Hypothalamus and Pituitary I/II Flashcards
where is the pituitary gland located?
sits in the sella turcica of the sphenoid bone
The pituitary gland is separated into which 3 lobes?
anterior
intermediate
posterior
the normal pituitary gland is made up of the anterior and posterior parts called…?
Ant = Adenohypophysis Post = Neurohypophysis
what hormones are secreted by the posterior pituitary gland?
oxytocin
ADH - “bright” spot on MRI
what hormones are secreted by the posterior pituitary gland?
TSH ACTH FSH and LH GH Prolactin endorphins
what is one major difference between anterior and posterior gland hormone secretion?
anterior pit. - indirect control through release of regulatory hormones
poster pit. - direct release of hormones
what hormones are secreted by the intermediate lobe of the pituitary?
endorphins cleaved from pre-opiomelanocortin (POMC) which gives ACTH and beta-endorphin
MSH (melanocyte-stimulating hormone)
GnRH stimulates which hormones in the ant pituitary?
FSH and LH
GHRH stimulates which hormones in the ant pituitary?
GH
SS inhibits which hormones in the ant pituitary?
GH and TSH
TRH (thyrotropin releasing hormone) stimulates which hormones in the ant pituitary?
TSH and prolactin
Dopamine inhibits which hormones in the ant pituitary?
prolactin
CRH stimulates which hormones in the ant pituitary?
ACTH, MSH, endorphins
what sources can you test to measure hormones?
- Capillary puncture
- Venipuncture
- Arterial stick
- Urine specimens (clean catch)
- 24 hr urine
- tissue bx (thyroid)
what are you measuring using the 24hr urine sample and for what condition?
catecholamines and metabolites for pheochromocytoma
Types of Testing available in Endocrinology
Hormone levels (direct, free, total, antibodies, precursor, ratios), Suppression tests, Stimulation tests, Imaging tests, Biopsies
How are hormones w/longer half lives and not bound by proteins measured?
directly with a random test (ie. TSH)
How are hormones bound to proteins measured?
Measure free and total fractions (ie Total T4 and free T4)
Precursor hormone levels examples? what is it used to evaluate for?
Androstenedione, prohormone for estrogen and testosterone
hyperadrenergic states
- congenital adrenal hyperplasia
- ovarian hyperplasia or tumor
What hormone ratio can be measured for infertility?
FSH:LH ratios
when should you measure cortisol levels?
Perform first venipuncture between 6 and 8 AM
what factors affect the timing of certain hormone level testing?
Pulsatile/episodic
Shorter half lives
Measure hormones at particular times of the day OR
24 hour urine collection methods
How do you gather information about feedback loops for hormone levels?
Measure the precursor hormone and the end product of that hormone’s action
ie.
TSH and T4
PTH and calcitrol
when are suppression tests used to measure hormone levels?
when HYPERfunction of the gland is suspected
ie. pt has excess cortisol
what is an example of a suppression test?
Dexamethasone suppression test (synthetic glucocorticoid)
when can you do a stimulation test?
suspected HYPOfunction (low cortisol)
example of stimulation test?
ACTH Stimulation test
Test adrenals response to synthetic ACTH
What are disorders of the hypothalamus?
Tumors (ie. craniopharyngioma)
Inflammation ( lymphocytic hypophysitis)
Metastatic tumor (breast, lung)
Infiltration (sarcoidosis, histiocytosis, hemochromatosis)
what are disorders of the hypothalamaus often asoc. with??
loss of posterior pituitary function
i.e central diabetes insipidus
Vasopressin MOA
V-1 a receptors mediate pressor activity
V-1b or V-3 receptors modulate ACTH secretion
V-2 receptors mediate renal handling of water excretion and promote coagulation factor VIII action
Where are the baroreceptors that stimulate ADH?
carotids
Vasopressin V-2 agonists uses which hormone?
Antidiuretic Hormone – ADH
How does Vasopressin use ADH?
to decrease water excretion in central diabetes insipidus and nocturnal enuresis
also, increase circulating levels of factor VIII and improve platelet responsiveness
what is diabetes insipidus?
