Pathology of the Endocrine System 2008 of the Endocrine... · Malocclusion and tooth gaps ......
Transcript of Pathology of the Endocrine System 2008 of the Endocrine... · Malocclusion and tooth gaps ......
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Pathology of the Endocrine SystemPathology of the Endocrine System
JantimaJantima TanboonTanboon, MD, MD
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1. Endocrine 2. Paracrine
3. Autocrine 4. 4. NeuroendocrineNeuroendocrine
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HYPOTHALAMUS
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PITUITARY GLAND
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Bitemporal Hemianopsia
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Craniopharyngioma
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Normal Anterior and Posterior Pituitary GlandNormal Anterior and Posterior Pituitary Gland
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10/27/2008 13Reticulin stain
Pituitary AdenomaMacroadenoma > 1 cm
Microadenoma
Hormone produced +/-
Mass effect/Stalk effect
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Prolactin from Lactotroph
Prolactinoma: 1st MC pituitary adenoma
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Hyperprolactinemia
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Growth Hormone from Somatotroph
Growth hormone adenoma: 2nd MCMacroadenomaPituitary dwarfism: GH deficiency in Children
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Hypothalamus
Anterior pituitary
Growth hormoneGrowth hormoneGrowth promotingGrowth promoting action AntiAnti--insulin effectinsulin effect
LiverLiver
Protein synthesisProtein synthesis
Bone and cartilage
Body organs
Muscle
Linear growth
Size and function
Muscle mass
Adipose tissue
CHO metabolism
LipolysisFFA use
Glucose use
Adiposity Blood
glucose
IGF-1
insulin level (at initial)insulin level (at initial)insulin resistant (prolong GH insulin resistant (prolong GH
excess) at periphery despite excess) at periphery despite insulin increase soinsulin increase so…… 10/27/2008 18Gigantism Acromegaly
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Coarsening of facial featuresMacroglossiaMalocclusion and tooth gapsAcral enlargement
Thick and coarse skin
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ACTH from Corticotroph
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Cushing diseaseCushing disease
HypercortisolismHypercortisolism by pituitary adenomaby pituitary adenomaHyperpigmentationHyperpigmentation
NN-- terminal fragmentterminal fragment ACTHACTH ββ--LPHLPH
γ-MSH α-MSH CLIP γ-LPH ββ--endorphinendorphin
ProopiomelanocortinProopiomelanocortin: : POMCPOMC
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Cushing syndromeCushing syndrome
Adrenal glandAdrenal glandEctopic ACTHEctopic ACTH
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Nelson syndromeNelson syndrome
Corticotroph adenoma
After adrenalectomy
Loss of inhibitory effect
Mass effects
Hyperpigmentation
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LH, FSH from Gonadotroph
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HypopituitarismHypopituitarism
7070--90% (90% (≥≥75%) 75%) parenchymalparenchymal losslossCongenital (rare)Congenital (rare)AcquiredAcquiredNonNon--functioning adenomafunctioning adenomaIschemic necrosisIschemic necrosisAblation by surgery or radiationAblation by surgery or radiationInflammatory lesionInflammatory lesionMutation PitMutation Pit--11
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Sheehan syndromeSheehan syndrome
Postpartum necrosis of anterior pituitaryPostpartum necrosis of anterior pituitary
PregnancyPregnancyHypertrophy/Hyperplasia of Hypertrophy/Hyperplasia of LactotrophLactotroph
Not increase blood supplyNot increase blood supply
Blood loss during deliveryBlood loss during delivery
