Diseases of adrenal gland

ADRENAL GLANDSADRENAL GLANDS

• ANATOMY: 2 GLANDS WITH A TOTAL WEIGHT OF 6 TO 10

GRS. • CORTEX (80-90%)• Glomerulosa (Mineralocorticoid)• Fasciculata( Gluco>Sex)• Reticularis ( Sex>Gluco)• MEDULLA(10-20%)• Epinephrine

• Glucocorticoids: Cortisol and corticosterone

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CONTROL OF SECRETION: CONTROL OF SECRETION: ACTH LEVELSACTH LEVELS

ACTH HAS A COMPLEX CONTROL REGULATION:– C.R.F.– CIRCADIAN RYTHM (Highest 8:00 a.m.-

Lowest 12:00 p.m.)– PULSES– NEGATIVE FEED-BACK– RESPONSES TO INTERNAL /EXTERNAL

STIMULI


ACTH ACTIONS:ACTH ACTIONS:

HYPERTROPHY OF ADRENAL GLANDS CELLS

INCREASE IN CHOLESTEROL UPTAKE INCREASE IN DESMOLASE ACTIVITY INCREASE IN STEROID SYNTHESIS RELEASE OF STORAGE AND NEW STEROIDS

INCREASE LIPOLYSIS( FATTY ACIDS MOVILIZATION) INCREASE INSULIN RELEASE INCREASE SKIN PIGMENTATION


GLUCOCORTICOID GLUCOCORTICOID HORMONESHORMONES

ARE “ESSENTIAL” FOR LIFE

ARE “CATABOLIC” HORMONES

ARE “PERMISSIVE”HORMONES


GLUCOCORTICOID GLUCOCORTICOID HORMONES AFFECTS:HORMONES AFFECTS:

CARBOHIDRATES METABOLISM PROTEIN METABOLISM LIPID METABOLISM ELECTROLYTE / WATER BALANCE STRESS OR EMERGENCY SITUATIONS CARDIOVASC. SYSTEM FUNCTION RENAL FUNCTION , SKELETAL MUSCLE C.N.S., HEMATOPOIETIC SYSTEM IMMUNE SYSTEM, GASTRIC ACID SECRETION, SKIN,

CONECTIVE TISSUE GROWTH RATE AND DEVELOPMENT


CORTISOLCORTISOL

CARBOHYDRATE METABOLISM– INCREASE GLUCONEOGENESIS– INCREASE HEPATIC GLYCOGENOLYSIS– DECREASE PERIPHERAL GLUCOSE UPTAKE

– NET EFFECT: INCREASE IN GLUCOSE LEVELS TO AVOID HYPOGLICEMIA

– ANTIINSULINIC ACTION


PROTEIN METABOLISMPROTEIN METABOLISM

INCREASE PROTEIN BREAKDOWN (GLUCONEOGENESIS)

DECREASE PROTEIN SYNTHESIS

NET EFFECT: CATABOLISM AND ANTIANABOLISM STATE WITH NEGATIVE NITROGEN BALANCE


LIPID METABOLISM:LIPID METABOLISM:

SLIGHT DIRECT LIPOLYTIC EFFECTENHANCE THE LIPOLYTIC EFFECT OF

EPINEPHRINE, GROWTH HORMONE.INCREASE LIPOGENESIS IN OTHERS

NET EFFECT: OBESITY WITH CHARACTERISTIC DISTRIBUTION


HYDROELECTROLYTE HYDROELECTROLYTE BALANCEBALANCE

MINERALOCORTICOID EFFECT SODIUM RETENTION POTASSIUM SECRETION HYDROGEN SECRETION WATER RETENTION

NET EFFECTS: HYPOKALEMIC METABOLIC ALCALOSIS WITH HYPERVOLEMIA


CARDIOVASCULAR CARDIOVASCULAR SYSTEM:SYSTEM:

PERMISSIVE ACTION TO:– CATECHOLAMINES VASOCONSTRICTION– DECREASE IN VASCULAR PERMEABILITY– NET EFFECT: INCREASE IN BLOOD PRESSURE

