Pathology of adrenal gland - PowerPoint Presentation

Slide1

Pathology of adrenal gland

By:

Shifaa

’

Qa’qa

’Slide2

adrenal glands:

cortex

medullaSlide3

ADRENOCORTICAL

HYPERFUNCTION

(HYPERADRENALISM)

Cushing syndrome

hyperaldosteronism

adrenogenital

or

virilizing

syndromesSlide4

Hypercortisolism

and Cushing Syndrome

Elevation in glucocorticoid levels

ACTH-dependent Cushing syndrome

ACTH-independent Cushing syndromeSlide5

Exogenous/iatrogenic -------- MC

Endogenous:

hypothalamic-pituitary diseases:

1-

hypersecretion

of ACTH by pituitary adenoma-Cushing disease--

70%

2-

corticotroph

cell hyperplasia

3-

Corticotropinreleasing

hormone (CRH)–producing tumor

- non-pituitary neoplasms ,

10%

?---ectopic ACTH, ectopic CRH

- adrenocortical neoplasms---adenoma, carcinoma—

15-20%

- Primary cortical hyperplasiaSlide6
Slide7

The

pituitary

in Cushing syndrome:

Crooke hyaline change ????Slide8

adrenal glands

in Cushing syndrome:

Cortical atrophy

(2) diffuse hyperplasia,

(3)

macronodular

or

micronodular

hyperplasia, (4) an adenoma

(5) carcinomaSlide9

bilateral cortical atrophy

:

Exogenous glucocorticoids

The

zona

glomerulosa

is of normal thickness in such cases ?????Slide10

Diffuse hyperplasia

:

ACTH-dependent Cushing syndrome

Both glands are enlarged (each 30 g)

Macronodular

or

micronodular

hyperplasia

:

- primary cortical hyperplasia

-

macronodules

: 3 cm or greater

-

Micronodules

: 1 to 3 mm pigmented nodules (

lipofuscin

)Slide11

Functional adenomas or carcinomas of the adrenal cortex

:

adenomas: yellow, capsules, less than 30 g

Carcinomas:

nonencapsulated

, 200 to 300 g

the adjacent adrenal cortex and that of the contralateral adrenal gland are atrophicSlide12

Clinical Features:

Cushing syndrome

:

hypertension and weight gain

truncal

obesity, moon

facies

, buffalo hump ???

decreased muscle mass and proximal limb weakness

hyperglycemia,

glucosuria

, and polydipsia,

cutaneous

striae

(loss of collagen/ catabolic)

Osteoporosis (

resorption

of bone/ catabolic)

Infections (suppress the immune response)

Hirsutism

menstrual abnormalities

mental disturbances (mood swings,

depression,and

frank psychosis)

Skin pigmentation:

Extraadrenal

Cushing syndrome caused by pituitary or ectopic ACTH secretionSlide13
Slide14

Hyperaldosteronism

Primary

Secondary Slide15

Secondary

hyperaldosteronism

:

- activation

of the renin-angiotensin

system

increased

levels of plasma

renin

Causes:

- Decreased

renal

perfusion (renal

artery stenosis)

- Arterial

hypovolemia

+ edema

(congestive heart

failure, cirrhosis,

nephrotic

syndrome)

- Pregnancy (estrogen)Slide16

Primary

hyperaldosteronism

:

suppression

of the renin-angiotensin system

-

decreased plasma

renin

activity

Causes:

bilateral nodular hyperplasia of the adrenal glands

(60%)

Adrenocortical adenoma

(35

%)---

Conn

syndrome

Adrenocortical carcinoma

familial

hyperaldosteronism

(aldosterone synthase

gene,

CYP11B2)Slide17

Aldosterone-producing

adenomas:

solitary,

small

(less than 2 cm in diameter

)

well-circumscribed

bright yellow

Spironolactone bodies ????

the adjacent

adrenal cortex

and that of the contralateral gland

are ????????????Slide18

Clinical

Features:

Hypertension

primary

hyperaldosteronism

may

be the most common cause of

secondary hypertension

Hypokalemia

neuromuscular

manifestations (weakness

,

paresthesias

, visual

disturbances, and

tetany

)Slide19

Treatment:

surgical

excision

aldosterone antagonistSlide20

Adrenogenital Syndromes

Androgen excess --------

virilization

adrenocortical

neoplasms ---- Carcinoma

congenital adrenal hyperplasia

isolated

syndrome or in combination with features

of Cushing disease------ ACTHSlide21

congenital adrenal

hyperplasia (CAH)

:

autosomal

recessive

- Enzyme defect ---- adrenal

steroid biosynthesis (

cortisol)

increase

in

ACTH

Adrenal hyperplasia

androgens with

virilizing

activity

- Certain enzyme defects

also may impair aldosterone secretion, adding

salt loss

to the

virilizing

syndromeSlide22

21-hydroxylase deficiency (

CYP21A2 gene)

11β-

hydroxylase deficiencySlide23

the adrenals

are hyperplastic bilaterally

Brown

adrenomedullary

dysplasia

Hyperplasia of

corticotroph

(

ACTH-producing) cells

is present in the anterior pituitarySlide24

Clinical

Features:

perinatal period,

later childhood,

Adulthood

excessive androgenic activitySlide25

Females:

masculinization,

clitoral

hypertrophy

and

pseudohermaphroditism

in

infants

delayed

menarche,

oligomenorrhea

,

hirsutism

, and acne in

postpubertal

girls

.Slide26

In

males:

enlargement

of the external genitalia and other evidence

of precocious

puberty in

prepubertal

patients

Oligospermia

in

older patientsSlide27

-

sodium

retention and

hypertension

11β-hydroxylase

deficiency, the

accumulated

intermediary steroids

have mineralocorticoid

activity.