AgalactiaAgalactia, amenorrhea, hypothyroidism, , amenorrhea, hypothyroidism, adrenocorticaladrenocortical insufficiencyinsufficiency
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Pituitary apoplexyPituitary apoplexy
SSudduddenen neurologic impairment neurologic impairment
HHeadacheeadache,, visualvisual symptomssymptoms,, alteredalteredmentalmental statusstatus,, andand hormonalhormonal dysfunctiondysfunction
Hemorrhage and/or infarctionHemorrhage and/or infarction
Tumor (adenoma)/ normal pituitaryTumor (adenoma)/ normal pituitary
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Oxytocin
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Vasopressin: Antidiuretic hormone
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Diabetes Diabetes InsipidusInsipidus: DI: DI
ADH deficiencyADH deficiencyClinical: Clinical: PolyuriaPolyuria, thirst, , thirst, polydipsiapolydipsiaCentral DICentral DINephrogenicNephrogenic DIDI¼¼ associated with associated with craniopharyngiomacraniopharyngioma
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Syndrome of inappropriate ADH Syndrome of inappropriate ADH secretion: SIADHsecretion: SIADH
Water retention, Water retention, hyponatremiahyponatremia, , hypotonicityhypotonicity
Excess ADH: Excess ADH: ParaneoplasticParaneoplastic secretion: Small cell lung CAsecretion: Small cell lung CA
Tumor trauma inflammationTumor trauma inflammationPulmonary lesionPulmonary lesion
Brain lesionBrain lesion
Drugs Drugs
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PINEAL GLAND
Melatonin: sleep inducerSerotonin: neurotransmitterGerm cell tumorsPineocytoma
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THYROID GLAND
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Thyroglossal Duct Cyst
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Follicular cell
Colloid
Thyroglobulin
T4
T3
Parafollicular cell (C-cell)
Calcitonin
Thyroid gland
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Essential for normal development of CNS and skeleton
Essential for cell division and maturation
Neonatal cells
Lipolysis, glycolysis, and gluconeogenesisincreased to raise blood metabolite levels and cellular metabolite use
Increases expresstion of enzymes necessary for energy production
Nucleus
Increased heat production, oxygen demand, heat rate, and stroke volume
Stimulates growth, replication and activity; basal metabolic rate is raised
Mitochondria
Increased demand for metabolites, e.g. glucose
Stimulates the Na+/K+
ATPase pumpCell membrane
Physiological results
Intracellular effectsSite of actionActions of T3Actions of T3
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Hypothyroidism
Cretinism Myxedema
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Congenital hypothyroidismCongenital hypothyroidism
CretinismCretinism
Endemic cretinismEndemic cretinismNeurologic cretinismNeurologic cretinism
Hypothyroid cretinismHypothyroid cretinism
NonNon--endemic cretinismendemic cretinismThyroid Thyroid dysgenesisdysgenesis
Others Others
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Proteoglycans accumulation in extracellular matrix: Myxedema
Boggy face, puffy eyelids
Edema of hands and feets
Enlarged tongue
Thickening mucous membrane in larynx
Ecchymoses
Lethargic somnolent
Memory loss, slow mental process
Paronoid/depression/severe agitation
Sensory defect
Cerebellar ataxia, slow DTR
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GoitrousGoitrous hypothyroidismhypothyroidism
Impaired synthesis of thyroid hormoneImpaired synthesis of thyroid hormone
Dietary iodine deficiencyDietary iodine deficiency
TSH compensateTSH compensate euthyroideuthyroid
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Diffuse Non-Toxic Goiter
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Nodular/Multinodular Goiter
Further develop toxic nodular goiter
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Hashimoto Hashimoto thyroiditisthyroiditis
