Adrenal and retropetionium - PowerPoint Presentation

Slide1

Adrenal and retropetioniumSlide2

Disorders of the Adrenal Cortex

Hyperaldosteronism:

Hyperaldosteronism

may be

secondary to stimulation

of the renin-angiotensin system from renal

artery stenosis

and to low-flow states such as congestive heart

failure and

cirrhosis.

Primary hyperaldosteronism

results from autonomous

aldosterone secretion

,

leads

to suppression of renin secretion

. Hypokalemia.

Most cases result from a solitary

functioning adrenal

adenoma (∼70%) and idiopathic bilateral

hyperplasia (30

%). Adrenocortical carcinoma and

glucocorticoid-suppressible hyperaldosteronism

are

rare.

Symptoms and

Signs:

hypertension

,

muscle weakness, polydipsia, polyuria,

nocturia

, headaches

, and fatigue. Weakness and fatigue are related to

the presence

of hypokalemia.

Diagnostic Studies

Laboratory

Studies

Hypokalemia.

plasma aldosterone concentration–to–plasma

renin activity

ratio of 1:25 to 30 is strongly suggestive of the diagnosis

.

Radiologic Studies.

CT scans with 0.5-cm cuts in the

adrenal area

can localize

aldosteronomas

with a sensitivity of 90

%.

MRI scans are less

sensitive but

more

specific.

Selective venous catheterization

and adrenal

vein sampling for

aldosterone.

Scintigraphy with 131I-6

β-

iodomethyl

noriodocholesterol

(

NP-59) also

may be used for the same purpose.

Treatment:

Unilateral tumors producing aldosterone are best managed

by adrenalectomy.

For the other

patients, medical

therapy with spironolactone,

amiloride

, or

triamterene is

the mainstay of management.Slide3

Cushing’s Syndrome.

Cushing described patients with a

peculiar fat

deposition, amenorrhea, impotence (in men

), hirsutism, purple

striae

, hypertension, diabetes, and other features that

constitute the syndrome.

Today, the term

Cushing’s syndrome

refers

to a

complex of symptoms and signs resulting from

hypersecretion of

cortisol regardless of etiology.

In contrast,

Cushing’s

disease

refers

to a pituitary tumor, usually an adenoma, which leads

to bilateral

adrenal hyperplasia and

hypercortisolism

.

Although most individuals have sporadic

disease.

Cushing’s syndrome

may be found in MEN1

families.Slide4

Etiology

of Cushing’s syndrome

ACTH-dependent (70%)

• Pituitary adenoma or Cushing’s disease (∼70%)

• Ectopic ACTH

production

a

(∼10%)

• Ectopic CRH production (<1%)

ACTH-independent (20%–30%)

• Adrenal adenoma (10%–15%)

• Adrenal carcinoma (5%–10%)

• Adrenal hyperplasia—pigmented

micronodular

cortical hyperplasia

or gastric inhibitory

peptide-sensitive

macronodular

hyperplasia (5%)

Other

• Pseudo-Cushing’s syndrome

• Iatrogenic—exogenous administration of steroids

_________________________________

a

From

small cell lung tumors, pancreatic islet cell tumors,

medullary thyroid

cancers,

pheochromocytomas

, and carcinoid tumors of the

lung, thymus

, gut, pancreas, and

ovary.

ACTH

= adrenocorticotropic hormone; CRH =

corticotrophin-releasing hormone

.Slide5

Patients with major

depression, alcoholism

, pregnancy, chronic renal failure, or stress

also may

have elevated cortisol levels and symptoms

o

hypercortisolism

. However

, these manifestations resolve with treatment

of the

underlying disorder, and these patients are deemed to

have pseudo-Cushing’s

syndrome.Slide6

Symptoms and

Signs ;

Progressive

truncal obesity is

the most

common symptom, occurring in up to 95% of patients.

