ENDOCRINE SYSTEM

PATHOLOGY

Mousa Al-Abbadi, MD, FCAP,CPE, CPHQ,FIAC,ABMQ

Professor of Pathology & Cytopathology

University of Jordan

College of Medicine

MY DUTIES• 5 lectures; 90 minutes each

• Simplify

• Understand the concepts

• Help U all Understand…understand…

understand X 10…only then memorize and

recall

• Answer questions & inquiries

• Respect

YOURDUTIES

This Book is your

main source of

knowledge &

EXAMQUESTIONS

YOURDUTIES• ON TIME ATTENDANCE

• Attendance will be taken at the beginning of lecture this system.

• No entrance after 8 am or 9:30 am

• Plz…plz…plz…NO CHATTING during lecture

• Understand first then memorize and recall

• Respect to the process

• NO MOBILE

• No inquiries about the nature

of the exam…I tellyou

PLEASE DON’T ASK THESE

QUESTIONS ATALL

• How many questions on my material?

• What should we concentrate on?

• Are the slides enough?

• Should we memorize this or that?

• Is this or that required?

[YOU SHOULD NOT ONLY STUDY

FOR THEEXAM]

[YOU ARE NOT STUDYING FOR ME

EITHER]

[YOU ARE LEARNING SO THAT YOU

WILL BE A GOOD CARING &

THOROUGH PHYSICIAN WHO WILL

APPLY THE STNADRAD OFCARE]

REMEMBER“Success in life is

90% hard work and

10% talent, luck and

high IQ”

“ALSOREMEMBER”IF YOU ARE LATE….YOU

MAY LOSE YOUR PATINET

INTENDED LEARNINGOBJECTIVES

• Brief review of the anatomy, physiology and biochemistry of human endocrine system.

• Clear understanding of hyper-function and hypo-function of different glands and grasp the concept of positive and negative feedback control.

• Understand the pathogenesis of pituitary adenomas and its hyper-function associated neoplasms.

• Comprehend common causes and features of hypopituitarism.

• Grasp the general features and causes of hyperthyroidism and hypothyroidism.

• Recognize and understand common autoimmune thyroid diseases including Hashimoto thyroiditis.

ILOs….continue

• Absorb the pathology of common benign thyroid diseases including subacute granulomatous thyroiditis (de Quervain thyroiditis), subacute lymphocytic thyroiditis, and Gravesdisease.

• Recognize all the features of the common diffuse and multi-nodular goiter.

• Recognize the pathology of common thyroid neoplasms, adenomas and carcinomas and understand the concept of evaluation by fine needle aspiration for pre-management diagnosis.

• Understand the clinicopathological characteristics of parathyroid gland diseases including hyper-parathyroidism (primary and secondary) and hypo-parathyroidism.

• Brief review of normal insulin physiology and glucosehomeostasis.

ILOs….continue

• Grasp the detailed understanding of the pathogenesis of type 1 & type 2 diabetes mellitus and the differences between these two.

• Recognize other types of diabetes mellitus.

• Recognize and understand the acute and chronic complications of diabetes mellitus.

• Understand and recognize common neuroendocrine pancreatic tumors such as insulinomas andgastrinomas.

• Grasp the features of adrenocortical hyperfunction syndromes including Cushing syndrome, hyperaldosteronism, and adrenogenital syndrome.

• Recognize the pathology of benign breast epithelial tumors

• Understand the pathophysiology of primary and secondary adrenal insufficiency; acute and chronic (Addison disease).

ILOs….continue

• Grasp the detailed understanding of the pathogenesis of type 1 & type 2 diabetes mellitus and the differences between thesetwo.

• Recognize other types of diabetes mellitus.

• Recognize and understand the acute and chronic complications of diabetes mellitus.

• Understand and recognize common neuroendocrine pancreatic tumors such as insulinomas and gastrinomas.