MC for nonMC for non--endemic hypothyroidismendemic hypothyroidismChronic lymphocytic Chronic lymphocytic thyroiditisthyroiditis, , strumastrumalymphomatosalymphomatosaAutoimmune disease: Autoimmune disease: antithyroidantithyroid antibodyantibodyEarly stage: Early stage: HashitoxicosisHashitoxicosisCan develop: Can develop: Other autoimmune diseases, BOther autoimmune diseases, B--cell cell LymphomaLymphoma
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Graves disease
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Graves diseaseAutoimmune diseaseAutoimmune disease
ThyroidThyroid--stimulating stimulating immunoglobulin (TSI)immunoglobulin (TSI)******
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Other Other ThyroiditisThyroiditis
Acute Acute thyroiditsthyroidits
SubacuteSubacute ((granulomatousgranulomatous) ) thyroiditisthyroiditis
Silent Silent thyroiditisthyroiditis
Riedel Riedel thyroiditisthyroiditis
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Acute Acute thyroiditisthyroiditis
Infectious: Bacteria, fungusInfectious: Bacteria, fungus
Fever, chill, malaise, swollen neckFever, chill, malaise, swollen neck
MC: MC: Streptococcus, Staphylococcus, Streptococcus, Staphylococcus,
PneumococcusPneumococcus
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SubacuteSubacute ((granulomatousgranulomatous) ) thyroiditisthyroiditis
GranulomatousGranulomatous thyroiditisthyroiditisDe De QuervainQuervain thyroiditisthyroiditisNon Non suppurativesuppurative thyroiditisthyroiditisViral infection:Viral infection:CoxackieCoxackie, Mumps, Influenza, , Mumps, Influenza, EchoviruresEchovirures,,AdenovirusesAdenoviruses
Transient:Transient:Pain, fever, malaise, fatigue, enlarged thyroid, Pain, fever, malaise, fatigue, enlarged thyroid, tender tender
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Silent Silent thyroiditisthyroiditis
Painless Painless thyroiditisthyroiditis
Lymphocytic Lymphocytic thyroiditisthyroiditis
Painless thyroid enlargementPainless thyroid enlargement
SelfSelf--limited hypothyroidismlimited hypothyroidism
Post partum periodPost partum period
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ReidelReidel thyroiditisthyroiditisExtrathyroidal soft tissue
Fibrosis of other organs
Hard/ fixed → suspicious CA
Unknown etiology
Autoimmune ?
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NeoplasmsNeoplasms of the thyroidof the thyroid
Solitary nodulesSolitary nodules
Young patientsYoung patients
Nodules in malesNodules in males
HxHx of radiationof radiation
Hot nodules (benign)Hot nodules (benign)
AdenomaAdenoma
Papillary CA (75Papillary CA (75--85%)85%)
Follicular (10Follicular (10--20%)20%)
MedullaryMedullary CA (5%)CA (5%)
AnaplasticAnaplastic CA (<5%)CA (<5%)
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Follicular Adenoma
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Follicular CarcinomaCapsular invasion
Vascular invasion
Hematogenous spread
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Papillary Thyroid CarcinomaPapillary Thyroid Carcinoma
MC thyroid carcinomaMC thyroid carcinomaLymphatic spreadLymphatic spreadMC in children and young adolescentMC in children and young adolescentIodine excessIodine excessRadiationRadiationGenetic factorsGenetic factorsFamilial Familial adenomatousadenomatous polyposispolyposisMutation of Mutation of RETRET (10q11.2)(10q11.2)
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Fine Needle Aspiration Cytology (FNA) Thyroid Gland
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AnaplasticAnaplastic carcinomacarcinoma
Undifferentiated thyroid carcinomaUndifferentiated thyroid carcinoma
ElderlyElderly
Develop fromDevelop fromLongLong--standing goiterstanding goiter
LowLow--grade thyroid cancergrade thyroid cancer
Radiation Radiation
Rapid enlarged mass, Aggressive tumor:Rapid enlarged mass, Aggressive tumor:
