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Title: ENDOCRINE PHYSIOLOGY AND PATHOPHYSIOLOGY


1
ENDOCRINE PHYSIOLOGY AND PATHOPHYSIOLOGY
  • Barb Bancroft, RN, MSN, PNP
  • www.barbbancroft.com
  • bbancr9271_at_aol.com

2
General Anatomy
  • Limbic system (Temporal lobe)
  • Hypothalamusthe big cheese
  • Pituitary glandanterior and posterior lobesthe
    Master Gland
  • TARGET GLANDS
  • Thyroid gland
  • Parathyroid glands (4)
  • Adrenal glandscortex and medulla
  • Endocrine portion of the pancreasIslets of
    Langerhans (Insulin, Glucagon)
  • Endocrine portion of the kidneyerythropoietin
    (EPO)
  • Ovaries and testicles
  • Your NEWEST ENDOCRINE ORGAN?
  • BELLY FAT (visceral obesity)

3
Lets start at the top
  • Hypothalamus is the link between the brain
    (temporal lobe/limbic system) and the master
    glandthe pituitary gland
  • The hypothalamus sends messages to the anterior
    and posterior pituitary gland which in turn send
    their message to target organs
  • Once the target organ receives the message and
    performs the appropriate action, it sends a
    message BACK to the pituitary and hypothalamus
    to
  • TURN OFF the messagethis is known as negative
    feedback

4
Analogystart at the topthe BIG CHEESE
  • Chief Nursing Officer, Director of Nursing, Dean
    of the Nursing School (the hypothalamus)--Sends
    her MEMO via EMAIL to

5
Analogythe Middle woMan
  • The MEMO can be either DO something or STOP
    doing something
  • This memo goes to the
  • Heads of the Departments, Nursing Supervisors
    (the pituitary gland)relay the message to

6
Analogythe worker bee
  • Floor Nurses, student nurses (the TARGET
    ORGANS)that do all of the work
  • Ok, OK, OKIll get it done

7
Enough already!
  • When you have performed the required work, you
    (the target organ) send a message back to TURN
    OFF the messages from the higher ups
  • This is known as NEGATIVE feedback

8
Who are the memos/messengers?
  • Releasing factors/hormones (DO IT!) or inhibiting
    factors/hormones (STOP DOING IT) from the
    hypothalamus via a capillary network to the
  • The anterior pituitary gland which in turn
    releases either a stimulating or inhibiting
    hormone which in turn interacts with a receptor
    on the target organ to perform a certain task
  • The hypothalamus sends a direct message via
    neuronal axons to the posterior pituitary to
    release hormones that interact with target
    tissues

9
Example
  • The Hypothalamus sends thyrotropin (an affinity
    for) releasing hormone (TRH) to
  • The anterior pituitary which in turn sends
    thyroid stimulating hormone (TSH) to
  • The thyroid. The thyroid releases thyroxine (T4)
    and tri-iodothyronine (T3)
  • Once enough T4 and T3 are released to boost
    metabolismthe message returns to the pituitary
    and hypothalamus to TURN OFF
  • NEGATIVE FEEDBACK
  • TRH -
  • Hypothalamus
  • TSH - negative (off)
  • Pituitary --
  • Thyroid
  • T3, T4

10
What if something goes wrong?
  • Lets start at the bottom with the TARGET ORGAN,
    thyroidhypthyroidism
  • Decreased T3, T4 feeds back to the pituitary
    gland and hypothalamuspump out more TRH and TSH
    to stimulate a thyroid as the thyroid continues
    to die and T3, T4 are not being produced, the
    TRH and TSH continue to rise

11
Too much or too littlehyper- or hypo-
  • If the problem is in the TARGET organits a
    PRIMARY disorderPRIMARY HYPOTHYROIDISM
    (Hashimotos thyroiditis is an example)
  • If the problem is in the pituitary its a
    SECONDARY disorderSECONDARY HYPOTHYROIDISM
    (removal of pituitary/radiation)
  • If the problem is with the hypothalamus its a
    TERTIARY disorderTERTIARY or CENTRAL
    HYPOTHYROIDISM
  • (Pituitary and hypothalamic dysfunction may also
    be referred to as CENTRAL dysfunction)

12
So, to diagnose thyroid problems
  • If its primary hypothyroidism, the thyroid will
    not be able to produce thyroid hormonesdecreased
    circulating T3, T4
  • This feeds back to the pituitary gland and saysI
    NEED A LITTLE HELPso the pituitary ramps up the
    production of TSH and the hypothalamus ramps up
    the production of TRH
  • TSH and thyroid measurements will show decreased
    thyroid hormones and an increased TSH

13
So, to diagnose thyroid problems
  • If the problem is in the pituitary, ie. Secondary
    hypothyroidism
  • The pituitary will NOT be able to produce TSH to
    stimulate the thyroidso
  • Thyroid hormones will be low or non-existent AND
    TSH will be low since the pituitary gland is NOT
    WORKING.

14
Lets prepare an egg in the ovary for
ovulationeggs live in follicles, follicles
produce estrogen
  • The Hypothalamus releases gonadotropin releasing
    hormone (GnRH)message to the
  • The Anterior pituitary gland to release follicle
    stimulating hormone (FSH)
  • FSH stimulates the target organ, the ovary, to
    prepare a follicle/ egg/estrogen
  • Egg prepared? Estrogen released? Job done.
  • Feedback to turn off the system

15
SO then, what is PRIMARY ovarian
failuremenopause!!
  • Over the years the ovaries have a preprogrammed
    dropout of eggs /estrogen/and follicles--less and
    less estrogen, the negative feedback to the
    pituitary gland saysSomething is wrong, I need
    MORE estrogen
  • The pituitary RAMPS up its production of
    FSHthinking that will helpmore FSH, more FSH
  • FSH is a diagnostic marker of menopausemore later

16
Historical highlight
  • An Italian medical student, Bruno Lunenfeld, in
    the early 1960s had an epiphany. At the time, he
    recognized that during menopause womens urine
    was likely to contain high levels of the hormones
    that stimulate ovulation. Of course, finding a
    regular source for of such urine presented a
    problem. At a conference in Italy, however,
    Lunenfeld met the nephew of Pope Pius and
    discussed his idea. The nephew of the Pope
    responded how about using the urine of
    postmenopausal nuns?
  • Buckets of urine were collected from nuns in
    convents in Italythe fertility drug? Clomid
    (clomiphene)

17
Lets get back to the original concept Secondary
or tertiary ovarian failure?
  • Hypopituitarismsomething has destroyed the
    pituitary gland and FSH can no longer be produced
    (low or no FSH, low or no estrogen)
  • Causes? Pituitary adenoma, other pituitary tumors
    and cysts, sarcoidosis, Sheehans necrosis
    (hemorrhage during delivery shuts off blood
    supply to anterior pituitary)
  • Hypothalamic dysfunctionPrader-Willi Syndrome,
    Kallmans syndrome

18
Prader-Willi Syndrome
  • First described in 1956 by Andrea Prader
     (19192001) and Heinrich Willi (19001971)
  • A rare genetic hypothalamic disorder
    characterized by a chronic feeling of hunger that
    can lead to excessive eating and life-threatening
    obesity incomplete sexual maturity
  • Used to be the fat lady in the circus120
    pounds by age 6 350 pounds by age 12
  • With the recent benefits of early diagnosis and
    ongoing interventions, the obesity rate among
    children with PWS has decreased to be similar to
    the typical population.