• Grasp the features of adrenocortical hyperfunction syndromes including Cushingsyndrome, hyperaldosteronism, and adrenogenital syndrome.

• Recognize the pathology of benign breast epithelial tumors

• Understand the pathophysiology of primary and secondary adrenal insufficiency; acute and chronic (Addison disease).

• Recognize common adrenocortical tumors and its general features.• Understand the pathology of common adrenal medulla tumor including

Pheochromocytoma, Neuroblastoma and other neuronalneoplasms.

• Understand the concept of multiple endocrine neoplasia type 1 and 2 and its pathogenesis

GENERAL CONCEPTS OF ENDOCRINESYSTEM:

• Basics of Hormonephysiology– Cell surface receptor binding hormones (GH)

– Intracellular receptor binding hormones (ER)

• Feedback inhibition

• Laboratory chemical testing

• Pathology:

1. Hyper or hypo production

2. End organresistance

3. Neoplasms (functional or non functional)

PITUITARY:

PITUITARYDISEASES:• Hyperpituitarism: hormones, usually anterior

pituit. adenomas, primary morecommon

• Hypopituitarism: hormones (ischemia, surgery, radiation or inflammation). Or non functional adenoma with pressureeffects

• Local mass effects: sella turcica changes by radiology, visual field defects (chiasm, bi-temporal hemianopsia). ICP symptoms (headache, nausea,vomiting).

• Sometimes: they cause seizures, obstructive hydrocephalus, and cranial nerve palsies

PITIUITARYAPOPLEXY:• Sudden acute hemorrhage

into pituitary tissue or

neoplasm; causing rapid

enlargement

• Sudden severe headache,

diplopia and hypopituitarism

• Acute neurosurgical

emergency/maybe fatal

(specially ACTH sudden

deficiency

ANTERIOR PITUITARYTUMORS:

• The most common are benign adenomas

• Can be functional, non functional or silent; all may cause mass effect

• P. Adenoma of anterior lobe is the most common cause of hyperpituitarism

• Microadenoma (< 1cm) or Macroadenoma (> than 1 cm)

• Non functional ones: late presentation and may causehypopituitarism

PATHOGENESIS:1. G-protein mutations: most common

2. Familial gene mutations: MEN1,

CDKN1B,…

3. Molecular defects: cyclin-D1, TP53,

RB, RAS oncogene (aggressive tumors

and pituitary carcinomas)

MORPHOLOGY:

LACTOTROPH ADENOMAS(PROLACTINOMAS):

• Most frequent hyperfunctioning (30%)

• IHC of tumor cells +ve for PRL

• Clinically: amenorrhea, galactorrhea, loss of

lipido, infertility

• Earlier and easier to diagnose in younger

females )in contrast to older F andmales)

• Serum PRL level usually >200 μg

SOMATOTROPHADENOMAS:

• 2nd mostcommon

• Gigantism in children and acromegaly in

adults

peripheral• Diabetes mellitus due to

resistance to insulin

• Slow growing and usually macroadenomas

• Gonadal dysfunction, muscle weakness, HT,

arthritis, CHF, risk of GITcancers

CORTICOTROPHADENOMAS:

• Hypercortisolism “Cushingsyndrome”

• When the cause is ACTH producing adenoma “Cushingdisease”

• Usually microadenoma

• S.Times large one develop after surgical removal of adrenal glands to treat CS (Nelson syndrome) mass effect no hypercortisolism

• Hyperpigmentation due to MSH

OTHER ANT. PITUIT.NEOPLASMS

• Non functioning Gonadotroph adenomas

(FSH and LH), mainlyFSH

• Thyrotroph adenomas: 1%, rare cause of

hyperthyroidism

• Most are usually non functioning and may

cause hypopituit due to mass effect and

apoplexy

• Carcinomas are rare and aggressive

HYPOPITUITARISM:• Occurs when >75%tissue loss

• Congenital are rare; moreacquired

• S.times associated with posteriorpit dysfunction (Diabetes insipidus)