System

Manifestation

General

Weight gain—central obesity,

buffalo hump, supraclavicular

fat pads

Integumentary

Hirsutism, plethora, purple

striae

, acne, ecchymosis

Cardiovascular

Hypertension

Musculoskeletal

Generalized weakness,

osteopenia

Neuropsychiatric

Emotional lability, psychosis,

depression

Metabolic

Diabetes or glucose

intolerance, hyperlipidemia

Renal

Polyuria, renal stones

Gonadal

Impotence, decreased libido,

menstrual irregularitiesSlide7

Diagnostic

Tests:

confirm

the presence of Cushing’s syndrome and

to determine

its

etiology.

characterized

by elevated

glucocorticoid levels that are not suppressible by

exogenous hormone

administration and loss of diurnal variation.Radiologic Studies:

CT and MRI

scans.

Radioscintigraphic

imaging.

Treatment:

Laparoscopic adrenalectomy is the treatment

of choice

for patients with

adrenal adenomas

. Open

adrenalectomy is

reserved for large tumors (≥6 cm) or those suspected to

be adrenocortical

cancers. Bilateral adrenalectomy is curative

for primary

adrenal

hyperplasia. Slide8

The treatment of choice in Cushing’s disease is

transsphenoidal

excision

of the pituitary

adenoma.

Pituitary irradiation has been used for

patients with

persistent or recurrent disease after surgery.

Patients with ectopic ACTH production are best

managed by

treating the primary tumor.Slide9

Adrenocortical Cancer.

Adrenal carcinomas are rare

neoplasms with

a worldwide incidence of two per 1 million.

The majority

are

sporadic,

but adrenocortical carcinomas

also occur

in

(Li-

Fraumeni syndrome

) and

MENIN

(multiple endocrine neoplasia type 1

).

Symptoms and Signs

Approximately 50% of

adrenocortical cancers

are

nonfunctioning.

The remaining secrete

cortisol

(30

%), androgens (20%), estrogens (10%), aldosterone (2

%),

or

multiple hormones (35%).

Diagnostic

Tests:

measurement of serum electrolyte levels to rule out

hypokalemia, urinary

catecholamines

to rule out

pheochromocytomas

, an

overnight 1-mg dexamethasone suppression test, and

a 24-hour

urine collection for cortisol and 17-ketosteroids to

rule out

Cushing’s syndrome.

CT and MRI

scans.

FDGPET

or

PET-CT scans may have some utility in

distinguishing benign

from malignant

lesions.Slide10

Treatment:

The most important predictor of survival in

patients with

adrenal cancer is the adequacy of resection.Slide11

Sex Steroid

Excess:

Adrenal adenomas or

carcinomas that

secrete adrenal androgens

lead to

virilizing

syndromes. Although

women

with

virilizing tumors develop hirsutism,amenorrhea, infertility, and other signs of masculinization,

suchas

increased muscle mass, deepened voice, and temporal

balding,

men

with these tumors are more difficult to diagnose

and, hence

, usually present with disease in advanced stages.

Children with

virilizing

tumors

have accelerated growth,

premature development

of facial and pubic hair, acne, genital

enlargement, and

deepening of their

voice.

Feminizing

adrenal tumors

are

less common

and occur in

men

in the third to fifth decades of

life. These

tumors lead to gynecomastia, impotence, and

testicular atrophy

.

Women

with these tumors develop irregular

menses or

dysfunctional uterine bleeding. Vaginal bleeding may

occur I postmenopausal

women. Girls with these tumors

experience precocious

puberty with breast enlargement and early menarche.

Diagnostic

Tests: lab teste.

Eg

androgen

precursor

,

plasma or urine as

17-ketosteroids, etc.Slide12

Treatment

Virilizing

and feminizing tumors are treated

by

adrenalectomy

. Malignancy

is difficult to diagnose histologically

but is

suggested by the presence of local invasion, recurrence,

or distal

metastases.

Adrenolytic drugs such as mitotane,

aminoglutethimide

, and

ketoconazole may be useful in controlling

symptoms in

patients with metastatic disease.Slide13

Disorders of the Adrenal Medulla

Pheochromocytomas

:

Pheochromocytomas

are

rare

tumors

with

prevalence rates ranging from 0.3% to 0.95% in

autopsy series

and approximately 1.9% in series using

biochemical screening

. They

can occur at any age

, with a

peak incidence in

the fourth

and fifth decades of life

, and have no gender predilection.

Extra-adrenal tumors, also called functional

paragangliomas

.

