endocrinology exam i.doc

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Endocrinology First DayWednesday, September 04, 1996

Polyuria is a symptom that the patient may not be aware of, anemia is another examplethe above situations are of symptomatic patients that are unaware of itactual 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 cortisolmay have an ectopic tumor (or) a hyperplastic over adrenal production

Cushings Syndrome is elevated cortisolcan be caused by an atopic ACTH tumormost common is the exogenous use of corticosteroids

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 activities1 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 amountsare controlled by targetingare very premisquous

Monday, September 16, 1996 - afternoon hour


Determination of baseline values

BASELINESlets 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 rangeRBC degradation of hemoglobin produces bilirubin if production exceeds elimination then the value goes up, we measure the net effecthuge 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 degradeinterpret 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 anemicsome diseases have histologic criteria for acute and chronic distinctionssometimes we use different antibody types to stage a diseaseprodromal 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)


Endo Exam Reading for first exam Chapter 199 page 11761185Hormone ActivityHormone Concentration

the more hormone that you have the more biological activity we may expect from this hormone

Innate Mechanism of endocrine activitythere is a homeostatic relationship btw the body and the hormone levels

Receptors in relation to hormone concentrationwo receptor there is no hormone activity

Ligand - a substance that interacts with a receptor with hihg specificity receptor is within the cell membrane


Thyroid Gland produces T4the 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 senariowhen the receptors on a particular organ all become bound with hormone aprocess called down regulation occcurs in which the number of receptor sites on the organ is diminished is a rapid process - occurs in nanosecondsthere 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 diseaseexample of why signs and symptoms of disease are a poor indicator of disease

Peptide Hormone

1. Cell Surface Receptor2. “Second Messanger”3. Biological Amplification4. 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 a form of negative feedback systemCoffee 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 cAMPIn 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 autoantibodythese 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 intracellulartend to modulate sythesis by turning genes on and off activates receptor and brings about a conformational change for that hormonethis dictates where it is and what gene is going to turn on very specific one protein gene message into mRNA and then translate into proteinthe steroid hormone goes to a particular genedifficult to mimic steroid hormone


The next quiz will cover “The Anterior Pituitary”

Biorhythms rthythmsin the release of hormones are common in almost all endocrine systemscan occur over:testosterone - minutes to hourscortisol - daily estrogen -weeksthyroid - months- seasonal changes

Biorthyms


1. Hormonal Rthymicity Due To:

1. Neurogenic factors sleep assoc. w/ (cortisol)2. Environmental factors3. 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 densitometerthe densitometer spike in the gamma region is called the Mspike - stands for myelomaissue that has gone wrong is the plasma cell called a plasma cell dyscrasia,aka - Light Chain Disease

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 hydroxylaseif the person has kidney disease we find drop offs in this enzyme and falling vit. D levelsthe 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

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 bodyinitially we were not able to measure the products of the hypothalamus so people use to think it was the pituitary

Pituitary GlandIts products control a lot of other glands.Target glands of the pit. hormones:

TSH the clinical result is hypothyroidismpat. presents clinically as hypo this is a secondary formthe primary defect is seconday to a pit dysfunction

Review of the pit hormones:1. ACTH (corticotropin) 2. Growth hormone3. Prolactin4. Thyrotropin (TSH) 5. Follicle Stimulating hormone (FSH) 6. Lutenizing Hormone(LH)

ACTH - Corticotropinproduced by the pit.cheif target for this is the adrenal glandsbinds to cell surfaces and uses cAMP ( so we know it is a classic peptide hormone)

stimulates lipolysis in fat cellsamino acid and glucose uptake in musclesecretion of growth hormoneinsulin secretion, these actions are not significant at normal levels (?)

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 achesinsulin 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 productionACTH levels seem to be highest in the morning and lowest in the eveningabnormal means different from everyone else - but does not mean is clinically significant

ACTHstimulated 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 levelsuremiabeta adrenergic antagonistsalpha adrenergic agonistsStress (traumatic, surgical, infection)hyporglycemia (fasting)hepatic cirrhosis vasopressinestrogensglucagon (seen in hypoglycemic states)

f.u.- b.a.s.h.h.- v.e.g

GH is inhibited by:emotional deprivationalpha adrengeric antagonist (opp. of above)beta adrenergic agonist (opp. of above)hyperglycemia


increasing fatty acid levels (opp. of above)obesitysomatotropincortisol (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 effecti.e. inverse relationhip btw. glucose & GH

Age related decline in growth hormone normalGH def. in an adult clinical significance of not clear

coronary heart diseasebest way to test for is a stress testanother way is through glycolytic stressesin normal individual - induce hyperglycemia there GH levels should drop

thyrotropin synthesis in the thryrotophic cellsfound 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 productionstimulation of the ductal epithelium of the mammary tissueat delivery estrogen levels drop thereby removing the inhibition of prolactin by estrogenHigh levels of estrogen during pregnancy inhibits prolactin

Lutenizing Hormone (LH) acts on Lidig cells to produce testosteronethis hormone is controlled by GRH (Gonadotropin releasing Hormone)Look up FSH (Follicle Stimulating Hormone)

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. The extent of hormone deficiency A, B, C3. Duration & rapidity of the onset4. Age a 50% reduction in GH more recognizable in a 12 year old than a 50 year old5. Gender

Thyroid function panel - the best way to evaluate is the thyroid disease

Endocrinology reading for the quiz on next Wednesday 1206 - 1221


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

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



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 Hyperprolactinemia1. Clinical features2. Elecated Prolactin levels 15 to 20 ng/ml to 10,000 ng/ml3. Prolactin levels less than 200 ng/ml are almost never of tumor origin

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 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 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



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 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 = 10T3 5T7 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 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 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



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

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



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 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 certain2. 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 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

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 cases2. There is a great amount of etiologic heterogenity btw Type I and II3. “Diabetogenic” gene interaction with external factors4. 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

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and in some but not all patients there is altered cellular immunity in type I

Pathogenesis of Type I Diabetes

Autoimmune DiseaseGet these overheads from Saunders Talked about viruses and its role with diabetes The cause and etiology of diabetes is unknown 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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