By Shifaa Qaqa adrenal glands cortex medulla ADRENOCORTICAL HYPERFUNCTION HYPERADRENALISM Cushing syndrome hyperaldosteronism adrenogenital or virilizing syndromes ID: 745423
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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 hyperplasiaSlide6Slide7
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 secretionSlide13Slide14
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, SDHDSlide38Slide39
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