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72 Cards in this Set
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Where would cells secreting GH and cells secreting ACTH be found in the pituitary (be as specific as possible)?
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Anterior Pituitary (Adrenohypophysis)
GH= tend to cluster laterally ACTH= tend to cluster in the midline |
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What is the difference between central and nephrogenic diabetes insipidus?
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Central: Inadequate release of ADH from the Hypothalamus-Pituitary (H-P). (Ex: Tumor, Infection/Inflammation, Infiltration (granulomas), hereditary, etc.)
Nephrogenic: Kidney's don't respond to ADH (X-linked V2 receptor problem or Auto Recessive Aquaporin 2 problem) |
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What radiologic sign would you NOT expect to see in the MRI of a patient with congential Diabetes Insipidus?
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Bright spot on Posterior Pituitary (Neurohypophysis) which signifies collection of ADH.
not seen in congenital DI cases |
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What are the different receptor types of ADH/vasopressin and what are their activities?
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V-1a: pressor activity
V-1b (= V3): ACTH activity V-2: renal handling of water excretion & coag. factor VIII action |
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What do we use Vasopressin V-1 agonists for?
What about Vasopressin V-2 agonists? |
V-1 agonist: treat systemic hypotension, decrease blood flow in GI hemorrhage, enhance coronary blood flow
V-2 agonist: decrease water excretion in DI (more ADH, less peeing) or during nocturnal eneuresis. Hemophilia A, vWdisease, and post-surgery- improve clotting response |
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What is Desmopressin?
What is the benefit of using this drug over others analogues? |
Desmopressin= vasopressin aka. AVP analogue (L-arginine changed to D-arginine)
Increased half life and has virtually no pressor activity, so it's effective at selectively treating fluid loss by kidney. |
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What would urine osmolarity, urine volume, and plasma osmolarity be in a person with Central DI?
What would happen to these values if you then treated them using Desmopressin? |
Central DI:
urine osmolarity= Low (high volume) urine volume= High plasma osmolarity= High (less water being held in) With AVP treatment: urine osmolarity= Increased (less volume, more solutes) urine volume= Decreased plasma osmolarity= Decreased (more water being held in) |
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What is the most frequent sellar tumor of childhood and adolescence?
How does it look? What is it's common presentation? |
Cranipharyngioma (3% of all tumors)
- Cystic filled with lipid rich fluid ("motor oil") - Hypothalamic tumor coming from Rathke's pouch. Bascially sxs of hypopit- Growth retardation, Pubertal delay, and also space occupying lesion (vomitting, visual field, headache, etc.) |
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What other conditions, besides a pituitary tumor, can cause pituitary cell enlargement?
(ex: pregnancy) |
- Pregnancy (inc. metabolic needs, physiologic hyperplasia)
- Hypogonad, hypothyroid (end organ problems, decrease neg feedback) - GnRH secreting tumor (ectopic or within hypothalamus) - Somatomamotrophic hyperplasia (Carney syndrome): GH + PRL increase |
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What is the most common human neoplasm?
What is the most common tumor-associated hormone loss to occur? what is the least common? |
Discrete Pituitary Tumor
GH > LH/FSH > TSH > ACTH |
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What clinical manifestations would be seen in a person with lateral extension of a pituitary tumor?
Inferior erosion of the tumor through the sphenoid sinus causes what clinical presentations? |
Can impinge 3,4, and 6 cranial nerves. EOM defects, as well as some pupillary responses.
Headache and clear fluid coming from nose (CSF leak!) |
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What is the size of a macroadenoma? a microadenoma?
What is a pituitary incidentaloma and how common is it? How does it get treated? |
Macro= >1 cm, Micro= <1 cm
Incidental finding on MRI or autopsy of pituitary adenoma. 10% of population on MRI. Measure prolactin levels- no treatment just management if levels wnl. |
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What are some characteristic signs of prolactinomas in women and in men?
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Women: infertility, oligo/amenorrhea (prolactin inhibits GnRH, so less LH/FSH), galactorhea
Men: longstanding erectile dysfunction (not as obvious initially), headache, visual field loss |
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What is the effect of Dopamine receptor blockers (ex: anti-psych meds) on Prolactin secretion?