• Causes:

– Non funct adenomas (masseffect)

– Sheehan syndrome (ischemic necrosis): pregnancy, shock, DIC, Sickle CD,trauma, ICP,iatrogenic causes and other less commcauses

HYPOPITUITARISM:CLINICALLY

• Depends on the deficient hormone

• Pituitary dwarfism in children

• GnRH: amenorrhea and infertility inwomen

• Hypothyroidism and hypoadrenalism

• Prl: no lactation postpartum

• Hypopigmentation ( MSH)

POSTERIOR PIYUITARYSYNDROMES:

• ADH deficiency (Diabetes inspidus): polyuria.

• Causes: head trauma, surgery and

inflammatory conditions. Maybe idiopathic.

• Central (see above) or nephrogenic DI

(unresponsive renal tubules)

• Thirst and polydipsia; severe dehydration if

untreated. Serumsodiumand urine

specific gravity (dilute urine)

SYNDROME OF INAPPROPRIATE ADH

SECRETION(SIADH):

• Ectopic ADH (small cell carcinoma of lung and

other causes)

• Hyponatremia, cerebral edema, neurologic

dysfunction

• No peripheral edema

THYROID

THYROIDDISORDERS:

• Very common diseases

• Hypo and hyperthyroidism

• Thyroiditis (autoimmune and others)

• Enlargement (Diffuse and Multinodular

Goiter MNG)

• Neoplasms

HYPERTHROIDISM / THYROTOXICOSIS

• T3&T4 with TSH (most sensitive)

(HighTSH)

TSH (PRIMARY)/ T4,T3

CAUSES OFHYPOTHYROIDISM:

MOSTCOMMOM

AU

TO

IMM

UN

ETH

YR

OID

DIS

EA

SES

Hashimoto thyroiditis

Granulomatous thyroiditis (de Quervain)

Subacute lymphocytic thyroiditis

HASHIMOTO THYROIDITIS (CHRONIC

LYMPHOCYTICTHYROIDITIS)

• Most common cause of hypothyroidism in areas with no iodine deficiency

• Gradual hypothyroidism (rarely initial transient Hashitoxicosis)

• Middle aged females (45-60years)

• Autoimmune destruction of thyroid epithelial cells, high anti-thyroid antibodies

• Increase risk for papillary thyroid carcinoma and B-cell NH lymphoma

SUBACUTE GRANULOMATOUS(DE

Quervain)THYROIDITIS

• Granulomatous thyroiditis, more acute

with neck pain, firm thyroid

• ? Virally associated or induced

• Females, 30-50 years

• Maybe initial transient thyrotoxicosis

followed by hypothyroidism

• Self limiting disease (6-8 weeks)

OTHER LESSCOMMONTHYROIDITIS:

• Subacute lymphocytic thyroiditis: middle

aged women, post partum, initial transient

thyrotoxicosis then gradual hypothyroidism.

Autoimmune with circulating antibodies.

Gland is usually normal size. Lymphocytic

thyroiditis

• Riedel thyroiditis: IgG4 associated disease,

stony-hard thyroid due to severe fibrosis

GRAVES DISEASE (TOXIC DIFFUSEGOITER)

• Described by Robert Graves in 1835

• Most common cause of endogenous hyperthyroidism

• Triad: thyrotoxicosis + opthalmopathy (exopthalmos) + dermopathy (pretibial myxedema)

• Autoimmune, HLA-DR3 andCTLA-4

• Women, 20-40 years

GRAVES DISEASE (TOXIC DIFFUSE

GOITER)

AUTOANTIBODIES OF GRAVESDISEASE:

+ Sometimes

TSH-binding

inhibitor Ig,

may cause

hypothyroidism

HISTOLOGY

EXOPTHALMOS PRETIBIALMYXEDEMA

DIFFUSE AND MULTINODULARGOITER:

• Very common; most common thyr disease

• Impaired hormone synthesis, iodine deficiency

• TSH, hyperplasia & hypertrophy

• In most cases; euthyroid; rarely goitrous hypothyroidism

• Endemic or sporadic. Females

• Initially diffuse then multinodular

• Clinically: mass effects andcosmetic

• Rare: toxic MNG (Plummer syndrome)

PATHOLOGICFEATURES:

THYROIDNEOPLASMS:

• Benign >>>>>>> malignant.