Pheochromocytomas

often

are

called the

10 percent tumor

because 10

% are bilateral, 10% are malignant, 10% occur in

pediatricpatients

, 10% are extra-adrenal, and 10% are familial.

Pheochromocytomas

occur in families with MEN2A

and MEN2B

in approximately 50% of patients

.

MEN1

syndrome.

Symptoms and

Signs:

Headache, palpitations, and

diaphoresis constitute

the “classic triad”

of

pheochromocytomas

.

Cardiovascular

complications,.

The

most common clinical sign is hypertension.

may be paroxysmal

with intervening

normotension

, sustained with paroxysms

or sustained hypertension alone.

Sudden

death may occur

in patients

with undiagnosed tumors who undergo other

surgeries or

biopsy.Slide14

Diagnostic Tests

Biochemical

Studies:

24-hour urine samples for

catecholamines

and their

metabolitesas

well as by determining plasma

metanephrine

levels.VMA measurements are slightly less sensitive and specific.Extraadrenal

tumors

secrete norepinephrine, whereas epinephrine

is the

main hormone secreted from adrenal

pheochromocytomas

.

Radiologic

Studies:

o

localize tumors

and to assess the extent of spread once

th

diagnosis has been

made with biochemical tests.

CT

scans, MRI scans,

Metaiodobenzylguanidine

(

MIBG) is

taken up and concentrated by vesicles in the adrenal

medullar cells

because its structure is similar to norepinephrine

.

131I-radiolabeled

MIBG

especially those in ectopic positions.Slide15

Treatment:

The medical management of

pheochromocytomas

is aimed

chiefly at blood pressure control and volume repletion.

long-acting α-blockers such as

phenoxybenzamine

are

started 1 to 3 weeks before surgery

β-Blockers such as propranolol often need to be added preoperatively in patients

who have

persistent tachycardia and arrhythmias

β-

Blockers

should only

be instituted after adequate α-blockade and hydration

to avoid

the effects of unopposed α stimulation (i.e.,

hypertensive

crisis and congestive heart failure

).

Adrenalectomy is the treatment of choice for patients

with

pheochromocytoma

.

to resect

the tumor

completely with minimal tumor manipulation or

rupture of

the tumor capsule.Slide16

Hereditary

Pheochromocytomas

Malignant

Pheochromocytomas

:

Malignancy usually

is diagnosed

when there is evidence of invasion into

surrounding structures

or distant metastases.

The Adrenal

Incidentaloma

Adrenal

lesions discovered during imaging performed for

unrelate

reasons

are referred to as

incidentalomas

.

Adrenal

Insufficiency:

may be primary, resulting from

adrenal disease

, or secondary, due to a deficiency of

ACTH. Treatment

must be initiated based on clinical

suspicion alone

, even before test results are obtained, or the

patient is

unlikely to survive.Slide17

multiple endocrine neoplasia type I (

MEN I

), which consists of parathyroid, pituitary, and pancreatic (

or duodenal

) tumors.

MEN2A:

MTC,

pheochromocytoma

,

primary hyperparathyroidism.

MEN2A is associated with medullary thyroid carcinoma

and pheochromocytoma or parathyroid adenoma

MEN2B:

MTC,

pheochromocytoma

,

Marfanoid

habitus

,

mucocutaneous

ganglioneuromatosis

MEN2B is associated with medullary

thyroid carcinoma

,

marfanoid

habitus, mucosal neuromas,

and

ganglioneuromatosis

.Slide18

RETROPERITONEUM

Surgical

Anatomy:

The retroperitoneum is defined as the space between the

posterior envelopment

of the peritoneum and the posterior body

wall.

The retroperitoneal space is bounded superiorly

bythe

diaphragm, posteriorly by the spinal column and

iliopsoas muscles, and inferiorly by the

levator

ani

muscles

.

Retroperitoneal

Infections:

Retrocecal

appendicitis, contained

perforation of duodenal ulcers,

iatrogenic perforation

with esophagogastroduodenoscopy or

endoscopic retrograde

cholangiopancreatography, and complicated

pancreatitis may

all lead to retroperitoneal infection with or

without abscess

formation.Slide19

The site of pain may

be variable

and can include the back, pelvis, or thighs.

Erythema may

be observed around the umbilicus or flank.

