Download Endocrinology First Day

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Endocrinology First Day
Wednesday, September 04, 1996
Polyuria is a symptom that the patient may not be aware of, anemia is another example
the above situations are of symptomatic patients that are unaware of it
actual dx may be very difficult
What is the function of the thyroid it is to make thyroid hormone
90% of patients with hypothyroidism have Grave’s Disease
The most common causes of endocrine disorders bla bla bla
very few diseases do we know the cause of very few
EXAMS
last class did very poorly
Unit exams are over the reading assignments
first exam is 2 weeks from today
Wednesday, September 11, 1996
talked most of the first hour about comp board gripes
look up the purpose of thyroid hormones
the effector of the endocrine system are the hormones
effector = hormone
diabetes is due to improper utilization, most or many of the diabetics have normal to
0elevated insulin levels
the classic model of the primary signal of a hormone don’t fit or explain a # of endocrine
diseases
signs and symptoms
there is a problem with ulitilizing symptoms example not all people have a butterfly rash
with Lupis
Cushings syndrome and disease very different disorders
Cushings Disease pituitary tumor
hyperpigmentation (caused by cortisol)
both have elevated cortisol ( responsible for most symptoms except hyperpigmentation)
ACTH drives the adrenal gland to produce cortisol
may have an ectopic tumor (or)
a hyperplastic over adrenal production
Cushings Syndrome is elevated cortisol
can be caused by an atopic ACTH tumor
most common is the exogenous use of corticosteroids
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a symptom = the result of something
pituitary hormone produces ACTH  drives the adrenal gland to produce cortisol
POMC large precursor molecule contains a # of large peptides
one being betaendorphin
undergoes post translational cleavage hyperpigmentation ( by)
increasing melanocyte # increasing pigment
hyperpigmentation could explain brown elbows
General Concepts of endocrine effectors: - usu. two aspects to a hormone:
1 hormone > # of activities
1 activity > # of hormones
males in general have a higher hemoglobin level
testosterone  stimulates production of erthropoietin
testosterone does what it does the same way every time, but it has a number of acitivities
carbon tetrachloride kills the liver, brain, depends on the effector tissue, it did the same
thing to both but the impact is different
testosterone acts on the same cell every way it is the cell it acts on
one biologic activity is under the control of many hormones
example the control of glucose a # of things are reponsible for this
thyroxine stimulates the appetite
more mechanisms to protect against hypoglycemia, than hyperglycemia
peptide hormones are those hormones just made up of peptides or proteins
steroid hormones steroid nucleus
compare and contrast a peptide hormone, mechanistically, chemically and
functionally
how are they the same:
all hormones
present in small amounts
are controlled by targeting
are very premisquous
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Monday, September 16, 1996 - afternoon hour
Determination of baseline values
BASELINES
lets use bilurubin as an example 0.2 1.2, the first time you see the patient there bilirubin
level is 1.2 mg/dl which is with in the normal range
RBC degradation of hemoglobin produces bilirubin if production exceeds elimination
then the value goes up, we measure the net effect
huge excess capacity overwhelms the capacity of the normal liver
babies destroy blood cells quickly because they have too many when they begin to breath
on there own, this exceeds the capability of their small livers and they become jaundiced,
the light UV bilirubin absorbs it and causes in to degrade
interpret a value of 1.2 now and a bilirubin value of .2 a year ago this represents a 6 fold
increase most peoples bilirubin is very stable maybe they started to exercise a great deal,
what ever it is the cause needs to be established
baseline value can help you fine tune normal
reason to order a lab test is - the staging or grading a disease e.g to determine how anemic
some diseases have histologic criteria for acute and chronic distinctions
sometimes we use different antibody types to stage a disease
prodromal acute continuing on to convalesence (on the mend) or chronic
last reason to order a lab test is
Defense Defensive Chiropractic (self protection, malpractice, negligence)
Wednesday, September 18, 1996
Endo Exam Reading for first exam Chapter 199 page 11761185
Hormone Activity
Hormone Concentration
the more hormone that you have the more biological activity we may expect from this
hormone
Innate Mechanism of endocrine activity
there is a homeostatic relationship btw the body and the hormone levels
Receptors in relation to hormone concentration
wo receptor there is no hormone activity
Ligand - a substance that interacts with a receptor
with hihg specificity
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receptor is within the cell membrane
Thyroid Gland produces T4
the T4 levels elevate slightly but the heart rate doesn’t go up
when the thyroid begins to produce too much T4 we need to shut down the concentration
does this by inhibiting TSH
which doesn’t stimulate the thyroid
thyroid hormone levels drop - it shuts off the normal production
but not tumorous production
hyperthyroidism hypothetical senario
when the receptors on a particular organ all become bound with hormone a
process called down regulation occcurs in which the
number of receptor sites on the organ is diminished
is a rapid process - occurs in nanoseconds
there is both a quanitative - when excess hormone there is diminished numbers and
qualitiative the affinity changes to the hormone
a person can have elevated levels of thyroid hormone and not suffer any of the
symptoms the explanation is the above
During periods where there are diminished hormone levels there also appears to be no
effect b/c the number of receptors is up regulated i.e.amount of hormone present is more
effectively used
for most hormones only 10% is bound to the receptor therefor- we can fully saturate the
system with 10%
A lot of people with diabetes don’t have anything wrong with the pancreas, but may have
a problem with the receptor
typically as the hormnone concentration goes up the receptor number goes down
type II diabetes is usually a receptor disease
example of why signs and symptoms of disease are a poor indicator of disease
Peptide Hormone
1.