Inability of the kidney to concentrate urine with passage of copious and inappropriate volumes of dilute hypotonic urine
polyuria and often polydipsia
What med can you give to tx central diabetes insipidus and how does it work?
desmopression = can dramatically decrease UO and corrects high Na and osmolarity
what is the problem in central diabetes insipidus, Na or water?
WATER
Causes of central diabetes insipidus?
Idiopathic: 30 – 50%
CNS/pituitary surg, trauma, anoxic encephalopathy
Primary tumors, craniophyrngioma, suprasella germinoma, pinealoma
Metastatic tumors (leukemia and lymphoma)
Granulomatous Disease
Hereditary (Autosomal dominant)
Pregnancy
How can you screen for Central diabetes insipidus?
screen w/ 24 hr urine collected by the pt
pregnancy can cause which types of central diabetes insipidus?
partial central diabetes or nephrogenic insipidus
d/t markedly increased levels and activity of vasopressinase (oxytocinase)
Presentation of Central Diabetes Insipidus?
after brain surg or significant brain injury (anoxia, trauma, hemorrhage)
acute w/ unremitting sustained thirst and polyuria
preference for cold liquids esp. water w/ continued thirst and polyuria day & night
what 2 things are found in DM and central diabetes insipidus? and how can you distinguish btwn the 2 conditions?
polyuria
polydipsia
order a glucose to make sure not DM (also Ca, K, Cr)
how can you dx Central Diabetes Insipidus?
“Water Deprivation Test” aka Dehydration Test
what can you expect to see on a water deprivation test?
Expect S(sodium) and S(osm) to be high end of ref range or high at start
W/ fluid deprivation U(osm) plateaus w/ significant rise after Desmopresin (ADH analog) injection
ADH is not high
Nephrogenic diabetes insipidus
No response to Desmopressin injection
Plasma ADH is elevated before and after dehydration
Primary polydipsia (PPD)
Serum(Na) and S(osm) may be mid range or low-normal at start
in CDI thirst improves but in PPD it does not
How can you tx neurogenic (central) DI?
Primarily aimed at decreasing urine output (increase ADH)
Replacement of fluid losses is also important
- hypernatremia can occur if thirst is impaired or the patient has no access to water
what is the problem in central DI?
deficient secretion of ADH
How does desmopressin (DDAVP) work on central DI?
Potent anti-diuretic –>
reduces nocturia, providing adequate sleep; control of diuresis during the day
which form of Desmopression is more potent?
Nasal form»_space; oral
if pt has incomplete response to desmopressin what are alternative meds??
Chlorpropamide
Carbamazepine (anti-szr)
Clofibrate (hyperlipidemia)
what is the problem in nephrogenic DI?
resistance of the kidneys to the effects of ADH
no response to DDVAP
DI and SIADH: where is the water and where is the sodium?
DI: peeing a lot of water, hypernatremia (Decreased serum sodium and osmolality)
SIADH: retaining lot of water, hyponatremia
What is the clinical hallmark of ADH?
HYPONATREMIA
(<135 meq) without evidence of relative water excess
MC of adult nephrogenic DI?
chronic lithium use or hypercalcemia
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what is the tx for nephrogenic DI?
Thiazide diuretic in combination with a low salt diet
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Inappropriate ADH leads to
volume expansion due to water retention
Volume expansion over-rides sodium handling with inappropriate urinary sodium loss
SIADH acute vs. chronic
Acute is documented to be < 24 hrs
Chronic is >24hrs or not documented < 24 hrs
Causes of SIADH?
Ectopic Production: malignancy
Baroreceptor Dysregulation: CNS, pulmonary, transient
Multifactorial (central and peripheral): drugs
sxs of hyponatremia
Moderate/ severe: N w/out V, confusion, HA
Severe: V, somnolence, seizures, glascow scale <8
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SIADH Tx
restrict fluid intake w/ gental administration of hypertonic fluids
what is the problem of SIADH?
excess volume
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Lesions: Craniopharyngioma
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What is the most frequent sellar tumor of childhood and adolescence?
craniopharyngioma (hypothalamic tumor)
where do craniopharyngiomas arise from?
