CM- Endo -1- Hypothal & Pituit lect 1-4
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| Where is the hypothalmus found | anterior part of the fllor of the third ventricle below and in front of the hypothalamic sulcus
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| What hormones are secreted by the hypothalmus | TRH, GnRH, GRH, CRH
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| What is the function of the following hormones and where is it secreted from TRH | TRH- Thyroid Releasing hormone from hypothalmus stimulates TSH and Prolactin in the Ant. Pituitary
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| What is the function of the following hormones and where is it secreted from GnRH | Gnrh- Gonadotropin releasing hormone from hypothalmus stimulates secretion of FSH and LH
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| What is the function of the following hormones and where is it secreted from GRH | GRH- Growth hormone releasing hormone from hypothalmus stimulatess secretion of GH
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| What is the function of the following hormones and where is it secreted from CRH | CRH- Corticotropin releasing hormone from hypothalmus
stimulates release of ACTH
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| Where is the pituitary found | Found in the sella turcica surrounded by sphenoid bone covered by dura mater
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| Where is the optic chiasm in relation to the pituitary and why is this relevant | optic chiasm is superior to the pituitary gland this is important because tumors in the pituitary can compress the optic chiasm causing visual field defecits
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| What is the connection between the hypothalmus and pituitary called | called the hypophyseal stalk
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| how is the pituitary divided | anterior and posterior divisions
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| Primary secretory division of the pituitary takes up around 80% of the gland | anterior pituitary
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| What are the hormones secreted from anterior pituitary | GH- growth hormone
Prolactin
ACTH
TSH
FSH
LH
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| What type of cell in the anterior pituitary makes GH | somatotrophs
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| What type of cell in the anterior pituitary makes Prolactin | Lactotrophs
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| What type of cell in the anterior pituitary makes ACTH | corticotrophs
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| What type of cell in the anterior pituitary makes TSH | thyrotrophs
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| What type of cell in the anterior pituitary makes FSH and LH | Gonadotrophs
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| part of the pituitary that is actually a down growth from the hypothalmus and secretes two peptides | posterior pituitary
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| what are the two peptides secreted by the pos. pituitary | Oxytocin and Vasopressin
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| What is the function of oxytocin and where is it secreted from | acts on uterine smooth muscle to initiate contractions and stimulates lactation in the mammary ducts. Secreted from pos. pituitary
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| What is the function of vasopressin and where is it secreted from | Also known as Anti Diuretic Hormone it increases water resorption at the distal tubule in the kidney and allows for concentration of urine. Secreted from the pos. pituitary
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| What are the functions of growth Hormone (GH) where is it secreted from | promotes linear growth of bone
inhibits the effect of insulin by impairing glucose uptake by cells
-release stimulated by low blood sugar
-release inhibited by high blood sugar
-somatostatin inhibits its release
secreted from ant. pituitary
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| What effects do low and high blood sugar have on Growth Hormone (GH) | Low blood sugar stimulates GH
high blood sugar lowers GH
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| What effect does somatostatin have on Growth hormone (GH) | inhibits growth hormone
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| What is the function of Prolactin and where is it secreted from | stimulates lactation in postpartum period
promotes breast development during pregnancy to prepare for milk production
-inhibits
-inhibited by dopamine
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| What is the function of ACTH and where is it secreted from | stimulates the adrenal gland to produce cortisol and androgens secreted from Ant. Pituitary
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| What is the function of TSH and where is it secreted from | stimulates iodine uptake by thyroid gland
stimulates release of T4 and T3
resembles hCG
-Inhibited by somatostatin, dopamine, and excess cortisol
-Secreted from Ant Pituitary
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| What is the function of FSH & LH and where is it secreted from | FSH and Lh stimulates ovaries and testes to produce sex steroids
-LH stimulates testosterone and estrogen in male leydig cells
FSH and LH stimulate sperm maturation
LH- in females stimulates corpus leteum to make progesteron and LH spike causes ovulat
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| What does LH and FSH do in men | LH stimulates testosterone and estrogen in male leydig cells
LH and FSH are both needed for sperm maturation
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| What do LH and FSH do in females | LH stimulates the corpus luteum in females to produce progesterone for placental development
LH also causes ovulation with mid cycle spike
