endocrinology 02012012

8/2/2019 Endocrinology 02012012

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List all the hormones secretedby the anterior pituitary

"My FLAT PiG"

MSH - melanotropinFSH - stimulates sex organsLH - stimulates sex organs

ACTH - adrenal growth and steroidogenesisProlactin - stimulates lactation

GH - stimulates somatic growth via IGF-1and is counter-regulatory to insulin

Which hormones in theAnterior pituitary are

produced by the basophils?

B FLAT

Basophils produce FSH, LH, ACTH, TSH

These hormones have a common alphasubunit. The beta subunit determines

specificity.

Which hormones in theAnterior pituitary are

produced by the acidophils?

GPA

GH, Prolactin are producedby Acidophils

List 6 signs and symptoms ofa prolactinoma

Impotence

Amenorrhea (Prolactin inhibitsGnRH)

Gynecomastia (male breasts),

Galactorrhea (abnormal milkproduction)

Headache

Bitemporal hemianopsia (loss ofperipheral vision)

General hypopituitary symptoms(if "mass effect" is present)

List a common clinicalcorrelation that can mimic a

prolactinoma

Dopamine antagonists (ex: antipsychotics)cause galactorrhea, amenorrhea, impotence,

etc due to loss of dopamine inhibition onprolactin

tudyBlue Flashcard Printing of Endocrinology http://www.studyblue.com/servlet/printFlashcardDeck?deck

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What is the treatment for aprolactinoma?

First line: Bromocriptine or cabergoline(dopamine agonists)

Second line: Transsphenoidal surgicalresection for large tumors

NOTE: Bromocriptine can also be used inthe treatment of Parkinson's disease.

What classic sign/symptom is this patient mostlikely experiencing?

Bitemporal hemianopsia (loss ofperipheral vision)

You must do a visual field test (during thePE) on a patient with signs or symptoms

of a prolactinoma!

Other sx: amenorrhea, gynecomastia,

galactorrhea, etc.

Compare and contrastAcromegaly and Gigantism

Both are caused by pituitary adenoma thatsecretes growth hormone

GH secretion in childhood prior to skeletalepiphyseal closure = Gigantism

Lengthening of long bones

GH secretion in adulthood after

epiphyseal closure = AcromegalyThickening of bones

List 6 clinical signs and sx ofAcromegaly

Coarsening of skin/facialfeatures

Thickening hands and feet

Prognathism (an overbite orunderbite)

Large tongue with deep furrows

Deep voice

Peripheral neuropathies due tonerve compression

List three treatments for apituitary adenoma that secretes

growth hormone

1) Surgery or radiation2) Octreotide: somatostatin analogue that

inhibits GH release from the anteriorpituitary


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3) Pegvisomant: GH receptor antagonistblocking the production of IGF-1


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List the hormones involved in thehypothalamic pituitary axis and theirrelationships (inhibition/stimulation)

TRH --(+)--> TSH, ProlactinCRH ---(+)--> ACTH, MSH

Dopamine --(-)--> ProlactinGHRH ---(+)--> GH

Somatostatin ---(-)--> GH, TSH

GnRH ---(+)--> FSH LH


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List three normal reasons foran increase in GH

Stress1.

Exercise2.

Hypoglycemia3.

Ingesting glucose should cause adecrease in IGF-1, if it doesn't,

you dx GH secreting tumor

List two physiologic controlsthat cause and increase in

AVP secretion

1) An increase in serum osmolality is sensedby osmoreceptors in hypothalamus whichrelease AVP into the systemic circulation

2) Baroreceptors sense a decrease in bloodvolume (5-10%) and afferent inputs to the

hypothalamus for more ADH

What are the signs andsymptoms of diabetes

insipidus?

Intense thirst and polyuria (over 3L/24hrs),together with an inability to concentrate urine

Serum osmolarity is high (>290 mOsm/L),urine osmolarity is very low (


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What is the treatment fornephrogenic diabetes

insipidus?

Adequate hydration, hydrochlorothiazide*,indomethacin, or amiloride

*Thiazides increase renal Na excretion ECF volume contraction GFR

proximal tubular reabsorption of water and

Na less water and Na are lost as urine

What is the Syndrome ofInappropriate Antidiuretic

Hormone and what are thecauses?

SIAHDoccurs when too much ADH isproduced by the posterior pituitary (tumor), a

lung tumor, or a lung infection.

Medications such as chlorpropamide canalso cause inappropriate ADH secretion

List 5 signs andsymptoms of SIADH?

Euvolemic hyponatremia - (Body respondsby decreasing Aldo/Na reabsorption...

bringing in free water and dumping Na)

Abnormal mental status

Convulsions

Fatigue

Headache

Irritability

Normal blood pressure, no

edema, etcUrine osmolarity will usually be be

higher than serum osmolarity

Name threetreatments for SIADH

1) Free water restriction if asymptomatic2) Demeclocycline: inhibits the actions of

ADH in the kidney.3) Hypertonic (5%) saline if severe CNS

changes, such as seizures

CAUTION: Rapid correction of hyponatremia

can lead to central pontine myelinolysis

Discuss central pontinemyelinolysis and its cause

Rapid correction of hyponatremia can lead tocentral pontine myelinolysis

Damage of myelin sheath of pons patientbecomes "locked in": muscles paralyzed with

exception of eye blinking, but cognitive


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function is intact


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What are thefunctions of

oxytocin?

During labor: stimulates cervical,vaginal distention and uterus

contraction

Used clinically for: acutepostpartum hemorrhage and

to induce labor

After labor: in the presence ofoxytocin, nipple stimulation will "let

down" breast milk

What are 3 adverseeffects of oxytocin?

1) Hyponatremia2) Seizures

3) Subarachnoid hemorrhage

Name the types of vitamin Dand their sources

Vitamin D3 (cholecalciferol) - Sunlight/Skinand MILK!!

