Diseases of adrenal cortex & medulla - PowerPoint Presentation

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Diseases of adrenal cortex & medulla

Ali Al Khader, M.D.

Faculty of Medicine

Al-Balqa’ Applied University

Email: ali.alkhader@bau.edu.jo

Lecture outlineAdrenocortical hyperfunction (Hyperadrenalism):

-Hypercortisolism (Cushing syndrome)

-Primary hyperaldosteronism

-Adrenogenital (

virilizing

) syndromes…excess androgens

Adrenocortical insufficiency

Adrenocortical neoplasms

Tumors of the adrenal medulla:

-Pheochromocytoma

-Neuroblastoma

Hypercortisolism (Cushing syndrome)

Exogenous (Iatrogenic)

The most common

Endogenous

ACTH-dependent

ACTH-independent

-Pituitary

t

umor (mostly

ACTH-secreting

m

icroadenoma

)

-Rarely: increased

CRH (from

hypothalamus)

= Cushing disease

Ectopic ACTH

…e.g., lung

small cell

carcinoma

Less common than

-Adrenal adenoma

-Adrenal carcinoma

-Hyperplasia (a subset

of them is seen in McCune-Albright syndrome (GNASmutations))

Middle-aged

males more

Young adult females more

-Thinning of hair

-Acne-Red cheeks-Moon face-Supraclavicular fat pad-Increased body and facial hair-Hypertension-Diabetes-Immunodeficiency-Weight gain-Purple striae-Pendulous abdomen-Thin extremities with muscle atrophy-Ecchymosis resulting from easy bruising-Menstrual abnormality-Thin skin and subcutaneous tissue-Slow wound healing-Mental/psychological manifestations

Elsevier. Kumar et al. Robbins and

Cotran

pathologic basis of diseases

9

th…

Reproduced

with permission

from Lloyd RV, et al (

eds

): Atlas of

Nontumor

Pathology: Endocrine Diseases.

Washington, DC, American Registry of Pathology, 2002.)

Cushing syndrome, laboratory diagnosis

Cushing disease

-ACTH is not suppressed

with low-dose dexamethasone

…urinary steroid secretion

is not decreased

-ACTH is suppressed with

high-dose dexamethasone

…urinary steroid secretion

is decreased

No response to high-

or low-dose dexamethasone

Ectopic ACTH

Adrenal tumor

ACTH is already lowand cortisol excretionis not affected by low- or high-dose

dexamethasone

Primary hyperaldosteronism

Autonomous overproduction of

aldosterone, with resultant suppression of the

renin-angiotensin system

and decreased plasma renin

activity

Causes:

Bilateral idiopathic hyperaldosteronism…

the most common

Bilateral nodular hyperplasia

Older age & less severe hypertension than

h

yperaldosteronism due to adrenal tumor

Adenoma (

Conn syndrome

)or carcinoma

Middle-aged women more

2ry Hyperaldosteronism:

…in response to activation of the renin-angiotensin system…characterized by increased levels of plasma renin…seen in conditions of decreased renal perfusion

The most common cause of 2ry hypertension

Primary hyperaldosteronism, clinical features & diagnosis

Hypertension with resulting left ventricular hypertrophy and cardiovascular compromise, strokes & MIs

Hypokalemia (weakness,

paresthesias

, visual disturbances, and

occasionally frank tetany)

Elevated plasma aldosterone to renin ratio …if

this screening test is positive, a confirmatory aldosterone suppression test (by salt or captopril for example)

must be performed …if the aldosterone levels are still high and the renin levels are still low

after the suppression test, the diagnosis is confirmed

Adrenogenital (virilizing) syndromes

Adrenocortical neoplasms

Congenital adrenal hyperplasia (CAH)

Carcinomas more than adenomas

The most

common enzymatic defect in CAH is 21-hydroxylase deficiency…a spectrum of severity depending on the mutation

Cortisol is not synthesized

(&/or aldosterone)