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MedullaryMedullary thyroid carcinomathyroid carcinoma
CC--cellcellCalcitoninCalcitonin, serotonin, ACTH, , serotonin, ACTH, somatostatinsomatostatinPrecursor lesion: CPrecursor lesion: C--cell hyperplasiacell hyperplasiaMutation of RETMutation of RET
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PARATHYROID GLANDS
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HypercalcemiaHypercalcemia
Solid tumor: lung, breast, head and neck, Solid tumor: lung, breast, head and neck,
renal cancerrenal cancer
Hematologic malignancy: multiple Hematologic malignancy: multiple
myelomamyeloma
Clinically apparent Clinically apparent hypercalcemiahypercalcemia
Asymptomatic Asymptomatic hypercalcemiahypercalcemia
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Hyperparathyroidism
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Hyperparathyroidism
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ENDOCRINE PANCREAS
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Endocrine pancreasEndocrine pancreas
EndodermalEndodermal derivativesderivativesFour major cell types:Four major cell types:ββ 68% insulin 68% insulin αα 20% glucagon20% glucagonδδ 10% 10% somatostatinsomatostatinPP 2% pancreatic polypeptidePP 2% pancreatic polypeptide
Two minor cell types:Two minor cell types:D1 D1 vasoactivevasoactive polypeptidepolypeptideEnterochromaffinEnterochromaffin cell serotonincell serotonin
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Obesity
BMI 25-29.9 = overweight
BMI >40 = obese
Male
Waist > 102 cm (40 inch)
Waist: hip ratio > 0.9
Female
Waist > 88 cm (35 inch)
Waist: hip ratio > 0.85
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Hyperglycemia Hyperglycemia Advanced Advanced glycationglycation end product (AGE)end product (AGE)
CrosslinkingCrosslinking polypeptidespolypeptidesResistant to Resistant to proteolyticproteolytic enzymeenzymeAGE residues in plasma proteinsAGE residues in plasma proteins
Activation of protein Activation of protein kinasekinase CCVEGFVEGFVasoconstrictor: Vasoconstrictor: endothelinendothelin 11Vasodilator: endothelial nitric oxide Vasodilator: endothelial nitric oxide synthasesynthase
((eNOSeNOS))ProfibrinogenicProfibrinogenic molecules (TGFmolecules (TGF--ββ))ProcoagulantProcoagulant molecule (PAImolecule (PAI--1)1)ProPro--inflammatory cytokinesinflammatory cytokines
PolyolPolyol pathways in nerve lens kidneyspathways in nerve lens kidneys
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ADRENAL GLANDS: CORTEX
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Adrenal glandsAdrenal glands
1.1. GlucocorticoidsGlucocorticoids ((cortisolcortisol): ):
Z Z fasciculatafasciculata/Z /Z reticularisreticularis
2.2. MineralocorticoidsMineralocorticoids ((aldosteronealdosterone):):
Z Z glomerulosaglomerulosa
3.3. Sex steroids (estrogens and Sex steroids (estrogens and
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Hypercortisolism
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HypercortisolismHypercortisolism
Endogenous Endogenous hypercortisolismhypercortisolism
7070--80% primary ACTH 80% primary ACTH hypersecretionhypersecretionACTHACTH--producing producing microadenomamicroadenoma****
CorticotrophCorticotroph cell hyperplasiacell hyperplasia
20% primary adrenal 20% primary adrenal neoplasmsneoplasmsAdrenal adenoma/ adrenal carcinomaAdrenal adenoma/ adrenal carcinoma
Primary cortical hyperplasiaPrimary cortical hyperplasia
10% ectopic ACTH by non10% ectopic ACTH by non--pituitary tumorspituitary tumorsS ll ll i f h l ***S ll ll i f th l ***
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Physiological effects of Physiological effects of cortisolcortisol and the symptoms of and the symptoms of CushingCushing’’s syndromes syndrome
infection, poor healing, infection, poor healing, peptic ulcerationpeptic ulceration