Vitamin D2 (ergocalciferol) - Diet

Breast milk is relatively vitamin DDEFICIENT! It is important to supplementthis vitamin, especially in darker skinned

newborns

Explain how vitaminD is activated

Vitamin D3 (skin) and Vitamin D2 (diet) 25OH vitamin D (in liver) ----> 1,25 OH2vitamin D (via 1-hydroxylasein kidney)

Macrophages can also convert vitamin D toit's active 1,25 OH2 form (cause of

hypercalcemia in sacroidosis)

List the four effects of Vitamin

D on Ca2+ and Phosphate

Increase in both [Ca2+] and [phosphate]

Increase intestinal Ca2+absorption via (calbindin-D-28K)

Increase intestinal phosphateabsorption

Increase renal Ca2+ andphosphate reabsorption


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Increase bone resorption of Ca2+

and phosphate


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Name 4 factors that regulate1-hydroxylase and their

effect on this enzyme.

serum calcium, serum phosphate, PTHlevels --- All INCREASE activity (more D)

1,25-OH2 vitamin D inhibits its ownproduction by inhibiting 1-hydroxylase.

Note: High phosphate from CKD inhibits1-hydroxylase

How does PTH effect bones?(describe the biochemistry)

Binding of PTH to its receptor on osteoblasts osteoblasts secrete M-CSF and RANK-L,which stimulate osteoclasts to break down

bone and release calcium.

Describe the mechanism ofPaget's Disease and a

possible underlying cause

Massive bone turnover due to osteoclasticand osteoblastic activity abnormal bone

architecture

May be caused by a slow virus infection (eg,paramyxoviruses such as measles or

respiratory syncytial virus).

List the three phases ofPaget's Disease

1. Hypervascular/Osteolyticphase

2. Intermediate phase3. Quiescent phase

List the three stages of boneactivity in thehypervascular/ostolytic phase

of Paget's disease.

Excessive in osteoclastic activity shaggy lytic bone lesions.

1.

Massive osteoblastic response (alkaline phosphatase) production of woven "mosaic

bone" that is weak (radiolucent),thick and highly vascular

2.

Mosaic bone is replaced areas ofhighly cellular lamellar bone with

irregular "cement lines"

3.


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Describe the bones activity inthe intermediate stage of

paget's disease

Osteoclastic activity is stillpresent, but osteoblastic

activity predominates

Descrive the activity andphysical features of bone

during the Quiescent phase ofPaget's disease

osteoblastic activity eventuallydeclines

Sclerotic bone:- enlarged/widened bones

- absent Haversian systems- marrow spaces replaced by

vascular fibrous tissue

List the signs and symptomsof Paget's disease. List at

least 4 key symptoms.

Enlarged/widened bones that are weak:

Skull headaches; hat size;hearing loss (if ear canal

involvement)

Weight bearing bones bonepain especially at night,

pathologic fractures

What are the 2 potentialcomplications of Paget's

disease

Pagetoid bone is highly vascular with

extensive arteriovenous shunting that maysignificantly blood flow cardiac output compensatory left ventricular hypertrophy

and, in severe cases, high-output heartfailure.

Small risk of developing into osteogenicsarcoma

What are the characteristiclab findings of Paget'sdisease

Serum levels:

- normal calcium, phosphate,parathyroid hormone

- alkaline phosphatase


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What is the treatment forPaget's disease?

Bisphosphonates (eg,alendronate, pamidronate,

etidronate) are first-line

agents

What is the mechanism forPrimary Osteoporosis Type I

(Postmenopausal)

Estrogen deficiency increased activity ofRANKL/RANK and therefore osteoclasts

1. Osteoclast activity (bone resorption)2. Osteoblast activity (bone formation

compensates but unable to keep up withosteoclast activity)

Name 5 classic characteristics of 22q11.2Deletion Syndrome (aka DiGeorge

Syndrome or velocardiofacial syndrome)

CATCH-22: microdeletion of central portionof chromosome 22

Cardiac defectsAbnormal facial features

Thymic aplasia - leads to T cell malfunctionCleft palate

Hypocalcemia: due to hypoparathyroidism22

List 5 common causes ofvitamin D deficiency

Vitamin D deficient diets (mostcommon)

1.

GI malabsorption of fat-solublevitamins

1.

Renal osteodystrophy: chronicrenal failure 1--hydroxylase

activity

2.

Aluminum-containing phosphate-binding antacids (mechanism?)

3.

Phenytoin (seizure drug)4.

Obesity (D is trapped by fat!)5.

What are the two types ofricketts? What are the

common lab findings forboth?

Calcepenic rickets (most common)Serum levels: Calcium

Phosphate Parathyroid hormone (PTH)

Alkaline Phosphatase


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Phosphopenic rickets (rare): low Phos,normal PTH, Calcium, and Vit D


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What is the commonmechanism for Rickets and

Osteomalacia?`

Vitamin D Deficiency leads to decreasedCa increased PTH levels decreasingphosphate, and mineralization of newlyformed bone matrix (osteoid) Rickets

(children) & osteomalacia (adults)

Qualitative defects in bone formation versus a quantitative defect like osteoporosis

List the clinical findingsspecific to Rickets (i.e., not

found Osteomalacia)

Failure of mineralization leads to changes inthe growth plate (increased width and

disorientation) and bone (cortical thinning,bowing)

Genus varus

Rachitic "rosary chest": bonyprominence at costochondral

junctions

Harrison's sulci: indentations inlower ribs

Craniotabes: softening of skullbones

Growth retardation

What is the correct term for this condition?What disease causes this?

Genus varus inRickets

What are thesymptoms of

osteomalacia?

Diffuse bone pain, which is distinctly differentfrom osteoporosis, which is painless, unlessthere is a fracture.


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What are the two types ofparathyroid cells and what are

their functions?