2.
3.
4.
Cell Surface Receptor
“Second Messanger”
Biological Amplification
the first event that this receptor does is to stimulate or activate the second messenger
a casscade of events one being the generation of many molecules of Cyclic AMP
Response proteins from production can turn the system off
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a form of negative feedback system
Coffee is a stimulant with the active ingredient being caffeine
caffine inhibits phosphodiesterase (inhibitor) so stimulation
caffeine inhibits phosphodiesterase  increase in cAMP produces of more phos.
Everything is fine until you stop drinking caffeine 
no energy, constipated because
now none of the phosphodiesterase is inhibited and it is degrading all of your cAMP
In 3 or 4 days phospho levels return to normal
when you inhibit the net effect is stimulation
What are some other second messengers calcium
Agonist vs Antagonist
Agonist materal, subs., molecule that activates, stimulates (mimincs real ligand)
receptor
Antagonist blocks receptor from binding normal ligand eg. graves disease due to
something binding to the TSH receptor an autoantibody
these act like TSH and are more potent
one molecule can cause more than TSH
Febrile states - change the structure of a lot of proteins which alter function and hence
you are toast
Steroid hormone
receptors tend to be intracellular
tend to modulate sythesis by turning genes on and off
activates receptor and brings about a conformational change for that hormone
this dictates where it is and what gene is going to turn on
very specific one protein gene message into mRNA and then translate into protein
the steroid hormone goes to a particular gene
difficult to mimic steroid hormone
Wednesday, September 25, 1996
The next quiz will cover “The Anterior Pituitary”
Biorhythms rthythms
in the release of hormones are common in almost all endocrine systems
can occur over:
testosterone - minutes to hours
cortisol - daily
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estrogen -weeks
thyroid - months- seasonal changes
Biorthyms
1. Hormonal Rthymicity Due To:
1. Neurogenic factors sleep assoc. w/ (cortisol)
2. Environmental factors
3. time delay factors feedback delay
Hormonal Transport
1. Water soluble (peptide) hormones require no transport proteins
2. Water insoluble (steroid) hormones do require transport proteins
A.. Transport proteins are either general or specific
1. General - albumin or pre-albumin
2. Specific - thyroixine binding globulin or cortisol binding globulin
1. The specific transport proteins are not exclusive
2. A specific hormone can be transported by a general transport protein
Prealbumin - has all the functions of albumin but it is a molecularly distinct species.
Electrophoresis - similar to chromotography separation based on size, electro separates
on the basis of size and charge
Multiple Myeloma - the reversal of the A/G ratio is in reference to the #s and not the
migration on cellular acetate
Bence Jones protein is heat stable
MM most definitive is to do an electo analysis of the serum of the urine
will see a huge concentration of gamma globulin protein on the strip
can be done with the densitometer
the densitometer spike in the gamma region is called the Mspike - stands for myeloma
issue that has gone wrong is the plasma cell
called a plasma cell dyscrasia,
aka - Light Chain Disease
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Free or unbound and bound
free is the only one that has any activity
only one that can interact with a receptor
T4 + TBG > T4TBG
Endocrine Pathology
1. Abstract or subhormonal secretion due to:
1. Abnormal or absent endocrine gland
2. Abnormal development of the gland
3. normal gland is destroyed by secondary process
4. idiopathic
2. Hormone excess due to:
1. Cushing’s Disease - Tumors adrenal cortex
2. hyperparathyroidism - hyperplasia parathyroid
3. Grave’s Disease - autoimmune thyroid
4 thyroiditis - iral thyroid
3. Production of abnormal hormones
1. Gene mutations of hormone structure/ function
2. incomplere processing of hormone precursors
EG > H
precursor post translational modification
Vitamin D 1,25 (OH)2 - requires liver and the kidney enzymes
Kidney contains alpha hydroxylase
if the person has kidney disease we find drop offs in this enzyme and
falling vit. D levels
the person goes up with renal osteodystrophy (bone disease secondary to kidney disease)
4. Resistance to hormone action:
1. Target tissue response defect
2. qualitative receptor defect
3. Quanitative receptor defect
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5. Abnormal hormone transport
1. Deficient transport protein
2. Very rare (if ever) cause of hypo or hyperfunction
3. “artifical” circumstances = cortisol and cirrhosis
Wednesday, October 02, 1996
The pituitary dysfunction
Hypothalamus - master gland of the body
initially we were not able to measure the products of the hypothalamus so people use to
think it was the pituitary
Pituitary Gland
Its products control a lot of other glands
.