Suppresses the action Suppresses the action and production of and production of immune cells; inhibits immune cells; inhibits the production of the production of cytokines and cytokines and antibodiesantibodies
Immune systemImmune system
Fat redistributed to the Fat redistributed to the face, trunk, causing a face, trunk, causing a moon face, buffalo moon face, buffalo hump and abdominal hump and abdominal stretch marksstretch marks
Stimulate Stimulate lipolysislipolysis and and fatty acid level in the fatty acid level in the
bloodblood
Fat metabolismFat metabolism
Related pathology Related pathology in Cushingin Cushing’’s s
syndromesyndrome
Effect of Effect of cortisolcortisolProcess/Process/system affectedsystem affected
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Physiological effects of Physiological effects of cortisolcortisol and the symptoms of and the symptoms of CushingCushing’’s syndromes syndrome
Depression Depression insominainsominapsychosis and psychosis and confusionconfusion
Influences fetal and Influences fetal and neonatal neuron neonatal neuron development; development; influences behavior influences behavior and cognitive function, and cognitive function, augment the actions of augment the actions of the sympathetic the sympathetic systemsystem
Nervous systemNervous system
Suppression of growth Suppression of growth in childrenin children
Suppresses the Suppresses the secretion of anterior secretion of anterior pituitary hormones pituitary hormones ACTH, LH, FSH, TSH ACTH, LH, FSH, TSH and GHand GH
Endocrine systemEndocrine system
Related pathology Related pathology in Cushingin Cushing’’s s
syndromesyndrome
Effect of Effect of cortisolcortisolProcess/Process/system affectedsystem affected
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Physiological effects of Physiological effects of cortisolcortisol and the symptoms of and the symptoms of CushingCushing’’s syndromes syndrome
Muscle weakness Muscle weakness and wasting; thin and wasting; thin easily bruising skineasily bruising skin
protein protein breakdown in breakdown in skeletal muscle, skeletal muscle, skin and bone to skin and bone to release amino acidrelease amino acid
Protein metabolismProtein metabolism
Hyperglycemia and Hyperglycemia and diabetesdiabetes
blood glucoseblood glucoseStimulate Stimulate gluconeogenesisgluconeogenesisPrevent glucose Prevent glucose uptakeuptake
CHO metabolismCHO metabolism
Related pathology Related pathology in Cushingin Cushing’’s s
syndromesyndrome
Effect of Effect of cortisolcortisolProcess/Process/system affectedsystem affected
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Physiological effects of Physiological effects of cortisolcortisol and the symptoms of and the symptoms of CushingCushing’’s syndromes syndrome
Osteoporosis Osteoporosis Ca absorption from Ca absorption from the gut the gut
Ca excretion in the Ca excretion in the kidney kidney
Ca Ca resorptionresorption from from bonesbones
Calcium metabolismCalcium metabolism
Hypertension and heart Hypertension and heart failurefailure
Weak Weak mineralocorticoidmineralocorticoidactions; raise Na and actions; raise Na and water retentionwater retention
Water metabolismWater metabolism
Related pathology Related pathology in Cushingin Cushing’’s s
syndromesyndrome
Effect of Effect of cortisolcortisolProcess/Process/system affectedsystem affected
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Cushing Disease, Cushing syndrome
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DexamethasoneDexamethasone suppression testsuppression test1.1. Cushing diseaseCushing disease (pituitary)(pituitary)
ACTH highLow dose cannot suppressHigh dose can
2.2. Ectopic ACTHEctopic ACTHACTH highBoth low dose and high dose cannot
3.3. Adrenal tumorAdrenal tumorACTH lowBoth low dose and high dose cannot
