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THE ROLE OF HYPOTHALAMUS IN HOMEOSTASIS

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THE ROLE OF HYPOTHALAMUS IN HOMEOSTASIS Powered By Docstoc
					THE ROLE OF HYPOTHALAMUS IN HOMEOS TAS IS

  1.   Exp lain ro le of each of the following in hu man thirst and control of serum osmolality.

       Hypothalamic dri nking center        Stimu lation results in drin king behavior
               Angiotensin                  Powerful stimu lator of thirst
                  ADH                       Fine tunes water balance
                Osmostat                    Small changes in serum os molality are noted here
              Baroreceptors                 Important control over hypovolemia and hypotension

  2. (2 & 4) Clinical diagnosis of DI (telling different btwn central, nephrogenic, compulsive water drinking) and common
  causes.
           a. Characteristics of DI:
                     i. Thirst
                    ii. Polyuria
                   iii. Dehydration in the face of water deprivation
           b. Co mmon causes:
                     i. Post-surgical/Post-trauma (most common)
                    ii. Congenital
                   iii. Neoplasm
                   iv. Granulo matous disease
                    v. Pituitary infarct ion
           c. Clin ical Diagnosis
                     i. Water deprivation test
                             1. admit pt into controlled environ ment w/out any water
                             2. pts weighed frequently and test stopped if excessive weight loss occurs
                             3. serum and urine os molality checked hourly:
                                       a. Normal pts: serum osmolality rise then plateau
                                       b. DI pts: seru m osmo lality rises into a range indicating dehydration
                            4. when dehydration or plateauing of urine osmolality occurs, in jection of DDVP is
                               ad min istered
                                           Central              Brisk rise in urine os molality
                                        Nephrogenic             No further change in urine osmolality b/c kidney is incapable
                                                                of responding to ADH
                                Compulsi ve water drinker Dehydration alone causes max urine concentrations

  3.   Tests indicating differences btwn DI and DM
           a. Seru m osmo lality
           b. Urine osmolality
                          Conditi on            Serum Osmol ality                  Urine Os mol ality
                   DI                         High                      Low (no taste b/c it’s mainly water)
                   DM                         High                      High (sweet taste)
                   Co mpulsive polydipsia     Low                       Low
                **Pts w/DI or DM will mainly d rin k cool water to quench their thirst.
                **Pts w/ compulsive polydipsia will drin k anything due to their psychiatric condition

  5.   Use laboratory results to distinguish btwn dilutional, depletional, and delusional hyponatremia and SIADH secretion
                                       Eti ology                            Clinical Findi ngs           TB Na      TBW
                       -loss of water and Na seen                -postural drop in BP >10 mmHg           ↓        Norm o r ↓
                       w/vomiting or d iarrhea                   (suggestive of decr. Vo lu me)
        Depletional                                              -lack of sweat ing; dry mucous mem
                                                                 -skin turgor (kids only)
                                                                 -flat jugular veins
                       -excessive oral water consumption         -peripheral edema (p resacral edema)    Normal ↑
        Dilutional     -admin of Na poor IV solutions            -elevated JVP
                                                                 -CHF
                       Artifact of lab measurement;              Seen w/ Hyperlipidemia                  Normal Normal
        Delusional                                                         Hyperproteinemia
                                                                           Hyperglycemia


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     6.   Summary of SIADH
                                                                               Causes
      Sodium                        Dx               CNS Disorders                Drugs                Other           Treatment
-TB Na = normal        1. Hyponatremia & hypo-       1. Trau ma          1. Cancer chemo           1. Chest        -recognition
-TBW = ↑               osmolality                    2. Surgery          drugs                     disorders
  -water is both       2. Continued renal            3. Stroke           2. Carbamazep ine         (pneumonia)     -fluid restrict ion
intra & extra          excretion of Na in face of    4. Metabolic        (anticonvulsive- low
cellu lar therefo re   hyponatremia b/o volume       Encephalopathy      serum Na can              2. Ectopic      -reserve Na for
there is no edema      overload                      5. Subarachnoid     present as seizures)      production      life threatening
                       3. Format ion of urine less   hemorrhage          3. Ch lorpro mazine       (lung           situations
                       than maximally dilute         6. Subdural         4. Ch lorpropramide       tumors)         -if raise serum
                       4. Clinical absence of        hemorrhage          5. Clofibrate                             Na too quickly,
                       volume deplet ion or                              6. Th iazide d iuretics   3. Idiopathic   can demyelinate
                       overload                                          (contract volume;         (most           pons  death
                       5. Normal renal, adrenal                          filter less water and     common)         (central pontine
                       and thyroid function                              potentiates action of                     myelinolysis)
                                                                         ADH)

     7.   Outline   role o f hypothalamus in appetite control and eating behavior
              a.     Balancing energy intake and output
              b.     Limb ic system plays sig role in food-seeking behavior
              c.     Satiety center = ventro medial nucleus of hypothalamus (destruction is follo wed by onset of voracious food
                     consumption)

     8.   Make diagnosis of anorexia/bulimia nervosa based on hx and PE of pt.


THE ANTERIOR PITUITARY

1. Name hypothalamic factors that control the release of that hormone and indicate the effect on hormone release for each fac to r
           Pituitary Hormone                                       Hypothalamic Factor
            Growth hormone              GHRH
                                        Growth hormone release-inhibit ing hormone (somatostatin)
                Prolacti n              Prolactin releasing factor
                                        Prolactin release-inhibit ing factors (dopamine and part of Gn RH)
           Thyrotropin (TS H)           TRH
     Pro-opi omelanocortin (POMC) CRH
         contains w/in it ACTH
                   LH                   Gn RH
                                        Lutein izing hormone release-inhibit ing factors
                   FS H                 Gn RH


     2.  List tumors found in the region and describe symptoms and causes.
               Tumor                         Symptoms/Presentation of Pit Tumors                                Causes
Prolacti n secreting                   1. incidentally found as part of investigation of
Non-secreting (null cell)              another problem (ie sinusitis)
Growth hormone secreting               2. syndrome of hypersecretion of ant pit hormone
ACTH secreting                         3. syndrome of hyposecretion of one or more
Others (craniopharyngioma)             ant/post pit hormone
                                       4. co mpression of local structures (optic nerve)
                                       5. co mb ination of above