– STRESS OR EMERGENCY SITUATIONS– PREVENTS “HYPOGLICEMIA, SHOCK AND

DEATH)


SKELETAL MUSCLE SKELETAL MUSCLE SYSTEMSYSTEM

BONE FORMATION– DECREASE COLLAGEN SYSTEM– DECREASE OSTEOBLAST ACTIVATION– ANTAGONIZE VIT. D ACTIVATION– INCREASE RENAL CALCIUM EXCRETION– NET EFFECT: OSTEOPOROSIS, DECREASE

IN OSEUS MATRIX, AND DECREASE IN BONE REABSORPTION


MUSCULAR SYSTEMMUSCULAR SYSTEM

DECREASE CONTRACTILITY AND STRENGTH

MUSCLE ATROPHY (PROTEIN CATABOLISM)


CENTRAL NERVOUS CENTRAL NERVOUS SYSTEM:SYSTEM:

DECREASE SEIZURE THRESHOLD

PSIQUIATRIC DISORDERS


HEMATOPOIETIC SYSTEM:HEMATOPOIETIC SYSTEM:

INCREASE LIFE SPAN OF RED BLOOD CELLS

INCREASE PLATELETS NUMBERINCREASE NEUTROPHILS NUMBERDECREASE MONOCYTES,

LYMPHOCITESDECREASE EOSINOPHYLS AND

BASOPHILS


CONECTIVE TISSUE:CONECTIVE TISSUE:

DECREASE COLLAGEN SYNTHESIS

– SKIN ATROPHY

– CAPILLARY FRAGILITY


GROWTH AND GROWTH AND DEVELOPMENT:DEVELOPMENT:

DECREASE GROWTH– DECREASE PROTEIN SYNTHESIS– DECREASE BONE FORMATION

– DECREASE FIBROBLASTIC ACTIVITY


IMMUNE SYSTEM:IMMUNE SYSTEM:

DECREASE MACROPHAGE RESPONSES TO M. I. F.

DECREASE RECEPTORS NUMBER TO I gE


ANTI-INFLAMMATORY ANTI-INFLAMMATORY EFFECTS:DECREASEEFFECTS:DECREASE

CAPILLARY PERMEABILITYLEUCOCYTE MIGRATIONFIBRIN SYNTHESISLYSOSOMAL STABILIZATIONPG AND Tx SYNTHESISFIBROBLAST PROLIFERATION



CAUSES OF CUSHING´S CAUSES OF CUSHING´S SYNDROMESYNDROME

I.-ADRENAL HYPERPLASIA– A) Secondary to pituitary ACTH

overproduction 1.-Pituitary –hypothalamic dysfunction 2.-Pituitary ACTH –producing micro or

macroadenomas B) Secondary to ACTH or CRH-producing

nonendocrine tumors (bronchogenic carcinoma, carcinoid of the thymus, pancreatic carcinoma, Bronchial adenoma)


CAUSES OF CUSHING´S CAUSES OF CUSHING´S SYNDROMESYNDROME

II.-ADRENAL NODULAR HYPERPLASIA

III.-ADRENAL NEOPLASIA– A) Adenoma– B) carcinoma– IV.-EXOGENOUS, IATROGENIC CAUSES

A) Prolonged use of glucocorticoids B) Prolonged use of ACTH


ADRENALSADRENALS

• Adrenal CortexAdrenal Cortex• Adrenocortical Hyperfunction (hyperadrenalism)Adrenocortical Hyperfunction (hyperadrenalism)• Adrenal secretes 3 major groups of steroidAdrenal secretes 3 major groups of steroid hormoneshormones

a)a) glucocorticoids (cortisol) – Cushing glucocorticoids (cortisol) – Cushing SyndromeSyndromeb)b) mineralocorticoids (aldosterone) – mineralocorticoids (aldosterone) –

hyperaldosteronismhyperaldosteronismc)c) androgens – virilizing syndromes androgens – virilizing syndromes


