Practical 1
Adrenal and parathyroid glands
Dr.Ashraf A.fatah Deya
Normal Adrenal glands= weighs from 4 to 6 grams Head,
body and tail
.
Adrenal Cortex
Zona glomerulosa
Zona fasciculata
Zona reticularis
3
Practical 4:Pathology of Parathyroid &Adrenal Glands
• By the end of this session, the student should:
• Identify the various conditions of parathyroid and
adrenal glands associated with morphological
changes (microscopic and gross).
•  Robbins Basic pathology 9th edition pg - 734 738
Adrenal glands hyperfunction state
1.
2.
3.
Adrenal cortical hyperplasia= Cushing Syndrome.
Congenital Adrenogenital syndrome=(sex steroid hormones)
Adrenal cortical adenoma\Associated with Hyperaldosteronism =
(Conn’s syndrome).
4.
Cushing syndrome= role of corticotropin level to rule out
(Pituitary/Hypothalamic-Based Hyperplasia\adenoma, Paraneoplastic
(Ectopic) Production (lung ca), primary cortical adenoma\hyperplasia).
5.
Neuroblastoma (catecholamine precursors and their metabolites, e.g.
metaphrine and pro-metaphrine).
6.
Phaeochromocytoma (catecholamine precursors and their metabolites,
e.g. VMA, metaphrine and pro-metaphrine)
-
A) Atrophied adrenal glands
B) Normal adrenal glands
C) Adrenal hyperplasia
Case No- 1
• Q1 Write two clinical
examples for the
morphologic features
shown in photo No (A)
=atrophy?
• A1= Adrenal atrophy
• 1) Addison’s disease (10% ) OR
90% in TB
• b) Long term corticosteroid
therapy shuts off
• A2= Adrenal hyperplasia
• Q2 Write four clinical
• a) Pituitary adenoma secreting
examples for the
ACTH (Pituitary -Cushing's
morphologic features
disease).
shown in photo No (C) ?
• b) Ectopic ACTH production• = hyperplasia
(paraneoplasia- Cushing's
syndrome).
• Q3- describe the
• c) Congenital Adrenogenital
morphological appearance
syndromes.
of C?
• D) Idiopathic hyperplasia
Case No -2
• The parents of a girl
notice that she has
developed features that
suggest puberty over
the past 6 months.
• On physical
examination, she has
few sex characteristics
with Ambiguous
genitalia.
• Lab investigationincreased pituitary
ACTH production,
Markedly elevated
Testosterone
Answers- Case No -2
• Q1- what’s the most likely the diagnosis?
• Congenital Adrenal Hyperplasia (Adrenogenital Syndrome)
• Q2-What would be the adrenal status\
morphology in this patient?
• Bilateral enlarged hyperplastic adrenals (upto 16 g) with
cerebriform appearance
• Q3- What is the etiology of this condition?
• Autosomal recessive disorders characterized by enzymatic
defects (5 enzymes) in cortisol synthesis e.g 21-hydroxylase
• Q4-Write 4 other investigations, which are helpful
in reaching the final diagnosis?
• Q5- What’s the complications of this syndrome?
Answer- case-2= Congenital Adrenal Hyperplasia
adrenal hyperplasia.
A4= 1- S. cortisol level (a.m\
. • Congenital
Normal cortex
p.m)(Decrease)
2- S. Aldosterone ( Decrease)
3- ACTH level
( Increase)
4- Increased levels of
Progesterone , 17-OHprogesterone, and
dehydroepiandrosterone
(DHEA)  Testosterone .
4-Abdominal ultrasound
Looking for adrenals
A5- Sexual development
abnormalities,
Hypertension, Adrenal
insufficiency, Sodium
imbalances.
•
replaced by clear-cell nodules
Normal cortex replaced by
clear-cell nodules “lipid depleted”.
Differential diagnosis:
1- Adrenal cortical hyperplasia
2- Beckwith-Wiedemann
syndrome:
13
Consequences of C-21 hydroxylase deficiency: 
 Impairs the synthesis of both cortisol and aldosterone
Summary of Adrenogenital Syndromes
Laboratory
21-OHase
Deficiency
11-OHase
Deficiency
17-Ketosteroids
↑
↑
17-Hydroxyprogesterone
↑
↑
17-Hydroxycorticoids
↓
↑
Mineralocorticoids
↓
↑
15
Case No- 3
• A 28-year-old, otherwise
healthy man sees his physician
because he has had headaches
for the past 2 weeks.