19
So many examplesweve talked about two
  • HPTHypothalamic-anterior Pituitary-Thyroid-axis
  • HPOHypothalamic-anterior Pituitary-Ovarian
    (gonadal)-axis
  • BUT THERE ARE OTHERS
  • HPAHypothalamic- anterior Pituitary-Adrenal axis
  • HPTHypothalamic-anterior Pituitary-Testicular
    (gonadal)-axis
  • HPBHypothalamic anterior Pituitary-Breast
  • AND MORE
  • Hypothalamus posterior pituitary target organ
    kidney, breast, uterus

20
The Hypothalamus (under the thalamus)
  • The hypothalamus is, millimeter for millimeter,
    the most powerful subdivision in the brain.
  • It weighs about 4 grams, is the size of an
    almond, and constitutes no more than 1 percent of
    total brain volume
  • But it packs a powerful punch
  • The critical link between the cerebral cortex,
    the limbic system, and the hormonal output of the
    master gland, the pituitary

21
The hypothalamus
  • Contains numerous clumps of neurons (nuclei)
    regulating appetite and satiety, thirst
    (osmoreceptors), growth and reproduction, sex
    drive and sexual orientation, temperature
    regulation, sleep, 24-hour biological clock

22
Who runs the entire show?
  • The suprachiasmatic nucleus (SCN) of the
    hypothalamus coordinates all of the activities of
    the hypothalamus (appetite and satiety, thirst,
    temperature, sexual function, hormonal
    production, emotions, and blood pressure)
  • The SCN also regulates the activity of the pineal
    gland and the secretion of melatoninthe
    sleep/wake cycle

23
How does our biological clock work?
  • Light hits the retina and specialized cells send
    the message to the SCN
  • The SCN sends the message to the pineal gland
    which in turn influences the secretion of
    melatonin sleep/wake cycle
  • Quite a few genes are involved with your
    biological clock
  • One is cleverly called the CLOCK gene and is not
    working properly in patients with bipolar disease
  • Lithium resets the biological clock
  • Stops the manic phase and helps the patient
    re-synchronize to a 24-hour day

24
Other nuclei of the hypothalamus the appetite
and satiety center
  • Appetite center and norepinephrinePrednisone,
    Remeron (mirtazapine),
  • Satiety center and serotonin (fenphen) atypical
    antipsychotics block a specific serotonin
    receptor, which in turn stimulates appetite and
    weight gain (especially Clozapine and olanzapine)

25
Inhibiting and Releasing Hormones (Factors) from
the hypothalamus
  • Most of the activities of the hypothalamus are
    carried out by inhibiting or releasing hormones
  • Thyrotropin Releasing Hormone (TRH)TSH
    (pituitary)thyroid gland
  • Gonadotropin Releasing Hormone (GnRH)FSH, LH
    (pituitary)ovaries and testicles
  • Corticotropin Releasing Hormone (CRH)ACTH
    (pituitary)adrenal cortex
  • Somatropin GH (pituitary)lots of tissues
  • Prolactin Inhibiting Factor (PIF) and Prolactin
    Releasing Factor (PRF)milk-producing glands of
    the female breast

26
Examples of inhibiting and releasing factors from
the hypothalamus
  • Prolactin-releasing (promote lactation) hormone
    (PRH) stimulates the secretion of prolactin
    (PRL) from the anterior pituitary gland (WHEN
    NECESSARYlactating moms would be a good reason
    to release prolactin releasing hormone)

27
However, the USUAL message is to INHIBIT the
release of prolactin from the pituitary
  • Prolactin-inhibiting factor (PIF) from the
    hypothalamus inhibits the secretion of prolactin
    from the anterior pituitary (THANK GOODNESS)
  • Who would want to lactate on any given day
    WITHOUT a baby to lactate for?
  • Wet nurses

28
Wet nurse
  • A woman can only act as a wet-nurse if she
    is lactating. It was once believed that a
    wet-nurse must have recently undergone
    childbirth. This is not necessarily true, as
    regular breast suckling can elicit lactation via
    a neural reflex of prolactin production and
    secretion.  Some adoptive mothers have been able
    to establish lactation using a breast pump so
    that they could feed an adopted infant.
  • There is no medical reason why women should not
    lactate indefinitely (some 3rd world countries
    breast feed children up to the age of five) or
    feed more than one child simultaneously (known as
    'tandem feeding')... some women could
    theoretically be able to feed up to five babies.

29
Examples of inhibiting and releasing factors from
the hypothalamus
  • Gonadotropin-releasing hormone (GnRH)
    stimulates the pituitary to release LH and FSH
    (follicle stimulating hormone) to stimulate the
    gonads triggers hormonal secretion from the
    ovaries and testicles and jump starts puberty in
    kids

30
Girls fat tissue and puberty
  • Girlsfat early puberty
  • Aromatase in fat tissue converts testosterone to
    estradiol and triggers early puberty
  • Leptin (from adipocytes) sends a signal to the
    hypothalamus to produce GnRH and saysshes
    READY!
  • OPPOSITE problem--Female Athlete Triadthin (no
    adipose tissue) with disordered eating,
    amenorrhea /oligomenorrhea, and osteopenia/porosis

31
Pubertyin girls
  • When does puberty start?
  • Breast development (thelarche) at 10 in
    Caucasians and before 9 in African-Americans
  • Pubic hair one year later
  • Menarche two years after breast development
  • 27 of AA girls have breasts at 7 7 Caucasian
    girls
  • Precocious puberty is under 8 in C girls and
    under in AA girls
  • B B Supergrow?
  • Diet? Fat, Fat tissue?
  • Environmental estrogens? PCBs, PBBs, DDE,
    phthalates, BPA

32
Boys, fat tissue, and delayed puberty
  • Boys fat delayed puberty
  • Aromatase in fat tissue converts testosterone to
    estradiol and delays their development

33
Synthetic GnRH drugs
  • We make synthetic drugs that mimic the functions
    of GnRH
  • Leuprolide(Lupron, Eligard) nafarelin (Synarel),
    goserelin (Zoladex), buserelin (Suprefact/Suprecor
    )
  • We can use these drugs to boost fertility OR we
    can use these drugs to DOWNREGULATE the function
    of the ovaries and testicles

34
Endometriosis of the small bowel
  • Use of GnRF drugs to downregulate the gonadal
    secretion of estrogen
  • after 10 days of administering these drugs
    hypogonadism develops via downregulation of
    receptors
  • When used to downregulate endometriosis
    symptoms, the symptoms will get WORSE initially,
    due to the flare effect (increase in LH and
    FSH)

35
The GnRH agonistsother uses
  • Also used for hormonally-stimulated cancers such
    as prostate cancer to downregulate testosterone
    to reduce hormonal stimulation of the prostate
    (hormonal castration)
  • causes gynecomastia in men (the old days we used
    DESdiethylstilbesterol to change the hormonal
    environment in men)
  • Downregulate hormonal stimulation in breast
    cancer patients (as above)
  • Used to delaying puberty in precocious puberty
    cases
  • shrink uterine fibroids