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     3.   Indicate whether symptom is caused by excess or deficiency of an anterior pituitary hormone
   Hormone                                            Excess                                                     Deficiency
Growth hormone         Gigantism if epiphyses not fused                                       Growth failure or dwarfism (loss of GH receptor)
                       Acromegaly of epiphyses fused
     Prolactin         Amenorrhea (high prolactin inhibits GnRH), impotence, dec              Inability to breast feed, infertility?
                       libido,
                       Galactoria, infertility, delayed puberty
   LH an d FS H        Precocious puberty, Polycystic ovary syndrome (rare)                   Amenorrhea, impotence, infertility, delayed
                                                                                              puberty, dec libido
       TS H            Hyperthyroidism                                                        Hypothyroidism
      ACTH             Cushings Syndrome                                                      Addison’s disease w/out or w/only mild
                       Nelson’s syndrome                                                      mineralocorticoid deficiency

     4.   List three conditions that can cause hyperprolactinemia apart fro m p rolactino ma and list the classes of drugs that can cause
          this condition.
                                              Causes
                    Drugs                                               Other                                           Treatment
1. major tranquilizers                             1. Primary hypothyroidism (TRH stimulates         1. Bromocriptine: inhibits prolactin release
2. metoclopramide (dopamine antagonist;            prolactin)                                        and shrinks tumor
stop nausea in pts; block dopamine in brain)       2. Damage to pit stalk (kinking of stalk by         -pts may be intolerant of SE
3. h2 receptor blockers                            large non-secreting tumor)                          -life long t x necessary
4. alpha-methyl dopa (Aldomet)                     3. Empty sella syndrome (neck of dura that        2. surgery: 50% recurrence rate in 15 yrs
5. Tricyclic antidepressants                       surrounds pit is not right causing stretching     3. radiotherapy: not used in US
6. Benzodiazepines                                 of stalk and squishing of pit by CSF)
                                                   4. Prolactin secreting pit tumor
      Excessive levels of prolactin directly inhibit release of LH and F SH from pit. Prolactin, in the presence of estrogen and ot her hormones,
      primes the breast to produce milk. This can lead to a clinical syndrome in which a young woman will stop having periods, will have milk
      secretion from the breasts but will not be pregnant.

     5.   Make diagnosis of acromegaly, hypopituitarism, pituitary hypoplexy.
  Condition                 Definition/Causes                               Features                                     Treatment
                  Excessive GH production by               -wide feet, thick skin                         1. surgery
                  pituitary tumor  increased IGF-1        -jaw protrusion (over/under bite)              2. radiotherapy (tx pts not cured by
                  production by the liver. IGF-1 is        -heavy brow and ridges                         surgery)
                  responsible for the excessive growth     -oily skin, wide fingers                       3. Bromocriptine: helps control GH
                  that takes place.                        -headache (frontal retro orbital)              secretion but does not normalize it
                   -before puberty  gigantism             -impaired glucose tolerance or overt DM        4. Long acting somatostain
 Acromegaly        -after puberty  Acromegaly             -acral growth and prognathism                  (octreotide): normalize GH levels but
                                                           -arthritis complaints                          expensive
                                                           -soft tissue growth
                                                           -visceromegaly
                                                           -proximal muscle weakness
                                                           -menstrual irregularities
                                                           -increased sweating
                  -tumor                                   Treatment of Hypopituitarism:                  4. ACTH ↓:
                  -pit apoplexy                                                                             -syn ACTH dx only
                  -surgery                                 1. Growth Hormone:                               -cortisol def tx w/
                  -radiotherapy                              -genetically engineered GH                      *p.o. prednisone,
                                                           2. LH/FS H:                                       *cortisone acetate,
                                                             -estrogen/testosterone                          *Fludrocortisone for
   Hypopit                                                   -infertile  human menopausal                mineralocorticoid def
                                                           gonadotropin                                   5. Vasopressin:
                                                           3. TS H ↓:                                       -aqueous vasopressin : short acting
                                                             -syn TSH for pit testing                       -DDAVP: longer acting
                                                             -Levothyroxine                                 -clofibrate, chlorpropramide,
                                                                                                          hydrochlorothiazide, carbamazepine
                                                                                                          (these are not really used b/o oral
                                                                                                          DDAVP)

                  Hemorrhage into pit gland or pit         -rupture into CSF may mimic                    1. stabilize pts w/fluids and steroids
                  tumor severe enough to result in         subarachnoid hemorrhage                        2. CT/M RI quick
  Pituitary       compression of perisellar structures     -cranial nerve palsies                         3. earl operative decompression
  Apoplexy        or to produce signs of meningeal           -lateral to sella turcica: nerves in
                  irritation                               cavernous sinus that move eyes 
                                                           double vision
                                                             -superiorly: optic chiasm  acute
                                                           visual field defects
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THE ADRENAL GLAND

  1.   Define Cushing’s syndrome and list the four categories of causes.
           a. Cushing’s Syndrome Defin ition:
                     i. Caused by excessive circulating levels of Cortisol (anything that causes increase in Cortisol level)
           b. Four categories of causes
                     i. Excessive production of CRG
                            1. fro m hypothalamus
                            2. fro m Ectopic source
                    ii. Excessive production of ACTH
                            1. by pit adenoma (Cushing’s disease; 80% of cases)
                            2. fro m Ectopic source (rare)
                   iii. Excessive production of Cort isol by adrenal gland
                            1. adrenal adenoma
                            2. adrenal carcino ma
                   iv. Exogenous admin istration of glucocorticoid (iatrogenically: most common cause)

  2.   When given a typical case history, make a diagnosis of Cushing’s Syndrome.
          a. Clin ical Features of Cushing’s Syndrome
                    i. Central obesity (potato-stick man appearance)
                   ii. Supraclavicular and preauricu lar fat pads
                  iii. Hypertension
                  iv. Impaired glucose tolerance
                   v. Oligo menorrhea, hirsuitism, acne
                  vi. Purple striae due to loss of sub Q tissue b/o catabolic state therefore can see underlying veins
                  vii. Pro ximal muscle weakness: can’t get out of squat b/o catabolic state
                 viii. Easy bruising b/c CT not as strong
                  ix. Depression
                   x. Growth retardation in children (can’t g row b/c steroids are counteractive)