-

Salt

(sodium) wasting

21-hydroxylase deficiency, the enzymatic defect is severe enough to produce mineralocorticoid

deficiency.Slide28

Neonate:

Ambiguous

vomiting

,

dehydration, and

salt wasting

.

Treatment

of

CAH: exogenous

glucocorticoidsSlide29

ADRENOCORTICAL NEOPLASMS

Hyperadrenalism

functional

adenomas:

hyperaldosteronism

, Cushing syndrome

Carcinoma:

virilization

, rare

Non-functionalSlide30

ADRENAL INSUFFICIENCY

Primary: acute

chronic

Secondary Slide31

Acute Adrenocortical Insufficiency

chronic adrenocortical

insufficiency--- acute crisis----

after any

stress

patients

maintained

on

exogenous

corticosteroids

:

rapid

withdrawal of

steroids

failure

to

increase steroid doses---- stress

Massive adrenal

hemorrhage:

Anticoagulant therapy, DIC, pregnancy, overwhelming sepsis

(Waterhouse-

Friderichsen

Syndrome)Slide32

Waterhouse-

Friderichsen

syndrome:

Neisseria

meningitidis

septicemia---endotoxin--- DIC

Pseudomonas spp

.,

pneumococci

,

Haemophilus

influenzaeSlide33

Chronic Adrenocortical Insufficiency:

Addison

Disease:

Causes:

- autoimmune

adrenalitis

,

- infections: tuberculosis

,

fungi

- the

acquired immune deficiency

syndrome (AIDS): infections,

kaposi

sarcoma

metastatic

cancer: lung and

breast carcinomas

Amyloidosis

Sarcoidosis

Hemochromatosis Slide34

Autoimmune

adrenalitis

:

Mc

two

autoimmune

polyendocrine

syndromes (APS)

:

APS1

:

chronic

mucocutaneous

candidiasis and abnormalities of

skin, dental

enamel, and nails (ectodermal dystrophy)

, organ-specific autoimmune

disorders (autoimmune

adrenalitis

,

autoimmune

hypoparathyroidism

, idiopathic

hypogonadism

,

pernicious

anemia)----- autoimmune

regulator (

AIRE

)

Gene

APS2

: adrenal insufficiency and autoimmune thyroiditis

or type

1

diabetes

Adrenal

:

lymphoid

infiltrateSlide35

Secondary Adrenocortical Insufficiency

hypothalamus and

pituitary disorders

low serum

ACTH

prompt

rise in

plasma cortisol

levels in response to ACTH

administration

no hyperpigmentation

Adrenal: Atrophic cortex, intact medullaSlide36

Clinical Features

of adrenocortical insufficiency:

- progressive

weakness and easy

fatigability

- Gastrointestinal disturbances (anorexia

,

nausea, vomiting, weight loss, and

diarrhea)

hyperpigmentation

of the skin and mucosal surfaces:

primary

adrenal

disease

hyperkalemia,

hyponatremia

,

volume depletion

, and

hypotension

:

primary

adrenal

disease

Hypoglycemia

acute adrenal

crisis

: stress---

intractable

vomiting, abdominal pain,

hypotension, coma

, and vascular collapse. Death follows

rapidly unless

corticosteroids are replaced immediatelySlide37

ADRENAL MEDULLA

Pheochromocytoma

:

rule of

10s:

10%

extraadrenal

-

--------

paragangliomas

10

% bilateral, but 50

% in familial cases

10%

malignant

10% no hypertension (paroxysmal)

25% familial

germline

mutation in one of 6 genes:

RET (MEN2), NF1, VHL, SDHB, SDHC, SDHDSlide38
Slide39

the definitive diagnosis

of malignancy

in

pheochromocytomas

is based

exclusively on

the presence of metastasesSlide40

Clinical

Features:

- Hypertension

(abrupt, sustained or episodic )

tachycardia, palpitations

, headache, sweating, tremor, and a sense

of apprehension

Sudden cardiac death

(arrhythmias)

ACTH and

somatostatinSlide41

The laboratory diagnosis of

pheochromocytoma

is

based on demonstration of

increased urinary

excretion of free

catecholamines

and their

metabolites, such

as

vanillylmandelic

acid

and

metanephrines

.

Isolated benign

pheochromocytomas

are treated with

surgical excision

.

With

multifocal lesions, long-term

medical treatment

for hypertension may be required.Slide42

MULTIPLE ENDOCRINE NEOPLASIA SYNDROMES

Inherited

younger

age

multiple endocrine

organs

Multifocal

Asymptomatic stage

of endocrine

hyperplasia

more aggressiveSlide43

Multiple Endocrine Neoplasia

Type 1

AD

MEN1 gene (tumor

supressor

)

,

ch

11

3 Ps:

Parathyroid

(hyperplasia, adenomas)– 80-95%

Pancreas

(

gastrinomas

,

insulinomas

)

Pituitary (

prolactin adenoma)Slide44

Multiple Endocrine Neoplasia

Type 2

AD

RET (proto-oncogene), ch 10Slide45

MEN type

2A:

Thyroid: Medullary

carcinoma

Adrenal medulla:

pheochromocytomas

Parathyroid: parathyroid gland hyperplasiaSlide46

Multiple

Endocrine

Neoplasia

Type

2B:

Thyroid (as 2A)

Adrenal

medulla (as 2A)

Extraendocrine

manifestations

:

-

ganglioneuromas

of mucosal

sites (gastrointestinal tract, lips, tongue

)

-

marfanoid

habitus