FSH- stimulates estrogen required in the development of ovarian follicles. Stimulates spermatogenesis
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| What are some common and not so common pathologies that can causes of hypopituitarism | -Space occupying tumors that compress the hypothalmus or pituitary gland
-Radiation or surger
-Empty Sella
-Vascular events such as sheehan's syndrome or pituitary apoplexy
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| What is empty sella | structural defect where the pituitary is falttened on the floor of the sella
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| What is sheehan's syndrome | severe hemorrhaging during delivery causes infarction of the pituitary
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| What is Pituitary apoplexy | Hemorrhage/infarction of the pituitary due to trauma, tumor, anticoagulation, or sickle cell anemia
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| What are the clinical features of anterior pituitary destruction or deficiency in hypothalamic stimulators | Hypogonadism, Hypothyroidism, andrenocortical deficiency, Growth hormone deficiency
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| What would hypopituitarism causing hypogonadism appear as clinically | decrease in sex drive, impotence, amenorrhea
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| what would hypopituitary causing hypothyroidism appear as clinically | mental slowness, constipation, cold intolerance, and weight gain (slugs)
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| What would hypopituitary causing adrenocortical deficiency appear as clinically | weakness, nausea, fever, hypotension(that doesn't respond to IV fluids)
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| What would hypopituitary causing growth hormone deficiency appear as clinically | epsiodic hypoglycemia with fasting, short stature
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| How would you diagnose hypopituitary | test target gland hormones- T4/T3. testosterone, and cortisol, if they are low you need to measure pituitary hormones
-Check TSH, FSH, LH, ACTH, and prolactin
low levels suggest hypothalamic/pituitary deficiency
high levels suggest target gland probl
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| How are tumors of the pituitary classified | classified according to size and hormone production
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| What is a pituitary tumor less than 10mm called and what is one greater than 10mm called | microadenoma vs macroadenoma
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| Are pituitary tumors often malignant | no but they can cause local invasion and expansion tumors can cause visual field defects by compressing optic chiasm
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| What is a somatotroph adenoma | tumor causes excess GH
M=F
usually seen in 30-40yr olds
slow growing
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| what type of pituitary tumor causes acromegaly, gigantism w/ soft tissue growth, sleep apnea, thickening of skin, spade like blunt fingers, carpal tunnel syndrome and hyperinsulinism | Somatotroph adenoma
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| How do you diagnose a somatotroph adenoma | check blood glucose, elevated blood calcium and phosphorus levels, elevated somatomedins, elevated GH levels, GLUCOSE TOLERANCE TEST, finally MRI
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| What would you see on a normal glucose tolerance test vs someone with somatotroph adenoma | Give 100gm glucose then measure GH levels
normal- decrease in GH to less than 5ng/mL at 60 minutes
Acromegaly- may decrease GH levels but not below 5ng/mL
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| what is the treatment for a somatotroph adenoma | transphenoidal surger: gamma knife 80% success rate for small tumors
Radiation 4500-5000 rads 60-80% success
Bromocriptine: dopamine agonist given orally can decrease GH levels
Octreotide: a somatostatin analogue decrease GH given sub Q
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| what is the most common form of pituitary tumor | lactotroph
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| What is the pituitary tumor called that secretes excess prolactin | lactotroph or prolactinoma
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| When are similiar signs and sypmtoms of a lactotroph seen | side effects are similiar to those seen during pregnancy
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| What are the s/sx of a lactotroph adenoma | galactorrhea, in women menstrual disorder, in men hypogonadism, weight gain, irritability, hirsutism
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| How to dx a lactotorph adenoma | -first do a pregnancy check (hCG) because it is the most common cause of amenorrhea
-check prolactin level micros secrete 30-100ng/ml macros over 200 ng/ml
check visual field- a deficit would warrant an MRI because tumor could be compressing optic chia
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| how do you tx lactotroph adenomas | -dopamine agonist
bromocriptine when fertility is wanted
oral birth contrl if fertility is unwanted
-cabergoline like bromocriptine
Transphenoidal surger generally 20% recurrence rate
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| Type of pituitary tumor that causes excess glucocorticoids | ACTH secreting tumors
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| What is the difference between cushing's disease and cushing's syndrome | cushing disease tumor is in the pituitary
cushing syndrome tumor is in the adrenal gland or lung(bronchocarcinoma)
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| Who is more likely to have acth secreting tumor and when is it most often seen | F:M 8:1
seen in 20-40 year olds
80-90% are microadenomas that often invade locally
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| what are the s/sx of cortisol excess (acth secreting tumor) | weight gain