• Most are adenomas

• Risk increases when:

– Solitary nodule > than multiple ones

– Male nodules > than female ones

– Age < than 20 or > than 70 year

– Family Hx. And hx, of radiation

– Cold nodule >>>>>Hot nodules

FINE NEEDLEASPIRATION:

• Simple and cost effective diagnostic approach

• It is now the standard for evaluationof

thyroid nodules

• The accuracy is very good and currently it is

well-standardized

FOLLICULARADENOMAS:

• Almost all adenomas are follicular

• Autonomous adenoma; driver mutations in

TSH stimulation; rarely RASmutations

• Solitary, well-circumscribed with intact thick

capsule. Bland cells or Hurthle cell (Hurthle

cell adenoma). Occasional atypia can be seen

• Intact capsule is the main distinguishing

feature from follicular carcinoma

PATHOLOGIC FEATURES OFFA:

HURTHLE CELLADENOMA:

THYROIDMALIGNANCIES:

• Relatively common but not aggressive

• More common in females

• Risk factors: ionizing radiation (Chernobyl

1986) and iodine deficiency

PAPILLARYCARCINOMA 85% LYMPH NODEMETASTASIS

FOLLICULARCARCINOMA 5-15% HEMATOGENOUSSPREAD

ANAPLASTICCARCINOMA < 5%; VERYAGGRESSIVE

MEDULLARY CARCINOMA (C-CELLS) 5%, MAYBE PART OF MEN2SYNDROMES

LYMPHOMA 1% B CELL NONHODGKIN

PAPILLARY THYROID CARCINOMA

• Most common

• Relatively indolent, 10 year survival > than 95%, even with lymph node metastasis

• Uni and multifocal

• Preoperative dx by FNA isaccurate

• Nuclear features most important

• Features: papilae, nuclear grooves, pseudonuclear inclusions, psammoma bodies, Orphan Annie eye nuclei

FOLLICULARCARCINOMA

• Women, 40-60 years

• > common in iodine deficient regions

• Solitary coldnodule

• Hematogenous spread to bone, lung and liver

• 50% die within 10 years

• Capsular and vascular invasion is the

distinguishing feature from F.adenoma

Capsular invasion

Vascular invasion

ANAPLASTIC

CARCINOMA

• < than 5%

• Undifferentiated

carcinoma

• Very aggressive, 100%

mortality

• > than 65 years

• 25% have hx of previous

well-differentiated

thyroid carcinoma

MEDULLARYCARCINOMA:

• Arise from C cells (parafollicular cells) that secretes Calcitonin (increase level and hypercalcemia)

• 70% sporadic, 30% familial (MEN 2A&B)

• RET receptor tyrosine kinasemutations

• Sporadic 50-60 years; familial younger

• Multicentric, contain amyloid

• RET +ve family members require prophylactic thyroidectomy

Amyloid

Calcitonin +ve by IHC

PARATHYROIDGLAND:• PTH secreted by Chief cells.