What is the relationship between Estrogen and Prolactin? |
DA receptor blocker = decreased DA, increased Prolactin
Estrogen/Progesterone will inhibit Prolactin effects on breast, however promote Prolactin secretion. (So women on birth control pills can have irregular periods and slightly elevated prolactin!) |
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What is the first line treatment for Prolactinomas?
What are some examples of this and how does it work? |
Pharmacology- Dopamine Agonists (inc DA, dec. PRL)- shrinks the tumor!
Bromocriptine= great clinical success, bad side effects Cabergoline= better side effects, expensive *high doses of these drugs associated with valvular heart disease (activate valvular serotonin receptors) |
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What might cause GH excess that contributes to Gigantism?
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- GH secreting tumor
- GHRH secreting tumor - something that dysregulates Somatostatin secretion (inhibitory effects) |
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What are some signs and symptoms of Acromegaly?
What is the most common cause of this condition? |
Acral enlargement (soft tissue), prognathism, frontal bossing, hyperhydrosis, oily skin, cardiomyopathy, vesiculomegaly, macroglossia, sleep apnea, hypercalciuria due to kidney enlargement, carpal tunnel etc.
*Macroadenomas seen in >70% of population |
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A patient who you have previously diagnosed with carpal tunnel syndrome now comes to your office with the new complaint that he sweats a lot (hyperhydrosis). What condition are you now concerned he has, and what interview questions would you ask to tease it out?
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Be concerned about Acromegaly!
Ask about changes in size of hands/feet. Ask for previous pictures to compare him with now (driver's license, wedding photo, etc.) |
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What feature would you see on the hand x-ray of a patient with Acromegaly?
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Distal tufting of the terminal phalanges (bone is trying to grow but there's nowhere to go).
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What diagnostic scheme would you use if you suspected Acromegaly in a patient (i.e. what would you test for and what would it mean if it came out positive or neg)?
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1. IGF-1 levels (not GH which is pulsatile in secretion)
If normal- dismiss diagnosis If elevated- do confirmatory Glucose Tolerance Test (Glucose should suppress GH). If Normal- dismiss dx, If high- Acromegaly. |
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What are somatostatin analogues?
What are they used for? |
SST= Hormone that inhibits GH. Analogues= cleaved from pro-hormone. Have specific activity for different Somatostatin receptors (there are 5)
Treat Acromegaly (suppress IGF-1 synthesis) Treat TSH-secreting tumor (suppress TSH) GI endocrine tumors (suppress GI hormone secretion) *20% get gallstones (sludge) |
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What is the difference between ooctreotide and octreotide LAR? What other medication fits into this class?
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Octreotide- short acting, interacts with SST1 and SST5
Octreotide LAR: long acting, given monthly (test dose with octreotide 1st in case they have adverse rxn!) Lanreotide gel (similar activity to octreotide) |
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What pancreatic cells secrete somatostatin and why might increased SST cause hyperglycemia?
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Secreted by delta cells. Can make you Hyperglycemic because of decrease glucagon and insulin.
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How do GH receptor antagonists such as Pegvisomant work?
What surgical procedures can be used for pituitary and hypothalamic tumors? |
Prevent receptor dimerization by binding to and thus blocking a portion of one receptor's binding site.
Transphenoidal (nose) Open frontal (more intensive, more risks) Radiation (Gamma knife) |
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What are hallmarks of hypopituitarism in women and in children?
What are some physical signs of these patients? |
- abnormal growth in kids
- abnormal menstruation in women - slightly overweight, pale, fine wrinkled skin, atrophic genitalia, diminished axilary and pubic hair |
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What genetic mutations might cause hypopit (hint: think of transcription factors)?
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HEXS1
Prop-1 Pit-1 T-PIT (ACTH regulation, associated with red hair and obesity) |
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What are the 8 I's of hypopituitarism?
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1. Invasion: tumors, metastsis
2. Infarction (sheehan, apoplexy) 3. Infiltration (sarcoid, histiocytosis, hemochromatosis) 4. Injury (TBI) 5. Immunologic (auto-immune) 6. Infection (TB) 7. Iatrogenic: surgery, radiation 8, Idiopathic |
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What medication could be given to individuals with Growth hormone Insensitivity?
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Mecasermin: a recombinant IGF-1 linked to recombinant IGF binding protein 3
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A 62 year old former baseball player, comes to your office. He is feeling less athletic and fit and his muscles aren't as big as they used to be. He has heard about GH supplementation and knows a couple of his friends who have taken it . You run some initial labs that indicate that the pituitary is working just fine.