Rathke’s Pouch remnants that extend into the diencephalon during development
Childhood presentation of craniopharyngioma?
growth retardation, pubertal delay, visual field loss, vomiting
disorders caused by functional pituitary tumors?
Acromegaly (excess GH)
Pituitary dependant Cushing’s Disease (ACTH)
Prolactinomas w/ prolactin assoc. hypogonadism
Central hyperthyroidism d/t TSH secretion
what anatomic damage can be caused by disorders of the pituitary?
Visual field loss, cranial nerve injury
Hypopituitarism
CSF leak
Diabetes insipidus : uncommon
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diffuse pituitary hyperplasia
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Pregnancy
Prolonged Primary Hypothyroidism & Hypogonadism
GhRH secreting tumors
Somatomamatotropic Hyperplasia in Carney Complex
Discrete pituitary tumor
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what should you measure to manage pituitary incidentaloma?
prolactin
pituitary tumor manifestations?
Intrasellar
tumor assoc. loss (GH>LH>FSH>TSH>ACTH)
Suprasellar
Lateral Extension
Inferior Erosion
how can pituitary hypothalamic lesions cause neurologic effects?
Tumor erosion with CSF leak
clinical manifestations and prevalence of prolactinoma?
signs of increased prolactinoma
40-45%
somatotroph adenoma clinical manifestation?
acromegaly
corticotroph adenoma clinical manifestation?
cushing’s disease
gonadotroph adenoma clinical manifestation?
compression sx hypopituitarism
null cell clinical manifestation?
compression sxs
hypopituitarism
thyrotroph adenoma clinical manifestation?
hyperthyroidism
compression sxs
Main function of prolactin:
Mammary gland development (puberty)
Initiation of lactation postpartum (pregnancy)
Secreted by lactotrophs of the anterior pituitary…
PROLACTIN in a pulsatile manner
what is prolactin inhibited by?
hypothalamic Prolactin Inhibitory Factor (dopamine)
prolactin suppresses ___ and lowers ___ which alters menses and fertility
GnRH
LH and FSH
prolactin stimulates adrenal androgen production which promotes…
weight gain and hirsuitism mostly in women
S/s of hyperprolactinemia in females
Irregular menstruation (*amenorrhea) *Infertility Headache Peripheral Vision Problems Moods changes/ depression *Galactorrhea Menopausal symptoms
S/s of hyperprolactinemia in males
*Impotence
*Infertility
Loss of libido
*Headache
*Peripheral Vision Problems
Moods changes/ depression
Galactorrhea
Gynecomastia
Causes of increased prolactin
Increased lactotroph number or secretion (pregnancy and hypothyroidism**)
Decreased prolactin disposal
what is the “stalk effect?”
2cm tumor is NOT prolatinoma;
dopamine effects decreased by stalk injury
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Fasting Serum Prolactin Levels should be measured in all pts w/??
what is included in a further w/u?
galactorrhea, gynecomastia and/or hypogonadism
MRI w/ and w/out contrast
GH secreting tumors may also express….
D2 receptors
Prolactin is under _____ control and predominant inhibitor is ______.
tonic inhibitory
Dopamine
Macro and microademonas can be tx’d w/ what types of drugs?
dopamine agonists
how soon after giving dopamine agonists for a macroademoa, will you see a detectable decrease in size?
w/in 24 hrs
What is the 1st line medication for a prolactinoma?
dopamine agonist Nota Bene
Etiologies of hyperprolactinemia?
Prolactinoma, other pituitary tumors, hypothalamic dz,
Chronic Kidney Failure,
cirrhosis or Liver Disease,
Spinal cord damage
Chest wall injury, severe Primary Hypothyroidism,
Anti-psychotic meds, radiation, Surgery, Idiopathic
what test can you order to measure prolactin levels?
basal (fasting serum) PRL levels
Which drugs can cause hyperprolactinemia?