36
Central precocious puberty
  • Histrelin acetate (Supprelin LA)first and only
    implant for the treatment of children with
    central precocious puberty
  • Steady flow of GnRH actually turns OFF the system

37
Congenital deficiency of GnRH
  • Kallmans syndrome
  • Anosmia
  • amenorrhea

38
Examples of inhibiting and releasing factors from
the hypothalamus
  • Growth hormone-releasing factor
    somatotropinstimulates the release of growth
    hormone from the anterior pituitary (released at
    night)
  • KIDS GROW AT NIGHTgrowing pains

39
Examples of inhibiting and releasing factors from
the hypothalamus
  • Corticotropin-releasing hormone (CRH)stimulates
    the release of ACTH (adrenocorticotrophic
    hormone) from the pituitary which in turn
    triggers cortisol release from the adrenal gland
  • Hypothalamicpituitaryadrenal axis

40
Lets move on to the the Pituitary gland
  • Pituitary comes from the Latin pituita, meaning
    phelgm,, also related to the Greek ptuo,
    meaning I spit. The Greek word, obviously, is
    vividly imitative and is the forerunner of the
    expletives Ptooey! and Phooey!
  • The Greeks and Romans believed that the brain
    secreted a mucoid substance that was discharged
    through the nose (ie, snot)
  • this notion was finally nixed in the 17th
    century but the name pituitary stuck

41
You actually have two separate pituitary
glandsthe anterior and the posterior pituitary
  • The posterior pituitary gland is a direct
    extension of the hypothalamus via the
    infundibulum (pituitary stalkactually
    infundibulum means funnel) and therefore is
    part of the nervous system
  • Neurons in the hypothalamus make and store
    hormones secreted by the posterior pituitary
  • Oxytocin and ADH (antidiuretic hormone, aka
    arginine vasopressin, AVP)
  • lower forms of animals have a middle pituitary

42
The anterior pituitary
  • The anterior pituitary is an embryologic
    outpouching of the posterior pharynx / roof of
    the mouth (Rathkes pouch) (GI tract)backs up
    through the craniopharyngeal canal and sticks
    itself to the posterior pituitary
  • the anterior pituitary gland is NOT part of the
    nervous system, its actually part of the GI
    tract
  • Craniopharyngioma

43
Anterior pituitary
  • To release hormones from the anterior pituitary,
    the hypothalamus has to send its releasing or
    inhibiting hormones via the capillary system
    (hypophyseal portal system)connects the
    capillary system of the hypothalamus with the
    capillary system of the pituitary
  • This capillary network is vulnerable to sudden
    loss of blood--
  • Sheehans necrosis of the anterior pituitary
    glandinfarction of the anterior pituitary during
    labor and delivery (sudden loss of blood via a
    hemorrhaging episode in the mom)

44
Anatomic location of the pituitary gland
  • The entire pituitary gland sits beneath the optic
    chiasm in a small bone called the sella turcica
    (turkish saddle)
  • If the pituitary enlarges (macroadenoma, for
    example), it will push up against the optic
    chiasm and cause a visual loss known as
    bitemporal hemianopsia or TUNNEL VISION
  • Prolactinoma in a graduate NP student at UVA
    (visual fields)

45
Bitemporal hemianopsia
46
Hormones of the anterior pituitary released in
response to hypothalamic factors
  • GH (Growth Hormone) (somatotropin)
  • FSH (Follicle Stimulating Hormone) (GnRH)
  • LH (Luteinizing Hormone)(GnRH)
  • TSH (Thyroid Stimulating Hormone)(TRH)
  • ACTH (Adrenocorticotropic Hormone)(CRH)
  • PRL (Prolactin)(PIF)

47
Hormones of the posterior pituitary
  • Oxytocin
  • ADH (Anti-diuretic Hormone) also known as
    Arginine Vasopressin (AVP)

48
Hormone of the posterior pituitaryOxytocin
  • The first peptide ever to be replicated outside
    the body was oxytocin (1953). Its released from
    the posterior pituitary gland during childbirth
    to bind with receptors in the uterus, where it
    stimulates uterine contractions to help expel
    the baby
  • Synthetic oxytocin, as we all know, is Pitocin
  • HISTORICAL HIGHLIGHT As early as 1902, people
    knew there was something in crude extracts of
    farm animal pituitary glands that could be used
    by obstetricians to aid women who had been in
    labor for a prolonged period

49
Oxytocin
  • Milk let-down response from the mammary glands
    for breast feeding
  • Uterine contractions during orgasm

50
What else does oxytocin do?
  • The Tend to and be a friend to hormonebonding
    hormone trusting higher levels in women
  • Helps us to read others minds
  • Cuddly, touchy-feely, earth-momma hormone
    calming effect
  • Estrogen enhances oxytocin

51
Oxytocinthe hormone of monogamy
  • Hormone of monogamy? Inspires trust
  • In prairie voles at least
  • Women have two genes for itmen? One gene and
    testosterone reduces oxytocin
  • Men and the wandering eye syndrome? HELLO???
  • Oxytocin nasal spray

52
PETS and oxytocin
  • Back to oxytocin and bonding
  • Oxytocin levels almost double in people and in
    dogs when humans talk to and stroke their
    canine/feline friends
  • Endorphins and dopamine levels also increase with
    pets

53
The second hormone of the posterior
pituitaryanti-diuretic hormone (ADH)
  • Also called arginine vasopressin (AVP) because in
    high doses it vasocontricts in low doses it
    conserves water
  • ADH is primarily regulated by osmoreceptors in
    the hypothalamus
  • HIGHEST ADH levels around 11 p.m. to
    midnightconserve H20
  • Dehydrated? High serum osmolarity? Produced in
    the hypothalamus, stored and released from the
    posterior pituitary gland ADH binds to AVP/ADH
    receptors on the distal tubules and collecting
    ducts of the kidney to increase water
    reabsorption to dilute the high serum osmolarity

54
Other conditions that boost ADH
  • Volume loss of 7-25 (hypovolemic shock), stress,
    trauma, pain, nicotine, morphine (one of the
    reasons for urinary retention in post-op patients
    on morphine)

55
Booze inhibits ADH
  • Especially BEER due to its hypotonicity and the
    fact that one usually drinks copious amounts

56
Other notes on ADH
  • ADH may also have something to do with memories
    formed during sleepgood sleep? Good memories?
    Elderly and sleep patterns and memory problems?
    Booze and sleep patterns and memory problems?
  • In older patients (or any patients for that
    matter) with chronic renal insufficiency, the
    kidneys stop responding to ADHmay result in
    nocturia/bed wetting
  • Kids with enuresisimmature response to ADH and
    problems with bladder sphincter tone

57
How do you treat enuresis in kids?
  • Night time bladder control is usually achieved by
    5 or 6 years of age if not?
  • Moisture alarms
  • Desmopressin (DDAVP) intranasally for sleep-overs
    and camp
  • Can also use a TCA to tighten the bladder
    sphincter (imipramineTofranil)