• Controlled mainly by free C+2 level in serum less than trophic hormones

• Hyper, Hypo and tumors (rare mass effects)

• Functions of PTH:

– Reabsorption of Ca from renal tubules

– Excretion of PO4 into urine

– Vit D conversion to active form

– Stimulates osteoclast activity on bone resorption

HYPERPARATHYROIDISM:

• Primary, secondary and tertiary

• Osteitis fibrosa cystica, Brown tumor of bone, nephrolithiasis, nephrocalcinosis and metastatic calcifications

• Primary HPT:

–Adenomas (85-95%, Hyperplasia (5-10%), carcinoma(1%)

–Mutations: Cyclin D1 gene on chromosome 1 or MEN1 mutations

CAUSES OFHYPERCALCEMIA:

ENDOCRIN

E

PANCREAS

pp = pancreatic

polypeptid

DIABETESMELLITUS:• A group of systemic metabolic disorders

characterized by chronic hyperglycemia

• Chronic hyperglycemia = multiple organ

damage

• Leading cause of ESRD, adult blindness, non-

traumatic amputations (USAdata)

• Prevalence: very common (see graphs)

• Huge health cost worldwide

Diabetes: A global

emergency

IDF 2016 : The 7th

Atlas

Diabetes and Prediabetes 1995-2016

** *

DIAGNOSIS:

CLASSIFICATION:5-10%

90-95%

PATHOGENEISIS OF TYPE I DM:

• Autoimmune disease; destruction of beta

cells, “insulitis” (ultimately insulindeficiency)

• Genetic susceptibility: HLA-DR3/4 and other

non-HLA genes CTLA4 & PTPN22

• Environmental factors: viruses (mumps,

rubella & coxackie B); intestinal dysbiosis

• Failure of self tolerance (regulatory T-cells:

Tregs) auto AB against beta cellantigens

PATHOGENEISIS OF TYPE 2DM:

• Multifactorial: genetics, environmental

and inflammation (NO

AUTOIMMUNITY)

• Insulin resistance + beta cell

dysfunction

• Insulin resistance is increased with

obesity; specially central

obesity

BETA CELLDYSFUNCTION:

1. Excess FFA(lipotoxicity)

2. Chronic hyperglycemia (Glucotoxicity)

3. Abnormal incretin effect

4. Amyloid deposition

5. Polymorphisms in genes that control

insulin

MATURITY ONSET DIABETES OF THE YOUNG(MODY):

• Resemble type 2 but occurs in young

patients, < than 25 years of age

• Gene mutations of beta cell function

CONGENITAL EARLY ONSETDIABETES

• Neonatal period diabetes

• Insulin receptor signaling mutations (insulin

resistance and hyperinsulinemia)

PANCREATICOGENICDIABETES:

• Hyperglycemia due to exocrine pancreas disease

• Heterogeneous: CF, Ch. Pancreatitis and Ca pancreas

GESTATIONALDIABETES:

• 5% of pregnancies (diabetogenicstate)

• Mainly insulin resistance due to increased

steroid hormones of pregnancy

• High risk of stillbirth if no early control

• Later in pregnancy: baby with macrosomia

• May need insulin to control sugarlevel

• Long term: higher risk ofDM

INITIAL

METABOLIC

PRESENTATION

AND ACUTE

METABLIC

COMPLICATIONS

POLYPHAGIA +

WT. LOSS = DM

UNTILL PROVEN

OTHERWISE

CHRONIC COMPLICATIONS OFDM:

• Result from chronic hyperglycemia

• Macrovascular and microvascular

• Macrovascular: MI, Stroke, LLischemia

• Microvascular: retinopathy, nephropathy and

neuropathy

• Varies among patients

• Tighter control of sugar delays almost all

these complications

PATHOGENESIS OF CHRONIC COMPLICATIONS

(GLUCOTOXICITY):

1. Advanced glycation end products (AGEs):

AGE-RAGEsignaling

– CK andTGFβ

– Procoagulant activity

– ROS

– Smooth muscle proliferation and matrix

2. Activation of protein kinase C:DAG

3. Disturbance of polyol pathways: GSH

MORPHOLOGY:PANCREAS

• number and size of islets (type 1)

• Amyloid

• number and size of islets (baby of Diabetic Mom)

• Insulitis

VASCULARCHANGES:

• Myocardial infarction: most common cause

of death in diabetics (accelerated

atherosclerosis)