Target glands of the pit. hormones:
TSH the clinical result is hypothyroidism
pat. presents clinically as hypo this is a secondary form
the primary defect is seconday to a pit dysfunction
Review of the pit hormones:
1. ACTH (corticotropin)
2. Growth hormone
3. Prolactin
4. Thyrotropin (TSH)
5. Follicle Stimulating hormone (FSH)
6. Lutenizing Hormone(LH)
ACTH - Corticotropin
produced by the pit.
cheif target for this is the adrenal glands
binds to cell surfaces and uses cAMP ( so we know it is a classic peptide hormone)
stimulates
lipolysis in fat cells
amino acid and glucose uptake in muscle
secretion of growth hormone
insulin secretion, these actions are not significant at normal levels (?)
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Levels of ACTH are highest in the morning and lowest in the PM
understand the role of ACTH in hyperthyroidism and hypothyroidism
nocturnal hypogylcemia wake up with head aches
insulin action isn’t the mechanism
excess ACTH increase uptake of glucose and is compounded by increase glucose
utilization example of extra endocrine activity
Circadian rythyms common in daily cycles of ACTH production
ACTH levels seem to be highest in the morning and lowest in the evening
abnormal means different from everyone else - but does not mean is clinically significant
ACTH
stimulated by CRF (+ CRF)
inhibited by cortisol (- Cortisol)
Hypothalamus  Pit  ( release of ACTH)  Adrenal gland  (release cortisol) 
which turns off the pit and  the pit turns off the hypothalamus
increased cortisol
the ACTH level will be low
we will call this an appropriate depression
Growth hormone- short kid with normal growth hormone why is the kid short ?
GH Effect activity is determined by two things
1. concentration and
2. activity
GH expression of activity is controlled by a variety of extraendocrine activities
GH secretion is augmented by:
falling fatty acid levels
uremia
beta adrenergic antagonists
alpha adrenergic agonists
Stress (traumatic, surgical, infection)
hyporglycemia (fasting)
hepatic cirrhosis
vasopressin
estrogens
glucagon (seen in hypoglycemic states)
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f.u.- b.a.s.h.h.- v.e.g
GH is inhibited by:
emotional deprivation
alpha adrengeric antagonist (opp. of above)
beta adrenergic agonist (opp. of above)
hyperglycemia
increasing fatty acid levels (opp. of above)
obesity
somatotropin
cortisol (high doses of)
increased glucose produces decreased GH effect so
We don’t see larger than normal children with hyperglycemia , conversely
decreased glucose increased GH effect
i.e. inverse relationhip btw. glucose & GH
Age related decline in growth hormone normal
GH def. in an adult clinical significance of not clear
coronary heart disease
best way to test for is a stress test
another way is through glycolytic stresses
in normal individual - induce hyperglycemia there GH levels should drop
thyrotropin synthesis in the thryrotophic cells
found in the central wedge of the gland and
makeup about 51% of the cells
TSH regulation
TSH synthesis is stimulated by thyrotropin releasing
T4 definitely turns off TSH, prob T3 and T4 does also ?????
Prolactin
involved in milk production
stimulation of the ductal epithelium of the mammary tissue
at delivery estrogen levels drop thereby removing the inhibition of prolactin by estrogen
High levels of estrogen during pregnancy inhibits prolactin
Lutenizing Hormone (LH) acts on Lidig cells to produce testosterone
this hormone is controlled by GRH (Gonadotropin releasing Hormone)
Look up FSH (Follicle Stimulating Hormone)
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chart in the action notes and book
Clinial conditions and abnormalities with these hormones:
Hypopituitarism - broad category that encompasses a lot of clinical pictures
unrecognized  Death
can go unrecognized
hyperpituitarism - usu. Secondary
Pan Hypopitiotarism all 5
1. The hormones involved 1, or 2 or 3 or 4
A decreased TSH
B decreased TSH and decreased ACTH
C decreased TSH and decreased ACTH and decreased LH
the clinical symptoms are related the particular hormone that is deficient
2.
3.
4.