The

diagnosis is

best established by

CT.

Management

includes identification

and treatment of the underlying condition, intravenous antibiotics

, and drainage of all well-defined collections.Slide20

Retroperitoneal

Fibrosis:

Retroperitoneal fibrosis is a class of disorders characterized

by

hyperproliferation

of fibrous tissue in

the retroperitoneum

.

may be a primary disorder as in idiopathic retroperitoneal

fibrosis, also

known as Ormond’s disease, or a secondary reaction

to an

inciting inflammatory process, malignancy, or medication.

Presenting symptoms depend on the structure or

structures affected

by the fibrotic process. Initially, patients complain

of the

insidious onset of dull, poorly localized abdominal

pain. Sudden-onset

or severe abdominal pain may signify acute

mesenteric ischemia

. Other symptoms of retroperitoneal

fibrosis may

include unilateral leg swelling, intermittent

claudication, oliguria

, hematuria, or dysuria.Slide21

findings on

physical examination

vary with the retroperitoneal structure

involved. Consequently

, findings may include hypertension, the

palpation of

an abdominal or flank mass, lower-extremity edema (

unilateral or

bilateral), or diminished lower-extremity pulses (

unilateral or

bilateral).

Laboratory evaluation and Many imaging modalities have been

used.

Once malignancy, drug-induced, and infectious

etiologies are

ruled out, treatment of

the retroperitoneal

fibrotic

process is

instituted. Corticosteroids, with or without surgery, are

the mainstay

of medical therapy. Surgical treatment consists

primarily of

ureterolysis or ureteral stenting and is required in

patients who

present with significant

hydronephrosis

.

Endovascular interventions for

iliocaval

occlusion

Cyclosporin

, tamoxifen

, and azathioprine have also been used to

treat patients

who respond poorly to corticosteroids.Slide22
Slide23

The outermost layer, the 

zona glomerulosa

 is the main site for production of 

aldosterone

.

Situated between

the glomerulosa and

reticularis the

zona

fasciculata

 is responsible for

prdoucing

glucocorticoids

. Such as

11deoxycorticosterone

, 

corticosterone

, and 

cortisol

The inner most cortical

layer, the

zona reticularis

 produces 

androgens

,mainly

dehydroepiandrosterone

 (DHEA), 

DHEA sulfate

 (DHEA-S), and 

androstenedione

 (the precursor to 

testosterone

) in humans.Slide24

Adrenal

Physiology

Cholesterol, derived from the plasma or synthesized in the

adrenal, is

the common precursor of all steroid hormones

derived from

the adrenal cortex

.

Mineralocorticoids:

aldosterone, 11-deoxycorticosterone (DOC),

and cortisol

.

Aldosterone secretion is regulated

primarily by

the renin-angiotensin

system.

Decreased renal blood

flow, decreased

plasma sodium, and increased sympathetic

tone all

stimulate the release of renin from juxtaglomerular cells.

Glucocorticoids:

cortisol, the major

adrenal glucocorticoid

, is regulated by ACTH secreted by the

anterior pituitary

, which, in turn, is under the control of

corticotrophinreleasing

hormone

(CRH) secreted by the hypothalamusSlide25

Functions of glucocorticoid hormones

Function/System

Effects

Glucose metabolism

Increased hepatic

glycoge

deposition, gluconeogenesis,

decreased muscle

glucos

uptake and metabolism

Protein metabolism

Decreased muscle protein synthesis, increased Catabolism

Fat metabolism

Increased lipolysis in adipose tissue

Connective tissue

Inhibition of fibroblasts, loss of collagen, thinning of skin,

striae

formation

Skeletal system

Inhibition of bone formation, increased osteoclast activity,

potentiate the action of PTH

Immune system

Increases circulation of

polymorphonuclear

cells; decreases numbers of lymphocytes, monocytes, and eosinophils; reduces migration of inflammatory cells to sites of injury

Cardiovascular system

Increases cardiac output and peripheral vascular tone

Renal system

Sodium retention, hypokalemia, hypertension via mineralocorticoid effect, increased glomerular filtration via glucocorticoid Effects

Endocrine system

Inhibits TSH synthesis and release, decreased TBG

levels, decreased conversion of T4 to T3