hypertension
hyperpigmentation
easy bruising
proximal muscle weakness
osteopenia
immune suppression
anti-inflammatory action
anti-allergic action
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| What should you think about when you see buffalo hump and/or centripital obesity and puprle stria on the trunk | cushing's disease
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| why do you see osteopenia and immunesuprresion in cushing's disease | the osteopenia results from increased renal excretion of calcium and immunesuprresion from decrease in antibody production
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| How would you diagnose an ACTH secreting tumor | 1st document cortisol excess with a 24hr urine collection
2nd document elevated ACTH level by serum
3rd do a dexamethasone suppresion test
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| What would you see with a dexamethasone test if the tumor is an ACTH | high dose of dexamethasone mimics cortisol so you should see a suppresion in pituitary ACTH by negative feedback which in turn suppresses endogenous cortisol if you have an ACTH secreting tumor the cortisol level should decrease 50%
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| if you have high cortisol and dexamethasone test didn't decrease cortisol by 50% whay type of tumor do you most likely have and how do you narrow down where it is located | you most likely have a tumor in the adrenal gland or lung. to determine if it is an adrenal tumor you should see a decrease in cortisol if you decrease ACTH if it is in the lung cortisol will remain constant since ACTH has no effect on lung tissue
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| What imaging technique are you going to use to locate a -pituitary tumor secreting ACTH -adrenal tumor secreting cortisol -lung tumor secreting cortisol | Pituitary tumor- MRI
Adrenal tumor CT Scan
Lung Tumor- CT scan
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| HOw does petrosal sinus sampling help a surgeon determine the location of a pituitary tumor | each petrosal sinus receives venous drainage from the ipsilateral pituitary higher levels of ACTH will be seen in the sinus on the same side as the tumor
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| what are the TX for ACTH secreting tumor | transphenodal resection
conventional radiation
ketoconazole -inhibits adrenal cortisol
metyrapone- inhibits conversion of cholesterol to pregnenolone which reduces adrenal cortisol production
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| what type of tumor has the only cases occur in men usually macroadenomas may be due to lon standing kleinfelters syndrome | Gonadotropin secreting tumor- most only secrete FSH
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| What are teh s/sx of gonadotropin secreting tumor | impotence or infertility
visual impairment due to compression of optic chiasm
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| how do you dx a gonadotropin secreting tumor | elevated FSH, low testosterone, MRI reveals large adenoma
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| s/sx of this pituitary tumor are hyperthyroid, goiter, no exopthalmos, diarrhea, fatigue and muscle weakness and is usually a macroadenoma | TSH secreting Tumor
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| how do you dx a TSH secreting tumor | elevated TSH, T3/T4, MRI shows large tumor and injection of TRH produces no increase in TSH production
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| what are the tx options for a TSH secreting tumor | transphenoidal surger
ablative therapy- with radioactive iodine
octreotide- long acting somatostatin decreases TSH shrinks tumor
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| this deficiency is found in children 6-12 months of age you have deceleration in growth velocity after normal birth weight short stature on physical exam slow linear growth | Growth Hormone Deficiency
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| How to dx growth hormone deficiency | low serum somatomedin (after ruling out malnutrition, liver disease, hypothyroidism, and congenital dwarfism)
Confirm by giving GH
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| What is the protocol for testing Growth hormone deficiency by administering Growth hormone | measure fasting GH levels
Give IV insulin until glucose falls to below 50 this should stimulate GH to above 6ng/dl if it is present
then inject exogenous GH should cause rise in somatomedin/GH level
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| how do you treat growth hormone deficiency | GH injections, most effective before puberty, improves lean body mass, controversial in adults
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| This pituitary hormone deficiency is rare and always associated with another pituitary deficiency | prolactin deficiency
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| how would you dx a prolactin deficiency | TRH stimulation test
obtain baseline levels
inject protirelin
prolactin levels should increase two fold if present
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| rare pituitary deficiency mimics adrenal insufficiency generally due to impaired secretion of CRH by hypothalmus or Exogenous steroid use that suppresses the pituitary | ACTH deficiency
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| what are the s/sx of ACTH deficiency | Nausea/vomiting
weakness/fatigue
Fever
Hypotension-****that doesn't respond to IV fluids
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| how do you dx an ACTH deficiency | CRH test
-obtain baseline serum ACTH
-Inject 1mcg/kg CRH as IV bolus
-recheck ACTH/cortisol at 15,30,and 60 mins
-ACTH should peak at 15mins
-Cortisol should peak at 30-60 min
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| What is the TX for ACTH deficiency | replace corticosteroids
-GOLD STANDARD hydrocortisone given orally 20mg am and 10mg pm doses can be tapered down as clinical signs improve.