Chief cells: produceparathyroid hormone (PTH)

Oxyphil cells: function is

unknown


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List the 4 actions ofParathyrdoid Hormone and

the overall result.

serum Ca2+and serum Phos

1) bone resorption of calcium andphosphate

2) PTH stimulates 1-hydroxylase in thekidney increased 1,25-(OH)2 vitamin D

production leading to intestinal absorption

of Ca2+

3) renal Ca2+ absorption ( urinary cAMP)4) kidney reabsorption of phosphate

Explain how PTH is regulated

by serum Ca2+ and Mg2+

free serum Ca2+ causes PTH

secretion. Ca2+-sensing receptors on chief

cells mediate these effects.

Mild decreases in Mg2+

stimulate PTH

secretion, while severe decreases in Mg2+

inhibit PTH secretion and produce symptomsof hypoparathyroidism.

What are common causes ofmagnesium deficiency?

Common causes of

Mg2+: diarrhea,aminoglycosides,

diuretics, and alcoholabuse

What are 5 signs andsymptoms of hypercalcemia?

"Stones, bones and groans"

1) Mental status changes2) Kidney (stones)

3) Muscle weakness4) Cardiac Arrythmias

5) Constipation (groans)6) Osteitis fibrosa cystica - cystic bone filled

with brown fiberous tissue, causes (bone) pin

What are the three primarycauses for primary

hyperparathyroidism?

Single benign adenoma: majorityof cases

Hyperplasia of parathyroid glands:rare incidence

MEN (multiple endocrineneoplasia) I and IIA


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List the three most common causes ofsecondary hyperparathyroidism. What do

they all have in common?

Occurs when parathyroid glands arechronically stimulated by hypocalcemia to

release PTH

Chronic renal failure: decreasesCa absorption and decreased

hydroxylation of Vit D

GI Malabsorptive disorderRickets

List the primary cause oftertiary primary

Long standing hyperparathyroidism, usuallydue to chronic renal failure, progresses into

autonomous hypersecretion of PTH evenafter correction of chronic hypocalcemia

What are the lab values forprimary hyperparathyroidism

Calcium: HighPTH: High (or inappropriately normal)

Serum phosphate: lowUrine phosphate: high

Urine cAMP: high

If the PTH is normal consider Vit Dtoxicity,sarcoidosis, thiazidediuretics, milk-alkali

syndrome is a possible cause for thehypercalcemia

What are 5 pertinent labfindings for secondaryhyperparathyroidism

Calcium: LOW (this is the cause!)

PTH: HighSerum phosphate: low, normal, or highdepending on kidney function

Urine phosphate: low, normal, or highdepending on kidney function

Alk phosphatase: high

P will be low hypocalcemia is due to a GIproblem, and high if due to CKD

What cells produce calcitoninand what is its function?

Parafollicular cells (C cells) of thyroidproduce calcitonin

Calcitonin is released due to increasedserum calcium. It serves to decrease boneresorption of calcium, therefore decreasing

serum Ca

This hormone opposes PTHNot normally important in Ca homeostasis


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What are 4 classic signs andsx of hypocalcemia

1) Tetany2) Carpal-pedal spasms (Trousseau's sign)

3) Prolonged QT interval4) Parasthesias (numbness and tingling of

extremities)

What is the cause of VitaminD dependent Rickets Type 2

NOT ON BOARDS (1/5/12)- A mutation in the vitamin D receptor (on

liver? kidney?)- Commonly associated with allopecia

What is the cause of VitaminD dependent Rickets Type 1

NOT ON BOARDS (1/5/12)- A mutation in the alpha 1

hydroxylase enzyme

Type 1 = alpha 1

What are the 4 characteristiclab findings of

hypoparathyroidism

- Low serum calcium- High serum phosphate

- Low serum Vit D- Low PTH

What are 3 classic signs andsx of hypoparathyroidism?

Hypocalcemic symptoms:

tetany, neuromuscularirritability, carpal-pedalspasms


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Describe the mutation responsible forPseudo-hypoparathyroidism and three

classic features of this disease. How is thismutation inherited?

Autosomal dominant kidneyunresponsiveness to PTH

Classic sign: Shortened metacarpals 4th and5th digits, hypocalcemia, short stature

Pseudohypoparathyroidism is caused by afault in the G protein receptor signaling

pathway in the kidney leading to decreasedurinary cAMP levels

What are the two PE signsthat indicate

hypoparathyroidism

Chvostek's sign: tapping the facial nerve -->elicit spasm of facial muscles

Trousseau's sign: cut off blood flow to distalarm with BP cuff --> carpal spasm

List all five layers of theadrenal gland and the

hormones they make (ifapplicable)

1) CapsuleCortex

2) Zona Glomerulosa --> MineralocorticoidAldosterone (salt)

3) Zona Fasiculata --> GlucocorticoidCotrisol (sugar) and sex hormones

4) Zona Reticularis --> Sex hormones (sex)5) Medulla --> Catecholamines (Epi &

Norepi)

List the primary regulatorycontrol for the three layers of

the adrenal cortex

1) ACTH, Renin-Angiotensin, Potassium --->Zona Glomerulosa

2) ACTH (from CRH) --> Zona Fasiculata3) ACTH (from CRH) --> Zona Reticularis

List the primary regulatorycontrol for the adrenalmedulla

Preganglionic sympatheticfibers to the chromaffin cellsin the medulla


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Explain the mechanismbehind the hyperplasia, in

congenital adrenal

hyperplasia

All congenital adrenal enzyme deficienciesare characterized by enlargement of the

adrenal glands due to an increase in ACTHstimulation (due to the decreased levels of

cortisol)

Describe the pathophysiologybehind 17 alpha hydroxylase

deficiency

A congenital adrenal hyperplasia that resultsin the inability of pregnenalone and

progesterone to convert to17-hydroxypregnenalone (percursor to

cortisol and sex hormones)

Leads to increased aldosterone (back-up)and decreased cortisol and sex hormones

Describe the classic signsand sx of 17 alpha

hydroxylase deficiency

1) Hypertension (too much aldo/Na)2) Males become pseudohermaphroditic due

to low levels of testosterone3) Females will have normal genital

development, but will not have enoughestrogen to develop secondary sex

characteristics

Describe the pathophysiologybehind 21-hydroxylase

deficiency

MOST COMMON congenital adrenal

hyperplasia that results in the inability ofProgesterone and 17-Hydroxyprednisone toconvert into 11-deoxycorticosterone and 11

deoxycortisol, respectively.

