Turner’s syndrome, or skeletal disorders
What percentile gets pts have evaluated for GH deficiency?
less than 25th percentile in height velocity
How do you treat ACTH deficiency?
glucocorticoids (PO)
hydrocortisone twice daily or prednisone daily
How do you treat ACTH deficiency if partial hypopituitarism?
may only need glucocorticoids during times of stress (like sepsis in the ICU)
Prolactinomas
prolactin - secreting pituitary adenomas
microprolactinoma <10mm (1cm) in size
- more common in women because the first sign they see is missing periods
macroprolactinoma >10mm (1cm)
- more common in men
What medications can you use to help shrink prolactinomas?
dopamine agonists (ideally D2)
- bromocriptine (D1 and D2 receptors)
- Cabergoline - more specific for D2 receptor
Cabergoline
D2 agonist used to shrink prolactinomas
long half life (can dose twice a wekk)
contraindications: uncontrolled HTN or known sensitivity in the liver
take at bed time, might have N/ HA, dizziness, or mental fogginess
Which prolactinomas are candidates for gamma knife radiotherapy?
tumors must be at least 5mm from the optic chiasm (any closer they can’t have the surgery)
Hypopituitarism
diminished or absent secretion of >1 pituitary hormones
development often slow and insidious
clinical presentation depends upon etiology of hypopituitarism
Which is more likely to cause hypofunction, large pituitary adenomas or small pituitary adenomas?
large pituitary adenomas
What kinds of trauma can result in hypopituitarism?
severe head trauma
physically abused children suffering closed head trauma
subdural hematomas
What infections can cause hypopituitarism?
TB
syphilis
fungal infections - rare unless immunocompromised
Isolated anterior pituitary hormone deficiencies
GH deficiency - usually in childhood
ACTH - RARE; lymphocytoic hypophysitis
Gonadotropin: hypogonadotropic hypogonadism –Kallman’s Syndrome
TSH deficiency - rare
PRL - sign of severe hypopiutitarism
What are the early and late hormone deficiencies seen with hypopituitarism?
early = GH
late = PRL
What is the normal progression of hormone deficiencies in hypopituitarism?
GH then LH and FSH then TSH then ACTH then PRL
How can you tell the difference between pituitary failure and primary gland failure?
pituitary failure = LOW levels of TSH, ACTH, LH and FSH
primary gland failure = HIGH TSH, ACTH, LH, FSH
When is stimulation testing used?
dx adrenal insufficiency and GH deficiency
ACTH is monitored before
cosyntropin is administered and then cortisol and aldosterone are measured after
What does it mean if ACTH is high during stimulation test, and cortisol and aldosterone are low?
primary AI (adrenal gland failure)
What does it mean if ACTH is low during stimulation test and cortisol is low and aldosterone is high?
Central AI (pituitary or hypothalamic failure)
When do you see isolated GH deficiency?
in children
typically marked short stature more than 2.5 SD below the mean
this dx would be excluded if a child was of normal height and bone age
How do you dx GHD?
growth hormone deficiency
this would have to be in a child of short stature
Low GH, IGF1, IGFBP3
ACTH deficiency
secondary d/t it being a problem with the pituitary gland itself
How do you treat ACTH deficiency?
glucocorticoids (PO)
hydrocortisone twice daily or prednisone daily
if partial hypopiutiatrism, may only need glucocorticoids during time of stress
How do you treat TSH deficiency?
levothyroixine PO –titrated based on FT4 and T3
How does the treatment of hypopituitarism change when there is concomitant adrenal insufficiency?
treat with glucocorticoid s prior to treatment with levothyroxine to avoid adrenal crisis
What is the treatment for gonadotropin deficiency?
women: estorgen/progesterone
men:
testosterone
What is the treatment for GHD?
hGH (sc only)
titrate based on IGF-1
Sheehan’s Syndrome
Hypopituitarism secondary to infarction
often see postpartum d/t increased aldosterone or metabolic need of pituitary during pregnancy? theories.
