Pituitary and Hypothalamus II Flashcards
What is the physiology of GH
most abundant pituitary hormone, released from somatotrope cells in pulsatile way (stable during day)
half life is 12-16 hours
Secretion stimulated by GHRH (hypo) and inhibited by GHIH (SS)
*Peak level 1 hr after onset of deep sleep
What is IGF-1
GH stimulates IGF production in liver
IGF1 stimulates growth in epiphyseal plates of long bones (linear growth in kids)
-When absent= Laron type dwarfism
What are the 3 phases of post-natal growth
Infantile: first 2 yrs, rapid growth (30-35 cm)
Childhood: constant 5-7cm/yr (prepubertal dip)
Pubertal: 8-14cm spurt/yr (2/2 increasing gonadal steroids and GH secretion)
-velocity falls to 0 when adult growth is met
Explain constitutional vs genetic short stature
Constitutional: 2SD below mean height for kids
Genetic: child grows in parental range, but normal velocity
How do you diagnose short stature
H&P (pattern- slow growth progressively deviating from previous growth percentile)
IGF-1 (not GH)
GH stimulation test
What other disease states can cause IGF to be low (besides short stature)
Hypothyroidism
DM
Renal failure
-poor nutrition
The gold standard for diagnosing GH deficiency is
GH stimulation test! (insulin induced hypoglycemia)
Measure serum glucose and GH before, 15, 30, 60, 90, and 120 min after injecting insulin- If they have a deficiency, GH will not rise when you give insulin
-Can also do with arginine (measure serum GH at 0, 30, 60, 90, 120)
**Must correct thyroid deficiency first
How do you treat GH deficiency
SubQ Somatropin (humatrope pen): qd adults, 3/week kids -Kids need to take until they reach puberty, then retest GH deficiency; adults, forever
If you are suspicious of short stature, what do you do
get bone age with wrist radiograph
IGF-1
confirm with GH stimulation test
refer to peds endocrine (kids with multiple pituitary deficiency rarely recover as adults)
What is pituitary gigantism
excess linear growth 2/2 excess GH secretion (but most kids with tall stature do NOT have pituitary gigantism)
Can be 2/2 GH secreting tumor, or GnRH secreting tumor
Before you are sure it is pituitary gigantism, r/o
genetic tall stature
precocious puberty (can block with Luprin)
hyperthyroidism
Klinefelters syndrome (dysmorphic features, neurocog problems)
-get bone age, thyroid function test, sex steroid concentration, karyotype, and GH related studies
What tests can you use to Dx gigantism
IGF-1 level: will be high
GH suppression (OGTT**): when you give 75g glucose, GH should fall <2. if higher, then gigantism
MRI w/ and w/o
What is Acromegaly
hypertrophic and degenerative injury to soft tissues, joints, heart/CV system, respiratory disturbances, and intermediary metabolism
*MCC is pituitary macroadenoma
Takes 10-12 years before diagnosis is made (avg age 40-45)
What are Sx of acromegaly
-enlargement of tongue, liver, spleen, thyroid, salivary glands, kidney, prostate
-OSA, narcolepsy
-low renin, high aldosterone, hypercalcuria, high VD
*enlargement of hand and feet, frontal bossing, jaw malacclusion, arthritis, carpal tunnel, myopathies
Oily skin, skin tags, colon polyps, hyperhidrosis, cardiomyopathy, CHF, L/RVH, HTN
-Menstrual abn, galactorrhea, hirsutism, low libido, ED
Acromegalic lab values include
hyperglycemia
hyperprolactinemia
Do acromegalic patients live long
2-3x mortality rate 2/2 CVD and cancer
Reduced survival by 10 years
-If you lower GH w/ Tx, mortality returns to normal
If you suspect acromegaly, what should you do
Get IGF-1 test; if high, OGTT
How do you treat Acromegaly (non-pharm, pref)
- *TSS; curative for discrete micro and macro! (complications higher in kids)
- Radiation: adjunct therapy
The great thing about TSS is
GH secretion falls to normal w/o loss of other pit hormones
GH falls to nl w/in 1-2 hrs post-op
serum IGF falls to nl in 7-10 days
Negative aspects of radiation for excess GH
delayes efficacy and panhypopit in kids (GH, gonadotropin, and thyrotropid deficiencies)
learning disabilities, emotional changes, obesity
How do you treat acromegaly with meds
-Bromocriptine (dopamine analog)
-Octreotide*, Pasireotide (SS analogs):
octeo is short acting and suppresses SSTR2&5
-GH receptor antagonists
*Goal is to get IGF-1 to normal range!
*Bromo+Octreo in kdis is great!
Long term acromegaly management is
eval GH secretion q3-4 months w/ clinical exams, IGF-1, and OGTT
eval ant pit annually w/ gonadotropin deficiency (amenorrhea, adnrogen deficiency), and thyroixine and cortisol
eval adenoma size w/ MRI yearly for first few years post-op; semi-annual visual field assessment
colonoscopy q3-4 yrs if 50+, annual cardio exam
How do you treat different pit/hypothalamus tumors
Microadenoma (<10mm): TSS
Macroadenoma: surgery less likely to cure
Giant pit tumor (30-40mm): difficult to manage
Hypothalamic tumor (craniopharyngioma): TSS, transfrontal
Prolactinoma: Meds first!
Other treatments for tumors are
conventional radiation
gamma knife radiation
Hallmark of hypopituitarism is
abnormal growth in kids
abnormal menses in women
Hypopituitarism patients often look like this
slightly overweight, pale, fine wrinkled skin, atrophic genitalia, diminished axillary and pubic hair
Genetic causes of hypopituitarism are
structural defects
Isolated hormone defect/mutation
intrapituitary tumor
extrapituitary tumor (compresses)
Vascular (sheehan’s syndrome, pituitary apoplexy, ischemic infarct)
Injury: damage to stalk, pit, or hypothalamus
What is Kallman’s syndrome
Anosmia and hypogonadism 2/2 Low GnRH
MCC of hypopituitarism in adults
Pituitary tumor pit tumor s/p surgery/radiation pit tumor w/ hemorrhage Hypothalamic tumor Trauma (TBI)
Hallmarks of concussion are
confusion and amnesia
Overview of general tests to get when you suspect…
Primary organ failure: measure trophic hormone
Secondary organ failure: measure end-organ
How is aging related to hypothalamus and pituitary
Menopause (high LH/FSH)
Andropause (decline of LH/FSH, and testosterone in men)
-Decline in E2, T, DHEA- but NOT TSH, T4, cortisol, and PRL