Leads to decreased levels of aldo andcortisol, respectively, and an increase in sex

hormones

Describe the classic signsand sx of 21-hydroxylasedeficiency

1) Hypotension (low aldo)2) Masculinization/female

pseudohermaphroditism (clitoromegaly)3) Hyperkalemia (low aldo)

4) Volume depletion due to salt wasting -->can lead to hypovolemic shock in newborns

5) Increased serum renin (due to volumedepletion) with low serum aldo


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Describe the venous drainageof adrenal gland

Left adrenal gland drainage: left adrenal vein--> left renal vein --> inferior vena cava

Right adrenal gland drainage: right adrenalvein --> inferior vena cava

Describe the pathophysiologyof Pheochromocytoma

Neuroendocrine tumor of adrenal medullachromaffin cells (arise from neural crest

cells) that secretes catecholamine (norepi,epi, and dopamine) into the blood stream

Most common tumor of the adrenal medullain adults. Associated with MEN 2A and 2B.

List the five episodichyperadrenergic symptoms of

pheochromocytoma

The 5 P's of Pheo

Elevated blood PressurePain (headache)

PerspirationPalpitations

Pallor

Symptoms occur in spells (unknownmechanism)

What is the treatment forpheochromocytoma?

Alpha antagonists: phenoxybenzamine(non-selective and irreversible)

Followed by surgery to remove the tumor

What are the typical lab

findings ofpheochromocytoma? Name 4

(three are UA results)

1) Elevated plasma catecholaminesElevated urinary biproducts of the

catecholamines- Dopamine --> HVA

- Norepi --> VMA- Epinepherine --> metanepherines


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What its the "rule of tens" forpheochromocytoma

10% malignant10% bilateral

10% extra-adrenal10% familial (Men 2A or 2B)

10% calcify10% kids

Describe the pathophysiologyof Neuroblastoma

Neuroendocrine tumor derived from neuralcrest cells. Most often found in adrenal

medulla but can also be found anywherealong sympathetic chain.

Causes elevation in catecholamines andurinary HVA

Most common extracranial solid cancer ininfancy

What 4 complications/clinicalsymptoms are associated

with neuroblastoma.

1) Spinal cord compression2) Weakness

3) Bone lesions4) Swollen neck and abdomen

** Hypertension is uncommon!**

What are the 2 lab findings ofNeuroblastoma? What is the

clinical significance of thesecond?

1) Homovanillic acid (HVA) a breakdownproduct of dopamine is found in urine

2) Overexpression of N-myconcogene isassociated with rapid tumor progression

Waterhouse-Friderichsen syndrome

Acute adrenocortical insufficiency associatedwith meningococcal septicemia

Massive hemorrhage within adrenal glandsleads to hypotension and shock, with

widespread purpura.


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What is the pathophysiology of thisdiagnosis?


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Describe the pathophysiologyof Primary Addison's disease

and 6 common causes.

Adrenal Atrophy or destruction leading toabsence of hormone production in all 3

cortical divisions. Caused by:1) Autoimmune

2) TB granuloma3) Infarction of adrenal gland

4) HIV

5) Waterhouse-Friderichsen syndrome6) DIC (disseminated intravascularcoagulation)

What are the classic signsand symptoms of Primary

Adrenocortical Insufficiency(Addison's)

1) Hyponatremic volume contraction2) Hyperkalemia

3) Constipation, diarrhea, fatigue4) Skin hyperpigmentation*

*ACTH is high, trying to make more cortisol.Melanocyte-stimulating hormone MSH

shares the same precursor molecule asACTH

List three ways to diagnosePrimary Addison's

1) Hyperpigmentation2) Abnormal cosyntropin (synthetic ACTH)

stimulation test: subnormal response ofplasma cortisol following cosyntropin is

definitive and diagnostic of adrenocorticalinsufficiency

3) Abnormal metyrapone test: ACTH, butno in 11-deoxycortisol

What is the treatment ofAddison's disease?

1) Fluid replacement for hypovolemin shock2) IV dexamethasone

3) Eventual syntheic mineralocorticoidreplacement

What is the pathophysiology of SecondaryAdrenocortical Insufficiency and name three

things that distinguish it from primarydisease.

Decreased production of pituitary ACTH

Secondary Adrenocortical Insufficiency is notassociated by hyperpigmentation (no MSH)

If given cosyntropin (synthetic ACTH),cortisol will rise appropriately


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List the 5 functions of Cortisol(BBIIG)

1) Upregulates alpha 1 receptors to maintainBlood pressure

2) Decreased Bone formation (inhibits

osteoblasts and GI Ca2+

absorption)3) Anti-Inflammatory

4) Decreases Immune function (inhibition ofPLA2 IL-2 via lipocortin)

5) Increases nutrient catabolism(Gluconeogenisis)

List the 3 steps leading tocortisol production and how it

is regulated

1) Paraventricular nucleiof the hypothalamusrelease CRH

2) CRH stimulates corticotrophs in anteriorpituitary to synthesize POMC --> ACTH and

MSH3) ACTH increases steroid hormone

synthesis in the adrenal cortex by activatingcholesterol desmolase

4) Cortisol inhibits the release of CRH

Explain the three results of aDexamethasone suppressiontest and what they indicate

1) Low dose causes suppression of ACTH:Normal

2) ACTH is still produced after low dosedexamethasone: Cushing's disease (pituitary

adenoma)3) ACTH is still produced after high dose

dexamethasone: Ectopic ACTH producingtumor

List the three actions (and thelocation of action) of

Mineralocoritoids(Aldosterone)

Late distal tubule/collecting duct

1) renal Na+

reabsorption by principalcells

2) renal K+ secretion by principal cellscells

3) renal H+ secretion bu -intercalatedcells

Excess aldo = hypokalemia and metabolicalkolosis are common, hypernaremia is rare!