-prednisone/decadron must be converted by the body to cortisol for action
-DURING STRESS dose should be 100mg/8
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| Why do you need to increase the dose of hydrocortisone given to 100mg every 8hrs for an ACTH deficient patient during stress and illness | because cortisol is the stress hormone it is needed during these times to ensure proper body function
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| What are the likely causes of a TRH deficiency | insufficient production of TRH by the hypothalmus
pituitary adenoma compressing thyrotropic cells
previous pituitary surgery
pituitary destruction by trauma or hemorrhage
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| what are the s/sx of TRH deficiency | looks like hypothyroidism
-fatigue
-weight gain
-constipation
-menstrual irregularities
-dry skin/hair loss
SLUG EFFECT
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| How do you dx a TRH deficiency | check TSH and T4 if both are low
inject TRH
should see an increase in TSH if the lesion is in the hypothalmus
if no increase in TSH the lesion is in the pituitary
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| What is the TX for TRH deficiency | replace thyroid hormone with synthroid or levoxyl
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| What are common causes of gonadotropin deficiencies | hypothalamic/pituitary tumors compressing gonadotroph cells (most common is craniopharyngioma)
-Prior pituitary surgery
-Prolactinomas secreting excess prolactin inhibit fsh/lh
-congenital defect (kallman's syndrome)
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| What is the most common tumor that causes gonadotropin deficiency by compressing gonadotrophs | craniopharyngioma
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| autosomal dominant familial syndrome with deficiency in GnRH so NO FSH/LH associated with hypoplasia/atrophy of the olfactory bulb | Kallman's syndrome
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| what are the s/sx of kallman's syndrome | undescended testes
gynecomastia
delay in puberty and associated growth spurts
anosmia-lack of smell
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| how would you dx kallman's syndrome | -check GnRH, FSH, LH, testosterone ALL will be low
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| What is the TX for Kallman's syndrome | pulsitile GnRH
testosterone replacement given 100-300mg/month
This fixes all problems except infertility
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| What is the synthetic version of oxytocin called | pitocin
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| How does estrogen affect action of oxytocin | estrogen lowers the threshold of smooth muscle membrane potential enhancing the effect of Oxytocin on causing uterine contraction
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| What effect will oxytocin have on uterine smooth muscle | oxytocin may cause contraction in quiescent uterus or increase contraction strength and frequency in active uterus
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| What is the reflex release of oxytocin | as baby leaves the uterus it causes dilation of uterus, cervix, and vagina this causes release of oxytocin creating stronger contractions to push the baby out. more dilation occurs more oxytocin is released
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| HOw is oxytocin involved in lactation | oxytocin gets released after stimulation of nipple which then causes the mammary duct cells to contract and eject the milk
-this is inhibited by stress
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| What is the other name for Vasopressin | ADH (anti diuretic hormone)
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| What are the effects of vasopressin (ADH) | at the kidney: increases water resorption in distall collecting duct concentrating urine
Cardiovascular: causes vasoconstriction increasing B/P in hypovolemia, ADH maintains peripheral perfusion
LIVER: increases GLUCOGENOLYSIS
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| What effect would increased plasma osmolality have on vasopressin (ADH) | Vasopressin would be released to increase water resorption to counteract the increased osmolality
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| What effect would a decrease in total body water have on vasopressin (ADH) | vasopressin would be released to increase water resorption to combat the dehydration and hypovolemia.