What do you tell him regarding GH supplementation in pts. without pituitary defects? |
GH secretion normally decreases in frequency with age
IGF-levels are lower in healthy aging adults GH treatment has no impressive benefits on muscle strength, bones etc. Side effects- carpal tunnel, fluid retention, hyperglycemia. *only approved in the wasting of HIV/AIDS pts. |
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What is the clinical hallmark of SIADH?
Describe the pathology of this condition. |
Clinical hallmark= hyponatremia with evidence of water excess
*ADH leads to water retension, however Na+ is not corrected for and you end up getting low sodium. |
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What are some causes of Syndrome of inappropriate ADH?
Are patients Hypovolemic, Euvolemic, or Hypervolemic? |
1. Ecotopic ADH: (ex: small cell cancer)
2. Baroreceptor dysregulation (pressure sensor is off, infection, hemorrhage in CNS, thoracic baro-receptor in pneumonia pts.) 3. Drugs: ex: Antidepressants, Antipsychotics, chemo, etc. Euvolemic pts (no edema, no dehydration) |
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What is the treatment approach to patients with SIADH?
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- Restrict fluid intake + give hypertonic fluids (gently!)
- Drugs: ex: demeclocycline and Li+ impair renal respnse to ADH - Vasopressin antagonists *block V2 receptor, Conivaptan (IV), Tolvaptan (PO) |
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What is the difference between "Hypogonadotrophic Hypogonadism" and "Hypergonadotrophic Hypergonadism"?
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Hypo= Secondary, low GnRH, thus low gonadal hormones
Hyper= Primary, despite a high GnRH, there is still low gonadal hormone. End organ dysfunciton. |
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The release of what hormones is controlled by GnRH?
What do these hormones control the release of? |
GnRH (from hypothalamus) controls release of:
LH, FSH, HCG --> Testosterone and inhibin B (neg feedback for FSH), E2, progesterone |
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What is the role of Activin and Follistatin?
When measuring testosterone levels, what are we mainly measuring? |
Activin- stimulates FSH secretion
Follistatin- inhibitor of Activin *both released by gonad, extra-gonadal tissue We are measuring total test. (so mainly testosterone bound to SHBG since there is only 2% free test) |
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Endocrine 1st principles. Complete the following:
1. If you suspect hormone excess... 2. If you suspect hormone deficiency... 3, If you suspect end organ hormone failure... 4, Suspect secondary organ failure... 5. Interpret lab results in... |
* always do the opposite of what you think
1. Hormone excess- suppress it 2. Hormone deficiency- stimulate it 3. Organ failure- measure trophic hormone (ex: TSH) 4. Secondary organ failure- measure end-organ hormone (T4,T3) 5. Context! |
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Why is it that the treatment for Precocious Puberty and hypogonadic function is to administer GnRH?
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In hypogonadism- give pulsatile GnRH dose so that LH/FSH secretion mimics physiologic pulsatile secretion.
In Precocious puberty, give GnRH at a large, constant dose to downregulate GnRH receptors. |
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What is the role of GnRH agonists?
What about Antagonists? |
They both decrease FSH, LH and thus estrogen/testosterone
GnRH agonists can be used to prevent precocious pubery and in cases of prostate/ breast cancer (to decrease estrogen and testosterone production).*high level shuts off LH and FSH (due to feedback) Antagonists- are used to suppress LH surge and prevent premature ovulation (assisted reproduction). |
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What is Kallman's syndrome?
Is hypogonadotrophic or hypergonadotrophic? |
Failure of GnRH neurons to migrate along olfactory placodes due to X-linked mutation in anosmin (that allows GnRH to migrate). Also olfactory bulbs fail to form.
Loss of smell and hypogonadism (cryptorchidism, small testes, microphallus) --> hypogonadotrophic hypogonadism (2ndary) |
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What is considered CDGP (constitutional delay of puberty) in boys? in girls?
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2-2.5 SD later than mean age
Boys, mean= 14 Girls, mean= 13 |
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What is Eunuchoidsm?