  3.   Cushing’s Disease vs Cushing’s Syndrome
             a. Cushing’s Syndrome
                     i. Term used for clin ical features of Cort isol excess of ANY CAUSE
                    ii. If untreated, significantly shortens life
             b. Cushing’s Disease
                     i. Term used when syndrome is caused by excessive secretion of ACTH by PITUITARY ADENOMA
       **pts w/adrenal adenomas producing Cortisol usually present w/a relative excessive production of gluc ocorticoid and lil
       evidence of mineralocorticoid or androgen excess
       **Pts w/ACTH producing tumors show signs of glucocorticoid excess but b/c very high levels of ACTH stim
       mineralocorticoid and androgen production and more likely to have evidence of hypert ension, serum K abnormalities and
       virilization

  4.   Indicate the place of the following tests:
            Test                    When used                                          Description of test
  Diurnal cortisol         Screening test                 Test cortisol levels in the morning  it should be high
  variation                                               Test cortisol levels at mid-night  it should be the lowest
  Overnight                Screening test                 -Pt receives dexamethasone dose at 11pm
  dexamethasone                                           -Next morning, pt has cortisol levels tested
  suppression test (DST)                                  (Dexamethasone is a powerful glucocorticoid which suppresses the natural
                                                          o/n production of ACTH causing cortisol levels to be low in the morning in
                                                          normal individuals)
                                                          -No suppression of cortisol in these situations:
                                                            -stressed pt
                                                            -Cushing’s Syndrome
                                                            -excess OH consumption rapidly metabolizes dexamethasone
                                                            -pt on meds that enhance hepatic degradation of dexamethasone
                                                            -pt on estrogen  cortisol-binding globulin is 
  24 hour for urine free   Screening test                 -need 2 urine specimens back to back
  cortisol                                                -Important facts:
                                                            -not affected by obesity, hepatic enzyme induction, increased steroid
                                                          binding globulin



                                                                                                                                       4
           Test                      When used                                                Description of test
Standard DST              Used to make a diagnosis of           -collect 2 24-hr urines for urinary free cort isol (serves as baseline)
                          Cushing’s in pts w/+                  -pt then treated w/low-dose dexamethasone for 48 hrs during wh ich
                          screening tests                       pt has to continue to collect urine for urinary free cortisol
                                                                -Normal pts: dexamethasone will cause fall of >50% in urinary free
                                                                cortisol production
                                                                -Pt then treated w/ high-dose dexamethasone for another 48 hours
                                                                and urine is collected
                                                                -pts w/cushing’s will show suppression of urinary free cort isol
                                                                -pts w/adrenaladenoma or adrenal carcino ma will show no
                                                                suppression (test requires 6 consecutive days of urine collection)
ACTH levels               Distinguish pituitary fro m           -Cushing’s syndrome fro m adrenal cause: unmeasurable ACTH
                          adrenal Cushing’s                     -Pit production of ACTH is suppressed by the constantly elevated
                                                                cortisol levels fro m autonomous adrenal production
                                                                -ectopic ACTH production causes extremely high levels
                                                                -Normal ACTH  Cushing’s: wh ile the level is in normal range,
                                                                there is lack of d iurnal variation and thus over 24 hours there is
                                                                excessive ACTH being produced
CT/M RI of pituitary                                            -ectopic ACTH:
                                                                  -b ronchial carcinoids
                                                                  -pancreatic tumors
                                                                -ACTH tu mors in the pit g land are too small to be revealed by CT

5.   Given results of a standard DST, d istinguish among normals, Cushing’s disease, and Cushing’s syndrome
                    Normal pt                                Cushing’s disease               Cushing’s syndrome
-dexamethasone cause a fall of more than 50%        -suppression of urinary free       -NO suppression of urinary free
in urinary free cortisol production                 cortisol                           cortisol

6.     Treat ment for pt based on hx and lab findings
           a. Pituitary surgery (if small tu mor, resect and pt will be cured)
           b. Radiotherapy (reserved for those pts who do not respond to surgery; more effective in children but can cause
                growth failure)
           c. Adrenal surgery
                      i. adrenalectomy  accelerated growth of p it adenoma high levels of A CTH skin p ig mentation b/c
                          ACTH contains w/in it the structure of MSH
                     ii. expanding pit lesion comp ress local structures and this symptom co mplex is referred to as Nelson’s
                          syndrome
           d. Drugs
                      i. Metyrapone: inhib its adrenal steroid prodcution temorarily
                     ii. Ketoconazole: inhibits adrenal steroid production (inexpensive)
                    iii. OPD’D’D’: for carcino ma (causes adrenal necrosis)
           e. Ectopic source: surgery

7.     Made diagnosis of hypoadrenalism, confirm d iagnosis with tests, and treatment options for these pts
     Hypoadrenalism                   Clinical features                              Diagnosis                                  Treatment
                       -hyperpigmentation of skin if ACTH levels       **ACT H has less of an effect on          Acute hypocortisolism (emergency)
                       are high                                        mineralocorticoid and androgen            1. Fluids: 0.9% NaCl in large volumes
                       -pale skin of ACTH levels are low               production**                              b/c pt is volume depleted
Glucocorticoid         -hypotension
deficiency             -anorexia, nausea, vomiting, wt loss            1. Determine if the adrenal gland can     2 hydrocortisone sodium succinate
                       -hypoglycemia (no effect of corticosteroid on   secrete cortisol by giving ACTH im or     (Solucortef) 100mg iv bolus followed by
                       liver)                                          iv for 3 days.                            10mg/hr iv (balanced glucocorticoids
                       -lethargy, confusion, psychosis (rare)            -10 hypoadren: no response              and mineralocorticoids is not provided
                       -Na loss, hypovolemia (hypotension),              -20 : stepwise  in cortisol on each    by dexamethasone)
Mineralocorticoid      azotemia                                        successive day
deficiency             -hyperkalemia                                                                             -it pt ndiagnosed, draw cortisol level and
                       (DDx is SIADH; but in SIADH Na and K will       2. Find out if the hypothal-pit-adrenal   ACT H level then tx pt; once stabilized
                       be low)                                         axis work by inducing hypoglycemia so     tx w/dexamethasone to facilitate testing
                       -loss of pubic and axilary hair in F            the brain sends signals to hypothal and   -long term replacement: p.o. prednisone
                       -decreased libido in F                          pit to put out more GH and ACTH to        or cotisone acetate
Androgen deficiency                                                    induce gluconeogenesis and                -if mineralocorticoid supplementation is
                                                                       catecholamine release                     necessary then gludrocortisone is added