58
Too much ADH? Too little ADH?
  • Too much? The Syndrome of Inappropriate ADH
  • Too little? Diabetes Insipidus

59
Digression Diabetes insipidus or diabetes
mellitus?
  • What does diabetes mean? To siphonwhat are you
    siphoning? URINE
  • Is it sweet or honeyed? mellitus
  • Is it tasteless ?-- insipid
  • Dr. Thomas Willis Taste thy patients urine,
    for if it be sweet
  • Nurse, take a swig of that Oh, thats so
    sweet!
  • Yuckthat doesnt taste like anythingits
    insipid

60
Too little ADH?
  • Diabetes Insipidusdisorder of water balance
    caused by the non-osmotic renal loss of water
    leading to the excretion of a large volume of
    dilute urine
  • Up to 18 L per day4 to 6 L is the lowest
    threshold for symptoms urine specific gravity is
    less than 1.005
  • Incidence? Rare most cases occur in adulthood
    nephrogenic and familial forms in kids

61
Causes of Diabetes Insipidus
  • Central DIcomplete or partial deficiency of ADH
    from the posterior pituitary gland head trauma,
    post-surgical (1 to 6 days after surgery),
    tumors, infections (TB, syphilis, toxoplasmosis,
    encephalitis, meningitis, sarcoidosis),
    cerebrovascular disease
  • nephrogenic diabetes insipidusunresponsiveness
    of the ADH/AVP receptors on the kidney to ADH
  • Congenital--rare inherited, X-linked recessive

62
Diabetes Insipidus (DI)classification
  • Acquired medications (lithium, amphotercin B,
    demeclocycline (Declomycin), cisplatin,
    aminoglycosides, rifampin
  • Dipsogenic DIexcessive and inappropriate fluid
    intake due to a defect in the thirst mechanism

63
Lithium
  • Inhibits water reabsorption in the collecting
    duct through impairment of cyclic AMP and
    frequently precipitates a transient polyuria in
    patients taking therapeutic doses
  • Greater than 25 of patients have a persistent
    defect in concentrating capacity 1 year after
    discontinuing Lithium
  • Demeclocycline (Declomycin) also inhibits cyclic
    AMP but the effect is fully reversible (hence,
    why its used for the Syndrome of Inappropriate
    ADH)

64
Too much ADH? Syndrome of inappropriate ADH
(SIADH)
  • TOO MUCH water without conserving the appropriate
    electrolytes this causes a DILUTIONAL
    problemespecially problematic is the low sodium
    (hyponatremia)
  • CNS w/excess ADH releasebleeding/hemorrhage,
    CVA, DTs, GBS, head trauma, hydrocephalus,
    infections, tumors
  • Drugsbromocriptine, carbamazepine (Tegretol),
    cyclophosphamide (Cytoxan), Desmopressin (DDAVP),
    ecstasy, haloperidol (Haldol), nicotine, opiates,
    SSRIs, TCAs, phenothiazines, vinblastine,
    vincristine
  • Neoplasms (ectopic ADH secretion)Small cell lung
    cancer (SCLC), prostate cancer, duodenal
    carcinoma, mesothelioma, lymphoma, pancreatic
    carcinoma, thymoma

65
Clinical presentation
  • Symptoms are dependent on the degree of
    hyponatremia and the rapidity at which it
    develops
  • At serum levels lt 125 mEq/L, patients may present
    with muscular weakness, nausea, headaches,
    lethargy, ataxia, and psychosis to cerebral
    edema, increased ICP, seizures and coma

66
Treatment of SIADH
  • Correct the low sodium but NOT TOO FAST
  • If the onset was rapid, you can correct rapidly
  • But if onset is not known, go slowly
  • 1-2 mEq/L/hour for the first 3-4 hours and by no
    more than 0.5 mEq/L thereafter, for a maximum
    correction of 10 mEq/L per 24 hours
  • Fluid restriction
  • Check sodium levels and volume status q2 hours

67
Treatment of SIADH
  • Hypertonic saline reserved only for treatment of
    acute or symptomatic SIADH
  • Oral salt tablets
  • Loop diuretics
  • Demeclocycline diminishes responsiveness of
    kidneys to ADH, resulting in increased water
    secretion

68
Anterior pituitary dysfunction
  • Panhypopituitarism
  • Decreased TSH, FSH, LH, ACTH, GH

69
Pituitary dysfunction
  • Too much or too little of a specific
    hormonecongenital lack of cells producing
    specific hormones, OR
  • Cells that produce one specific hormone can lose
    control and produce an excess of that hormone
    (functioning pituitary adenoma)

70
Growth hormone--functions
  • Released in response to somatotropin from the
    hypothalamus
  • Produced primarily during sleep results in
    saltatory growth (not linear)
  • GH is an anabolic hormonebuilds you up by
    increasing amino acid uptake to build muscle
    stimulates growth of bone, cartilage, soft
    tissue decreases fat tissue
  • Human growth hormone and the Black
    Marketathletes and endurance sports (Lance
    Armstrong, Barry Bonds)
  • Growth hormone from cadaver pituitary glands was
    responsible for CJD (Creutzfeldt-Jakob Disease)
    in a small number of patients receiving the
    injections
  • Growth hormone impairs insulin action and is
    known as a counter-regulatory hormoneincreased
    growth hormone secondary diabetes

71
Growth hormone
  • Natural decline in growth hormone that occurs
    with aging (somatopause) GH deficiency in
    adultsdecreased muscle mass, increased body fat
    around the middle decrease exercise capacity
    osteopenia, sarcopenia, diminished well-being
  • Sound familiar? ?
  • About 50 of persons over 65 may be considered
    biochemically GH deficient

72
Growth hormone? Too much, Too little?
  • Pituitary dwarf
  • Lack of cells (somatotropes) that produce GH
  • Treatment?
  • Recombinant GH

73
The most famous pituitary dwarf
  • Colonel Tom Thumb (Charles Stratton) and his
    lovely wife, Lavinia Stratton (1841-1919)

74
Growth hormone treatment for kids with pituitary
deficiency of GH
  • Used to use extracts from cadaver pituitary
    glands until patients developed Creutzfeldt-Jakob
    dementia and died from the transfer of the prion
    in the pituitary tissue
  • Recombinant GH is now used for patients with
    growth hormone deficiency
  • 52,000 for 5 years of treatment injections 3x
    per week
  • May also be used for idiopathic short
    statureusually gain 3-6 cm (about 2.3 inches)
  • Black market for athletes fountain of youth
    for those who can afford it???