Dopamine-receptor “antagonists”
Dopamine-“depleting” agents (methyldopa, reserpine)
INH, TCA’s, Verapamil, estrogens, antiandrogens, opiates
What labs are included in a work-up of autonomous prolactinoma vs. other etiologies?
Fasting PRL FSH, LH estradiol testosterone TSH renal/hepatic panels ß-hCG in females
what imaging should you order for a prolactinoma work-up?
MRI of pituitary and brain
T or F: most microadenomas progress to macroadenomas
FALSE.
do not!
tx of microprolactinomas
Dopamine agonists – Bromocriptine twice daily with food
+/- surgical resection
drug of choice for infertility or pregnant pt’s seen with abn. prolactin levels?
bromocriptine
Nonpharmacologic tx options for prolactinemia and prolactinoma?
Transsphenoidal resection
Surgical resection
Radiation therapy
Acromegaly is assoc. w/ hormone staining of?
GH +/-
prolactin
when does GH peak?
w/in an hour after the onset of deep sleep
GH secretion is controlled by what 2 factors?
hypothalamic and peripheral
GHRH releases
GHIH (somatostatin) inhibits
when is IGF-1 produced?
in liver after stimulation by GH
IGF-1 stimulates growth of…
epiphyseal plates of long bones
what does absence of GH result in…
dwarfism (laron type)
what are the 3 phases of post-natal growth and characteristics?
Infantile phase- 1st 2yrs of life
Childhood - relatively constant
Pubertal phase - effects of increasing gonadal steroids and GH secretion
Constitutional short stature
2 SDs or more below the mean height for children of that sex and chronologic age
Genetic short stature
Constitutional short stature in children of short parents
growth velocity is normal but consistently 3-5th percentile on growth curve
pathologic causes of short stature?
GH deficiency Intrauterine growth retardation Infections (rubella, CMV) Maternal drug/alcohol usage Genetic syndromes (Turner's syndrome) Chronic systemic dz (Cancer, CF, renal insufficiency, GI dz) Psychosocial dwarfism
Diagnostic approach to short stature (3 steps)?
History and Clinical Presentation
IGF-1 Levels
GH Stimulation Tests
H&P key finding for short stature?
slowed growth that progressively deviates from a previously defined growth percentile on growth curve
does the child have any noticeable dysmorphic features or disproportionate short stature?
Chromosomal abnormalities
Intrauterine infections
Maternal exposures
Disproportionate short stature (rickets)
Possible genetic factors or aspects in the child’s history that could lead to short stature?
Heights of relatives
Presence of health prob’s in the fam
H/o early/late puberty in fam members
Mom’s pregnancy, labor and delivery
Multiple measurements of the child’s ht and wt from birth
Child’s general health, nutritional state, past illnesses, injuries and stresses
Does the child have growth failure?
Children should grow 5 cm per year from age 2 yrs until the onset of puberty
X-ray of the hand and wrist (compare bone development to ht and chronological age)
If H&P suggest GH deficiency measure…
plasma IGF-1 level
Concentration of IGF-1 reflects the concentration of secreted GH
Poor nutrition ___ IGF-1 despite normal levels of GH.
lowers
low levels of IGF-1 in conditions other than GH deficiency include:
Hypothyroidism
Diabetes mellitus
Renal failure
macroprolactinoma on imaging will touch…
the optic chiasm
“Gold standard” in the diagnosis of GH deficiency
GH Stimulation Tests
if IGF-1 is low
GH stimulation tests slide 98???
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etiology of GH deficiency
Hypothalamic causes:
Idiopathic decr. GHRH secretion
hypothalamic tumors
Pituitary causes: Pituitary tumors Trauma Surgical removal Irradiation Idiopathic Secretion of abnormal GH molecules
Tx of GH deficiency in children
MC preprations subcutaneous administration Somatropin
Growth hormone therapy should continue until…
growth ceases
should retest GH deficient children after completion of growth
which children rarely recover GH as an adult?
children w/multiple pituitary hormone deficiences