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 8.   Abnormal body distribution of hair in femailes and tx options for those w/hirsutism.
         a. Abnormal hair d istribution:
                   i. Lip, chin, middle chest hair
                  ii. Male pattern pubic hair
         b. Treat ment options
                   i. Suppresion of ovary w/oral contraceptives
                           1. Oral contraceptives reduce circulating free testosterone levels and antagonize androgens of skin
                           2. Non androgenic progestin-containing pill – Demu lin- is a good choice
                  ii. Suppression of adrenal gland w/prednisone (given in evening) or spironolactone stops excessive hair
                      growth
                 iii. Hair that is already present will not respond to hormonal t x; this can be treated by cosmetic methods

 9.   Clin ical finidings expected in male/female infant w/adrenogenital syndrome
           a. Adrenogenital syndrome
                       i. Makes lil g irls lil boys
                      ii. Makes lil boys  lil men
           Female                            Male                                           Causes                              Treatment
Classical:                      Classical:                      1. 21-hydroxylase                                         Replacement therapy
  -neonatal ambiguous           -late neonatal to infancy:         -necessary for synthesis of cortisol  pts have        w/cortisol and
genitals                          -pigmented scrotum            cortisol deficiency                                       mineralocorticoid
  -occasionally male              -70% salt losing state           -17-hyroxylase is a precursor of cortisol that is
phenotype                       -early childhood:               accumulated; this along w/progesterone produes a salt-    In pts w/mild form, give
  -70% have salt losing state     -penile growth                losing tendency   renin activityaldo which            only cortisol which
                                  -pubic hair                   needs 21 hydroxylase                                      suppresses ACTH and
Non-Classical:                    -rapid linear growth            -if def is partial, aldo is synthesized and there is    reduces production of
 -late infancy: clitoromegaly     -musculature                 compensation for salt losing tendency                     androgen
 -childhood: pubic hair,                                          -if def is complete, no aldo synthesis is possible
growth                         Non-Classical:                    -17-hydroxylase can lose its side chain and give rise
 -Adol: abnormal menses,         -childhood: pubic hair, tall   to androstenedione which is metabolized in the
         hirsutism, acne        stature                         periphery to testosterone
 -Adult: hisuitism,              -adol: not known                 -These defects in adrenal steroidogenesis cuases a
          oligomenorrhea,        -adult: not known              rise in ACTH  “spill over of precursor into androgen
          infertility                                           pathway and excessive adrenal androgen production
                                                                2. Other causes of hirsuitism and virilisation:
                                                                   -testicular tumors
                                                                   -ovarian tumors
                                                                   -adrenal tumors
                                                                   -renal tumors

 10. Define Conn’s syndrome, ind icate typical clin ical and lab findings and indicate how d x is made.
         a. Conn’s syndrome:
                  i. Aldosterone secretion by adrenal adenoma (60%) o r hyperplasia (40%)
                 ii. Typical presentation: hypertension AND hypokalemia (cause muscle weakness, paraestheisa, tetany)
                iii. Dx: measure aldosterone under standard conditions and CT scans of adrenal gland (false positives)
                         1. 10 aldosteronism: renin levels are ext remely lo w
                         2. 20 aldosteronism: renin levels are high
                iv. Treat ment:
                         1. Surgical if adeno ma found
                         2. Spironolactone: inhibits efects of aldosterone on renal tubule; usually corrects hypertension and
                              hypokalemia

 11. Made diagnosis of pheochromocytoma and outline a p lan to confirm d x by lab investigation
        a. Pheochromocytoma sympto ms
                  i. Hypertension/postural hypotension (pheochromocytoma is a rare cause of hypertension but it is co mmon
                     in pts w/pheochromocytoma)
                 ii. Headache
                iii. Sweating
                iv. Palpitations
                 v. Nervousness
                vi. Weight loss
                vii. Frequently symptoms are paro xys mal



                                                                                                                                              6
              b.   Diagnosis:
                         i. Pts w/pheochromocytoma are usually relatively vo lu me depleted  btwn bursts of catecholamine
                            secretion their blood pressure may be normal and they have p ostural hypotension
                        ii. Dx made by showing excessive secretionof catecholamines on 24 hr u rine co llections
              c.   Treat ment
                         i.  and  blockers ( blockers alone may lead to severe hypertension due to unopposed  stimulation)
                        ii. Ideally : surgery
                       iii. Metyrosine: tyrosine hydroxylase inhib itor can also block catecholamine formation


THE MAL E GONAD

1. Indicate when puberty should be considered delayed and give list of possible causes.
          a. Testicular enlargement and/or appearance of sexual hair is expected by age 15
          b. Causes:
                  i. Idiopathic, often familial (puberty may not occur until age 20)
                  ii. Associated w/chronic malnutirion or systemic disease
                  iii. Gonadal insufficiency:
                              1. primary hypergonadotrophic
                                     1. Klinefelter’s syndrome
                                     2. Anorchia (kids w/out testes)
                                     3. Noonan’s syndrome (look like turners w/webbed neck)
                                     4. Mumps orchitis (mu mps have tropism for gonads)
                                     5. Cryptorchidis m (bilateral)
                              2. Secondary hypogonadotrophic
                                     1. panhypopit (congenital or acquired )
                                     2. isolated Gn RH deficiency
                                     3. Kallmann’s syndrome
                                     4. Praeder-Wlli syndrome
                                     5. Laurence-Moon-Biedi syndrome
                                     6. Holoprosencephaly

2. Indicate how height and arm measurements can be used to suggest a dx o f delayed puberty.
          a. In hypogonadal boys, long bones continue to grow and they grow more relat ive to the trunk. Th is is the eunuchoid
              body habitus which is characterized by long arms and legs relative to the over-all height (refer to diagram on page 56)

3. In a boy w/gynecomastia, indicate possible causes, outline plan for investigation, and possible t x for this condition if idiopathic.
          Causes:
          a. obesity (psuedogynecomastea)
          b. glandular tissue
          c. tumor
          d. 10 hypogonadism (b/o high LH and FSH levels)
          e. chronic liver disease (accelerated conversion of androgen to estrogen in periphery)
          f. EtOH abuse (inhib ition of testosterone production in testis by OH  breast enlargement)
          g. Adrenal/testicular tu mors (produce estrogen)
          h. Drugs
                  i.Dopamine blockers (clorpro mazine)
                  ii.Sp ironolactone (painful gynecomastia)
                  iii. Marijuana
          i. hyperprolactinemia
          j. hyperthyroidism