5.
The extent of hormone deficiency A, B, C
Duration & rapidity of the onset
Age a 50% reduction in GH more recognizable in a 12 year old than a 50 year old
Gender
Thyroid function panel - the best way to evaluate is the thyroid disease
Endocrinology reading for the quiz on next Wednesday 1206 - 1221
Wednesday, October 09, 1996
He will be giving the overheads to Forrest for us to copy.
3 Patients with clinically apparent hypothyroidism which patient has primary, secondary
and tertiary
The question would be: TRH, TSH, T4 elevated, normal or depressed
With primary TRH would be increased or decreased, this is due to competing signals;
TSH up; T4 down
Seondary T4 down; TSH down because this is primary secondary hypothyroidism,
TRH up, up
Tertiary TRH down, TSH down, or up or down; T4 down
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The most common cause of primary is autoimmune destruction of the thyroid gland,
pituitary the most common is a tumor, Hypothalamic either a tumor or a neuroendocrine
problem
A Goiter is a hyperplastic condition due to iodine deficiency.
We almost always do simulataneous check several different hormones when checking the
thyroid gland.
The booster action of the pituitary may be able to bolster a failing thyroid by increasing
FSH
Wednesday, October 23, 1996
remembering that hypopituitarism there isn’t such a distinct identifiable clinical picture,
extend of hormone defic, what they are and how long they have been deficient
Hyperpituitarism is more distinct because, most often hyper involves the over
production of a sinlge hormone, the clinical result is more confined and characteristic
can be primary or secondary can reactive or conpensatory
the far most common cause of hyper is a tumor functional
there are lots of ways to classify tumors one way is functional and nonfunctional
functional tumore tend to be malignant but not always
malignant referrs to its ability to metastasize
a tumor can be histologically benign, but are malignant due to there location like a
glioma
physiologically malignant or functional tumors in the endocrine system are common the
problem with this endocrine system is under the control of a number of other features
turn on and turn off feedback inhibition
if the source of the TSH is from a functional tumor but there is no feedback inhibition
because there are no feedback physiological controls
nondifferentiated means it becomes more primitive
they look like a very undifferentiated cell doesn’t have contact inhibition many of these
cells are immortal
they do not respond to normal physiological control mechanism refractory to feedback
inhibition
hyperpit brand name diseases AmennorrheaGlactorrhea Syndrome
Hyperprolactinemia is the most common form of pituitary hyperfunction and is most
often due to a functional ademona of the pituitary. These functional tumors are present in
as many as 25% of infertile women
Cininal features in females oligomenoorrhea or amenorrhea, lactation, mild hirtutism,
infertility
In males impotence, decreased ligibdo, lactation
Diagnosis of Hyperprolactinemia
1. Clinical features
2. Elecated Prolactin levels 15 to 20 ng/ml to 10,000 ng/ml
3. Prolactin levels less than 200 ng/ml are almost never of tumor origin
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normal levels of prolactin is 510 in females males may almost be zero
the magnitude of the elevation is quite definative
Primary ACTH Hypersecretion (Cushing’s Disease)
in about 90% of cases the cause of ACTH hypersecretion is the result of a functional
basophilic adenoma or bilateral hyperplasia (cortical) of the pituitary
The vlincial features are essentially the same as those produced by adrenocortical
ademoans and affect females in the 3060 yeat old age group most often
Cushing’s Disease and Cushing’s Syndrome
Cushing’s disease id a primary pituitary disorder (functional adenoma) wiht an
oberproduction of ACTH by causing secondary hypercorisolism
2, Syn hyeprcortisolism due to exogenous cortisol administration or overproduction by
adrenal , pgs 89 sn and sx
Cushing’s central obesity, hypertension, amenorrhea, hirtuism, muscular atrophy, weight
gain?. osteoporosis and compression fractures, increased capillary fragility, impaired
wound healin, hyperglycemia, increased skin pigmentation elbows, knees, knuckles
Diagnosis of Cushing’s Disease typical clinical findings, elevated plasma cortisol (50%),
elevated urinary freecortisol (8590%), plasma ACTH elevated or inappropraite for
cortisol level, differential adrenal tumor, ectopic ACTH production
Free cortisol means that it is unbound major cortisol binding globulin is cortisol
binding globulin, it is bound to albumin or prealbumin these act as the transport for the
hormones that are not soluble
receptors only recognize the unbound form
the definitive or sensitve would be the free urinary cortisol levels
loss of the normal diurnal variation and somewhat diffinitive for both ACTH and
Cortisol
ACTH disease have elevated ACTH levles, Syndrome decreased levels
Cortisol disease increased, syndrome increased
Cushing’s syndorme most common cause of the Cushinoid features are exogenous
administration of cortiosteriods, or bilateral adrenal hyperplasia, these symptoms are
reversible once they get off steroids
prime example of ACTH from an ectopic source is an oat cell carcinoma of the lung,
have symptoms of Cushing’s
Dethamexasone suppression if ectopic it will have no effect, then we know that this is