75
Pituitary adenoma producing too much growth
hormone
  • BEFORE the epiphyseal plates close
  • GIANTISM, diabetes, soft bone matrix
  • I dont hate little people.
  • The story of David and Goliath (Goliath was a
    pituitary giant)loss of peripheral vision
    softening of temporal bones
  • Davids slingshotthwack! Epidural hematoma
    felled the GIANT the little guy wins in the end

76
Tallest manAlton, Illinois claim to fame
  • Robert Wadlow with his father Harold
  • 1918-1940
  • 811
  • Alton, Illinois

77
Pituitary adenoma producing too much growth
hormone
  • AFTER the epiphyseal growth plates
    closeacromegalyenlargement of the acrals or
    small bones enlargement of soft tissues
  • Deep voice
  • Hirsutism, diabetes

78
Prolactinoma
  • A benign tumor of the pituitary can produce too
    much prolactin (prolactinoma) triggering breast
    milk production in NON-lactating females (men
    almost never have galactorrhea)
  • Other symptoms?
  • Location? Headaches/visual field defects (more
    later)
  • Amenorrhea, infertility
  • Sexual dysfunction and loss of libido in both
    males and females
  • Emotional labilityguys cry more girls cry all
    of the time quivering lip

79
Dopamine plays a major role
  • In the release of pituitary hormones
  • Inverse relationshiplow dopamine results in an
    increased release whereas increased dopamine
    inhibits the release
  • Prolactinomas benign pituitary tumors producing
    too much prolactin can be treated medically by
    increasing dopamine and inhibiting prolactin
  • Old drug used? Bromocriptine new drug?

80
Cabergoline (Dostinex)
  • Cabergoline is used to treat different types of
    medical problems that occur when too much of the
    hormone prolactin is produced.
  • It works by inhibiting the production and release
    of prolactin from the pituitary gland.
    Cabergoline use is usually stopped when prolactin
    levels have normalized for 6 months. It may be
    prescribed again if symptoms of excess prolactin
    return.

81
Inverse relationship between dopamine and
prolactin
  • Bromocriptine/Parolodel used to be prescribed to
    increase dopamine in order to decrease prolactin
    and subsequent milk production for moms who did
    not want to breast feedPROBLEM? Boosting both
    dopamine receptors in the brain caused movement
    disorders (dyskinesias) in the mom
  • WHOA!

82
Follicle stimulating hormonethe Preparation of
an egg
  • Follicle egg estrogen
  • FSH (follicle stimulating hormone prepares the
    egg for release from the ovarian follicle) also
    stimulates spermatogenesis in males

83
Hypothalamic-Pituitary-Ovarian axis and oral
contraceptives
  • Oral contraceptives feed back to the pituitary
    gland and the hypothalamus to shut off the
    endogenous axis and inhibit ovulation
  • Pills in the 60s and 70s vs. todays pills
  • 80-100 mcg/pill vs. 20-30 mcg/pill
  • The early OCs would stop an elephant from
    ovulating
  • Todays OCs? The egg is preparedmiss a pill
    and you ovulate

84
COCs in perimenopausal women
  • Vasomotor symptomsa COC containing 30 mcg of
    estrogen per day90 will have complete relief of
    symptoms within 2 months that dose will
    inhibit ovulation
  • (Shargil AA. HRT in perimenopausal women with a
    triphasic contraceptive compouns a three year
    prospective study. Int J Fertil 1985 301518-28)

85
Adrenocorticotropic hormone
  • Released in response to CRH from hypothalamus
  • ACTH triggers the release of cortisol from the
    adrenal cortex cortisol is a catabolic
    hormoneit breaks down tissues to give you
    energy (in the form of glucose) during times of
    stress known as a glucocorticoid
  • Increased ACTH between 2 - 6 a.m. resulting in
    the highest cortisol levels between 6 8 a.m.

86
ACTH the molecule
  • Pro-opiomelanocortin3 substances contained
    within this molecule
  • Endorphins (opio)
  • MSH (melanocyte stimulating hormone)humans dont
    have MSH per selower animals doespecially those
    that changes color in conformity with their
    environment the size of their intermediate lobe
    positively correlates with the ability to change
    color
  • Cortinstimulates cortisol from adrenal cortex

87
Target Organs
  • Thyroid gland
  • Parathyroid gland (not under control of the
    hypothalamus/pituitary)
  • Adrenal gland
  • Ovaries
  • Testicles

88
The thyroid gland
  • Two lobes composed of multiple follicles with
    thyroglobulin in the middle of the follicles the
    thyroid gland is under the influence of TSH from
    the anterior pituitary which in turn is under the
    influence of TRH from the hypothalamus
  • TSH stimulates iodine uptake from the diet and
    the thyroid produces T4 (thyroxine) and T3
    (tri-iodothyronine) T4 is the pro-hormone
    converted to T3 20 to 1 ratio of T4 to T3
  • T3 is the functioning hormone
  • Tissues obtain 90 of their T3 by removing 1
    iodine (deiodinating) T4

89
The thyroid gland
  • When thyroid hormones are released into the
    serum, the majority of both hormones are tightly
    bound to TBG (thyroid binding globulin) the
    physiologically active forms are
  • free or unbound When evaluating patients it
    is more important to pay attention to Free T4
    than total T4 the unbound or free forms provide
    the negative feedback signals to the pituitary
    and hypothalamus

90
Thyroid hormone
  • What does thyroid hormone do?
  • Thyroid hormone affects most body tissues by
    increasing the rate of protein, fat, and glucose
    metabolism as a result it increases heat
    production and body temperature
  • Normal linear growth requires thyroid hormone
  • Brain growth in kids requires thyroid
    hormoneprimarily 1st two postnatal years400
    grams at birth (primarily neurons/gray matter
    thyroid hormone stimulates growth of white
    matter/myelin to connect the neurons
  • Your personality
  • Normal periods, fertility

91
Diagnosis of thyroid dysfunction
  • Primary Hypothyroidismdecreased thyroid hormone
    (T4) production results negative feedback to
    pituitary and an INCREASED TSH
  • Secondary Hypothyroidism (pituitary
    dysfunction)decreased TSH and decreased T4
  • Hyperthyroidismincreased thyroid hormone
    production results in a DECREASED TSH with an
    increased T4
  • Secondary/tertiary hyperthyroidismRARE

92
Too little? Hypothyroidism
  • Autoimmune thyroiditisHashimotos
    thyroiditisantibodies to thyroid peroxidase
    (TPO) and thyroglobulin antibodies are present
  • Iatrogenicthyroidectomy, radioiodine therapy
  • Thyroiditissubacute thyroiditis (also known as
    De Quervains thyroiditis), silent thyroiditis,
    postpartum thyroiditis
  • Drugsmethimazole, PTU, iodine, amiodarone (40
    iodine by weight), lithium, interferons,
    thalidomide, sunitinib, rifampicin
  • Congenital hypothyroidismthyroid aplasia or
    hypoplasia, defective biosythesis or thyroid
    hormones
  • Disorders of the pituitary or hypothalamus
    (secondary or tertiary aka central)

93
Congenital hypothyroidism
  • cretinism
  • Where does the word cretin come from?
  • 18th century French crétin, from French
    dialectal, deformed and mentally retarded person
    commonly found in certain Alpine valleys, from
    Vulgar Latin christinus, Christian, human being,
    poor fellow, from Latin Chrstinus, Christian
    see Christian
  • too simple to sin

94
Adult with myxedema (severe hypothyroidism)
  • Ventilator and IV levothyroxine

95
Hypothyroidism
  • Exhaustion, somnolence, lethargy, depression,
    slow cognition
  • Dry hair, balding, loss of lateral third of
    eyebrows (Queen Annes eyebrows)
  • Bradycardia (thyroid hormone and the number of
    receptors on the SA Node)
  • Hypercholesterolemia, hyponatremia
  • Menstrual disturbances/Menorrhagia