1.1.Cushing SyndromeCushing Syndrome

a)a) any factor that causes any factor that causes cortisol (i.e., cortisol (i.e., glucocorticoids)glucocorticoids)

i)i) mainly due to administration of mainly due to administration of glucocorticoids (iatrogenic)glucocorticoids (iatrogenic)

ii)ii) hypersecretion of ACTH hypersecretion of ACTHiii)iii) hyperplasia or neoplasia hyperplasia or neoplasiaiv)iv) ectopic secretion of ACTH ectopic secretion of ACTH


• In hypersecreting ACTH (In hypersecreting ACTH (iiii above) above) “Cushing “Cushing Disease”Disease”

a)a) more often in women more often in womenb)b) 20-30 yrs 20-30 yrsc)c) in most patients, pituitary usually has in most patients, pituitary usually has small ACTH secreting adenomasmall ACTH secreting adenoma

i)i) less sensitive to (-) feedback control less sensitive to (-) feedback control on on ACTH releaseACTH release

d)d) anterior pituitary has areas of anterior pituitary has areas of corticotroph-cell hyperplasia without corticotroph-cell hyperplasia without adenoma adenoma


e)e) CRH from hypothalamus CRH from hypothalamusf)f) neoplasia/hyperplasia neoplasia/hyperplasia ~30% of cases ~30% of cases of Cushing of Cushing

syndromesyndromeg)g) most other case caused by most other case caused by ectopic ectopic sites of ACTH sites of ACTH

secretion (usually small secretion (usually small carcinoma of lung) carcinoma of lung)i)i) other sites have included pancreas, other sites have included pancreas,

thyroidthyroid• ClinicalClinical

a)a) patients who have exogenous patients who have exogenous glucocorticoids (i.e., cortisol)glucocorticoids (i.e., cortisol)

i)i) adrenals are atrophied due to adrenals are atrophied due to ACTH releaseACTH release

b)b) endogenous ACTH endogenous ACTH adrenal hyperplasia adrenal hyperplasia


c)c) known affects of glucocorticoids known affects of glucocorticoidsi)i) hypertension hypertensionii)ii) weight gain (“moon face” “buffalo weight gain (“moon face” “buffalo

hump”)hump”)iii)iii) atrophy of fast (type II) twitch atrophy of fast (type II) twitch

myofibers myofibers muscle atrophy and muscle atrophy and limb limb weaknessweakness

iv)iv) hyperglycemia and glucosuria hyperglycemia and glucosuriav)v) proteolysis and bone resorption proteolysis and bone resorption (osteoporosis) (osteoporosis) vi)vi) suppresses immune system suppresses immune system risk for risk for

infectionsinfectionsvii)vii) hirsuitism hirsuitismviii)viii) CNS CNS mood changes mood changes



HyperaldosteronismHyperaldosteronism

• Excessive levels of aldosteroneExcessive levels of aldosteronea)a) sodium retention sodium retentionbb) ) potassium excretion potassium excretion c)c) which results in which results in BP and hypokalemia BP and hypokalemia

• Primary or SecondaryPrimary or Secondarya)a) primary primary

i)i) autonomous overproduction of autonomous overproduction of aldosterone aldosterone renin-angiotensin renin-angiotensin system system

ii)ii) caused by adrenocortical adenoma caused by adrenocortical adenoma or or by hyperplasiaby hyperplasia


iii)iii) primary aldosterone secreting primary aldosterone secreting adenoma (in >80%) – “Conn adenoma (in >80%) – “Conn syndrome” syndrome”

iv)iv) carcinomas are rare carcinomas are rarev)v) no ACTH (-) feedback; therefore no ACTH (-) feedback; therefore other other

regions of adrenals are regions of adrenals are notnot atrophic atrophicvii) Conn syndrome more often in

adults whereas hyperplasia occur more often in childrenAdrenogenital Syndrome

• Caused by variety of diseasesa) primary gonadal disorders and


b) primary adrenal disorders

• Adrenal cortexAdrenal cortexa) secretes

i) dehydroepiandrosteroneii) androstenedione

b) both require conversion to testosterone in peripheral tissues

c) these adrenal androgen formation requires ACTHi) secretion can occur de novo or

through ii) excess ACTH secretion (e.g.,

Cushing Syndrome)


d) adrenal causes of androgensi) neoplasms (more likely to be

carcinomas)ii) adrenal hyperplasia

- group of autosomal recessive disorders causing cortisol production

with feedback in ACTH with resultant adrenal hyperplasia (e.g., congenital)

- the most common enzymatic defect in congenital adrenal hyperplasia

is 21-hydroxylase deficiency which accounts for ~95% of cases.