• Physical examination yields no
remarkable findings except for a
blood pressure of 170/110 mm
Hg. Trousseau’s Sign while
taking blood pressure.
– Lab investigations revealed
– Hypernatremia
– Hypokalemia
– ↑ plasma aldosterone level
– Normal glucose level
• An abdominal CT scan shows an
enlarged right adrenal gland.
• A right adrenalectomy is done;
the figure shows the gross
appearance of the specimen.
Q1-what is the
diagnosis?
Q2- Describe the
morphologic features?
Q3- write single
screening test of choice
for diagnosis?
Q4- write other causes
of primary
hyperalosteronism ?
18
Answer- Case No- 3 = primary hyperaldosteronism
(Conn syndrome).
• A3= The plasma
• A2=a) The gross specimen
aldosterone: Plasma renin
Yellow-orange tumor nodule
activity ratio > 30 is
in the adrenal cortex,
diagnostic.
localized, nodular, solitary,
circumscribed nature.
• (function or non-functional)?? • A4= common:
• 1- Unilateral Adrenal
adenoma (2\3).
• b) Histologic features :
• 2- Bilateral adenoma (1\3)
• The neoplastic cells are
vacuolated \clear because of
the presence of
• Less common:
intracytoplasmic lipid, with
• Unilateral Adrenal carcinoma <1%
mild nuclear pleomorphism. • Unilateral hyperplasia < 1%
No Mitotic activity &necrosis. • Familail cases < 1%
Case No- 4
• 40-year-old female sees her physician
because she has had headache,
weakness, and a 5-kg weight gain
over the past 3 months.
• On physical examination, her face is
puffy. Her temperature is 36.9°C,
pulse is 79/min, RR=15/min, BP=
160/75 mm Hg while lying down.
• A radiograph of the spine shows a
compressed fracture of T11.
• MRI- pituitary g. was clear.
• Laboratory findings (see table).
• Q1- Discuss the Lab findings and
what’s the value of doing
dexamethasone test,?
• Q2-what is the diagnosis?
• Q3- describe the morphology of the
excised gland?
Test name
concentration
Reference
value
Glucose
7.1 mmol\L
3.6 – 5.5
Serum Na+
150 mmol\L
135 - 145
Serum K+
3.1mmol\L
3.5 - 5
Plasma Cortisol
414 nmol\L
< 138
Dexamethasone
suppression test
Not
suppressed
in high dose
Free 24 Urine
cortisol-UFC
596 nmol\day 55 - 228
"moon facies,"
reddish face
thin upper extremity
truncal obesity
purple abdominal striae
22
Adrenal gland adenoma from a patient with Cushing's syndrome
C\S solid yellowish, circumscribe mimic fasciculata zone
23
Answer case No- 4 = Cushing syndrome
• A1= The dexamethasone suppression test (1mg at 22:00- 6days) is used to
localize the source of excess cortisol is employed in an attempt to induce
suppression of the hypothalamic–pituitary–adrenal cortical axis (HPAC)
• When Low-dose and High-dose dexamethasone trials secretion
Interpretation
• 1) Suppression occur in high dose= ACTH-secreting pituitary adenoma
• 2) Failure of suppression in high dose= Cushing syndrome resulting from
ectopic adrenocorticotrophic hormone (ACTH; corticotrophin) production,
ectopic corticotrophin-releasing hormone (CRH) production, and cortisol
secreting adrenal tumors.
• 3) Borderline  repeated + do further investigations.
• A2= Cushing syndrome due to adrenal cortical adenoma
• A3= Macroscopic:The cut surface of the adenoma is marbled yellow and
brown, atrophied compressed cortix.
• Microscopic: Cortisol-secreting adenoma showing cells with clear and dark
cytoplasm and foci of myeloid metaplasia.
various forms of Cushing syndrome
Lab test
Pituitary
Cushing’s
Adrenal
Cushing’s
Ectopic
Cushing’s
Serum
cortisol
Increased
Increased
Increased
Low-dose
DST
Cortisol not
suppressed
Cortisol not
suppressed
Cortisol not
suppressed
Urine for
free cortisol
Increased
Increased
Increased
Plasma ACTH
Normal * to
increased
Low
Markedly
increased
High dose
DST
Cortisol
suppressed
Cortisol not
suppressed
Cortisol not
suppressed
26
5- Adrenal cortical carcinoma. The hemorrhagic and necrotic tumor
compresses the upper pole of the kidney, Scattered atypical nuclei
.