• Gangrene and ischemia of lower extremities

• Hyaline arteriosclerosis (increase risk of HT)

• Diabetic microangiopathy: diffuse BM

thickening. Underlines diabetic retinopathy,

nephropathy and neuropathy

D. NEPHROPATHY: second to MI as a

cause of mortality

• Glomeruli: BM thickening, diffuse

mesangial sclerosis & nodular

glomerulosclerosis (Kimmelstiel-Wilson

lesion)

• Vessels: atherosclerosis and

arteriolosclerosis

• Pyelonephritis: acute and chronic and

occasionally necrotizing papillitis

OCULARCHANGES:• Retinopathy (sometimes total

blindness): micro-angiopathy based

–Nonproliferative retinopathy:hemorrhage,

exudate, aneurysms, edema, venous

dilatation

–Proliferative: neovasacularization, serious,

may cause bleeding and blindness

• Cataract

• Glaucoma

DIABETICNEUROPATHY:

• Mechanism: microangiopathy

• Peripheral > central

• Symmetric neuropathy, motor and

sensory (more common)

• Autonomous neuropathy: impotence, U.

bladder and GI tract

MANAGEMENT:• Strict glycemic control is key

• Type 1: insulin replacement therapy

• Type 2: diet, exercise, medications,

ultimately insulin therapy will be

needed

• HbA1c: long term monitoring level,

recommendation is to keep it below 7%

• LDL and HDL cholesterolcontrol

PANCREATIC NEUROENDOCINE TUMORS

(Pan NETs):

• Rare compared to exocrine tumors, 2%

of all pancreatic tumors

• Single or multifocal; functional or not

• Almost all have malignant potential

except insulinomas

• Mutations in tumor suppressor genes:

MEN1, PTEN or inactivating gene

mutations (ATRX)

INSULINOMAS:• Most commonPanNETs

• DX: Whipple triad (hypoglycemia + Symptoms

of hypoglycemia + relief of symptoms with

glu

• Symptoms: stupor, confusion, LOC

• 10% malignant potential (invasion and mets)

• Histology: giant islets + amyloid deposition

• Cured by surgical removal

GASTRINOMAS:• PanNET secretinggastrin

• Location: duodenum, peripancreatic tissue and

pancreas

• Zollinger-Ellison syndrome: gastrinoma +

increase gastric acid + severe peptic ulceration

• Ulcers: severe, multifocal and unusual location

• >50% of gatrinomas are malignant at dx

• 25% part of MEN-1 syndrome

ADRENAL CORTEX

GLAND

HYPERADRENALISM:

Cushing syndrom

e (cortisol)

Adrenogenital (androgens)

Hyperaldosteronism (mineralocoticicoid)

MOSTCOMMON

CUSHINGDISEASE

ENDOGENOUS CUSHINGSYNDROME:

HYPOTHALAMIC-PITUITARY

(CUSHING DISEASE) 70%

ECTOPIC

SECRETION OF

ACTH (10%)

PRIMARY ADRENAL

NEOPLASM(15-20)

- Female: male, 4:1

- 20-30s years

- Mostly pituitary

microadenoma

- Adrenals: bilateral

hyperplasia

- “ACTH dependent

Cushingsyndrome”

- Small cell

carcinomaof

lung is most

common

- ACTH and

sometimesCRH

issecreted

- Patientsdie

quickly

- Bilateraladrenal

hyperplasia

- Adenomas, and

rarely primary

hyperplasia or

carcinoma

- ACTH-independent

Cushingsyndrome

- cortisoland

ACTH

DIFFUSEHYPERPLASIA

PRIMARY PIGMENTED NODULAR HYPERPLASIA

ADRENOCORTICALADENOMA

Early: hypertension and

wt. gain

HYPERALDOSTERONISM:• Chronic excess aldosteronesecretion

• Primary or secondary

• Primary: autonomous aldosterone + suppression of renin-angiotensin systemand

serum renin activity. Causes:

➢Bilateral idiopathic hyperaldosteronism (most common)

➢ Neoplasm (adenoma: Conn syndrome) orcarcinoma

➢ Familial: Aldosterone synthase gene (CYP11B2)

SECONDARYHYPERALDOSTERNISM:

• aldosterone release due to activation of

renin-angiotensinsystem.

