Anterior Pituitary - Exam 3 Flashcards
The anterior pituitary is supplied by the ______ artery. The posterior pituitary is supplied by the _____.
anterior: superior hypophyseal artery and receives hypothalamic hormones through long portal vessels in vascular network
posterior: inferior hypophyseal artery and receives hypothalamic hormones to vascular network through DIRECT neural extension
Name the tropic hormones that are released by the AP and what hormone controls them in the hypothalamus
Hypothalamus -> AP
CRH->ACTH
TRH -> TSH
GnRH -> LH/FSH
Prolactin-releasing peptide -> Prolactin
Somatocrinin (stimulates) Somatostatin (inhibits) -> Growth hormone
Which hormone is usually in a SUPPRESSED state? What hormone is responsible for suppressing it?
Prolactin
is suppressed by prolactin-inhibiting factor (PIF) may be dopamine
Dopamine increases = _____ Prolactin. PRL remains in an inhibited state most of the time by _____
decreases
dopamine
What are the 5 types of endodrine CELLS in the AP, name them and what do they secrete?
somatotrophs = GH
lactotrophs = Prolactin
gonadotrophs = LH & FSH
corticotroph = ACTH
thyrotroph = TSH
What endocrine condition is commonly seen in chronic opioid users?
Hypopituitarism
63% of users will have this!
What is Prader-Willii syndrome?
rare genetic disorder that involves anorexia at birth to excessive weight gain preceding hyperphagia, and early severe obesity with hormonal deficiencies, behavioural problems, and dysautonomia. Growth hormone deficiency, hypogonadism, hypothyroidism, premature adrenarche, corticotropin deficiency, precocious puberty, and glucose metabolism disorders are the main endocrine dysfunctions observed
What is Kallmann syndrome?
a rare genetic disorder that prevents or delays puberty and causes a decreased sense of smell
What is Hypopituitarism?
Disorder in which all the hormones that are secreted in the AP do not function properly. S/S will present as a deficiency in those hormones.
GH: growth disorders
Gonadotropin: decreased sexual function, menstrual disorders etc etc
TSH: hypothyroidism in children and adults
ACTH: hypocortisolism
Prolactin: failure of lactation
Prolactin (PRL) is synthesized in _____. The MC cause of pituitary adenoma is ______.
lactotrophs
prolactinoma
Significant lactotroph cell hyperplasia develops during _____ in response to increased ____ and during first few months of lactation
pregnancy
estrogen
What are the normal serum levels of PRL? include men and women
men: 10-20
women: 10-25
PRL levels increase about tenfold during pregnancy and decline rapidly within 2 weeks of parturition UNLESS ?????. The increase in PRL is in response to the elevated ????. What stimulates an increase in PRL?
a women continues to breastfeed
estrogen and progesterone
Suckling
The magnitude of PRL increase is directly proportional to the degree of ????? due to estrogen - lactotrophs increase in pregnancy, therefore increasing the amount of PRL that can be released
preexisting lactotroph hyperplasia
Name 4 ways serum prolactin levels rise mildly and transiently
- Exercise, meals, sexual intercourse
- Breast exam, chest wall injury/infection (i.e. shingles)
- Minor surgical procedures, general anesthesia
- Stress of any kind - reduction of dopamine!
PRL secretion is _____. When is PRL at its highest?
pulsatile
occurring during non-REM sleep between 4-6am
circulating 1/2 life is 50 minutes
What are the effects of prolactin on lactation, reproductive function and sex drive
induces and maintains lactation
decreases repro function
suppresses sex drive
Reproductive function suppressed by ?????? also impaired gonadal steroidogenesis (LH/FSH). You will also see low ____ and _____.