Why is the cortisol low in ACTH stimulation test fo secondary or central AI?
even though ACTH is low d/t a pituitary problem
the cortisol is still low because the zona fasciculata has atrophied, so even in the presence of ACTH it won’t produce cortisol (at least not at first)
What are 4 things you need to rule out in children with GHD?
systemic diseases
hypothyroidism
Turner’s syndrome (girls -45X)
Skeletal disorders
if these are negative then assess IGF-1 and bone age (via hand xray)
What are early and late signs of pituitary adenomas?
early:
- hypogonadism and oligomenorrhea/amenorrhea
Late:
-mass effect: HA, peripheral visual deficit
What kind of visual deficits might you see with pituitary adenoma?
bitempotal hemianopsia
Prolactinoma
prolactin secreting pituitary adenoma
Microprolactinoma
<10 mm in size
MC in women
PRL level correlates with size or prolactinoma
Macroprolactinoma
> 10mm in size
MC in men
PRL level correlates with size or prolactinoma
How does a pt with prolactinoma present?
menstrual irregularities galactorrhea visual field defects HA libido potency failure
What is the main medical treatment for prolactinomas?
Dopamine
dopamine inhibits PRL secretion
Bromocriptine - D1 and D2 receptor agonists
Cabergoline - D2 receptor agonist –LONG half life, taken twice a week, take at bedtime
What are the non medicine treatments for prolactinomas?
typically if the tumor has become resistant to dopamine
transsphenoidal surgery
Gamma knife radiotherpay (only if tumor in >5mm from optic chiasm)
If you want to do gamma knife for a pituitary adenoma, what must you make sure?
that the tumor is at least 5mm from the adenoma
Post removal of a pituitary adenoma, what must be checked?
pituitary function must be assessed annually
Acromegaly
excess GH in adults
overgrowth of bones: skill, mandible
mean age 40 years
sxs usually 5-10 years prior to dx
Gigantism
excess GH in children
long bones affected
How do you dx acromegaly?
IGF1 - since you cant measure GH d/t it changing so much throughout the day
OGTT - oral glucose tolerance test
OGTT
oral glucose tolerance test done for acromegaly dx
Glucose and GH are indirectly related
given glucose and then measure GH in 1 and 2 hours
for a normal person GH would be low
for acromegaly or excess GH in general it does not suppress in the presence of glucose
When do you get imaging for acromegaly?
AFTER biochemical confirmation to determine etiology of GH excess
majority of cases pituitary adenoma >1cm
What is the treatment for acromegaly?
transsphenoidal surgery
-80-90% success in those with tumors <1cm
large tumors may require medical therapy
Somatostatin –inhibit GH secretion
Pegvisomant - GH receptor antagonist
Gamma knife radiotherapy
What kind of long term follow up is required for acromegaly pts?
colonoscopy every 3-4 years d/t increased risk of colon polyps
CV eval regularly
IGF1, OGTT
follow tumor size via MRI yearly
What is the criteria for cure with acromegaly?
Fasting GH very low
Glucose suppressed GH very low
Normal IGF1 (idk why this would be normal if it is stimulated by GH in the liver?)
Cushings Disease
pituitary adenoma secreting ACTH
typically <10mm
What is the dx for Cushings Disease?
24 hour urine free cortisol or late night salivary cortisol or low dose dexamethasone suppression test
What is the treatment for Cushings disease?
transsphenoidal surgery
If you have a gonadotropin secreting adenoma, which hormone is it producing more of?
FSH > LH
What is associated with MEN 1 but not MEN 2?
pituitary adenomas are only seen in MEN 1
3 Ps Pituitary adenomas (prolactinoma, GH) Parathyroid adenomas (or hyperplasia) Pancreatic tumors (gastrinoma, insulinoma)
Pituitary apoplexy
hypopituitarism d/t hemorrhagic necrosis of a tumor of pituitary gland infarction
endocrine emergency
What are the clinical sxs of pituitary apoplexy?
sudden onset of frontal HA visual acuity and field loss ophthalmoplegia AMS N/V fever hypotension
What is the treatment for pituitary apoplexy?
IV dexamethason
Transphenoidal surgery
What are causes of central DI?
AVP deficiency
Spontaneous DI
- infiltrative disease
- lymphocytic hypophysitis
- head trauma
- neurosurgery
How do pts with central DI present?
cannot go long without water
cant leave home without water
frequent urination throught day and night
What is the treatment for central DI?
replace fluids and DDVAP (desmopressin)
SIADH
elevated urine sodium excretion while on normal salt and water intake
hypoosmolality of ECF
What are the causes of SIADH?
tumors CNS disorders drug-induced pulmonary diseases prolonged exercise (marathon running)
What is the treatment for SIADH?
fluid restriction
How do you dx prolactinoma?
MRI
Which prolactinomas get surgery?
macro
ADH and aldosterone
ADH –H2O retention
Aldosterone - Na+ reabsorption