List three factors that regulatealdosterone secretion

Aldosterone is under tonic control by ACTH,but is separately regulated by the renin-

angiotensin-aldo system and by

potassium

Hyperkalemia & low BP will cause andincrease in aldo secretion

Angiotensin II increases the activity ofaldosterone synthase in the zona

glomerulosa


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What is renalosteodystrophy?

Bone lesions (osteoclastic resorption ofcortical bone subperiosteal thinning with

cystic degeneration, may or may not be"brown") due to primary or tertiarty

hyperarathyroidism caused by chronic kidneyfaliure

What is the pathophysiologyof renal osteodystrophy

Chronic renal failure activity of1--hydroxylase 1,25-(OH)-vitamin D

absorption of calcium from the gut hypocalemia production of parathyroidhormone (PTH) osteoclastic resorption

of cortical bone subperiosteal thinning withcystic degeneration cystic bone

lesions/tumors

What are three charateristicsof Osteitis Fibrosa Cystica

and what is the cause?

1) osteoclastic resorption of calcified bone2) Peritrabecular fibrosis

3) Cystic "brown tumors" in bone

Caused by prolonged, severehyperparathyroidism (Primary, secondary, or

tertiary)

Describe the pathophysiologyof Primary

Hyperaldosteronism (Conn'sDisease)

A single benign adrenal tumor (adenoma) or

bilateral hyperplasia of the adrenal glandsresult in overproduction of aldosterone

Elevated aldosterone levels Mildhypertension (due to Na/H2O retention),

hypokalemia (K dumping), metabolicalkalosis due to cell exchange of H for K.

NO hypernatremia!

What are 2 classic signs ofhypokalemia?

1) Muscle weakness

2) Cardiac changes visible onEKG (classically described as

U-waves)


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How is primaryhyperaldosteronism

diagnosed? (what do the labs

look like)

High aldosterone suppresses the secretion ofrenin. In primary hyperaldosteronism, low

levels of renin are seen.

By contrast, a high renin level suggestssecondary hyperaldosteronism as in

reno-vascular hypertension (due to RAS,CHF, chronic renal failure, etc)

What are 2 treatments forprimary hyperaldosteronism?

1) Surgery2) Spirinolactone to block thealdo being produced by the

tumor

What is the cause and effectof Secondary

Hyperaldosteronism. How is itdiagnosed?

CHF cirrhosis, chronic renal failure, nephroticsyndrome, and renal artery stenosis causelow renal vascular volume --> stimulates

renin-angiotensin system which increasesaldosterone production

Diagnosis: increased aldosterone levels withhigh plasma renin.

List the four causes ofcushings syndrome and their

respective levels of ACTH

Too much cortisol!

1) Iatrogenic steroid use --- low ACTH due tofeedback inhibition

2) Cushings disease (pituitary adenoma ofACTH) -- lots of ACTH

3) Ectopic ACTH tumor -- lots of ACTH4) Zona Fasiculata Adenoma -- low ACTH

due to feed back inhibition

What are the 5 of the 10classic symptoms ofCushing's syndrom

1) Hypertension (excess alpha 1)2) Weight gain

3) Proximal muscle weakness4) Buffalo hump

5) Eccymosis over arms and legs6) Moon face

7) Osteoporosis8) Amenorrhea

9) Immune dificiency10) Skin thinning and striae


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What are the three keycharacteristics of MEN 1?

And what is the most

common clinical complaints?

1) Parathyroid tumors2) Pitutary tumors (prolactin or GH)

3) Pancreatic endocrine tumors (Zollinger-ellison syndrome, insulinomas, VIPomas,

etc)

Clinically presents as: Kidney stones andstomach ulcers

How are all MEN (multipleendocrine neoplasia)syndromes acquired?

All via autosomal dominant inheritance

MEN 2A and 2B are specifically associatedwith the retgene, which causes a defect in

neural crest cells, the cell lines that give riseto the parafollicular cells in the thyroid and

chromaffin cells in the medulla.

What are the threecharacteristics of MEN 2A?

1) Medullary thyroidcarcinomas (secretes

calcitonin)2) Pheochromocytoma3) Parathyroid tumors

What are the threecharacteristics of MEN 2B?

1) Medullary thyroid carcinomas (secretescalcitonin)

2) Pheochromocytoma3) Marfanoid habitus/mucosal neuromas

What are neurophysins andwhat are their function?

Neurophysins are carrier proteins releasedfrom the posterior pituitary that carry ADH

from the supraoptic nuclei and oxytocin fromthe paraventricular nuclei, through the portalblood supply to the posterior pituitary.

Defects = diabetes insipidis


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Explain the process of insulinproduction, make sure to

name the cells responsible

Synthesized and secreted by pancreatic cells

Synthesized as proinsulin, which getscleaved to insulin & C-peptide (essential for

proper folding) and stored in secretion

granules

List the three types ofhypothyroidism and their

corresponding TSH values

1) Primary hypothyroidism (caused by thyroidhypofunction): TSH

2) secondary hypothyroidism (caused bypituitary hypofunction): TSH

3) tertiary hypothyroidism (caused byhypothalamic hypofunction): TSH

What are 5 common causesof primry hypothyroidism?

1) Hashimoto thyroiditis (chronic autoimmunethyroiditis)

2) Post ablation: surgical or I-131 radiation(people treated for Graves)

3) Iodine deficiency4) Drugs: lithium, amioderone, and

sulfonamides5) Subacute lymphocytic (painless)thyroiditis: 1/3rd of patients become

hypothyroid within 10 years

What is cretinism? How can itbe avoided?