Adrenal glands hypofunction state
Hypofunction of adrenal cortex.
Can be of two types:
A. Acute adrenocortical insufficiency - causes include:
1.Abrupt withdrawal of corticosteroids .
2.Waterhouse-Friderichsen syndrome.
B. Chronic adrenocortical insufficiency
1. Addison’s disease.
2. Chronic granulomatous adrenalitis.
3. Others (viral, bacterial, metastatic, etc..).
Case No-6
• A 32-year-old woman with SLE has
been treated with corticosteroid
therapy for several years, because
of recurrent lupus nephritis.
• She undergoes an appendectomy
for acute appendicitis.
• On postoperative day 2, she
becomes drowsy and develops
severe nausea and vomiting. She
then becomes hypotensive.
• Laboratory studies were requested.
Reference
value
135-145
Tests
Result
Na + level
128
mmol\L
K+ level
5.8mmol\L 3.5-5
CL- level
105mmol\ 95-105
L
Glucose
60mg\Dl
65- 99
Creatinine 1.3 mg\dL 0.5-1.2
• Q1- What’s the diagnosis, and
mention causes given in this
scenario?
• Q2- Identify the morphologic?
• Q3- differential diagnoses?
CO2
19 mol\L
BLOOD
CULTURE
Negative
24-32
Primary adrenal insufficiency. A thinned cortex shows
loss of normal zona fasciculata with clear cells.
Answer case No 6= Primary adrenocortical
insufficiency (Addison disease)
• A1 = Primary adrenocortical insufficiency (acute addisonian
crisis).
• Causes: 1) Long term corticosteroid therapy shuts off.
• 2) Stress of surgery
• 3) Autoimmune condition, e.g. SLE
• 4) Idiopathic
• A2= Adrenal atrophy - Long-term corticosteroid therapy shuts
off corticotropin stimulation to the adrenal glands, leading to
adrenal atrophy
• Residual cortical cells are hypertrophied and have compact
eosinophilic cytoplasm and enlarged nuclei (ACTH stimulation effect).
• Both gland Wt.= 3mg.
• A3-Adrenal hemorrhage, tumor, metastatic, infections, amyloid
Case 7- Adrenal- caseating granuloma of tuberculosisexample of chronic primary adrenal insufficiency= Addison's
disease is much more often the cause for chronic adrenal
33
insufficiency.
Case 7- Adrenal- caseating granuloma of
tuberculosis-
Case No- 8
• A 4-year-old, previously healthy
child died suddenly after
complaining of a fever, Marked
Skin purpura, sore throat , for
few days and suddenly
collapsed.
• At autopsy, her adrenal glands
are enlarged, and there are
extensive bilateral cortical
hemorrhages.
• Q1- What is most likely the
diagnosis, describe the
morphologic features?
• Q2- Write two underling
etiological factors?
• Q3- mention the main
complications of this condition?
These adrenals are black-red from extensive hemorrhage in
a patient with meningococcemia.
A1-Waterhouse-Friderichsen syndrome
A1-Microscopically:
• Hemorrhages, with necrosis of
both cortical and medullary
tissue.
• Little residual cortical
architecture is discernible.
A2=
1- Sepsis caused by
meningococcal infection.
2- Anticoagulant drugs.
3- Viral infection= CMV.
marked hemorrhagic necrosis with
acute adrenal insufficiency.
A3= Septicemia, DIC
Endotoxic shock, Death.
Parathyroid glands
Disorders of Parathyroid glands
1. Hyperparathyroidis
- Primary- Autonomous spontaneous overproduction
• of PTH, elevated calcium level.
- Secondary- PTH levels are raised, but serum
calcium is not elevated.
- Tertiary- Long-standing secondary
hyperparathyroidism
leads to autonomous hyperactive parathyroids e.g CRF.
2. Hypoparathyroidism
40
Case No- 9
TEST
VALUE
• A 40-year-old man visits
8.5- 10.5
SERUM
11.5
the physician because of
CALCIUM
mg\dL
weakness and easy
30-110
ALP
317
U\L
fatigability of 2 months'
S. PTH
127pg\ml 14- 66
duration.
• Physical examination yields
no remarkable findings.
• Laboratory studies 
What is the most likely cause
which is near the top of the of these ?
reference range.