         Treat ment:
                  a.   watchful wait ing
                  b.   removal of d rugs
                  c.   reduction mammop lasty (Danazo l blocks Gn RH fro m hypothalamus; To mo xifan/Ro lo xifan anti-estrogen tx)

4. Impotence: history, physical exam, and causes
                  a. History (pts w/low testoserone levels may not complain of impotence b/c their libido is low)
                            i. Nocturnal/mo rning erections
                           ii. Course: progressive, unrelenting, fluctuating
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                          iii. Situational dependency
                          iv. Associated drugs: drugs, alcohol, medical or surgical conditions, claudication, d iabetes neuropathy,
                                hyperprolactinemia
                  b.   Physical exam:
                            i. Measure size and consistency of testes
                           ii. Look for bulbocavernosus relfex
                          iii. Measure penile blood flow using doppler
                          iv. Peripheral sensation
                           v. Peripheral pulses/bruits
                          vi. Lab investigations
                                    1. DM
                                    2. serum testosterone, LH, FSH, prolact in

                  c.   Treat ment
                             i. Pharmacologic:
                                    1. alprostadil: intracaverous/intraurethral (dilates blood vessel directly , nerves don’t get
                                       involved)
                                    2. Sildenafil (viagra): facilitate erection; doesn’t cause one
                                    3. Physical measures:
                                            a. Vacuum pump system
                                            b. Implant


THE THYROID GLAND I

1.
Difference btwn total and free                 Total Thyroi d Hormone Assay                      Free Thyroi d Hormone Assay
thyroid hormone assays
Conditions that inhibit the              1. Starvation
converstion of T4 to T3                  2. Systemic Illness (Euthyroid-sick syndrome)
                                         3. Drugs:
                                           -anti-thyroid drugs
                                           -p ropranolol
                                           -A miodarone
                                           -radiocontrast dyes
                                           -g lucocorticoids
Causes of elevated TSH                       Appropri atel y Elevated Serum TS H                  Inappropriately Elevated TS H
                                         1. Primary hypothyroidism (T3 and T4             1. TSH-secreting pit adenoma
                                         levels low)                                      2. Peripheral resistance to thyroid hormone
                                         2. Decreased thyroid reserve (T3 and T4          (pts euthyroid or hypothyroid)
                                         levels are normal but require increased TSH      3. Pit resistance to thyroid hormone
                                         levels to keep them so)                           (pts hyperthyroid)
Indicate use of 131 I uptake and scan                        Uptake                                             Scan
                                         Amount of radioactiv ity taken up by the         Used to make a picture of where the
                                         thyroid gland and is a measure of its            radioactivity is taken up by the gland
                                         function                                         (uniformly, patchily, nodule)
Indicate use of TRH test                 Flat or blunted TSH response to TRH is consistent w/thyrotoxicosis
                                         TSH response to TRH cannot differentiate accurately btwn normals an d pts w/mild
                                         hypothyroidism
                                         TRH stim test is very sensitive at distinguishing btwn hyperthyroidism and normal




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2. Make clin ical diagnosis of thyroiditis, give DDx and indicate how to distinguish among the types clinically and by lab tes ting

               Thyroi ditis                                 Clinical features                                  Lab findings
                                              -fever                                           - WBC and ESR
Acute bacterial thyroi ditis                  -pain                                            - free T4
                                                                                               -absent 131 I uptake
                                                                                               -absent antithyroid antibodies
                                              Painless, mild, firm enlargement
Rei del’s struma                              Difficult to differentiate fro m in filtrating
                                              neoplasm
                                              -painless, mild enlargement of gland             -normal WBC and ESR
                                              -gland = nodular                                 -free T4 levels low
Hashimoto’s thyroi di tis                     -no fever                                        -anti-thyroid antibodies are co mmon
                                              -common cause of hypothyroidism                  (distinguish from nodular goiter which is
                                                                                               not ass. w/elevated antibodies)
                                              -pain in neck                                    - WBC and ESR
Subacute thyroi ditis                         -pain referred to jaw and ears                   -T4 elevated
(deQuervain’s thyroi ditis)                   -symptoms persistant for weeks                   -131 I reduced
                                                                                               -antithyroid antibodies not seen
                                                                                               -permanent hypothyroidism is rare
Post partum thyroi di tis                     Mild clinical presentation of
                                              hyperthyroidism

3. Pt presents w/solitary thyroid nodule, indicate an aproach to its investigation and treatment
          Investigation:    1. Palpation of neck to determine if nodule is truly solitary
                            2. Determination of pts thyroid status by measurement of T3, T4, TSH and anti-thyroid antibodies
                            3. Scan thyroid w/ 131 I. If nodule is hot most probably benign
          Tx of hot nodules that are causing hyperthyroidism is surgical or ablation w/radioiodine
          -Co ld nodules have possiblity of underlying malignancy
          -75-95% are benign adenomata or cysts
          -Needle biopsy is most cost effective

         Treat ment: suppress for 6 months w/Levothyroxine (any increase in size or failure to decrease calls for the need of a fine
needle aspiration or excisional biopsy)

THE THYROID GLAND II

1. Make clin ical diagnosis of hyperthyroidism.

           Clinial Features                                     Details
                                         Sweating
                                         Heat intolerance
                                         Palpitations
Adrenergic Excess                        Tachycardia
                                         Termor
                                         Lid lag/stare
                                         Nervousness, exc itability
Hypermetabolism                          Increased appetite
                                         Weight loss
                                         Perio rbital edema
Ophthal mol ogical                       Proptosis (pushing of eyeball forward)
                                         Chemosis (hump of conjunctiva due to edema)
                                         Opthalmoplegia (grave’s disease)
Cardi ac                                 Arrhythmia (atrial fib)
                                         Congestive failure
Muscle                                   Pro ximal myopathy
GI                                       Diarrhea/vomiting
Bone                                     Osteoporosis
                                         Hypercalcemia (metabolis m of calciu m increased