96
Hypothyroidism
  • decreased libido
  • dry thin pale skin, vitiligo
  • Weight gain (10-15 pounds), constipation (10 to
    15 poundshaha)
  • Generalized muscle aches and pains calf
    stiffness
  • carpal tunnel syndrome slow relaxing tendon
    reflexes
  • Pericardial and/or pleural effusions ascites
  • Cold intolerance
  • Normocytic anemia
  • youre not dead until youre warm and dead

97
Who should be screened?
  • Patients with Down or Turner syndrome
  • Patients taking certain drugslithium,
    amiodarone, thalidomide, interferons, sunitinib,
    rifampicin
  • Patients who have received radioiodine treatment
    or neck radiation
  • Patients who have had a subtotal thyroidectomy
  • Patients with type 1 diabetes and autoimmune
    Addisons disease

98
Classification of hypothyroidismbased on TSH
  • Normal TSH?
  • Adults presenting with symptomatic primary
    hypothyroidism often have a TSH level in excess
    of 10 µU/l, and decreased free T4
  • Mild primary hypothyroidism, aka, subclinical
    hypothyroidism, usually presents with a TSH 5-10
    µU/l but a free T4 within reference range
  • Secondary/central hypothyroidismTSH is low

99
Treatment of hypothyroidism
  • Levothyroxine therapy should be monitored by
    following the serum TSH
  • Initially, the TSH should be measured every 4 to
    6 weeks (reflecting the time required to achieve
    a steady state with a medication that has a
    one-week half life)
  • Patients often feel least symptomatic when the
    TSH is on the low end of normal
  • Overreplacement can increase the risk of AF and
    excessive bone loss (over age 60)
  • Monitor TSH every six months after stablization

100
Patient education
  • No supplements within 4 hourscalcium, iron or
    antacids w/aluminum hydroxide (interfere with
    absorption)
  • Levothyroxine has a half life of seven days in
    the bloodstream and it will take a week or more
    to start to feel better conversely, if one
    tablet is missed, there will be no noticeable
    effect
  • If muscle weakness, stiffness or cognitive
    defects are present, it may take up to six months
    to fully resolve
  • Levothyroxine should be taken on an empty stomach
    to maximize absorption
  • Small changes of levothyroxine dosage may be
    likely over your lifetime dose will likely
    DECREASE with aging

101
Levothyroxine
  • 1.7 µg/kg body weight approximately 100 µg daily
    for an average sized woman (60 kg) and 125 µg (75
    kg).
  • Start with lower dose for patients over 60 or
    those with CAD
  • When giving a trial of levothyroxine therapy for
    subclinical hypothyroidism, start with a dose
    close to a full replacement dose (75 or 100 µg
    daily), on the basis that it would be difficult
    to be sure if the symptoms might not be caused by
    hypothyroidism, until a therapeutic dose of
    levothyroxine has been tried

102
Target level
  • Dose should be adjusted to make the patient feel
    better, duh.
  • Usually within the lower half of the reference
    range (0.4 to 2.5 µU/l)
  • If the patient feels pretty well with a level in
    the upper half of the reference range, adjustment
    is not necessary

103
Hypothyroidism and infertility
  • Thyroid-related infertilityhigh levels of TSH,
    even though within normal limits, may be too high
    for fertility levels between 1-2 µU/l seem to be
    best for makin babies)
  • Even the presence of anti-thyroid antibodies
    WITHOUT clinical disease may cause reproductive
    problems
  • One of the first tests for infertility should
    ALWAYS include thyroid testing

104
Hyperthyroidism
  • 2 of women 0.2 0f men
  • Autoimmune disease --Graves disease,
  • toxic multinodular goiter
  • Iodine-induced hyperthyroidismamiodarone,
    radioiodine contrast media,
  • subacute thyroiditis
  • Factitious hyperthyroidism (taking levothyroxine
    for weight loss)

105
Hyperthyroidism
  • Weight loss despite normal/increased appetite
  • Diarrhea
  • Sinus tachycardia, palpitations, atrial
    fibrillation
  • Tremor
  • Fatigue, exhaustion, insomnia
  • muscle weakness
  • Hyperreflexia
  • Sweating, heat intolerance
  • Exophthalmos, proptosis

106
Graves diseasehyperthyroidism plus
  • Diffuse symmetrical enlargement (goiter) of the
    thyroid gland
  • Eyelid retraction
  • Corneal ulceration
  • Diplopia, papilledema, loss of visual acuity

107
Diagnosis of hyperthyroidism
  • Low TSH (less than 0.05
    µU/L
  • ?
  • Free T4 (FT4)
  • ?
  • High T4? Primary Hyperthyroidism
  • Low T4? Secondary hypothyroidism (pituitary)
  • Normal T4? Do a T3
  • High T3? Primary hyperthyroidism (T3
    thyrotoxicosis)
  • Low/normal T3? Subclinical hypothyroidism or
    non-thyroidal illness

108
Diagnosis
  • Thyroid scan using radioactive iodine--¹²³I
    (different from ¹³¹Iodine used to Tx
    hyperthyroidism to ablate the gland)high uptake
    with Graves disease, toxic multinodular goiter,
    solitary adenoma
  • Antithyroid peroxidase (TPO) antibody is present
    in autoimmune thyroid diseases such as Graves
    disease)

109
Treatment of hyperthyroidism
  • Radioactive iodine, antithyroid drugs, surgery
  • radioactive iodine, (I¹³¹)highly effective but
    usually requires lifelong replacement therapy due
    to total destruction of the gland overacting
    adenomas will take up the RAI and destroy the
    adenoma, leaving normal gland intact not used in
    PG due to destruction of fetal thyroid one
    dosesimple. Risk of hypothyroidism is 90

110
Treatment of hyperthyroidism
  • propothiouracil (PTU) or methimazole (Tapazole)
    to decrease T4 synthesis remission rate of
    30-50 in Graves disease methimazole is QD
  • Major side effectsdrug-induced hepatitis
    agranulocytosis (neutropenia)report any fever or
    sore throat
  • Thyroidectomy (subtotal)for patients who fail
    medication or RAI or who has an extremely large
    goiter causing dysphagia or airway compromise
    (complicationsrecurrent laryngeal nerve
    paralysis, hypoparathyroidism leading to
    hypocalcemia)

111
Treatment
  • Before the antithyroid drugs or RAI kick in,
    relief of symptoms (palpitations, tremor) with a
    beta blocker is important
  • Propranolol (Inderal) can be chosen20-40mg 2 to
    4 times a day, with added benefit of preventing
    the conversion of T4 to T3 but the inconvenient
    dosing schedule of 2-4 times/day
  • Atenolol (Tenormin) is a common choice---QD
  • In subclinical hyperthyroidism, some advocate
    treating the elderly because they are at an
    increased risk of atrial fib and osteoporosis

112
Thyrotoxic storm (thyrotoxicosis)
  • IV beta blocker to slow heart rate before heart
    failure kicks in
  • If febrile, dont use aspirin to decrease the
    temperatureASA releases more T4 from thyroid
    binding globulin and can make the thyrotoxicosis
    worse
  • Use acetaminophen for fever in these patients