• Clinical:a) congenital adrenal hyperplasia

i) bilateral adrenal hyperplasia- driven by ACTH

b)b) hyperplasia of ACTH producing cells is hyperplasia of ACTH producing cells is present in anterior present in anterior pituitarypituitary

c)c) clinical manifestation determined by clinical manifestation determined by specific specific enzyme deficiencyenzyme deficiency

i)i) androgens androgensii)ii) sodium homeostasis sodium homeostasisiii)iii) depending on severity of diseases, depending on severity of diseases, S & S usually present during S & S usually present during

infancy and early childhood and infancy and early childhood and less commonly during less commonly during childhood.childhood.


d)d) 21-hydroxylase deficiency causes 21-hydroxylase deficiency causes excessive excessive androgenic activityandrogenic activity

i)i) masculinization in females masculinization in females-- hirsutism hirsutism-- oligomenorrhea oligomenorrhea

ii)ii) in males, enlargement of external in males, enlargement of external genitalia genitaliae)e) some rare forms of congenital some rare forms of congenital adrenal adrenal

hyperplasiahyperplasiai)i) 17- 17--hydroxylase deficiency-hydroxylase deficiencyii)ii) in other forms of congenital adrenal in other forms of congenital adrenal

hyperplasia (e.g., 11hyperplasia (e.g., 11-hydroxylase -hydroxylase deficiency) deficiency)


-- accumulated intermediates accumulated intermediates steroids have sodium retention steroids have sodium retention properties properties

and subsequent and subsequent hypertension hypertensionf)f) congenital adrenal hyperplasia should be congenital adrenal hyperplasia should be suspected in suspected in

neonate with ambiguous neonate with ambiguous genitalia genitaliai)i) severe enzyme deficiency in infancy severe enzyme deficiency in infancy can can

be life threateningbe life threatening-- vomiting vomiting-- diarrhea diarrhea-- sodium loss (dehydration) sodium loss (dehydration)

ii)ii) in all cases, an androgen producing in all cases, an androgen producing neoplasm in the ovary must be R/Oneoplasm in the ovary must be R/O


Adrenal Insufficiency (adrenocortical hypofunction)Adrenal Insufficiency (adrenocortical hypofunction)• May reflect either primary adrenal disease (i.e.,May reflect either primary adrenal disease (i.e.,

primary hypoadrenalism) or secondary viaprimary hypoadrenalism) or secondary via decreased stimulation of the adrenals caused bydecreased stimulation of the adrenals caused by ACTH deficiency (e.g., Sheehan syndrome,ACTH deficiency (e.g., Sheehan syndrome, nonfunctioning pituitary adenomas and/or nonfunctioning pituitary adenomas and/or lesions of hypothalamus, etc.)lesions of hypothalamus, etc.)• Further divided (primary adrenocorticalFurther divided (primary adrenocortical insufficiency)insufficiency)

a)a) chronic primary adrenocortical chronic primary adrenocortical insufficiency (Addison Disease) orinsufficiency (Addison Disease) or

b)b) acute primary adrenocortical insufficiency acute primary adrenocortical insufficiency