inhibiting GnRH and gonadotropin secretion
low estrogen and anovulation
**_____ is the most common pituitary hormone hypersecretion syndrome in both men and women
Hyperprolactinemia
_____ are the most common cause of PRL levels >200 μg/L (normal level is about 10-20 for men and 10-25 for women). These are common in families with ____
PRL-secreting pituitary adenomas (prolactinomas)
MEN type 1 or 4
**Why would stalk compression cause hyperprolactinemia?
stalk compression would increase prolactin
kidney damage: increases prolactin
TRH increase: increases prolactin
**What are the causes of HYPERprolactinemia
Amenorrhea, galactorrhea, and infertility
decreased libido, weight gain, mild hirsutism
longterm: osteopenia and reduced muscle mass
**What are the hallmarks clinical presentation of hyperprolactinemia? What are some additional findings?
Hyperprolactinemia causes ____ and _____ in men. Name some clinical manifestations. Name some long term effects.
hypogonadotropic (decreased FSH/LH)
hypogonadism (decreased testosterone)
Decreased libido
Impotence/erectile dysfunction
Infertility
Gynecomastia
Galactorrhea - less common in men
longterm: osteopenia, reduced muscle mass, and decreased facial hair growth.
How are osteoporosis and estrogen related?
low estrogen levels lead to premature osteoporosis
In a normal women, estrogen helps promote new bone formation
When evaluating a pt for hyperprolactinemia, our PE should focused on testing for ____, _____ and _______. What is the major one and why?
chiasmal syndrome, and signs of hypothyroidism or hypogonadism
**specifically ask about HA and vision changes that could point towards a mass near/pressing on the optic chiasm
What are the labs you would want to order on a pt with Hyperprolactinemia? Why?
Serum prolactin concentration
TSH/T4
Serum Hcg: to check and see if pt is pregnant
CMP
Men: serum total and free testosterone, LH, and FSH
Women: estradiol, LH, and FSH
What are the pt education points with Serum Prolactin concentration in order to get an accurate result? What is normal value? What are some factors that can make serum prolactin increase? What is the result is 21ng/mL?
basal, FASTING, morning PRL level (normally <20 μg/L)
sleep
strenous exercise
emotional/physical stress
intense breast stimuation
high protein meals
Therefore, a slightly high value (21 to 40 ng/mL) should be repeated and confirmed before the patient is considered to have hyperprolactinemia
**What diagnostic study will offer us a def dx for a pituitary mass in a pt with hyperprolactinemia?
MRI to assess for mass if PRL level is found to be elevated and no other cause is determined, or if PRL > 200
What if the MRI is normal in a pt with hyperprolactinemia, what is the dx?
the diagnosis of idiopathic hyperprolactinemia is made.
What constitutes a MICROprolactinoma? What is the treatment?
microprolactinomas (< 1cm)
estrogen, estrogen/progesterone, or testosterone replacement
What is the treatment for MACROprolactinoma? What is the treatment for hyperprolactinemia without a mass/underlying cause?
dopamine agonist
dopamine agonists
hyperprolactinemia: If visual fields affected or patient is resistant to medical therapy, _____ is an option.
surgery
Why do you NOT give hormone replacement therapy to MACROprolactinomas?
the hormones could feed the macroprolactinoma
What is the MOA for Cabergoline and Bromocriptine? Which one is short/long acting? Which one do you give if the pt is trying to get pregnant? Which one has LESS SE?
Suppress PRL secretion and synthesis as well as lactotroph cell proliferation
Cabergoline: long- acting dopamine agonist
Bromocriptime: short- acting dopamine agonst give in pregnancy is desired
Cabergoline has LESS adverse effects and drug intolerance
**What are the common SE of dopamine agonists?
constipation, nasal stuffiness/congestion, dry mouth, nightmares, insomnia, and vertigo
Patients with Parkinson’s disease who receive at least 3 mg of cabergoline daily have been reported to be at risk for development of ______
cardiac valve insufficiency
recommend echo before starting therapy
How effective are dopamine agonists? Are they safe to take in pregnancy?