Disease due to severe fetal hypothyroidism

mental retardation

pot-bellied stomach

protruding umbilicus and tongues

- Mental retardation can be minimized whenthyroid hormone is administered in neonatal

period.

What is/are the most commoncause and symptoms of

congenital hypothyroidism?

Congenital hypothyroidism is mostcommonly caused by thyroid dysgenesis due

to thyroid aplasia/hypoplasia/ectopy

Hoarse cryMacroglossia

Enlarged fontanelles

Pot belly with umbilical hernia

Big puffy eyes and faces

Jaundice

Poor feeding and hypotonia


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What are 7 common signsand symptoms ofhypothroidism?

1) Cold intolerance2) Weight gain

3) Fatuige/depression4) Dry flakey skin

5) Myxedema (facia, periorbital)6) Bradycardia

7) Carpal tunnel

8) Slow deep tendon reflexes9) Constipation

What are the symptoms ofmyxedema coma and how do

you treat it?

Emergent hypothyroid condition

S/Sx: hypothermic stupor/coma,hypoventilation with CO2 retention,

hypotension

Treatment: respiratory support, intravenouslevothyroxine, cortis

What are the three types ofhyperthryoidism and what are

their corresponding TSHtrends?

1) Primary hyperthyroidism: TSH2) Secondary hyperthyroidism: TSH ; in the

rare case that a patient has secondaryhyperthyroidism due to a TSH-secreting

pituitary adenoma inject TRH and look for in TSH

What is the pathophysiologybehind the clinicalmanifestations ofhyperthyroidism

1) Hypermetabolic state (e.g., Na+/K+

ATPase activity): due to T4 and T32) Sympathetic nervous system

overactivity: T4 and T3 synthesis of adrenergic receptors adrenergic tone

List 7 common symptoms ofhyperthyroidism

1) Sweating, heat intolerance2) Weight loss

3) Warm, flushed skin4) Tremor, anxiety, palpitations

5) Opthalmopathy6) Increased bone turnover --> osteoporosis

7) Diarrhea8) Brisk tendon reflexes


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Explain the pathophysiologybehind the opthalmopathy in

non-graves thyroiditis

- SNS overstimulation of levatorpalpebrae superioris wide-eyed staring

gaze and lid lag- Note: true thyroid ophthalmopathy withexophthalmos (proptosis) is only seen inGraves disease, the exopthalmos has it's

own pathophysiology

List 3, non-thyroid-related, labtests that are important to

hyperthyroidism

1) bone turnover serum calcium(hypercalcemia)

2) glycogenolysis serum glucose(hyperglycemia)

3) LDL receptor synthesis serumcholesterol (hypocholesterolemia)

List the triad of clinicalfindings in Graves Disease?

1) Hyperthyroidism: nontenderhyperfunctional enlargement of the thyroid

2) Infiltrative ophthalmopathy: due toaccumulation of glycosaminoglycans and

adipose in retro-orbital tissue3) Infiltrative dermopathy: scaly thickeningand induration of the skin overlying the shinswith nonpitting edema (pretibial myxedema)

What is the would the radioactive iodinestudy look like in a patient with a Toxic

Adenoma of the thyroid?

Uneven 123I uptake withoccasional autonomous "hot"

nodules demonstrating 123

Iuptake

List the triad of clinical findings AcuteThyroiditis and how a radioactive iodine

study would appear. What is the commoncause & course of this disease?

123

I uptake - becuase T4 is in the bloodstream, not in the thyroid

- fever- painful thyroid- painful cervical lymphadenopathyCourse: Hyperthyroid, followed by

hypothyroid, followed by normalizationCause: Viral or bacterial infection


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Describe the radioactive iodine uptakepattern in Iatrogenic hyperthyroidism

(accidental or for diet reasons)

123

I uptake - decreased T4in thyroid due to feedback

inhibition

What is the pathophysiologybehind inflitrativeopthalmopathy?

TSI autoantibodies cross-react with orbitalpreadipocyte fibroblasts (which have TSHreceptors, wtf) causing them to synthesize

glycosaminoglycans

Accumulation of GAGs, fat and T cells in theretro-orbital space (esp muscle, but not

tendon) --> exopthalmos... not easily treated

What is the pathophisiologybehind Graves disease?

Type II Hypersensitivity

TSI (thyroid-stimulating immunoglobulin)auto-ab = IgG that binds and activates TSH

receptor

relatively specific for Graves

Anti- thyroglobulin and anti-thyroidperoxidase antibodies are often present

What are 5 featuresof Thyroid Storm

- Normally due to aggravated Graves- high fever (hyperpyrexia)

- tachycardia out of proportion to fever- tachyarrhythmias common cause of

death in patients with thyroid storm- shock due to heart failure and/or vomiting-

induced volume depletion- coma

What is the pathohysiologybehind Hashimoto Thyroiditis

Most common cause of hypothyroid.Auto-abs attack thyroid

1) Anti-thyroid autoantibodies (anti-Tg andanti-TPO)2) CD8+ T-cell mediated cell death

3) Cytokines activate TH1 IFN- recruitsand activates macrophages follicle

damage


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What are some complicationsof Hashimotos Thyroiditis?

risk of developing other autoimmunediseases

risk of primary thyroid lymphoma:- B-cell non-Hodgkin lymphomas, especially

extranodal marginal zone lymphomas of

MALT (mucosa-associated lymphoid tissue)type

Describe the clinical course ofsubacute thyroiditis. List 4

signs/sx.

1) Preceded by flu-like illness with sorethroat and fever, jaw pain, tender thyroid, and

a markedly elevated ESR2) Tender thyroid

3) Early phase can manifest ashyperthyroidism, as damaged gland spills T4

4) Resolves in 8ish weeks

Describe the pathophysiologyof Reidel thyroiditis and the

clinical consequences

Fibrous tissue replaces thyroidparenchyma, with fibrosis

extending beyond the thyroidcapsule into surrounding tissue.