                                                                                                                                           9
2. Distinguish among Graves’ disease, toxic nodular goiter, subacute thyroiditis by clinical and lab techniques
      Conditi on                    Cause                        Clinical Features                   Lab Fi ndings
Graves’ disease         AI thyroid stimu lating           -most common cause of               -anti-TSH antibodies
                        immunoglobulin b inds to          hyperthyroidism
                        TSH receptors                     -more co mmon in young
                                                          wo men
                                                          50% have opthalmopathy
Toxic nodul ar goiter Unknown                             -older adults
                                                          -uni/ multi nodular
                                                          -present as lump in neck
Subacute thyroi ditis   Viral (mu mps, co xsackie)        -painful (sore throat)              -T4 elevated secondary
                                                                                              to leak fro m gland
                                                                                              -may go on to
                                                                                              hypothyroidism

3&4. Diagnosis and Treatment of hyperthyroidism

                                           Clinical Di agnosis                                Treatment
                                                                             1. Beta blockers
                                                                               -b lock catecholinergic effects to get rid of
                            -TSH suppressed                                  anxiety symptoms
                                                                               -Propranolol
                            -free T3 and T4 elevated                           -Side Effects:
                                                                                   -Depression, Aesthenia, hypoTN
                            -131 I uptake = variable                           -CI in asthmatics
                              -up in Graves’                                 2. Antithyroi d drugs – 6 months
                              -low in thyroiditis                                -Methimazole and proly lthiouracil (PTU)
                                                                               -control metabolic sy mptoms
   Hyperthyroi dis m        -Gold standard = seldom used:                      -may induce remission in Graves
                              -TSH response to TRH = suppressed                -not useful in to xic nodular goiter
                                                                               -may cause skin rash/agranulocytosis
                                                                             3. Surgery
                                                                               -possibility of injury to recurrent laryngeal
                                                                             nerve or post-operative hypoparathyroidism
                                                                               -useful when there is a mass
                                                                               -low rate of hypothyroidism
                                                                             4. Radioi odine abl ation
                                                                               -100% incidence of post tx hypothyroidism
                                                                               -may precip itate thyroid storm
                                                                               - risk of opthalmopathy (prevented by tx
                                                                             w/corticosteroids




                                                                                                                               10
5-8
                            Causes                        Clinical Features                       Lab findings/Diagnosis                       Tre atment
                                            -usually asymptomatic at birth                   1. T SH elevated except in pit/hyp
                                            -presents w/in a few months as cretinism         failure                                1. L-thyroxine
                                            -part of DDx of growth delay and delayed
                                            puberty                                          2. free T4 decreased                   2. Tri-iodothyronine (T3) –
                      General information                                                                                           give inactive hormone and
                      about                 -hypothyroidism in adults: slow onset and few    3. TRH test variable                   convert to T3 as needed
 Hypothyroidism       hypothyroidism        symptoms
                                            -myxedema come (rare; precipitated by stress     4. 131I variable                       3. Combinations of T4 and
                                            – pneumonia, serious infection, MI – in those                                           T3
                                            w/severe undiagnosed hypothyroidism)
                      Hashimoto’s           -painless, mild enlargement of gland             -normal WBC and ESR
                      thyroiditis           -gland = nodular                                 -free T4 levels low
                                            -no fever                                        -anti-thyroid antibodies are
                                            -common cause of hypothyroidism                  common
                                                                                             (distinguish from nodular goiter
                                                                                             which is not ass. w/elevated
                                                                                             antibodies)
                      Idiopathic atrophy                                                     -antithyroid antibodies
                      Post-tx for Graves’                                                    Most commonly seen after
                                                                                             radioactive iodine
                      Pit/Hyp failure



THE FEMAL E GONAD

1. List the common causes of primary (and # 2) secondary amenorrhea and outline a diagnostic approach to the problem
                        Definition               Causes                          Details                                  Diagnostic approach
Primary           Young women who fail                          -delayed puberty                                Family Hx:
Amenorrhea        to menstruate             Hypothalamic/pit    -lack of GnRH or LH and FSH                       -history of delayed puberty
                                            uitary              -elevated prolactin
                                                                -other…Cushing’s                                Physical Exam:
                                                                -gondal dysgenesis esp in T urner’s               -breast development
                                            O varian            Syndrome                                          -presence of uterus
                                                                -genetic males                                    -somatic abnormalities
                                                                -polycystic ovaries                               -hirsuitism
                                                                Absent Mullerian structures                     Laboratory:
                                                                                                                  -measure LH, FSH, prolactin and
                                                                                                                estradiol
                                            Uterine                                                               -if LH and/or FSH elevated do
                                                                                                                karyotype (ovarian problems)
                                                                                                                  -if LH and FSH low – CT/MRI of head
                                                                                                                (look at pit/hyp area)
Secondary         Cessation of menstrual
Amenorrhea        periods in women          Most common
                  w/previously normal       cause: pregnancy
                  periods
                                                                -failure of LH surge required for
                                                                ovulation (stress, leanness, physical
                                            Hypothalamic        exertion, diet/eating disorders)
                                            causes              -r/o pregnancy
                                                                -induce period w/brief course of
                                                                progesterone (basal estrogen secretion is
                                                                intact; the brief course of progesterone
                                                                will cause w/drawal bleeding)
                                                                -post partum necrosis of pituitary
                                                                (Sheehan’s syndrome)
                                                                -primary/mets pit tumor
                                                                -pit granuloma
                                            Pit causes          -LH and FSH levels are usually low
                                                                -prog test produces no w/drawal bleeding
                                                                b/c estrogen is low
                                                                -hyperprolactinemia is the cause in about
                                                                25 % of cases of sec amen
                                                                AI ophritis and mumps orchitis                  -estrogen levels low
                                            O varian causes                                                     -no response to progesterone
                                                                                                                -FSH usually high
                                            Uterine causes      Severe endometriosis
                                                                Prog test neg (no lining to slough)




                                                                                                                                                             11
3. Indicate the place of the progesterone test in the diagnosis of excessive uterine bleeding and interpret the results found.