VERY effective!! prolacinoma tend to shrink quickly but max benefit may take up to a year
long term therapy is required unless adenoma is resected
OKAY to take with pregnancy
HYPOPROLACTINEMIA is due to low serum prolactin levels due to ???. **What is the clinical manifestation?
damaged lactotroph cells in anterior pituitary
**inability to lactate after delivery.
most of the time, pts will have another pituitary hormone deficiency in addition to hypoprolactinemia
**What are 3 possible causes of hypoprolactinemia?
Sheehan’s syndrome
Medications: dopamine agonists (inhibits prolactin release) or antiparkinson’s drugs
Tumors
**What is Sheehan’s Syndrome?
postpartum hypopituitarism caused by necrosis of the pituitary gland. It is usually the result of severe hypotension or shock caused by massive hemorrhage during or after delivery
aka traumatic event during birth
What are the two treatments for HYPOprolactinemia?
Dopamine antagonists or many antipsychotics (Haloperidol, Olanzapine, Metoclopramide)
or
Surgery
GHIH = ______
GH = _____
IGF-I = ______
GHIH = somatostatin
GH = somatotropin
IGF-I = somatomedin
GH induces _____ and impairs ____ by antagonizing insulin action. Also stimulates ____ and _____
protein synthesis
glucose tolerance (leads to hyperglycemia)
lipolysis
promotes lean muscle mass
What are the direct effects of GH?
Lipolysis: breaks down fats for energy and increases metabolism for other cells
Liver: promotes gluconeogenesis
increases insulin resistance in tissues: aka insulin cannot move glucose into cells and the blood glucose levels rise leading to the release of more insulin
What are the indirect effects of GH?
release of IGF-1 which in turns acts on bones, long bones and muscles
_____ is the most abundant AP hormone. What percentage of the total anterior pituitary cell population?
Growth Hormone
up to 50%
Secretion of GH is controlled by both hypothalamic and peripheral factors. Name some of both. When is GH at its highest?
hypothalamic: GHRH stimulates GH synthesis and release
Somatostatin: synthesized in the medial preoptic area of the hypothalamus and inhibits GH secretion
Peripheral factors: sleep, stress, exercise, decreased blood glucose levels
GH secretion is pulsatile, with highest peak levels occurring at night, generally correlating with sleep onset.
Describe when happens to GH as people age
GH secretory rates decline markedly with age so that hormone levels in middle age are about 15% of pubertal levels
____ is the major source of circulating IGF-. As GH levels increase, the liver _____. As GH levels decrease, the liver _____.
Liver
synthesizes more IGF-1
synthesizes less IGF-1.
Serum IGF-1 concentrations, what are the two trends?
Levels increase during puberty, peak at 16 years, and subsequently decline by >80% during the aging process.
IGF-I concentrations are higher in women than in men.
Growth hormone deficiency may result from ???? in the hypothalamus or pituitary, and can be congenital or acquired. Name some causes of acquired GH deficiency
disruption of the growth hormone axis
trauma, infections, cranial irradiation (that damages the somatotrophs)
Mortality in children with growth hormone (GH) deficiency is due almost entirely to other ????. What are they at higher risk for?
pituitary hormone deficiencies - not usually due to isolated GH deficiency
increased relative risk of death in adulthood from cardiovascular causes resulting from altered body composition and dyslipidemia
because Growth hormone helps decrease cholesterol levels
What is GH insensitivity caused by? **How is the dx made?
defects of GH receptor structure on target organs or signaling
The diagnosis is based on normal or high GH levels, with decreased circulating growth hormone binding protein (GHBP), and low IGF-I levels.
_____ is the single most important clinical manifestation of GHD. What are some other clinical manifestations?
Growth failure
short stature, micropenis, increased fat, high-pitched voice, and hypoglycemia
If you suspect a GH deficiency what areas should you focus on?
Birth weight and height
Height of parents
Timing of puberty in parents
Previous growth points - GROWTH VELOCITY!