1. 1. Addisons Disease (chronic)Addisons Disease (chronic)• Progressive destruction of adrenal cortexProgressive destruction of adrenal cortex

a)a) S & S usually do not appear until ~90% S & S usually do not appear until ~90% of adrenal gland of adrenal gland has been compromisedhas been compromised• Causes:Causes:

a)a) autoimmune adrenalitis autoimmune adrenalitisi)i) ~75-90% of all cases of Addison ~75-90% of all cases of Addison disease in disease in

developed countriesdeveloped countriesii)ii) sporadically or familial component sporadically or familial componentiii)iii) In ~50% of patients, autoimmune In ~50% of patients, autoimmune

cause affects only the adrenal cause affects only the adrenal glands whereas glands whereas the remaining the remaining patients also exhibit other patients also exhibit other

autoimmune disorders autoimmune disorders


-- Hashimoto Hashimoto-- Pernicious anemia Pernicious anemia-- Type I diabetes Type I diabetes-- idiopathic Hypoparathyroidism idiopathic Hypoparathyroidism

iv)iv) Type I and II polyglandular Type I and II polyglandular syndromesyndrome

--Type IType I: - autosomal recessive; : - autosomal recessive; mutations located on mutations located on

chromosome 21qchromosome 21q--Type IIType II: - strong link to : - strong link to

histocompatibility histocompatibility antigens (HLA-B8, HLA-antigens (HLA-B8, HLA-

DR3 and HLA-DQ5)DR3 and HLA-DQ5)


v)v) circulating antibodies to several circulating antibodies to several steroidal enzymes (e.g., 21 and steroidal enzymes (e.g., 21 and 17 17-hydroxylase) -hydroxylase) have been found have been found in all types of autoimmune in all types of autoimmune

adrenalitis adrenalitisb)b) Infections Infections

i)i) TB (accounted for ~90% of primary TB (accounted for ~90% of primary chronic adrenocortical insufficiency) chronic adrenocortical insufficiency) antituberculosis antituberculosis drugs have drugs have the the incidence of Addisons disease incidence of Addisons disease

ii)ii) Fungi (Histoplasma capsulatum and Fungi (Histoplasma capsulatum and coccidioides immitis)coccidioides immitis)

iii)iii) AIDS, due to contracting a variety AIDS, due to contracting a variety of of infectionsinfections


c)c) Metastatic neoplasms Metastatic neoplasmsi)i) common site of metastatic common site of metastatic

disseminated carcinomasdisseminated carcinomas ii)ii) carcinomas of breast and lung are carcinomas of breast and lung are source of source of

majority of metastases in majority of metastases in the adrenals the adrenalsiii)iii) other neoplasms from GI, other neoplasms from GI,

melanomas and hematopoietic melanomas and hematopoietic neoplasms may neoplasms may also metastasize to also metastasize to the adrenals the adrenals


• ClinicalClinicala)a) insidious onset with progressive insidious onset with progressive weakness weakness

and easy fatigabilityand easy fatigabilityb)b) GI disturbances are common complaint GI disturbances are common complaint

i)i) anorexia, vomiting, nausea, weight anorexia, vomiting, nausea, weight loss loss and diarrheaand diarrhea

c)c) In patients with primary disease, In patients with primary disease, melanocytes are melanocytes are stimulated with stimulated with hyperpigmentation (via hyperpigmentation (via ACTH ACTH precursor precursor hormone stimulation) hormone stimulation)

i)i) face, axilla,nipples, areola, perineum face, axilla,nipples, areola, perineumii)ii) hyperpigmentation is not seen in hyperpigmentation is not seen in primary primary

pituitary or hypothalamic pituitary or hypothalamic disease disease


d)d) Primary adrenal insufficiency Primary adrenal insufficiencyi)i) aldosterone aldosterone NaNa++ loss; loss; KK++

retention; volume depletion retention; volume depletion hypotension hypotensionii)ii) heart smaller than normal (? heart smaller than normal (?