How do these individuals look? |
Castration (induced) or some testosterone deficiency early on that causes
- poor muscle development, prepubertal fat distribution, high pitched voice, long arms relative to legs. epiphyseal plate continues to grow in long bones because of lack of high E2 levels |
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What are some reasons why a person might develop functional amenorrhea?
briefly describe the physiology of this process. |
1. Anorexia nervosa- low leptin, decreased GnRH secretion
2. Stress- increased Cortisol, decrease in pulsatile GnRH 3. Intense exercise- increased opioids (B endorphins), dec. GnRH pulsatile secretion- also a combination of low leptin |
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What are some indications in Men, of late onset hypogonadism?
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Note: Usually testosterone decline is normal after age 40.
Sexual sxs- low libido, erectile dysfunction, poor morning erections Physical sxs- difficulty w/ physical activity Psychological sxs- sadness, energy loss, fatigue |
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What is menopause? What is the level of FSH at this time?
What is the age limit for Primary Ovarian insufficiency? |
Natural loss of primordial follicles within ovary. FSH is high because inhibin decreases (as ovary runs out of follicles)
Primary Ovarian insufficiency: suspect if <40 y/o |
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What are some signs of Polycystic Ovary Syndrome?
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Elevated androgens-
- hirsutism, acne, male-pattern baldness - menstrual irregularity/ anovulation *it is a disorder of both the pituitary and the ovary |
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Name the disorder:
45XO 47XXY |
45XO= Turner's- gonadal dysgenesis
47XXY= Kleinfelter's- seminiferous tubule dysgenesis |
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What is normal penile length in newborns and in adults?
Testis size>4mL suggests...? |
newborn- 3.5 cm
adult- 12.4 +/- 2.7 cm |
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What are some signs of Kleinfelter's syndrome?
What are some signs of Turner's syndrome? |
Klinefelters: firm, very small testes (also gynecomastia, tall stature, some learning disability)
Turners: short stature, short/webbed neck, pubertal failure, primary amenorrhea. |
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Why is it that patient's with Klinefelter's syndrome have high FSH and LH despite seminiferous tubule dysgenesis?
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Seminiferous tubules typically make Inhibin to inhibit FSH levels (similar situation arises in women who undergo menopause).
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A malnourished toddler comes to your office. He is not growing well and you draw some blood to check growth hormone levels. They surprisingly come back elevated.
Explain this phenomenon. |
IGF-1 (released from liver) is dependent on nutritional status. Patient has poor nutrition so IGF-1 is low. There is less negative feedback on the pituitary and thus, excess GH.
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What are some genetic or innate causes of Congenital Hypopituitarism/ Growth Hormone Deficiency (GHD)?
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- Structural Deficits (Septo-Optic Dysplasia)
- Pituitary TF mutations (PROP-1, Pit1) - GH-1 gene mutation - GHR mutation/ signaling defect *Idiopathic/isolated (always include!) |
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What are some acquired causes of Growth Hormone Deficiency?
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- Tumor (craniopharyngeoma)
- Pituitary surgery/radiation - Trauma (concussion) - Inflammation (ex: autoimmune) - IGF-1 deficiency (typically after chronic illness or other disease state) |
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What are the clinical signs that someone has Growth Hormone Deficiency?
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- decrease growth velocity
- height < genetic target (parental heights) - Weight gain/dimpling - Hypoglycemia (possibly micropenis in infancy) - Midline defects (ex: cleft palate) - other Pituitary hormone deficiencies |
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If you suspect GHD in one of your young patients, what labs would you send and what do you expect the results to be?
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1. Bone age (hand scan)- delayed
2. IGF-1 LOW, IGF BP-3 LOW 3. Other pituitary hormone levels (may be low) |
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What effect does Hypothyroidism have on growth in children?
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- Delays growth and skeletal maturation
- Delays puberty - T3, T4 has permissive effect on GH secretion and direct effect on epiphyseal plate |
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A child comes in to your office because they have fallen off the normal growth curve. You take a history and note that they have been on long term steroids for Crohn's disease. What do you suspect is the cause of his growth delay?
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Chronic steroids= excess cortisol which impairs IGF-1 action and suppresses GH secretion
*other possibility = chronic illness |
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A child comes to your office because he is relatively short compared to their classmates. You assess the parents' height and note that they are both of short stature. Bone age of child shows no maturation delay. The child's growth chart shows normal growth velocity.
Should you treat the child with GH? |
Not medically indicated because this is Familial Short Stature (normal genetics and no growth delay).