General health of child
Nutritional history
The best way to evaluate height or weight measurements is to ????? and note: (3 things)
plot the points on a growth chart
Proportionality
Pubertal status
Evidence of genetic syndromes
Which children need to be evaluated for GH deficiency?
- Marked short stature, more than 2.5 SD below the mean (approx <0.5 percentile)
- Growth failure, growth should not drop more than 25%, i.e. should not go from 90th percentile to 10th percentile
- Less severe short stature (approx 0.5-3rd percentile) combined with growth failure and in the absence of an alt explanation
- Evidence suggesting hypothalamic-pituitary dysfunction (hypoglycemia, microphallus, cryptorchidism, optic nerve hypoplasia, intracranial tumor, or history of cranial irradiation), with decelerating growth, even if the child’s height is within the normal range.
- Evidence for deficits in other hypothalamic-pituitary hormones, either congenital or acquired.
What is the first step when evaluating a child for GH deficiency?
evaluate for other causes of growth failure, including chronic systemic disease, hypothyroidism, Turner Syndrome, and skeletal disorders
Name 4 tests can will help you determine evidence of GHD (Growth Hormone Deficiency)
GH stimulation test
Insulin-like growth factor-1 (IGF-I)
Insulin-like growth factor binding protein-3 (IGFBP-3) - Main carrier of IGF-I in body.
Bone age
How do you do the bone age test?
single X-ray of the left wrist, hand, and fingers. The bones on the X-ray image are compared with X-ray images in a standard atlas of bone development. The atlas is based on data from many other kids of the same gender and age. The bone age (also called the skeletal age) is measured in years
What is the assessment of GH difficult? Are random serum GH levels helpful?
because GH secretion is pulsatile, with the most consistent surges during stages 3 and 4 of sleep
Between normal pulses of GH secretion, serum GH levels are often low, below the limits of sensitivity of most conventional assays. This means random serum GH level is not helpful in diagnosing growth hormone deficiency (GHD)
**GH stimulation tests are a valuable diagnostic tool when combined with measurements of ____ and ____
IGF-I
IGFBP-3
**The GH stimulation test relies on both ____ and _____ stimuli. **Name 3 physiologic stimuli. Name some Pharmacological stimuli. How many times do you have to complete the test and it be abnormal in order to make the dx?
physiological or pharmacological stimuli.
**sleep, fasting, and exercise
L-dopa, clonidine, propranolol, arginine, and insulin-induced hypoglycemia
confirmed only if subnormal GH secretion is observed during two different GH stimulation tests - so they have to come back TWICE!
What are the important pt education points for a GH stimulation test? What is considered abnormal and points to a GH def?
These stimulation tests are performed after an overnight fast
If GH does not increase substantially, then it is considered a positive test (normal is rise to GH greater than 7, in GHD hormone levels will not increase substantially)
What is the diagnostic TOC for GHD?
MRI permits excellent visualization of the pituitary-hypothalamic system
MRI not available: choose brain CT with contrast (looking for pituitary tumor)
What is the treatment for GHD?
Recombinant GH (0.02–0.05 mg/kg per day subcutaneously) restores growth velocity in GH-deficient children to ∼10 cm/year
Somatropin (Genotropin, Humatrope, Norditropin, Nutropin, Omnitrope, Saizen, TevTropin)
What is the treatment for GH insensitivity? What are the GH levels like in these patients? What tests do you order?
the GH receptor is mutated so need to bypass the receptor and treat with IGF-I
GH levels normal or elevated in these patients
IGF-1 testing AND GH stimulation testing usually
GHD in adults in rare but can be caused by ____ and _____. What are some examples of how damage could occur
hypothalamic or pituitary somatotroph damage.
pituitary surgery
pituitary or hypothalamic tumor or granulomas
history of cranial irradiation
radiologic evidence of a pituitary lesion
childhood requirement for GH replacement therapy
unexplained low age- and sex-matched IGF-I levels
What is the sequential order of hormone loss ?
usually GH → FSH/LH → TSH → ACTH
aka if we lose GH we see the rest of the hormones follow because this is caused by pituitary damage as a whole
What are some clinical features of GHD in adults?