Cushing syndrome Cushing syndrome DxDxurine 24 hrs free cortisol
Loss of diurnal pattern of cortisol secretion
Cause of Cushing Cause of Cushing
syndromesyndrome
Dexamethasone
Serum ACTH
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Conn disease
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Secondary Secondary aldosteronismaldosteronism
Diagnosis:Diagnosis: aldosteronealdosterone, , serum serum reninrenin
renal perfusion renal perfusion
arteriolar arteriolar nephrosclerosisnephrosclerosis, renal artery , renal artery
stenosisstenosis
Arterial Arterial hypovolemiahypovolemia and edema (CHF, and edema (CHF,
cirrhosis, NS)cirrhosis, NS)
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HypoaldosteronismHyperaldosteronismAction Of Aldosterone
Clinical symptoms of hyper and hypoaldosteronism
Volume depletion and postural hypotension
Hypertension *Maintains extracellular fluid volume
Mild metabolic acidosisMetabolic alkalosisDecreases plasma H
HyperkalemiaHypokalemia* Decreases plasma K
Loss Na and loss waterPlasma Na concentration NOT change
Hypernatremia rarely occurs because of other mechanism regulating fluid volume
Increases plasma Na
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Ambiguous genitaliaAmbiguous genitalia
Hermaphroditism
True hermaphroditism
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17α-hydroxylase deficiencysex hormonecortisol
mineralocorticoidHypertension, hypokalemia: female no maturation
21β-hydroxylase deficiencycortisolmineralocorticoidsex hormone
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Salt wasting (classic) Salt wasting (classic) adrenogenitalismadrenogenitalismSalt wasting, hyponatremia, hyperkalemia
Acidosis, hypotension, CVS collapse, death
Shift production- virilization
Simple Simple virilizingvirilizing adrenogenitalismadrenogenitalism without without salt wastingsalt wasting
Less 21-hydroxylase defect
Genital ambiguity
NonclassicNonclassic adrenogenitalismadrenogenitalism
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11β-hydroxylase deficiencycortisolaldosterone and corticosteronesex hormone
Masculinization, hypertension (11-deoxycorticosterone acts as weak mineralocorticoid)
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Adrenal insufficiencyAdrenal insufficiencyPrimary acute Primary acute adrenocorticaladrenocortical insufficiencyinsufficiency
1.1. Chronic Chronic adrenocorticaladrenocortical insufficiency (crisis)insufficiency (crisis): : Stress Stress
2.2. Exogenous corticosteroidsExogenous corticosteroidsRapid withdrawalRapid withdrawal
Stress Stress
3.3. Massive adrenal hemorrhage Massive adrenal hemorrhage NewbornNewborn
Anticoagulant therapyAnticoagulant therapy
Post surgical pt with DICPost surgical pt with DIC
Bacterial infection: WaterhouseBacterial infection: Waterhouse--FriderichsenFriderichsen syndromesyndrome
Primary chronic Primary chronic adrenocorticaladrenocortical insufficiency: Addisoninsufficiency: Addison
Secondary Secondary adrenocorticaladrenocortical insufficiencyinsufficiency
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WaterhouseWaterhouse--FriderichsenFriderichsen SyndromeSyndrome
Bacterial infectionBacterial infectionNeisseriaNeisseria meningitidismeningitidis******HemophilusHemophilus influenzaeinfluenzaePseudomonasPseudomonasPneumoccociPneumoccociStreptococciStreptococciRapid progressive hypotension, Rapid progressive hypotension, shockshockDIC, skin DIC, skin purpurapurpuraAcuteAcute adrenocorticaladrenocortical insufficiencyinsufficiency
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Addison diseaseAddison disease
Primary chronic adrenal insufficiencyPrimary chronic adrenal insufficiency
Destruction of adrenal glandDestruction of adrenal gland
Detect when Detect when ≥≥ 90% has been destroyed90% has been destroyed
Autoimmune diseaseAutoimmune disease*** ***