• Associatedwith:

– renal perfusion (arteriolar nephrosclerosis,

renal artery stenosis)

– Hypovolemia and edema (CHF, Cirrhosis,

Nephrotic syndrome)

– Pregnancy

HYPERALDOSERONISMCLINICALLY:

• HT. Most common cause of secondaryHT

• LVH, strokes,MI

• K (50% of cases): weakness, paresthesia,

visual disturbances and sometimes tetany

• Treatment: surgery for adenomas and anti-

aldosterone agents for others

(spironolactone)

ADRENOGENITALSYNDROME:

• Group of disorders: excessandrogens

• Primary gonadal or primary adrenal

• Adrenal ones maybe associated with Cushing

• Adrenal neoplasm(carcinoma>adenoma)

• Congenital adrenal hyperplasia (CAH): AR,

enzymatic deficiency, most common is 21-

hydroxylasedeficiency

• Histology: bilateral adrenalhyperplasia

ADRENALINSUFFICIENCY:

ACUTE ADRENOCORTICALINSUFFICIENCY

• Acute on top of Chronic or sudden

withdrawal of long term steroid therapy

• Massive adrenal hemorrhage:

anticoagulant tx, DIC, pregnancy or

severesepsis.

• In sepsis: Waterhouse-Friderichsen

syndrome specially Neisseria

meningitidis

CHRONID ADRENOCORTICAL

INSUFFICIENCY: ADDISSONDISEASEAutoimmune adrenalitis 60-70% - Antibodies againstenzymes.

- Part of autoimmune

polyendocrine syndromes (APS1),

mutation of autoimmune

regulator gene (AIRE),

chromosome21.

- Mucocutaneous candida, dental,

skin and nail abnormalities

Infections - TB andfungi

AIDS - Infectious inorigin

Metastatic carcinoma - Lung andbreast

Secondary adrenocortical insufficiency:

hyopathalamic or pituitary in origin

ADRENOCORTICALTUMORS:• Functional adenomas: hyperaldosteronism and

Cushing syndrome. Virilizing neoplasms are more commonly carcinomas

• Adrenocortical adenomas: small, sometimes incidentally found at autopsy. 1-2 cm.

• Carcinomas: rare, large, infiltrative, at any age. Li-Fraumeni and Beckwith-Weidemann syndromes are inherited causes

• Mets to adrenal is >>>> than primary carcinomas

ADRENAL MEDULLA:

PHEOCHROMOCYTOMA

• The “10%” tumor

• 10% extraadrenal (paraganglioma)

• 10% bilateral (50% in familal cases)

• 10% malignant (> in extraadrenal sites)

• 10% not associated with HT

• 25% have germline mutations (RET in

MEN-2, NF1, VHL, and others

Laboratory diagnosis: increased urinary catecholamines

metabolites, vanillymandelic acid (VMA)

NEUROBLASTOMA:• Most common extracranial solid tumor

of childhood

• < than 5 years, sometimes infants

• Can occur anywhere, but abdominal is

the mostcommon

• Most are sporadic

MULTIPLE ENDOCRINE NEOPLASIA

SYNDROMES(MEN):• Inherited disorders, proliferative of multiple

endocrine organs

• Younger age groups

• Synchronous or meta-chronous in multiple

organs

• Often muti-focal in the sameorgan

• Often preceded by asymptomatic hyperplasia

• More aggressive than their sporadic

counterparts

Chromosome 11: MEN1

tumor suppressor gene

encodesprotein Menin

Chromosome 10: RET proto-

oncogene, +ve test, prophylactic

thyroidectomy

Goo

d

luck