ACTH is increased

In response to ACTH, no cortisol will be synthesized but the androgen

synthesis pathway will be activated instead

21-hydroxylase is required for synthesis of

c

ortisol

and aldosterone but not sex steroids

Adrenogenital (virilizing) syndromes, clinical features

The

onset of

clinical symptoms

may occur in the perinatal period, later

childhood, or

(less commonly)

adulthoodIn 21-hydroxylase deficiency:-Masculinization (

virilization) in females:

-In males:Enlargement of the external genitalia, precocious puberty in young patients. Most men

with CAH are fertile but some have failure of Leydig cell development and oligospermia

Clitoral

hypertrophy and pseudohermaphroditism in infants or oligomenorrhea, hirsutism, and acne

in postpubertal girls …an ovarian tumor must also be excluded

1/3: aldosterone deficiency and some may have risk

for acute adrenal insufficiency

Always rule out CAH in any neonate with ambiguous genitalia

Adrenocortical insufficiency

= Addison disease

= Adrenal crisis

Primary

Secondary

…due to ACTH deficiency

…mainly: lung & breast

Hyperpigmentation

No hyperpigmentation

Normal aldosterone

Fatigue

Vomiting

Diarrhea

Anorexia, nausea & weight loss

Hypoglycemia

Hyperkalemia

Hyponatremia

Hypotension

Elsevier. Kumar et al. Robbins basic pathology

10

th

…modified

Notes on adrenocortical adenoma and carcinoma

The most common adrenal malignancy is metastases (especially from the lung or breast)

Adenoma is usually nonfunctional and is usually discovered incidentally (

incidentaloma

)

“Functional” or “nonfunctional” cannot be predicted from morphology

Behavior is more important than morphology to differentiate between adenoma and carcinoma

PheochromocytomaA tumor of chromaffin cells

A cause of 2ry hypertension…mainly paroxysmal (with palpitations, sweating & tremor)

Rule of 10s:

10% of

pheochromocytomas

are

extraadrenal… =

paragangliomas10% of adrenal pheochromocytomas are bilateral

10% of adrenal pheochromocytomas are malignant10% of adrenal

pheochromocytomas are not associated with hypertension25% are familial…6 known genes (RET, NF1, VHL, SDHB, SDHC, SDHD)

There is usually base-line hypertension

C

atecholamine cardiomyopathy, or catecholamine-induced

myocardial instability and ventricular arrhythmias and cerebrovascular accidents are serious complications

Lab results: I

ncreased urinary excretion

of free catecholamines and their metabolites, such as

vanillylmandelic acid and metanephrines

Capillary network

Pheochromocytoma

Sustentacular

cells

Nest

Nest

Nest

This nested

p

attern is called:

Zellballen

pattern

Modified from: T

Karthikeyan

, D

Manimaran

, V

Mrinalini

. 

Multicentric

Paraganglioma Of The Bladder - A Rare Case Report

. The Internet Journal of Pathology. 2012 Volume 13 Number 2.

NeuroblastomaThe most common extracranial solid tumor of childhood…most commonly during

the first 5 years of life and may arise

during

infancy

It arises from primordial neural crest cells

Neuroblastomas may occur anywhere in the

sympathetic nervous system and occasionally within the brain, but they are most common in the abdomen (esp., adrenal medulla)

Homer Wright rosettes

Elsevier. Kumar et al. Robbins and

Cotran

pathologic basis of diseases 9

th

Neuroblastoma

Unfortunately, most (60% to 80%) children present

w

ith stage 3 or 4

4S tumors have an excellent prognosis with

minimal therapy, and it is not uncommon for the

primary or metastatic 4S tumors to undergo spontaneous

regression

*Age <18 months: favorable prognosis

*Certain genetic/chromosomal abnormalities are important in the prognosis (e.g., MYCN oncogene amplification is bad)*Certain histological features are important in the prognosis (

Gangliocytic differentiation is associated with favorable prognosis, high mitotic activity is bad)

*Stages 1, 2A, 2B & 4S are better than 3 & 4

Elsevier. Kumar et al. Robbins basic pathology

10th

…modified

Thank You