Changes in body composition: Reduced lean body mass, increased fat (increased waist/hip ratio), Hypoglycemic
Changes in lipid metabolism: hyperlipidemia
Cardiovascular dysfunction: GH stimulates myocardial hypertrophy, LV dysfunction, HTN
MSK: increased incidence of fractures secondary to reduced bone mineral content
Psych changes: ncreased incidence of depression, social isolation, fatigue
What is the testing for GHD in adults?
same as in children PLUS
Pharmacologic Growth Hormone Stimulation Test
**How do you interpret the Pharmacologic Growth Hormone Stimulation Test (insulin)?
**Should cause growth hormone to increase to >5ng/mL because we are stimulating hypoglycemia
**Severe GH deficiency has been defined as inability to produce GH levels >3ng/mL
need to know the numbers
What is the alt test for Pharmacologic Growth Hormone Stimulation Test - Insulin? When is it indicated?
GHRH + arginine test has also been proposed to be an equally sensitive alternative to insulin. Results are read the same.
diabetic patients or unable to tolerate insulin
Once the diagnosis of AGHD is unequivocally established, What is the treatment? What are the CI?
recombinant human growth hormone (rhGH, somatropin) injections
presence of an active neoplasm - could feed
intracranial hypertension
uncontrolled diabetes and retinopathy - why?
How do Recombinant human growth hormone rhGH (Somatropin) work?
Assists growth of linear bone, skeletal muscle, and organs by stimulating chondrocyte proliferation, lipolysis, protein synthesis, and hepatic glucose output
What are the monitoring requirements for anyone on Recombinant human growth hormone rhGH (Somatropin)?
fundoscopic exam: intracranial hypertension
Adults: IGF-1 every 1-2 months during titration, then semiannually at maintenance
Children: Monitor growth curve and physical exam with skeletal assessment with every visit
**What are some SE of Recombinant human growth hormone rhGH (Somatropin)? What are you at a higher risk of developing?
**fluid retention, joint pain, and carpal tunnel syndrome, myalgias and paresthesias
Hyperglycemia and DM can develop
_____ secrete GH from the Anterior Pituitary.
Somatotrophs
____ is the hormone that INHIBITS GH secretion from Anterior Pituitary.
somatostatin
_____ is another name for IGF-1.
somatodmedin
____ is a treatment for GH deficiency.
somatrophin
_____ is excess GH in adults after the bones fuse.
_____ is excess GH in children before the bones fuse
Acromegaly
Gigantism
**GH hypersecretion is usually the result of a ____- but may rarely be caused by extrapituitary lesions. Where are some common places for ectopic GH secreting tumors to be?
somatotroph adenoma
pancreatic, ovarian, lung, or hematopoietic origin
**What is the MC cause of GH hypersecretion?
chest or abdominal carcinoid tumor.
frontal bossing
increased hand and foot size
mandibular enlargement with prognathism
widened space between the lower incisor teeth
increased heel pad thickness
Increased shoe/glove size - tight rings
Coarse facial features
Large, fleshy nose
hyperhidrosis
deep and hollow-sounding voice
oily skin
arthropathy
kyphosis
carpal tunnel syndrome
proximal muscle weakness and fatigue
acanthosis nigricans and skin tags
What am I?
What is the normal onset?
Acromegaly
very slow moving and usually not dx for 10+ years
In acromegaly: generalized visceromegaly occurs, including _____, _____ and _____
cardiomegaly, macroglossia, and thyroid gland enlargement
The most significant impact of GH excess occurs with respect to the _____. What are some additional long term effects of GH excess?