from an exogenous source
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Acromegally versus Giantism
If prior to epiphyseal joint closure they are normal but just big
Acromegally they grow larger but not bigger, do not have linear bone growth
Acromegally typical clincal finding typically change in shoe with they get too narrow,
change in ring size, there is a variety of visceral disorders
Cushing’s cortisol excess symptoms appear in 1015 days
Growth hormone excess may take 51015 years
Acromegaly soft tissue swelling, hypertrophy of the extremitites and face, skin becomes
thickened, skin folds increase in prominence, increased hair growth and increase
pigmentation, visercomegaly liver, spleen, kidney, tongue, salivary glands, thyroid
enlargement with nodules, tufting of the terminal phalanges, osteophyte proliferation,
hypertorphic athropathy crippling arthritis, peripheral nerve damage due to entrapment
by tissue overgrowth
Diagnosis of GH Hypersecretion clincial signs and symptoms, elevated GH levels, GH
levels that are not suppressed by Glucose
we find more people with hypopituitarism than we use to prob, because we are better at
screening for it
Quiz next Wednesday is over ADH, Vassopressin
ADH the purpose of ADH is to prevent diuresis
one of the clincal consequences is polyuria an increased 24 hour urine output most of
the time there is also increased frequency
Clincal condition from an ADH defic Diabetes Insipidus
ADH the lack of ADH is also called diabetes insipidus
Frank ADH def Pituitary Diabetes Insipidus
there are people with DI have elevated ADH they have a failure of ADH to affect water
conservation, these people are said to have Nephrogenic Diabetes Insipidus
They have a kidney problem an ADH receptor defic either aquired or congenital
one of the cosequences of polyuria is that the increased h2o loss and elevation of NA
this is a condition we call hyperosmolality
When we study osmosis we are really considered with the intracelluar concentration of
Na, K
ADH acts and responds to the solute concentraion of the extracelluar fluid compartment
which is controlled by the intracellar concentraion????
What comes out of this cell it shrinks
Hypertonic encephalopathy children and puppies and susectible to massive diureses
they dehydrate
infants can diurese and be dead in 24 hours due to dehydration
if they live they will have perm braind damage
they can get very sick hypertonic encephalopathy
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how can you tell if someone is dehydrated one way to do this is urine specific gravity
urine specific gravity 1.005 and water 1.000 no units because specific gravity is a relative
measure with water as the standard
this is not a good measure
a mole of sodium chloride
we use serum osmolality and it is a commonly performed test look up the differnce btw
osmolality and normality check serum urine plasma as the osmolality decreases we
develop hypertonic encephalopathy
Differntial diagnosis
primary polydysia they drink alot and develop polyuria must determine what cause what
Wednesday, October 30, 1996
Thyroid Reading Hypo and Hyper
Rheumatoid Arthrititis, Lupis, and Rheumatic Heart Disease are all more frequent in
women
The most common cause have an autoimmune pathogenesis
There are prob more ways to exam the thyroid gland than any other single tissue
Thryroid Gland Elevation
Anatomical
Metabolic Indices of Thyroid Status
Tests of Thryoid Regulation
Tests of thyroid function
The thyroid gland is prob the only endocrine gland palpateabe
susectible to chemical and toxic injury
subject to intracit control mechanism
most common anatomical evaluation of the thyroid gland is
they all fail to give a clear indication of thyroid function
What is the function of the thyroid gland produce hormones T3 and T4
How do you access the thryoid gland levels of thryoid hormone
prior to the 60’s they were unable to detect these levels
we used metabolic indices of these these thyroid hormones control cellular metabolism
metabolism has nothing to do with nutrition
one of the common lab assessment in the 60’s was the basal metabolic rate
If hypothryoid they had a bad metabolism or too thin an under active metabolism
is this a valid test this is not a good test for hormonal level it does not measure
hormonal level,
body temperature is an index of body metabolism
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cellular energy utlilization of cellular efficiency how we measure basal metabolic rates
and we put a rubber hose into mouth and this tube was connected to a set of bellows
bags, the patient would lie there and breath the bellow was connected to a pin recorder
with paper, as paper was moving a graph would form
this graph was labels and after 5 minutes a line was formed representing the basal
metabolic rate
what did we actually measure respiration rate, complex and expensive, better way to
measure respiration rate is just to count
a better measure of hypo and hyper thryoidism is the heart rate either elevated or
depressed
The metabolic indices are a first or second generation test they do not evaluate what you
are interested in
Test of thryoid regulation
it is regulated by a number of other physiological functions
when identify a defic of thryoid hormone this doens’t mean there is a thryoid disease
There are lots of tests done to evaluate the thyroid gland