Chronic hypovolemia)Chronic hypovolemia)iii)iii) hypoglycemia (via glucocorticoid hypoglycemia (via glucocorticoid

deficiency) and impaired deficiency) and impaired gluconeogenesis gluconeogenesisiv)iv) acute stress in the patients (e.g., acute stress in the patients (e.g.,

infections, surgical procedures, infections, surgical procedures, trauma) may trauma) may initiate an “initiate an “acute acute adrenal crisisadrenal crisis””


-- intractable vomiting intractable vomiting-- abdominal pain abdominal pain-- hypotension, vascular collapse, hypotension, vascular collapse,-- coma coma-- death unless corticosteroids are death unless corticosteroids are

replaced replaced immediately. immediately.2. 2. Acute Adrenocortical InsufficiencyAcute Adrenocortical Insufficiency

• Rapid withdrawal of steroids (from previousRapid withdrawal of steroids (from previous treatment)treatment)• Massive adrenal hemorrhageMassive adrenal hemorrhage

a)a) destroy adrenal cortex destroy adrenal cortexi)i) may occur in patients maintained on may occur in patients maintained on

chronic anticoagulant therapychronic anticoagulant therapyii)ii) pregnancy pregnancy


iii)iii) DIC DICiv)iv) overwhelming sepsis (i.e., overwhelming sepsis (i.e.,

Waterhouse-Friderichsen syndrome) Waterhouse-Friderichsen syndrome)-- classically associated with classically associated with

Nisseria Nisseria meningitidesmeningitides septicemiasepticemia-- also can be caused by also can be caused by

pneumococci, Haemophilus pneumococci, Haemophilus influenza and pseudomonas sp.influenza and pseudomonas sp.

-- pathogenesis unclear (may pathogenesis unclear (may involve ETX induced vascular involve ETX induced vascular damage?) damage?)

-- DIC, shock, skin purpura DIC, shock, skin purpura-- more common in children more common in children-- massive adrenal clots massive adrenal clots



Adrenocortical NeoplasmsAdrenocortical Neoplasms• May be responsible for a variety ofMay be responsible for a variety of hyperadrenalismshyperadrenalisms

a)a) functional adenomas most commonly functional adenomas most commonly associated with associated with hyperaldosteronism and hyperaldosteronism and Cushing syndrome Cushing syndrome• A virilizing neoplasm A virilizing neoplasm high incidence to be high incidence to be carcinogeniccarcinogenic• Functional and non-functional adrenocorticalFunctional and non-functional adrenocortical neoplasms neoplasms cannotcannot be differentiated solely on be differentiated solely on basis of morphologybasis of morphology

a)a) hormone measurements hormone measurementsb)b) most adrenocortical adenomas do not most adrenocortical adenomas do not cause cause

hyperfunctionhyperfunction


• Adrenocortical carcinomas are rareAdrenocortical carcinomas are rarea)a) two rare inherited adrenal cortical two rare inherited adrenal cortical carcinomas carcinomas

i)i) Li-Fraumeni syndrome Li-Fraumeni syndrome-- autosomal dominant autosomal dominant-- predisposition to develop other predisposition to develop other

cancers due to mutations in p53 cancers due to mutations in p53ii)ii) Beckwith-Wiedemann syndrome Beckwith-Wiedemann syndrome

• Generally, adrenal adenomas are small (1-2cm)Generally, adrenal adenomas are small (1-2cm) whereas adrenal carcinomas are large, invasivewhereas adrenal carcinomas are large, invasive lesionslesions

a)a) adrenal carcinomas metastasize via adrenal carcinomas metastasize via lymphatics lymphatics and inferior vena cavaand inferior vena cava

i)i) mean survival is ~2 yrs. mean survival is ~2 yrs.


Adrenal MedullaAdrenal Medulla• Most important diseases of adrenalMost important diseases of adrenal medulla are the neoplasmsmedulla are the neoplasms

a)a) neuronal neuronali)i) neuroblastoma neuroblastomaii)ii) mature ganglionic cell tumors mature ganglionic cell tumors

b)b) chromaffin cells chromaffin cellsi)i) pheochromocytoma pheochromocytoma

• PheochromocytomaPheochromocytomaa)a) neoplasm composed of chromaffin cells neoplasm composed of chromaffin cells

i)i) synthesize and release synthesize and release catecholaminescatecholamines

b)b) familial syndromes (~10%) familial syndromes (~10%)