Hypothyroidism may occur.

List the three functional partsof the thyroid gland and their

functions

Thyroid follicular cells: synthesize, storeand secrete thyroid hormone

Colloid: central space in follicle wherethyroid hormone is stored as a component of

thyroglobulinParafollicular cells: synthesize and secrete

hormone calcitonin

Name the cancer that formsin parafolicular cells and itsimportant association

Medullary thyroid cancer,associated with MEN 2A and2B


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How would an radioactiveiodine study appear in a

patient with Graves?

Diffusely 123I uptake in thewhole thyroid gland

What would the radioactiveuptake scan look like in apatient with thyroid cancer

A COLD focal nodule, that is NOT taking upiodine becuase cancers do not normally

produce thyroid hormone.

What would the radioactiveuptake scan look like in apatient with thyroiditis?

Thyroiditis: 123Iuptake

Name the three mostcommon pharmacologic

treatments forhyperthyroidism

1) -blocker to control symptoms of SNS

tone AND decrease peripheral conversion ofT4 to T3 (mech unknown)2) Propylthiouracil: inhibition of the

organification and coupling steps of T4 & T3synthesis, also inhibits peripheral conversion

of T4 to T33) Methimazole: same as PTU, without

peripheral benefit. Category X.

Compare and contrast the

two different treatmentsinvolving iodine for

hyperthyroidism

1) High-dose iodine blocks release of T4and T3 into the circulation via Wolffe-Chaikoff

cycle2) High-dose radioactive iodine:

131I

(versus the123

I used in imaging studies) becomes concentrated in the thyroid gland

ablation of thyroid function


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Describe the biochemicalpathway that leads to the

formation of T4/T3

1) Iodine enters the follicular cell via Na-Isymporter, I moves to lumen via pendrin

channel2) Thyroid peroxidase:

Oxidizes I- to I0

Conjugates the I

0

to tyrosineresidues on thyroglobulin to formMIT & DIT. (organification)

Couples MIT and DIT to form T3and T4 (still attached to

thyroglobulin)

Describe how T4 & T3 arereleased into the blood

stream?

Iodinated thyroidglobulin is stored in thefollicular lumen. Upon stimulation by TSH,

follicular cells endocytoses thyroglobulin andlysosomal enzymes digest thyroglobulin,releasing T3 and T4 into the circulation.

Residual MIT and DIT are deiodinated bythyroid deiodinase. The I2 that is generated

is recycled to synthesize more thyroidhormone

What inhibits the Na-Itransporter in the thyroid

follicular cell?

The Na-I transporter isinhibited by thiocyanate and

perchlorate anions

Name two medications thatinhibit thyroid peroxidase

Thyroid peroxidase isinhibited by propylthiouracil(PTU) and methimazole!!!

Name the phenomenon in thethyroid that occurs due to

Iodine overload?

Wolff-Chaikoff effect: High levels of I- inhibit

thyroid hormone synthesis by blocking theorganification step.

Remember high levels of I can come from aCT or angiogram!


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How and where is T4converted to T3

T4 is deiodinated in peripherial tissue to T3by the enzyme 5'-deiodinase. T3 is

significantly more potent than T4.

What HLA type is associatedwith Hashimotos thyroiditis? HLA-DR5

Explain the pathogensis ofRiedel's thyroiditis and two

common physical examfindings

1) Thyroid is replaced by fiberous tissueleading to hypothyroidism

2) fixed, rock-like, painless goiter

Describe the pathophysiologybehind a Toxic Multinodular

Goiter

Focal patches of hyperfunctioning follicularcells that work independently of TSH due to

a mutation in the TSH receptor

Appear as hot nodules (increased uptake) oniodine study. Rarely malignant

Name the two types of cancer associatedwith Follicular cells along with theirassociations and prognoses

1) Papillary carcinoma: associated with

childhood radiation exposure, excellentprognosis, most common2) Follicular carcinoma: not associated with

radiation, less common, good prognosis


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What is the prognosis for apatient with Anaplastic

Thyroid Cancer. Who gets

this cancer?

VERY poor prognosis

Older patients

What are the four majoreffects of thyroid hormone?

Brain maturation- critical in neonatal period

Bone growth- via synergism with GH and IGF-1

Beta-adrenergic effects- increases the number of Beta 1 receptors

on heart muscleBMR

- Na/K-ATPase activity More O2

Explain the differencebetween free thyroid hormoneand bound thyroid hormone.

What is it bound to?

TBG (thyroxine-binding globulin) bindsmost T3 or T4 in peripheral blood

Only free T3 or T4 is active. TBG bound T3or T4 is inactive.

Conditions where TBG is increased ordecreased can affect total T3 or T4 levels.

(Pregnancy increases TGB, but thyroidcompensates)

Describe the pathophysiologyof Carcinoid Syndrome

Rare syndrome caused by neuroendocrinecarcinoid tumors that secrete high levels of

5-HT serotonin. The seritonin will beundetectable in the blood stream due to first

pass effect by the liver.

What 4 are the common sx ofCarcinoid syndrome?

Carcinoid

1) Cutaneous flushing2) Asthmatic wheezing

3) Right-sided valvular disease4) Diarrhea


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How do youdiagnose Carcinoid

syndrome?

Increased urinary secretion of 5 HIAA (5hydroxyindoleacetic acid) a degradation

product of serotonin

How do you treatCarcinoid syndrome?

Octreotide somatostatin analogue thatneutralizes serotonin

Surgical resection and chemotherapy with5-FU (fluorouracil) and doxorubicin

What is the pathophysiology, clinicalconsequence and important association of

Zollinger-Ellison Syndrome?

Gastrin secreting tumor of thepancreas or duodenem

Causes recurrent ulcers

Associated with MEN-1

Describe the hormonalabnormalities in Klinefelterssyndrome and their cause

Hyaliniaztion and fibrosis of the seminiferoustubules leads to lack of testosterone

synthesis- Increased LH and FSH

- Testosterone is low --> infertility andabsence of secondary sex characteristics

Define agranulocytosis, the primarysymptoms, and the cause. How would youproceed with a patient if you suspect this

condition?