How about using free serum T4 to evaluate thyroid function [T4] = [T4] + [T4 TBC]
this form is inert because the T4 receptors which are internal to the cell only recognize the
free form
for T4 to be expressed it requires the acitvity of a receptor
Suppose 1000 molecules of thyroid hormone roughly 999 are biologically inert and only
1 hormone has any biological activity
When we talking about nanograms of hormone activity
the single most important thing is the concentration of the unbound or the free
There is a test called the T7 test
T4 = 10
T3 5
T7 0.2 lots of doctors think that this is a mistake, there is no such thing as T7, the T7
value is calculated estimation of free T4, these were used that the free and the unbound is
the real measure, today we don’t have to guess or estimate we simply measure
T7 is a calcualted estimate of the free T4, now we just measure it directly
T7 is a good measure
Sinlge best test of thyroid function is the free T4
T4 and or T3 do you have to measure both or just one when do you need to measure
both
Why would we measure both to be more specific interested in knowing when clinical
suspicion might indicate a thryoid problem
What are the clinical signs and symptoms how do we predict
What would this cause or bring about in the patient
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What is the basic difference
Thyroid gland = 90% T4 and or T3 10%
Concentration [100]
[20]
of the concentration floating around these 20 molecules 16 or 80% of the T3
concentration comes from the T4 molecule
the rate controling determinate of the T3 concentration rather the conversion of T4 to
T3, that is why the T4 concentratio is the single most important for being informative
most of the T3 concentration in normal individuals is the result of T3 concentration
normally there is 4 times as much T4 as T3
the acitivity of T3 is about 4 times greater than T4 that refers to the potency
the 1/2 life of T4 is 46 times that of T3
For any substance we are using hormones the ultimate effect of a hormone on tissue is
determined by these 3 features the only thing we ever think about is how much, what is
the effective minimal dose
Do they have too much or too little
We understand the mechanism that controls the dose we can maintain an effect if we
decrease the concentration of the hormone a 50% reduction we can maintain this effect
by a 50% increase in the half life this is the times available inviv to do what ever it does
this is also emcompasses is it in the right form
Calcium has to be in an ionic state 50% of the calcium is bound one component is the
half life there are a variety
some other conditions alter the half life
The other activity is the potency
there a variety of condition with physiologic alterations
concentration and activity when we start to change these we begin to get different
responses at the targer organs
for next Wednesday hypo and hyper and be ready to havve an exam the first period the
second week
Wednesday, November 06, 1996
Actions of the thyroid hormones
The thyroid hormones affect many physiological processes and are necessary for the
optimal acticiity of numerous other hormones. Thus, abnormalities of thyroid function
can lead to gross alteration of nomrla physiology.
The thyroid hormones have been shown to:
block feedvack ingibition of pit TSH secretion
inhance the lopolytic respocse of adipose tussue
increase the number of mitochondria within target vells
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increase the rate of intestinal glucose absorption
Hypothalamic Piturtary Tyroid Axis
TRH secreted kkkkkk
Thyroid binding Globulins is the major binding carrier of the thyroid hormones,
mechanisms that control it are distinct from those that control thyroid gland production
looking at pregn or the pill elevate TBG
Albumin and prealbumin
Huge percentage of thyroid hormone that is biologically inert greater than 99 % of the
thryroid hormone is bound and has no activity
Remembering then that when we cli
Wednesday, November 13, 1996
Grave’s Disease tachycardia or prob better to say an elevated pulse is classic of Grave’s
disease, widened pulse pressure in this disease
almost all the symptoms are due to increased metabolic rate
Grave’s Opthalmopathy this finding in more than 50% of patients with Grave’s disease
and its almost never present with other forms of hypothyroidism
Pretibial Myxedema
Dx elevated T4 normal T3
The most definitive would decreased TSH
T4 production shuts down the production of TSH
Thyroid storm 2040% mortality rate, usually caused from superimposed stress could be
pregnancy
Hypothyroidism
Has many more causes or types
90% of the time failure of the thyroid to produce hormone due to Hashimoto’s Disease
Clinical Manifestations are due to both 1. Decreased Horomone levels 2. Myxedema
accumulation, these occur in the prolonged cases of hypothyroidism 36 years, this
material begins to accumulate it appears to be reversal if a euthyroid state can be
obtained
occult hypothyroidism symptoms are so nonspecific it may be considered accidently by
normal symptoms of aging
Weight gain, bradycardia, intolerance to cold, hearing loss, memory loss, vocal changes
the voice gets huskier or deeper
Dx decreased T4, increased TSH, increased cholesterol, mild anemia
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other classical findings include an increased cardiac shadow due to myxedemous