i)i) MEN2A and MEN2B MEN2A and MEN2Bii)ii) type I neurofibromatosis type I neurofibromatosisiii)iii) Von Hippel-Lindau disease Von Hippel-Lindau diseaseiv)iv) Sturge-Weber syndrome Sturge-Weber syndrome

c)c) Extra-adrenal source (~10%) Extra-adrenal source (~10%)i)i) carotid body carotid bodyii)ii) organ of Zuckerkandl organ of Zuckerkandl

d)d) are bilateral (~10%) are bilateral (~10%)i)i) may be as high as 50% in familial may be as high as 50% in familial cases cases

e)e) malignant (~10%) malignant (~10%)i)i) more common when arise in extra- more common when arise in extra- adrenal adrenal

sitessites


f)f) clinical clinicali)i) hypertension! hypertension!

-- chronic, elevated BP (~70% of chronic, elevated BP (~70% of cases) cases)

ii)ii) other hormones can be secreted other hormones can be secreted -- ACTH ACTH-- somatostatin somatostatin

iii)iii) dx dx urinary excretion of urinary excretion of catecholamines and metabolitescatecholamines and metabolites

-- vanillylmandelic acid vanillylmandelic acid-- metanephrines metanephrines

iv)iv) isolated pheochromocytomas isolated pheochromocytomas treated surgically treated surgically

-- multifocal multifocal medically treated medically treated


Multiple Endrocrine Neoplasia Syndromes (MEN)Multiple Endrocrine Neoplasia Syndromes (MEN)

• Group of inherited diseasesGroup of inherited diseasesa)a) hyperplasias, adenomas and carcinomas hyperplasias, adenomas and carcinomas of multiple of multiple

endocrine organsendocrine organsi)i) occur at younger age vs. cancers occur at younger age vs. cancersii)ii) arise in multiple endocrine organs arise in multiple endocrine organsiii)iii) even in one organ, they are even in one organ, they are

multifocalmultifocaliv)iv) tumors preceded by hyperplasia tumors preceded by hyperplasiav)v) more aggressive and recur more more aggressive and recur more frequently frequently

vs. sporadic tumorsvs. sporadic tumors


• MEN-1MEN-1a)a) inherited as autosomal dominant inherited as autosomal dominantb)b) is a tumor suppressor gene is a tumor suppressor gene

i)i) loss of MEN-1 therefore causes loss of MEN-1 therefore causes tumor genesistumor genesis

-- parathyroid (95% involved) parathyroid (95% involved)-- pancreas (>40%) pancreas (>40%)-- pituitary (>30%) pituitary (>30%)

• Parathyroid glandParathyroid glanda)a) primary hyperparathyroidism arising from primary hyperparathyroidism arising from

hyperplasia is a common feature of hyperplasia is a common feature of MEN-1 MEN-1


• PancreasPancreasa)a) leading cause of death in MEN-1 leading cause of death in MEN-1b)b) aggressive aggressivec)c) often functional tumors often functional tumors

i)i) gastrinomas (Zollenger-Ellison gastrinomas (Zollenger-Ellison syndrome)syndrome)

ii)ii) insulinomas and resultant insulinomas and resultant hypoglycemiahypoglycemia• PituitaryPituitary

a)a) most common in MEN-1 is prolactinoma most common in MEN-1 is prolactinoma


• MEN-2bMEN-2b (William syndrome) (William syndrome)a)a) involve also the thyroid involve also the thyroidb)b) adrenal (medulla) adrenal (medulla)c)c) major differences between MEN-2a and major differences between MEN-2a and MEN-2b is MEN-2b is

i)i) do not develop primary do not develop primary hyperparathyroidism (MEN-2b)hyperparathyroidism (MEN-2b)

ii)ii) develop at extra endocrine sites develop at extra endocrine sites-- lips lips-- tongue tongue-- GI tract GI tract

• MEN-2 carry RET ProtooncogeneMEN-2 carry RET Protooncogenea)a) persons are advised to have prophylactic persons are advised to have prophylactic thyroidectomy to thyroidectomy to

prevent carcinoma.prevent carcinoma.


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Diseases of adrenal gland