Infection: TBInfection: TB**, , HistoplasmaHistoplasma, , CoccidioidesCoccidioides, ,
AIDS: MAC Kaposi sarcomaAIDS: MAC Kaposi sarcoma
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Autoimmune Autoimmune polyendocrinepolyendocrine syndrome syndrome type 1 (APS1)type 1 (APS1)
= Autoimmune = Autoimmune PolyendocrinopathyPolyendocrinopathy, , CandidiasisCandidiasis, , EctodermalEctodermal dystrophy dystrophy (APECED)(APECED)
Autoimmune Autoimmune adrenalitisadrenalitis, , hypoparathyroidismhypoparathyroidism, idiopathic , idiopathic hypogonadismhypogonadism, pernicious anemia, pernicious anemia
AIREAIRE 21q2221q22
Autoimmune Autoimmune polyendocrinepolyendocrine syndrome syndrome type 2 (APS2)type 2 (APS2)
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Gradual onsetGradual onset
Asthenia: progressive weakness, easy Asthenia: progressive weakness, easy
fatigabilityfatigability
HyperpigmentationHyperpigmentation**: ACTH: ACTH
Arterial hypotension: Arterial hypotension: MineralocorticoidMineralocorticoid
activity, activity, hyperkalemiahyperkalemia, , hyponatermiahyponatermia, ,
AddisonAddison’’s diseases disease
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ADRENAL GLANDS:
MEDULLA
Neural crest
Cathecolamine
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Pheochromocytoma
Cathecholamine producing
Hypertension (surgically correctable)
Urine VMA/metanephrine
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Neuroblastoma
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MULTIPLE ENDOCRINE NEOPLASIA
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Multiple Endocrine Neoplasia (MEN) syndrome
Medullarycarcinoma+++
Medullarycarcinoma+++
C-cell HyperplasiaThyroid
MucocutaneousganglioneuromasMarfanoid habitus
Extraendocrinechanges
AdenomasPituitary
MEN IIB or IIIMEN II or IIA(Sipple syndrome)
MEN I (Werner)
RETRETMEN IMutant gene locus
Pheochromocytoma+++
Pheochromocytoma++
Cortical Hyperplasia++
Adrenal
Hyperplasia +AdenomasCarcinoma++
Pancreatic islets
Hyperplasia +++Hyperplasia +Adenomas
Hyperplasia +++Adenomas+
Parathyroid
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ParaneoplasticParaneoplastic syndromessyndromes: : EndocrinopathiesEndocrinopathies
ADH,ADH,ANFANF
Small cell CA lungSmall cell CA lungIntracranial tumorsIntracranial tumors
SIADHSIADH
ACTH, ACTH, ACTHACTH--like substancelike substance
Small cell CA lungSmall cell CA lungCA pancreasCA pancreasNeural tumorsNeural tumors
Cushing syndromeCushing syndrome
Causal mechanismCausal mechanismMajor form of Major form of underlying cancerunderlying cancer
Clinical syndromesClinical syndromes
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ParaneoplasticParaneoplastic syndromessyndromes: : EndocrinopathiesEndocrinopathies
Insulin Insulin Insulin like Insulin like substancesubstance
FibrosarcomaFibrosarcomaOther Other mesenchymalmesenchymalsarcomasarcomaHCCHCC
Hypoglycemia Hypoglycemia
PTHPTH--related peptiderelated peptideTGFTGF--ααILIL--11
SquamousSquamous cell CA cell CA lunglungCA breastCA breastCA kidneyCA kidneyCA ovaryCA ovaryAdult T cell Adult T cell leukemia/lymphomaleukemia/lymphoma
HypercalcemiaHypercalcemia
Causal mechanismCausal mechanismMajor form of Major form of underlying cancerunderlying cancer
Clinical syndromesClinical syndromes
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ParaneoplasticParaneoplastic syndromessyndromes: : EndocrinopathiesEndocrinopathies
ErythropoietinErythropoietinRenal cell CARenal cell CAHemangioblastomaHemangioblastomaHCCHCC
PolycythemiaPolycythemia
Serotonin, Serotonin, Brady Brady kininkinin, , ?Histamine?Histamine
CarcinoidCarcinoid tumortumorCA pancreasCA pancreasCA stomachCA stomach
CarcinoidCarcinoid syndromesyndrome
Causal mechanismCausal mechanismMajor form of Major form of underlying cancerunderlying cancer
Clinical syndromesClinical syndromes
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