infiltration, EKG in addition to bradycardia, a low voltage QRS complex
The vocal cords are very sensitive due to the accumulation of this material in the vocal
cords
other aspects myxedema colon or megacolon can go from mild to frank obstruction
can lead to loss of peristalsis
In both hypo and hyper pulse pressure is the difference btw the systolic and the diastolic
hyper increased systolic and decreased diastolic
hypo increased diastolic, and decreased diastolic
Hyperthyroidism is straight forward
Hypothyroidism is not so straight forward, lots of people have this and don’t know it
Onset of symptoms Grave’s Disease in 6 weeks symptoms, in Hypo 6 years and
symptoms
Wednesday, November 20, 1996
No class next week independent reading assignment on the adrenal cortex this is the
Wednesday after Thanksgiving
Quiz for Diabetes is from the lecture only this will be the final
Showed an overhead of Thyroid condition often hidden
This article was a good example of the nondescript nature of the disorder
JAMA found that it is cost effective to do thyroid screenings on women over 40
People don’t feel well and gets very tired
With respect to incidences of endocrine diseases another is diseases of the thyroid
diabetes research into diabetes falls under many different areas
Diabetes Mellitus is a truely heterogenious disorder primary disoreder of carbohydrate
metabolism with multiple etiologic factors that generally involve absolute or relative
insulin defic. or insulin resistance
In general diabetics have an insulin problem absolute or relative insulin defic
relative not enough insulin activity
The cause of diabetes Mellitus in individuals is unknown
Epidemiology the incidence is 600,000 cases a year
The prevalence is 2.53.5 million people he was guessing
The incidence is the number of cases that occur in a population in a year
the prevalence is the number of people with in a years time that have this disorder
With a cold the incidence can be higher than the prevalence
With diabetes it is difficult to determine how many people have diabetes
Part of the confusion of diabetes is who has it and who does not
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What clinical findings must be present before you tell the patient they have Diabetes
In the past there have been a number of criteria in which people were diagnosed
Typically use a glucose tolerance test to make this determination there are problems
with the test there are 2 different systems
OGTT is a fasting test the rational for this is that it is a challenge to determine how it
metabolizes a concentration of glucose prior tho that the glucose level is measured 30
minutes, 1 hr, 2 hr, 3 hr they are then plotted against the time versus glucose this is the
glucose tolerance curve
Method A might get
Method B might get negative using the same numbers
difficult for everyone to agree who has diabetes Method A or B and a third method the
good news is we don’t use any of these anymore we now use very straight forward valid
criteria to establish who does and does not have diabetes
almost no one who has diabetes almost no false positives or negatives now
Dx criteria there are three criteria only takes one to make the diagnosis: 1. Gross and
equivocal glucose elevation
if we use a normal value among people who don’t normally have diabetes we find
almost all diabetics having a fasting glucose less than 115, and nonfasting less than 200
If have a value of 600 2 ways this can occur Diabetes for one, and the other way is an
intravenous infusion
glucose is 600 the first thing we are going to do is to retest or confirm this have the
patient come back fasting and perform a fasting glucose if that fasting glucose is greater
than 140 that person is a diabetic
How can we be certain with only one number 95% of people 80115, 98% 70125, and
99.9 60120; there is almost no overlap in these numbers and this is how we can be
certain
2. Fasting > 140 mg/dl, on more than one occasion make sure this is not a mistake
Fasting glucose of 130 and a random sampling 275
3. OGTT 30 min, 1 0r 2 hour > 200 this is the patient I would perform the glucose
tolerance test on
With a value of 350 no need to do a glucose tolerance test because the disorder is clear
Patient comes in complaining of fallen off bike and they have a compound open fracture
would you take an Xray to make this clincal descision
why take the Xray if you can see that it is broken
In our career we will prob never need to take an a glucose tolerance test
When you do this 20% of the people throw up like take a 12 oz can of pepsi and pour
1/2 cup of sugar in it and drink it
Second Hour
80115 Normal
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75 > hypo
< 50 > hypo (clinical consequences)
Patient Trembly, Anxious, Shakey, Sweaty, Nervous, Heart Palpitations
Many times food ingestion the doctors in the 80’s said just eating something when in
fact eating caused these problems
hypertension have to know blood pressure to correctly identify having anemia
anemia Hct or RBC or Hgb
moron IQ
all of the above conditions have a criteria
Hypoglycemia need to know blood glucose
In the last 4 or 5 years we have been taught that an oral glucose tolerance test is worse
than worthless in hypoglycemia in that it gives you bad information
What is required to appropriately tell someone that they are suffering from hypoglycemia
must demonstrate Whipples Triad 1.S/S of decreased glucose 2. decreased glucose 3.