113
The Parathyroid Glands
  • 4 very small (size of a piece of rice) glands
    plastered to the back of the thyroid gland
  • Produce PTH (parathyroid hormone) which helps
    control serum calcium serum calcium levels low?
    PTH is released to stimulate the resorption of
    bone and release calcium into the serum serum
    calcium levels increase, bone matrix calcium
    levels decrease
  • serum calcium levels are tightly regulated any
    deviation, particularly an elevation indicates
    underlying pathology and merits a thorough
    evaluation
  • Major function of serum calcium is to exert an
    inhibitory control over neuromuscular excitability

114
Hypoparathyroidism
  • normal range of total serum calcium8.4-10.4
    mg/dl (2.1-2.7 mmol/L) adjust total seru calcium
    with level of albumin PTH range 15-75
  • 50 of total serum calcium is bound to albumin
    and is biologically IN-active
  • Therefore, if the serum albumin is low, the total
    calcium may provide a misleadingly low indication
    of free or ionized calcium (the functioning
    calcium)

115
Hypoparathyroidism
  • Too little PTH results in low levels of serum
    calcium and increased neuromuscular excitability
    also known as tetany
  • Calcium levels are below 8.4 mg/dl patients are
    confused, complain of parasthesias of the lips
    and fingertips positive Chvosteks sign (Cheek),
    and Trousseaus sign
  • Causesautoimmune destruction surgical removal
    during thyroidectomy
  • Rx give calcium IV or orally depending on
    calcium levels and patients condition

116
Primary hyperparathyroidism
  • Primary hyperparathyroidism is the most common
    cause of hypercalcemia and should be considered
    in anyone with an elevated calcium level
  • Peaks in 7th decade 75 are women men women
    before age 45
  • Head and neck irradiation in childhood and
    long-term lithium
  • Usually caused by a single adenoma

117
Hyperparathyroidism
  • Classic S S rarely seen in U.S. today because
    of early detection of calcium abnormalities on
    routine blood tests
  • Classic signshypercalcemic sx of nephrolithiasis
    (kidney stones), overt bone disease (stone and
    bone disease), neuromuscular symptoms
  • Symptoms todayweakness, easy fatiguability,
    anxiety, and cognitive impairment kidney stones
    in 4-15

118
Secondary hyperparathyroidism
  • Chronic renal failurecant excrete phosphorus,
    need to balance it with calcium so the
    parathyroids produce PTH to move calcium out of
    the bones to balance phosphorus vicious cycle
    eventually depletes bone
  • Malignancylow or undetectable PHT level rules
    out primary hyperparathyroidism and raises the
    possibility of cancer-associated hypercalcemia
  • Ovarian failureone of estrogens functions is to
    inhibit PTH no estrogen? Unopposed PTH

119
Adrenal glandtwo parts medulla (inner) and
cortex (outer)
  • Adrenal medullaproduces EPINEPHRINE (epion top
    of, nephros, the kidney) (adrenalin) and
    NOREPINEPHRINE (noradrenalin)
  • Fight-flight response
  • Visit Barb in Chicago at 2 a.m.
  • Take a wrong turn, 4 flat tires, transmission
    falls out of your car
  • Whats going to happen to you?

120
Fight/Flight responseacute stress response
  • Release of glucose, inhibition of insulin
  • Pupils dilate
  • Tachycardia, BP goes up
  • Bronchodilationrapid respirations
  • Vasodilate the large arteries to the arms and
    legs
  • Vessels in the skin constrict--pale
  • Hair on the back of the neck and arms stands up
  • What do your bowels WANT to do?

121
If I have told you once, I have told you twice
  • do NOT go to the emergency room with dirty
    underwear!

122
The biggest stress of the day
  • On a day-to-day basis the most stressful part of
    the day is GETTING OUT OF BED
  • Adrenal glands pump out norepinephrine,
    epinephrine, cortisol
  • Heart rate goes up, blood pressure goes up, blood
    glucose goes up
  • The liver releases newly synthesized clotting
    factors, platelets are stickier due to glucose ),
    inflammatory mediators are highest in a.m.
  • Increased risk of heart attacks within two hours
    of getting out of bed
  • How to avoid a heart attack?

123
Adrenal glandthe outer cortex
  • Corticosteroidscortisolrole in carbohydrate
    metabolism and the chronic stress responseboosts
    SUGAR
  • Mineralcorticoidsaldosteroneregulates salt and
    water homeostasis via renin/angiotensinboosts
    BLOOD PRESSURE
  • Adrenal androgenstestosterone, androstenedione,
    17-hydroxyprogesterone, dehydroepiandosterone
    (DHEA)

124
Excess cortisol? Clinical features in order of
frequency
  • Plethoric (red face)
  • Central obesitycortisol moves fat toward the
    center (Centripetal obesity)moon face
  • Catabolic hormone--breaksdown skeletal
    muscleskinny arms and legs
  • Amino acids used for gluconeogenesis and high
    blood sugars leading to Impaired glucose
    tolerance or frank diabetes
  • Aldosterone-like propertiessodium and water
    retention, and potassium excretionHypertension
    and hypokalemia

125
Excess cortisol
  • Menstrual irregularity in women, ED in men
  • Osteoporosismoves calcium out of bone
  • Protein breakdown in skin leads to thin skin over
    abdomen and purple striae (stretch marks)
    particularly over the abdomen and breasts

126
TOO MUCH CORTISOL?
  • Tendency to bruise easily Poor wound healing
  • Hirsutism and frontal alopecia (male pattern
    baldness)
  • Interscapular fat pad (buffalo hump)
  • supraclavicular fullness/fat pads
  • Acne
  • Depression
  • Cortisol is a powerful appetite stimulantcraving
    simple carbsboosting insulin and promotes fat
    storage

127
Hypercortisolismcauses?
  • Cushings diseasetoo much ACTH from the
    pituitary
  • Cushings syndromeadrenal tumor, excess
    ingestion of corticosteroids
  • Ectopic hormone production of too much
    ACTHbronchial carcinoid is the 1 cause

128
Hypercortisolism
  • Pituitary tumor? Cushings disease Increased
    ACTH triggers an increased production of cortisol
    from the adrenal cortex
  • Adrenal tumor? Elevated cortisol with negative
    feedback to pituitary and decreased ACTH
  • Exogenous administration of Prednisone or other
    corticosteroid

129
Cushings syndrome is difficult to recognize early
  • How many obese, mildly hirsute, hypertensive,
    glucose intolerant, women with irregular
    menstrual periods does the primary care
    practitioner see every year?
  • Easy test (dexamethasone suppression test)give 1
    mg of dexamethasone _at_ 11 p.m.
  • Draw an 8 a.m. plasma cortisol level a level of
    less than 5 mg/dl excludes the diagnosis

130
Treatment?
  • Depends on where the problem ispituitary
    adenoma? How big? Is it surgical? Treatment of
    choice
  • If cant treat surgically or dont find the
    sourceuse inhibitors of steroidogenesis such as
    ketoconazole or metyrapone (metopirone)
  • Bilateral adrenalectomy if necessary