May treat for psychosocial effects. |
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What is the role of love in the growth of children?
Would you prescribe GH for these children? |
GHD can be caused by neglect ("Psychosocial Dwarfism")
No. GH supplementation not needed (it is reversible if child is moved to nurturing situation). |
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Release of what hormones esponsible for the "growth spurt" associated with puberty?
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Sex steroids are needed for growth spurt.
They increase secretion of GH (isolated hypogonadism is a cause, albeit rare, of short stature). |
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A 14 year old boy comes in to see you. His parents are worried because all the boys in his class have begun to "change" and are much taller than he is. His parents are both average height and bones scans show he has delayed BA but no hypogonadism. Family Hx reveals that his dad was a late bloomer.
The family wants to start the boy on GH because they are afraid he will be short. What do you tell them? |
The boy has Constitutional Delay of Growth/ Puberty (strong family hx and no other abnormalities). GH is not needed because he will attain genetic target height (just later).
*note GH can be given to "jump start" puberty if they want. |
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An dark-skinned Indian woman living in England comes to your clinic. Her 1 year old child is not growing very well and she is worried. You do a social history on her and note that she wears a head scarf and her job requires her to stay home all day. She takes no multivitamins or supplements.
What should you think about as a possible cause of her child's poor growth? |
Vitamin D deficiency
Risk factors (not in sun, dark skin, no supplements). Possibly decreased levels of vit D during pregnancy, thus child is at risk. |
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Delayed bone age might indicate GHD, hypothyroidism, chronic illness, etc.
What are some differentials for normal bone age in a patient with short stature? |
1. genetic SS
2. idiopathic SS 3. skeletal dysplasia |
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What lab tests should you order if you suspect someone has growth retardation due to:
- GH status - Hypothyroidism - Chronic disease - Bone abnormalities - Genetic defect - Vitamin D |
- GH: test IGF-1/ IGFBP-3
- Hypothyroid: test TSH - Chronic disease: CBC, ESR, Celiac - Skeletal survey (bone age, etc.) - Genetics: Karyotype - 25 OH vit D level |
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What lab/ diagnostic tests would you do if you suspect the following causes of growth delay in children:
- GH deficiency - Hypothyroidism - Bone abnormalities - Genetic - vitamin D deficiency |
- GH deficiency: IGF-1/ IGFBP-3 levels (or stimulation tests)
- Hypothyroidism: TSH - Bone problems: Skeletal survey, bone age - Genetic: karyotype (possibly CMA?) - test 25 OH vit D level |
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What are two ways to stimulate GH release? Why would ever do this clinically?
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1. Inhibit SMS (dopamine, arginine, etc.)
2. Stimulate GHRH (clonidine- a2 adrenergic stimulant, insulin, hypoglycemia, glucagon) *use this to evaluate GH levels in suspected GHD patient. If GH is still low after stimulation, it may be confimatory. |
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What is the Pituitary MRI Triad?
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1. Small anterior pituitary
2. Absent/ Ectopic posterior pituitary 3. Abnormal stalk (interrupted or thin) *patients with these findings are at greater risk for multiple pituitary hormone deficiencies |
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What is rGH? How is it administered and what neurologic side effects should patients be warned about?
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Recombinant GH
Subcutaneous daily injections Can cause edema/pseudotumor cerebri |
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What is rGH? How is it administered and what neurologic side effects should patients be warned about?
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Recombinant GH
Subcutaneous daily injections Can cause edema/pseudotumor cerebri |
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A child is brought to your attention by a nurse who notices that she is way above her normal height. Examination of the child shows slight advancement in bone age. Her weight chart shows that it is accelerating at approximately the same rate as her height.
What is the likely cause of her excess growth? |
Exogenous Obesity
Nutrition stimulating IGF-1. Final height should be within normal genetic target. |
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A tumor in the ovaries resulting in excess growth of a child would be an example of what mechanism of growth excess?
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Precocious Puberty
Ovarian tumor causing estrogen release and promoting growth. |
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What is the difference between Gigantism and Acromegaly?
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Gigantism- excess GH before fusion of growth plate (increase in height as well)
Acromegaly- excess growth after growth plate fuses (no height gain, coarse facial features, excess body fat) |
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In a patient with suspected GH excess what one test is always indicated?
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MRI
Might be a pituitary adenoma (may or may not see visual field/ neurologic defects) |