4. Make diagnosis of polycystic ovary syndrome and indiate how it can be treated.

              History                  Lab investigations       Physical Exam           Physiological abn        Treatment
                                                                                                                 -Clomiphene:
              -always irregular        -FSH and estradiol       -look for androgen      - frequency in GnRH     induce ovulation
              periods                  levels elevated by do    excess, including       pulses                   when fertility is
                                       not cycle                body hair and true                               desired (avoid
              -10 amenorrhea or                                 virilism (21            -dysregulation of        hyperstimulation
              irregular periods        -progesterone induces    hydroxylase def or      androgen secretion in    and multiple
              folowed by               w/drawal bleeding        tumor producing         ovaried and adrenal      ovulation)
              oligomenorrhea and                                testosterone)           glands
              20 amenorrhea            -LH hi normal                                                             -OC: regulate
                                                                -ovarian                -cystic changes in       periods and suppress
Polycystic    -PCO accomp by:          -LH:FSH ration >2        enlargement             ovaries                  ovarian androgen if
Ovary           -DUB                                                                                             fertility is not
S yndrome       -infertility           -no mid-cycle surge of                           -hyperinsulinism         desired
                -hirsuitism            LH
                -obesity                                                                                         -S pironoloctone:
                                       -testosterone,                                                            suppress adrenal
                                       androstenedione,                                                          androgen
                                       estrone elevated
                                                                                                                 -Metformin: 
                                                                                                                 effect of
                                                                                                                 hyperinsulinism at
                                                                                                                 over and  hisuitism
                                                                                                                 and androgen
                                                                                                                 related problems

5. List cardinal features of menopause and tx for each
                    Cardinal Feature                                          Treatment
Anovulatory cylcles:
   -in years b4 menopause, ovulation becomes           -intermittenet progestin therpay can avert unnecessary
irregular either b/c the follicular phase rise in      hysterectomies
estrogen is not enough to trigger an LH surge or b/c
the remaining follicles are resistant to ovulatory
stimulus
Hot flashes:
   -vasomotor phenomenon ass. w/declining, estrogen    -Estrogen therapy
levels; rise in LH accompanies most flashes            -pure progestin/clonidine
Vaginal Atrophy:
   -vaginal dryness and burning                        -remain sexually active to lessen degree of vaginal
   -dyspareunia                                        atrophy 
   -urethral syndrom w/ or w/out urinary infect.       -prevented by hormonal therapy (systemic/local)
Osteoporosis:                                          CALCIUM !
   -most important consequence
Cardiovascular Disease:
   -#1 cause of death on post menopausals              -Estrogen
   - in ration of LDL:HDL after menopause

Characteristics of pts most likely to benefit fro m estrogen therapy:
        Thin, wh ite, sedentary, smoker, low Ca intake, uterus previously removed, mother w/dowager’s hu mp

Characteristics of pts LEAST likely to benefit fro m estrogen therapy:
        Obese, AF. A m, physically active, history of DVT, sister w/h x of breast cancer

6. Made diagnosis of PMS and suggest tx for symptoms
                   Definition                                        S ymptoms                                      Treatment
Dysmenorrhea, cramps and other physical          Physical:                                         -Stopping periods w/GnRH antagonism
disconforts that accompany ovulatory cycles;       Bloating, breast swelling/discomfort, pelvic    produces 75% reduction in symptoms
may be caused by prostaglandins                  pain, h/a, ankle swelling, bowel changes
                                                 Psychological:                                    -Used w/conjugated estrogen and progesterone
                                                   Irritability, agressiveness, depression,
                                                 anxiety, changes in libido

                                                                                                                                            12
7. List contraindications and relative risks of taking OC.
                                  -thrombotic d isorders
                                  -known/suspected cancer of breast/uterus
           Absolute               -impaired liver function
      Contraindications:          -pregnancy
                                  -undiagnosed vaginal bleeding
                                  -pregnancy ass. jaundice
                                  -hyperlip idemia
                                  Hypertension
                                  -diabetes
 Relati ve contraindicati ons     -heavy smoking
                                  -fam h x of CAD
                                  - > 35 years of age
           Cauti ons              -discontinue b4 surgery


LIPIDS

1. Identify those factors in pts hx/PE that indicate pt is candidate for hyperlipidemia screening
  Positi ve Risk Factors                                   Descripti on
Age                           Male > 45
                              Female >55 or premature menopause w/out HRT
Fam Hx                        Hx of premature co ronary heart disease
                                -M I, sudden death b4 age 55 in father/ male 1st degree relat ive
                                -sudden death efore age 65 in mother/female 1st degree relative
Smoking
Hypertension                  BP > 140/90 or currently taking antihypertensives
Low HDL                       <0.9 mmo l/ L3
Diabetes
Hypertrig lyceridemia         >2.3 mmo l/ L
Visceral obesity              Waist/hip ratio > 0.8 in wo men and > 0.9 in men
                              OR BMI >27 kg/m2
                              OR waist circu mference > 100 cm

2. List secondary causes and indicate how to screen for them
Cause                                        Details                                          Screening method
Causes primarily hypertrig lyceridemia       -DM                                              DM: fasting glucose
                                             -pancreatitis
                                             -Glucocorticoigs
                                             -ethanol
                                             -OC
Causes primarily hypercholesterolemia        -hypothyroidism                                  Hypothyroidism: measure TSH
                                             -nephrotic syndrome                              Nephrotic: seru m albu min/urinalysis
                                             -obstructive liver disease                       Liver: alkaline phosphatase

3. List those factors that have been found to be ass. w/and increased risk fo r CAD
      Risk Stratification                                       Details
Very low risk                     Men < 35 years of age and premenopausal women
                                  w/hypercholesterolemia and no other risk factors
Low risk                          Hypercholesterolemia and less than two risk factors
High risk                         No h/o atherosclerotic coronary artery disease who are at high
                                  risk due to hypercholesterolemia and simultaneous multip le
                                  risk factors for CVD
Very high risk                    People at very high risk fo r atherosclerotic co mplication due to
                                  previous CHD or other atherosclerotic disease




                                                                                                                                      13
 Results of Screening              LDL levels                                  Comments
Normal                       < 130 mg/d L                    -repeat cholesterol w/in 5 years
                                                             -general diet and risk factor management
Borderline High Risk         130-159 mg/dL                   (-) CHD and < 2 risk factors
                                                             -step 1 diet & annual check of total cholesterol
                                                             -screen for secondar hyperlip idemias
                                                             -screen for familial disorders
                                                             -consider age and gender
High Risk                    >160 mg/dL                      Same as previous