**cardiovascular system: Cardiomyopathy with arrhythmias
sleep apnea
DM
colon polyps
survival rate is decreased by an average of 10 years
**Overall mortality is increased about threefold and is due primarily to _____, _____ and _____.
cardiovascular, cerebrovascular disorders, and respiratory disease.
Why are random GH levels not useful?
because GH declines as we age and is puseitale and fluctuates throughout the day, highest in the morning.
How is the dx of acromegaly confirmed?
confirmed by demonstrating the failure of GH suppression to <0.4 μg/L within 1–2 h of an oral glucose load (75 g).
High glucose stimulates somatostatin release - GHIH
What is the goal of treatment for GH excess?
control GH and IGF-I hypersecretion, ablate or arrest tumor growth, restore mortality rates to normal, and preserve pituitary function
What are two primary treatments for GH excess?
Surgery: Transsphenoidal surgical resection is the preferred primary treatment
radiation
**What are some SE of Somatostatin analogues? What is goal?
Nausea, abdominal discomfort, fat malabsorption, diarrhea, and flatulence occur in one-third of patients, and these symptoms usually remit within 2 weeks
to decrease GH
Somatostatin analogue ____ suppresses postprandial gallbladder contractility and delays gallbladder emptying;
Octreotide
lanreotide
octreotide
pasireotide
Sandostatin
Sandostatin LAR
Signifor
Somatuline Depot
Are all examples of what class of medication?
Somatostatin analogues
Pegvisomant is in what medication class? What does it treat? What is the drawback?
GH Receptor Antagonists
GH excess
EXPENSIVE but effective
____ and _____ may modestly suppress GH secretion in some patients. They must be used in _____. When using _____ and ______ together may acheive better control than when used alone.
Bromocriptine and cabergoline: must be used in high doses to achieve therapeutic effect
octreotide and cabergoline
What is the summary of treatment for GH excess
oligomenorrhea
amenorrhea
infertility
decreased vaginal secretions
decreased libido
osteoporosis
What am I?
hypogonadism in women
decreased libido
impotency
infertility
decreased muscle mass
reduced beard and body hair growth
What am I?
hypogonadism in men
_____ is the most common presenting feature of adult hypopituitarism. Why?
hypogonadism
because the s/s are very bothersome to patients and they seek treatment
What is the source of error in primary hypogonadism? Secondary hypogonadism?
Primary: source of error is coming from the testicles
secondary: source of error is coming from the hypothalamus or pituitary
What labs do you need to order when working a pt up for hypogonadism? What is considered low?
Males: morning serum testosterone AND free testosterone
serum testosterone: below 240
free testosterone: below 35
LH/FSH
PRL
TSH
females: hCG, PRL, FSH/LH and TSH
____ can sometimes be used to confirm menopause
FSH
in secondary hypogonadism both _____ and ____ will be low. In primary hypogonadism, _____ is low and ____ is normal
LH/FSH and testosterone will be low
testosterone is low and LH/FSH is normal
What is the treatment for hypogonadism in men? What if the man is trying to have children?
Testosterone replacement: IM injection q 1-4 weeks
human chorionic gonadotropin (hCG) (equivalent to LH)
____ is a testosterone alternative for patients with an intact pituitary given by subcutaneous infusion
leuprolide (GnRH analog)
_____ 25-50 mg/day orally, can sometimes stimulate men’s own pituitary gonadotropins (if pituitary is intact), increasing testosterone and sperm production. Can also use to induce ovulation in females (50-100mg/day orally for 5 days every 2 months).
Clomiphene (Clomid)
What is the treatment for hypogonadism in females? _____ is used for ovulation induction. Follicular growth and maturation initiated using _______ or recombinant FSH; LH is injected to induce ovulation
Cyclical replacement of estrogen and progesterone to maintain secondary sexual characteristics, prevent osteoporosis
Gonadotropin therapy
human menopausal gonadotropin (hMG)