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| What is diabetes insipidus | insufficient vasopressin(ADH)resulting in-
inability to concentrate urine
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| What are the three types/causes of diabetes insipidus | neurogenic diabetes insipidus
nephrogenic diabetes insipidus
psychogenic polydipsia
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| Deficiency in Vasopressin(ADH) caused by -surgery in hypothalmus or pituitary -head trauma -active pituitary or metastic tumor -infiltrative disease of pituitary (histiocytosis, granulomas) -CNS infection -idiopathic (decreased vasopressin fibers) | Neurogenic causes of diabetes insipidus
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| Type of diabetes inspidues marked by -normal to elevated ADH w/poor renal response caused- -chronic renal disease -sickle cell -chronic K+ def -hypercalcemia -medication (lithium, fluoride, methoxyflurane anes, declomycin and colchicine) -cong defe | nephrogenic diabetes insipidus
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| type of diabetes insipidus also known as potomania caused by excessive drinking increased water load leads to inhibition of vasopressin(ADH) leading to water diuresis | Psychogenic diabetes insipidus
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| what are the s/sx of diabetes insipidus | hypernatremia (serum sodium >140), excessive thirst(polydipsia), large volume diluted urine (polyuria)>4L/day
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| how do you dx diabetes insipidus | inappropriately dilute urine w/ elevated serum osmolality leading to hypernatrimia
elevated serum osmolality (>295mosm/kg)
dilute urine osmolality (<200mosm/kg)
low urine specific gravity (<1.005)
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| What is a test that aid in testing for diabetes insipidus that must be done under close supervision as patient can become rapidly dehydrated | Water Deprevation test
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| What is the difference in baseline plasma and urine osmolality in nephrogenic/neurogenic vs psychogenic diabetes insipidus | nephro/neuro DI urine is dilute while palsma is highly concentrated
Psycho DI urine and plasma are both dilute due to excessive water intake
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| What is the protocol for carrying out a water deprevation test | -first obtain baseline plasman and urine osmolality
-deny patient fluids for 12-18hours
-measure ADH level
-to distinguish nephro from neuro inject aqeous vsopressin
-measure urine osmolality 1 hour after injection
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| What should you see with a normal, nehpro/neuro DI, and psychogenic DI individual after withholding water for 12-18 hours | normal person- will reduce urine output urine osmolality will increase
Nephro/Neuro- will maintain diluted urine output
psycho- will always increase urine osmolality
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| How do you distinguish nephrogenic vs neurogenic diabetes insipidus | inject aqueous vasopressin then 1 hour after injection measure urine osmolality
Nephr- no change in urine osm
Neuro- urine osmolality would increase
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| What is the TX for neurogenic DI | drug of choice is DDAVP or pitressin tannate
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| What is the TX for nephrogenic DI | salt restriction
thiazide diuretic
cholrpropamide, carbamazepine, increase ADH release from the pituitary
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| Inappropriate secretion of ADH in the face of low plasma osmolality excess water resorption causing volume expansion | syndrome of inappropriate secretion of ADH (SIADH)
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| What can cause syndrome of inappropriate secretrion of ADH | HEAD TRAUMA
malignant lung tumors
tuberculosis
Adrenal insufficiency
medications(clofribrate, tegretol, thiazides all stimulate ADH release)
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| How would you dx Syndrome of inappropriate secretion of ADH | hyponatremia
hypo-serum osmolality
normal renal function
normal thyroid tests(rules out myxedema)
urine is hypertonic
no adrenal insufficiency
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| How would you tx SIADH | fluid restriction for mild cases
severe cases may need normal saline IV to decrease hypo-natremia
Loop diuretics-decrease effect of ADH promote water loss
demeclocycline-causes reversible nephrogenic DI
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| Acromegaly is caused by | overproduction of GH
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| GH deficiency caused by | underproduction of GH
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| SIADH caused by | overproduction of vasopressin(ADH)
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| Diabetes insipidus caused by | underproduction of vasporessin(ADH), Poor functioning kidney, psychologic increase in water uptake
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| What is Sheehan syndrome | underproduction of any pituitary hormone
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| What does a pituitary adenoma cause | overproduction of any pituitary hormone depending on cell type involved in tumor
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| What is hypopituitarism | underproduction of any pituitary hormone
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