4. Outline Tx approach including use of diet, fo llow up testing and drugs
         *Diet and exercise: attempt to achieve ideal body weight
                           -limit total fat and cholesterol, especially saturated fats
                           -increase fiber in diet
                           -exercise about 20 mins 4 days a week
         *Pharmaco logical:
            Drug                                    How does it hel p                                        Side effects/ CI
                                -Inhibits VLDL synthesis in liver                            -ulcers, hypergycemia
   Nicotinic Aci d/Ni acin      -lowerd VLDL, cholesterol, TA Gs and LDL                     -hyperuricemia
                                -increases HDL                                               -hepatic tox
                                -admin w/ meals and w/ASA to minimize flushing               CI in d iabetics
                                Biel sequestrants                                            -sweat smells like rotten fish (eww)
    Cholestyramine and          -lowers LDL                                                  -constipation
         Colesti pol                                                                         -interfere w/thyroxine, gig, estrogen, BC
                                                                                             pills, warfarin
                                HM G CoA reductase inhibiro in liver                         -elevated liver en zy mes
            Statins             -decrease in hepatic cholesterol synthesis                   -myositis
                                -increase LDL receptor production
                                -hepatic uptake and catabolism of LDL enhanced
                                Major TA G lo wering action                                  Upper GI Problems: abd pain, cholecystitis
          Fi brates                                                                          Myositis
                                                                                             Potentiates anticoagulants
         Probucol               Increases catabolism of LDL and inhib its oxidation          Dec HDL >>LDL

                                             First choice                       Second Choice                       Third Choice
           LDL                   Statin/bile acid resins              Fibrates/probucol                  Niacin
       LDL w/ TAG               Statin                               Fibrate                            Niacin
      LDL w/ TAG                Fibrate                              Niacin
       TAG w/HDL                 Fibrate                              Niacin                             Fish oils/flax seed ground up




                                                                                                                                         14
CALCIUM

1. Recognize hypercalcemia and list common causes and outline emergeny t x.
2. Recognize hypocalcemia, indicate how d x can be confirmed by simp le bedside testing and indicate long term treat ment.
    Conditi on                   Causes                          Diagnosis               Testing                     Treatment
                   -10 hyperparathyroidism                                                                  Acute:
                   -Malignancy                           -GI; n/v, abd pain                                    -hydrate pt with
                     bone mets: breast cancer, prostate, -Neurolog ical:                                    normal saline; 5-10 L in
                   lymphoma, myeloma
                      w/out bone mets: hypernephroma,
                                                           -fatigue                                         first 24 hours
                   pancreatic cancer, squamous cell        -muscle weakness                                    -after adequate
                   carcinomas, head and neck tumors         -confusion/drowsiness                           hydration; diuresis
                   -Sarco idosis                                                                            w/furosemi de (inhibits
HypERcalcemi a -Familial hypocacuric                                                                        Ca resorption)
                   hypercal                                                                                    -Glucocorticoi ds:
                   -Hypervitaminosis D                                                                      works best w/sarcoidosis and
                                                                                                            vit D; ineffective in primary
                   -Milk-alkali syndrome
                                                                                                            hyperparathyroidism
                   -Hyperthyroidis m                                                                           - Phosphate
                   -Thiazide diuretics                                                                         -Calcitonin
                   -Immob ilization: stress of                                                                 -Plicomycin
                   gravity of bone causes bone to                                                              -Bis phosphonates :
                   remain calcified                                                                         inhibts bone resportion
                   -Paget’s disease
                   -removal o f parathyroid glands                                                          Long term:
                   during thyroid/head and neck                                                               -1-2 g d ietary Ca daily
                   surgery                                                                                    -Vit D supplements
                   -Idiopathic
                   -AI                                                                                      Acute:
                   -PTH resistance                                                                            -Chvostek’s sign
HypOcalcemia       -chronic renal failure (lack of                                                          (tapping on facial nerve
                                                                                                            causes spontaneous
                   Vit D synthesis)                                                                         contaction of facial muscles)
                   -malabsorption of Vit D                                                                    -Trousseau’s sign:
                   -Acute pancreatitis                                                                      carpal spasm after 5 mins or
                   -Osteoblastic metastasis                                                                 less of arm ischemia
                   -hypomagnesemia                                                                          Tx: 1-2 g calciu m
                                                                                                            gluconate over 10 mins
                                                                                                            followed by 1 g over 6-
                                                                                                            8 hrs




                                                                                                                                      15
3. Define osteoperosis and compare and contrast to osteomalacia
4. Assess pts risk of developing osteoporosis from h x and indicate what t x optins are availabe to prevent condition
   Condition                 Definition                       Signs/Symptoms                             Causes                           Tre atment
                  Failure to deopist proper amts   - bone mass                          Vit D related:
                  of mineral in newly-formed       -skeletal pain                          -vit D def (dietary, malabsorption)   PREVENTION: adequate
                  bone collagen matrix             -incidence of fracture                 -Impaired vit D metabolism:           calcium and vit D in diet
                                                   -skeletal deformity esp in children        liver disease
                  Dx by bone biopsy                (bow legs)                                 renal failure
                                                   -proximal muscle weakness                  drugs
Osteomalacia                                       secondary to low phosphorus levels       -target organ resistance to vit D
                                                                                              uremia
                                                                                              drugs
                                                                                              idiopathic
                                                                                         Non Vit D related:
                                                                                            Phosphate def
                                                                                            Hypophophatasia
                                                                                            Defects in formation of bone
                                                                                            Drug induced: fluorides,
                                                                                         diphosphonate
Osteoporosis      Loss of bone mass                Common in aging population            Primary: involutional, osteoporosis     PREVENTION
                                                   Determining bone density:             of juveniles                            -Ca in diet 1000-1500 mg f Ca
                  Ratio of mineral to organic       Estrogen def women                   Secondary: cushings,                    per day
                  matrix does not change            Plain x rays show osteopenia         hyperthyroidism, hypognadism,           -exercise to maintain bone
                                                    Long term glucocorticoid tx          DM, Ca def, alcoholism, myeloma,        mass and prevent falls
                  Both are decreased                Pts w/eating disorders               lymphoma, smoking, malnutrition,        -wt training
                                                    Pts w/hyperparathyroidism            liver disease                           -estrogen supplementation in
                                                                                                                                 menopause
                                                                                                                                 -Antiresorptive agents:
                                                                                                                                   -estrogen; given to women
                                                                                                                                 w/early menopause and given
                                                                                                                                 up to years post menopause
                                                                                                                                   -calcitonin
                                                                                                                                 -Stimulation of bone formation
                                                                                                                                   -sodium fluoride
                                                                                                                                   -PTH:
                                                                                                                                   -Growth factors
                                                                                                                                 -Bisphosphonates inhibit
                                                                                                                                 osteoclastic activity and
                                                                                                                                 thereby reduce bone resorption




                                                                                                                                                        16

				
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