131
ADDISONS DISEASEprimary adrenal cortical
insufficiency--JFK
  • Not enough adrenal corticol hormones? Decreased
    cortisol, decreased aldosterone, decreased
    testosterone
  • Feedback to Pituitary
  • Increased production of ACTH
  • Big molecule containing
  • Proopiocorticomelanin
  • 1) ACTH
  • 2) Melanocyte stimulating hormoneskin
    darkening
  • 3) Opiods (beta endorphins)happy

132
Signs and symptoms
  • Low blood sugar due to decreased cortisolmalaise
    and weight loss (90), fatigue, weakness (90)
  • Decreased aldosterone reduces blood pressure
    (low sodium and water) and increased potassium
    (hyperkalemia)
  • Decreased androgensdecreased libido
  • Increased ACTH to try to stimulate a dead
    adrenal cortexincreased pigmentation of lips,
    freckles, buccal mucosa, skin creases (80)

133
Addisons disease
  • PRESIDENT John F. KennedyOF COURSE HE WAS ALWAYS
    TAN and HAPPY why?

134
Treatment of Adrenal Insufficiencyreplace whats
missing
  • Prednisonelow or maintenance dose of 0.1 0.25
    mg/kg/day moderate dose 0.5 mg/kg/day normal
    maintenance dose is 5-7.5 mg per day
  • Hydrocortisone15-20 mg q a.m. 10-15 between 4-6
    p.m.
  • Fludrocortisone (Florinef)dose depends on blood
    pressure (orthostatic hypotension), or
    hyperkalemia decrease dose with edema or
    hypokalemia
  • Testosterone
  • During times of acute stress, steroids need to be
    increased

135
Acute adrenal insufficiency--emergency
  • Usually occurs in someone with chronic adrenal
    insufficiency who undergoes some from of
    significant stressMI, surgery , trauma
  • Sudden withdrawal of steroids (any patient who is
    on larger doses of steroids gt 20 mg/day of
    Prednisone for example) for 2 weeks or more has
    the potential for long-term suppression of the
    hypothalamic adrenal axis)
  • Unable to mount a stress response
  • IV hydrocortisone 100 mg IV then 50 mg q 6 hours
    x 4 then oral maintenance

136
Note about taking corticosteroids
  • Greater suppression of the HPA axis occurs when
    the doses are taken in the evening
  • Morning doses mimic the usual biological rhythm
  • Recovery of the HPA axis may take from a few
    months to a few years
  • Weaning off steroidsswitch to short-acting
    corticosteroids such as Prednisone or
    hydrocortisone on a BID basis Next, wean evening
    dose, leaving a solitary morning dose. By this
    time, hydrocortisone should be substituted for
    Prednisone.

137
Primary hyperaldosteronismConns syndrome
  • Too much aldosterone (usually due to an adrenal
    tumor)
  • Aldosterone retains sodium and water and excretes
    potassium (potassium-wasting)
  • Hypertension and hypokalemia
  • Carlotta and PICA

138
The OVARY
  • The hormones of the ovaryestrogen, progesterone,
    androgens
  • Primary ovarian failureestrogen and androgen
    deprivation
  • Androgen deprivationlower energy, loss of
    libido, loss of muscle mass
  • Estrogen deprivationestrogen has over 300
    functionsthe most noticeable symptoms of
    deprivation are the vasomotor symptoms

139
Digression just how many eggs/follicles do we
get, ladies?
  • At 6 months gestation ________________
  • At birth _____________
  • At age 30 ___________
  • At age 51.3 __
  • NO MORE EGGS
  • Primary ovarian failure

140
Peri-menopause
  • Transitional state from reproductive years to
    postmenopausal yearslength is variable--3 to 10
    years
  • Ovary is on a roller-coaster rideestrogen
    production is UP and DOWN
  • Variable menstrual cycles (greater than 7 days,
    different from normal)
  • FSH is rising (persistent elevations above 40
    IU/L or greater than 50 over 50 or greater than
    30 IU/L with estradiol less than 20 IU/L)

141
Vasomotor symptoms--Hot flashes
  • Lack of sleep
  • grouchy
  • Vaginal dryness
  • Also calcium is leaving bones at a rapid pace
    during first 3-5 years due to unopposed PTH
  • Newest info? Start low-dose estrogen

142
Polycystic Ovary Syndrome
  • The most common endocrine disorder affecting
    women of reproductive age
  • First described in 1922 (2 French MDs) who wrote
    a paper called
  • 5-10 of women

143
Polycystic Ovary Syndrome--diagnosis
  • National Institutes of Health Criteria
    (1990)must include hyperandrogenism/hyperandrogen
    emia anovulation or oligo-ovulation exclusion
    of possible related disorders
  • The Rotterdam criteria (2003)two of three
    cardinal abnormalitiesincluding oligo- or
    anovulation, androgen excess (hirsutismface,
    chin, pubis), and polycystic ovaries (ultrasound)
  • Androgen Excess and PCOS Society
    (2006)hyperandrogenism, ovarian dysfunction,
    exclusion of possible related disorders

144
Polycystic Ovary Syndrome
  • Lab Tests Increased ratio of LH to FSH
    (31)results in the ovaries producing an
    excessive amount of testosterone leading to the
    clinical manifestations of hyperandrogenism.
  • The LHFSH abnormality also results in the
    production of estriol, a weakened form of
    estrogen, resulting in a positive
    feedback-induced LH production. This increased LH
    production contributes to the development of
    ovarian cysts, anovulation and ovarian theca cell
    (androgen producing cells) hyperplasia
    hyperplasia stimulates further androgen
    productiona vicious cycle.

145
PCOSClinical presentation
  • Hirsutism50
  • Male pattern alopecia or acne20
  • Oligomenorrhea/amenorrhea50
  • Abnormal uterine bleeding30
  • Polycystic ovaries on ultrasound75
  • Obesity 50
  • Infertility resulting from sporadic ovulation

146
Complications of PCOS
  • The majority of women with PCOS, regardless of
    weight, have a form of insulin resistance that is
    intrinsic to the syndrome and is poorly
    understood
  • Obese women with PCOS have insulin resistance of
    PCOS AND the insulin resistance of adipositya
    double whammy!
  • T2DM is 10x higher in PCOS T2DM or impaired GT
    develops by age 30 in 30-50 of obese women with
    PCOS
  • Risk of fatal MI is 2x higher with severe
    oligomenorrhea
  • Increased risk of endometrial cancer due to
    unopposed estrogen stimulation

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Treatment of PCOS
  • Do you want to become pregnant? First-line
    treatment is clomiphene citrate
  • Clomiphene induces ovulation in 75 to 80
  • Metformin (Glucophage, Glumetza,
    Fortamet)produces an increase in menstrual
    cyclicity and ovulation rates reducing insulin
    levels along with altering insulins effect on
    ovarian androgen synthesis allows a return to the
    ovulatory state reduces circulating androgen
    levels by inhibiting ovarian gluconeogenesis and
    androgen synthesis
  • FIRST LINE THERAPY

148
Treatment of PCOS
  • Not in the mood to get pregnant?
  • Oral contraceptives with anti-androgen components
  • OCs offer endometrial protection from unopposed
    estrogen stimulation
  • Suppress LH secretion and increase the synthe
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