Loss of s/s, and normalization of the glucose then this person has hypoglycemia
Do the test and you find that it is 45 milligrams give them a banana and the blood
glucose goes up to 85 this was the easy part the tough part is to find out why it is
occuring
Next week we will discuss a variety of symptoms
The physiological threshold for glucose is 1525 the person can go into a coma and die
due to CNS depression due to lack of glucose
physical fitness is the ability to run a 26 miles marothon a good way to define physical
fitness
Could you in 3 months get in good enough shape to be able to do this
the same phenomenon for glucose tolerance test you have to prepare the patient
particularly for diabetics
3 days before Random 215 and Fasting 130 This is when you need to use a glucose
tolerance test
2000 calories, 200 grams of carbohydrate, patient should have a normal activity they
should not be chair bound but mobile, the forth one is that they should not be sick, they
should be under 60
You may not have typical ambulatory patients meaning a seditary life style may not have
a noraml glucose tolerance test
Next time we meet after our exam
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Wednesday, December 04, 1996
Oral glucose tolerance test
When an oral glucoese tolerance test is employed, it must be rigoursly controlled
Standard oral glucose dose (75 to 100 gm)
appropriate antecedent dkdkdk
Type I Insulin dependent, Juvenile onset, ketosis prone, brittle diabetes
These pateints have little or no endogenous insulin secretory capacity and develop
extreme hyperglycemia, ketosis, and associated symptomatology, unless treated with
exogenous insulin. This type, usually, but not always develops prior to early childhood.
These people are very prone to ketoacidosis if we look at all diabetics about 10% of
diabetes is type I, about 90% is type II
Islet Cell transplants have been going on for about 5 years, not talked about yet because
not univeral and the successful ones have only been off insulin for around a year.
What is the etiology of type I with human genome project they find particlualar genes
for diseases, one of the first genes they found was for the disease diabetes
Problem with calling it a genetic disease despite the fact that diabetes aggregates in
families and has a strong familial component, a precise genetic contribution to Diabetes
has been difficult to find.
1. NO specific genetic marker has been identified in all cases
2. There is a great amount of etiologic heterogenity btw Type I and II
3. “Diabetogenic” gene interaction with external factors
4. The actual transmission rate from generation to generation are low.
Twin studies < 40 Type I 50%
>40 Type II 100%
Transmission rates: 1 Type I parent > 25%
1 Type II parent > 1015%
HLA studies HLA BB 24X; HLA DR3 410 X; HLA DR4 410X
However, 3540% of the population get from Amy
Look up Penitance
and in some but not all patients there is altered cellular immunity in type I
Pathogenesis of Type I Diabetes
Autoimmune Disease
Get these overheads from Saunders
Talked about viruses and its role with diabetes
The cause and etiology of diabetes is unknown
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Genetic virus immunity
some people have a gentic predisposition that may tolerate a viurs infection might set up
an autoimmune response these antibodies may cross react with there own Beta cells
problem with this is we can’t always find the perfect genetics and the environment in
some individuals with diabetes
Clincial presentation of Type I these people have little to no endogenous and usually
present with abrupt clincial symptoms of polyuria, polydopsia, and poluphagia
weight loss, fatique and infections are common
ketosis or ketoacidosis
Type II diabetes Known as adult onset Non insulin depenedent, Adult onset,
Nonketotic, Stable diabetes
These patients retain significant endogenous insulin secretory capacity. Athough
treatment with insulin
Diabetics can develop gangrene
Diabetes is a disease of blood vessels and nerves
Complications why do they come about acute and chronic if can’t cure it supportive
care, acute ketoacidosis can die in as little as 24 hours
the acute complications of diabetes can occur in 2448 hours
the chronic complications 320 years for these to develop if we are treating acute
symptomatology
Chronic complications neurological the most common chronic disabling complication
is neurologic people don’t die from diabetic neuropathies but they prob have the greatest
impact on activities of daily living
People die of the vascular complications of diabetes renal failure, and cardiovascular
these are all vascular related disorders arteriosclerosis in the eye we can it retinopahty,
kidney nephropathy the bottom line is that diabetes is a disease of blood vessels and
nerves
Why do diabetics have renal failure the efferent and afferent arterioles the
cardiovascular, the lumenal narrowing the hyperlipidemia
What can we do for these diabetics within the last 25 years the chronic complications
that occur can be minimized by controling the glucose levels
The role of elevated lipds and atherosclerosis
We can help them with maintainance of a healthy life style
When adjusting these patients you need to monitor there glucose
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