• A radionuclide bone scan Write the most common
fails to show any areas of syndrome associate with
condition?
increased uptake.
• Tc99 scan was requested
CASE 9- Parathyroid adenoma
Parathyroid Tc99 scan
Parathyroid scan
following intravenous
administration of Tc99
(technetium-99msestamibi radionuclide
scan)
In addition to radiotracer uptake in both thyroid lobes, a small
area of increased activity inferior to the left lobe of the
42
thyroid, consistent with a parathyroid adenoma.
Primary Hyperparathyroidism- due to PTH adenoma
PTH ADENOMA
Brown tumor
Fibrosis of BM, hemorrhage and
a cluster of osteoclast giant cells
Parathyroid Adenoma
Primary Hyperparathyroidism
• Primary
• This entity was defined in part by Von Recklinghausen
under the term osteitis fibrosa cystica generalisata.
•  Parathyroid adenoma 80%
•  Hyperplasia 10-15%.
•  Parathyroid ca <5%
• Most likely syndrome: Multiple endocrine
neoplasia (MEN) type 1.
Case No- 10
• A 26-year-old woman with
a history of end-stage
renal disease (ESRD) and
(CHF). she had been on
vitamin D therapy-6\12,
for suspected renal
osteodystrophy.
• Q1- What’s the most likely
diagnosis, describe the
morphology?
• Q2- Mention other
helpful diagnostic tests?
TEST
VALUE
SERUM
CALCIUM
ALP
8.8mg\dL
8.5- 10.5
340U\L
30-110
S. PTH
110pg\ml
14- 66
Secondary hyperparathyroidism= Secondary Parathyroid
hyperplasia,- as a consequence of chronic renal failure.
4 glands are involve - Not like a case of adenoma +\- Little or
no adipose tissue. Note the pink oxyphil cells here.
48
Parathyroid Tc99 scan- indicated
Case-11
• An infant is born at term to a 25-year-old woman.
• On newborn physical examination, the infant is found to
have an enlarged abdomen, but there are no other abnormal
findings except for slightly elevated blood pressure.
• An abdominal ultrasound scan shows a right retroperitoneal
mass in the adrenal gland. The mass is resected surgically,
and histologic sections reveal small blue cells tumour.
• Lab investigation revealed elevated urinary metanephrine
level.
• __________________________________________
• Q1- Describe the morphologic features given in the photo
attached?
• Q2- What is the diagnosis?
• Q3- what is the clinical significance of (metanephrine)?
Answer Case No -
• A1= Gross appearance:
• Hemorrhagic, partially
encapsulated tumor has
displaced the opened left
kidney and is impinging on the
aorta and left renal artery.
• Microscopic: This tumor is
composed of primitive small
”blue” cells embedded in a
finely fibrillar matrix with
Homer-Wright rosettes
• A2= Adrenal neuroblastoma
• A3= Metanephrine– is
indicative of this tumor, which
is produce high levels of
catecholamine precursors and
their metabolites.
Case No- 12
• A 35-year-old man with
severe headaches and
marked hypertension,
undergoes surgical
resection of a left
suprarenal mass that
appeared gray and tan
centrally and yellowish on
the cortex.
• On microscopy, large pink
cells are arranged in nests
with capillaries between
them.
• Q1- What’s the most
likely diagnosis, describe
the morphology?
• Q2- Describe the “rule of
10s .”?
• Q3- Mention other
helpful diagnostic tests?
• Q4- Describe the
association with
pheochromocytoma and
MEN 2A and 2B.?
Answer case - Pheochromocytoma
• The tumor is enclosed within
an attenuated cortex and
demonstrates areas of
hemorrhage.
• The comma-shaped residual
adrenal is seen below.
• Other helpful diagnostic tests:
Urinary or serum
catecholamines such
• as vanillylmandelic acid
(VMA).
• ◆ Acute complications: Acute
LVF , pulmonary edema, MI,
ventricular fibrillation and
• and CVA, CHF, and death
Zell-Ballen pattern
55
Pheochromocytoma
• 1- Nests of cells with abundant cytoplasm- derived from .
Chromaffin cells “neural crest cells origin”.
• 2- Granules containing catecholamine are not visible in this
preparation.
• 3- It is not uncommon to find bizarre cells even in
pheochromocytomas that are biologically benign, and this
criterion by itself should not be used to diagnose
malignancy.
• Electron micrograph- tumor contains membrane-bound
secretory granules in which catecholamines are stored