Def: absolute PMN count less than 500/mL

Sx: Fever & sore throatCause: propylthiouracil and methimazole (inpatient with a history of hyperthyroidism)

Tx: d/c medication and order CBC with diff


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What is a lingual thyroid.What complications can occur

with treatment of this

problem?

Due to failure of migration, the thyroid caform at any part along the thyroglossal duct's

usual path, including the tongue = lingualthyroid. Sometimes this may be the only

thyroid tissue in the body and removal of themass can lead to life threatening

hypothyroidism.

What would the LH, FSH, Testosterone, andsperm count levels be in a patient with

Klinefelters syndrome?

LH: elevatedFSH: elevated

Testosterone: very lowSperm count: low

Due to the fibrosis of the seminiferoustubules & damage to the Leydig cells, testo isvery low and there is no feedback inhibition

to the pituitary.... LH and FSH are high.

What effect does a betablocker have on thyroid

hormone?

Beta bockers prevent the conversion of T4 toT3 in peripheral tissues. The mechanism

behind this effect is unknown

Thyroid hormone also increases the numberof beta receptors on cell membranes. Beta

blocker will mitigate this and decreasesympathetic tone.

Mutations in what gene areresponisble for the majority of

familial medullary thyroidcancers

A mutation that activates the proto-oncogene"RET". This is the underlying mechanism

behind medullary thyroid cancers in MEN 2Aand 2B

List three features of Marfanoid Habitus andthree clinical diseases associated with thisbody type.

1) Long limbs2) Arachnodactyly (abnormally long and

slender limbs)3) Hyperlaxity

- Marfan syndrome, MEN 2B,Homocystinuria


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Describe this man's appearance

Marfanoid habitus1) long limbs

2) Arachnodactyly3) Hyperlaxity (double

jointedness)

Where is ADHsynthesized?

ADH is sythesized in the supraoptic nuclei ofthe hypothalamus. Damage to the nuclei or

the pituitary stalk results in central DI.

While ADH is released from the posteriorpituitary (hypophysis), damage to this area

only causes transient DI, because ADH canstill be secreted from the pituitary stalk.

What does 5-alpha reductasedo and where does it

function?

5-alpha reductase convertstestosterone to DHT in target

tissues

Describe the effect of GnRHon hormone production from

the gametes

Normally GnRH release from thehypothalamus is pulsitile, leading to transient

release of LH and FSH, and thereforetestosterone

However, if GnRH levels are constantlyelevated, LH and FSH production is

suppressed

Describe the mechanism andclinical application of the drug

Leuprolide

Leuprolide is a long-long acting GnRHanalogue that causes eventual suppressionof the GnRH/LH-FSH axis and therefore a

decrease in testosterone and DHT. Precededby a "flair up" of testo and DHT.

Used to treat prostate cancer


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Explain the concept ofaldosterone escape

Explains why hypernatremia is rare inpatients with hyperaldosteronism

Increaed Na/Cl uptake by excess aldo leadsto hypervolemia. This triggers Atrial natruetic

peptide, which causes diurese andcompensatory Na loss. --> mild hypertension

due to volume expansion, but nothypernatremia

What is the clinicalpresentation of adrenal crisis?

What is the treatment?

Hypotension, Hypoglycemia, and tachycardiaPresenting with one or more of the following:

voimiting, abdominal pain, weight loss,hyperpigmentation

Tx: urgent administration of glucocorticoids isalways warrented when adrenal crisis is

suspected. You do not need lab confirmation.

Describe the hormonal axisinvolving leydig cells

Hypothalamus secretes GnRH --> Pituitarysecretes LH --> LH stimulates leydig cells to

produce testosterone --> Testosteroneinhibits the pituitary release of LH and the

hypothalamic release of GnRH

Describe the hormonal axisinvolving sertoli cells

Hypothalamus produces GnRH --> pituitarysecretes FSH --> FSH stimulates sertoli cells

to produce inhibin --> inhibin inhibits thepituitary from releasing FSH, but has no

effect on the GnRH production of thehypothalamus (LH and testo can keep going)

Sertoli cells are damaged.

What happens to thehormone axis involving the

testes?

No inhibin is produced, which allows the FSHto be produced unchecked (inhibin low and

FSH high). Testosterone and LH will beuneffected.


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List the 3 key characteristicsof a Glucagonoma

Rare pancreatic tumor that presents withnecrolytic migratory erythema

Patients are usually diagnosed as "diabetic"due to hyperglycemia

Other sx: stomatitis (gum inflammation),

cheilosis (corners of mouth), and abdominalpain.

What is the function ofdemeclocycline? What is it

used for? Side effects?

ADH antagonist used to treat SIADH

Side effects: nephrogenic DI,photosensitivity, abnormalities of bones and

teeth

Name four clinical syndromes (all discussedthis this section) that can be treated with

somatostatin

1) Acromegally2) Carcinoid syndrome

3) Gastrinoma4) Glucagonoma

What is the effect oftestosterone and estrogen on

bone growth

Sex hormones promote both growth andepiphysial plate closure, so the earlier they

are introduced the shorter the stature.

This is in contrast to GLP-1 (somatostatin-C),causes bone growth without epiphyseal

closure leading to gigantism.

Explain the cause ofamenorrhea in an anorexicpatient

Patients with anorexia nervosa oftenexperience amenorrhea due to loss ofpulsatile secretion of GnRH from the

hypothalamus. This leads to low estrogenproduction from the ovaries, but this problem

begins in the hypothalamus.


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List three scenarios wheredesmopressin (DDAVP) is the

standard treatment

1) Central Diabetes Insipidus2) Mild Von Willibrand's disease (also useful

in hemophelia A)3) Enuresis (bed wetting)


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