Endocrine Pa Tho Lecture

Pituitary Gland
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Pituitary Gland
• Found within the sella turcica,

a depression in the
sphenoid bone; weighs
0.5 grams and is <15
mm in diameter
• Releasing and inhibiting factors from the hypo-

thalamus are brought to the anterior lobe via a
portal system.
Pituitary Gland
• Two tissue types with a separate embryologic
origins.
• Adenohypophysis (a): secretory cells derived
from Rathke's pouch, an embrologic extension
of the primitive oral cavity.
• Neurohypophysis (b):
unmyelenated neural
tissue; direct extension
of the brain; attached
to the hypothalamus.
Normal Anterior Pituitary Gland
A- acidophil B- basophil D- chromophobe C- capillary

Somatotrophs Gonadotrophs
Immunoperoxidase techniques
Corticotrophs Thyrotrophs
Hyperpituitarism
• Secretion of one or more of the tropic
hormones of the anterior lobe.
• causes:
1) loss of feedback inhibition by target organ
hormones (low levels) to the hypothalamus
2) most often, an adenoma of the adeno-
hypophysis; 70% elaborate a single tropic
hormone: prolactin, GH, or ACTH. Rarely,
neoplasms secrete TSH, LH, and FSH.
Adenomas Classified as to Size
• Microadenomas: <10 mm
in diameter (most are non-
functioning )
• Macroadenomas: >10mm ;
extend beyond sella &
press on cranial nerves III,
IV, and VI, the cavernous
sinus, the hypothalamus,
or the optic chiasm. macroadenoma
Functioning Pituitary Adenoma
acidophilic adenoma,
immunostain
diffuse growth of acidophilic or diffuse growth composed solely

basophilic cells with loss of the of acidophilic cells producing
normal glandlike arrangement growth hormone or prolactin
Spade-like hand
due to excess of growth
hormone
3 siblings
Basophilic Adenoma
• composed of corticotrophs
• produces Cushing’s disease
Chromophobe Adenoma
prolactinoma
25% of pituitary adenomas; may present as SOL

with hormone insufficiency; 25% produce prolactin.
Neurohypophysis
• principal targets of oxytocin is the pregnant
uterus at parturition and the lactating breasts
• principal targets of vasopressin are the kidneys’
collecting ducts and the
peripheral arterioles.
• head trauma, extension
of local tumors, surgery
or radiation may disrupt
pituitary stalk causing
diabetes insipidus. (A) Herring bodies (accumulations of
neurosecretory granules), (B), capillary
and (C) pituicyte nuclei.
Thyroid Gland
Normal Thyroid
• From Gr thyreos shield
• Largest endocrine gland
• From endoderm of the
pharyngeal floor and 4 x 2 cm
ultimobranchial body;
C cells come from neural crest
• Connection to the oral cavity (thyroglossal
duct) is lost;(remnant= pyramidal lobe in 40%)
• Average weight= 15 to 35 gm at 15 yrs
Normal Thyroid Gland
• Anatomy: two lobes connected by a thin
isthmus and covered by a delicate capsule,
from which septa arise to divide gland into
irregular lobules (20-40 acini)
• Blood supply: superior and inferior thyroid
arteries from the external carotid artery;
superior and middle thyroid veins to EJV and
inferior to brachiocephalic vein
• Rich lymphatics (internal jugular and pre- and
paratracheal lymph nodes)
Normal Thyroid
Single layer, smooth

lining epithelium
Thyroiditis
• Acute thyroiditis
* Suppurative and nonsuppurative
• Subacute (granulomatous) thyroiditis
• Palpation thyroiditis
• Tuberculous thyroiditis
• Autoimmune thyoiditis
* Hashimoto’s thyroiditis
• Reidel’s thyroiditis
Subacute Thyroiditis
• De Quervain’s thyroiditis
• Granulomatous thyroiditis
• Pseudotuberculous thyroiditis
• Giant cell thyroiditis
• Cause: ? virus (from URTI); antibodies vs
mumps, measles, adeno-, rhinovirus; HLA-
Bw35– ? genetic predisposition
• Course: unresponsive to antibiotics,
spontaneous resolution in few months
Subacute Granulomatous Thyroiditis
Riedel's Thyroiditis
• etiology of this lesion is unknown.
• fibrosing reaction destroys thyroid
and invades the surrounding tissue
(mimics cancer).
• may cause hypothyroidism
• histologically: marked atrophy
of the parenchyma with replacement by
masses of dense collagenous fibrous
tissue. Focal lymphocytic infiltrates may be
seen.
Hashimoto’s Thyroiditis
• Most common form of autoimmune
thyroiditis
• Gender bias: women-to-men ratio 18:1
• Age: 30 to 50 years
• Presentation: painless enlargement of
thyroid, sometimes with dysphagia and
pressure symptoms
• Course: at start, euthyroid, later hypo-
thyroid
• Pathogenesis: both humoral and cell-
mediated immune mechanisms: 1)
genetically determined dysfunction of
antigen-specific suppressor T cells leads
to uncontrolled attack on follicular cells
by cytotoxic T-cell
2) unregulated helper T cell stimulation
of B cells leads to formation of auto-
antibodies
Dr. Hashimoto
growth retardation in a sibling

with Hashimoto’s thyroiditis
• Gross Pathology: symmetrically enlarged
thyroid 2 to 3 times (up to 200 gms); firm or
rubbery; smooth or lobulated gray to pale
yellow cut surface; thin unaltered capsule
• Histopathology: massive lymphoplasmacytic
infiltration of thyroid with lymphoid follicle
formation; atrophic gland with oncocytic
change in epithelial remnants
lymphocytic infiltrates
moderate gland
enlargement
immunofluorescence Hurthle-cells
• Associated with autoantibodies to
thyroglobulin, the microsomes of thyroid
epithelial cells, a thyroid cell surface
antigen, and a second colloid antigen.
• Tissue injury mediated both by the
cytotoxicity of the microsomal antibody and
by activity of specifically committed T cells.
Anti-microsome Anti-thyroglobulin
• Increased risk for malignant neoplasms,
especially malignant lymphoma and leukemia
• Course: may spontaneously remit in children
• Treatment: hormonal replacement; surgery
Hyperthyroid Hypothyroid
Graves’ Disease
• an autoimmune disease of unknown cause.

• antibodies stimulate increased growth
• anti-TSH receptor autoantibodies increase
thyroid synthesis and function of the thyroid.
Graves’ Disease
• The antibodies correlate positively with
active disease and relapse. With an
underlying genetic predisposition, immune
response may be incited by: 1)
pregnancy (especially postpartum)
2) iodine excess
3) lithium therapy
4) infections
5) steroid withdrawal.
Graves’
disease
normal state
Graves’ Disease
Adenomatous (Nodular) Goiter
• In early multinodular goiters, there are
areas of hyperplasia, which then
involute. The repeated hyperplasia and
involution result in nodules.
•The developed nodular goiter has a
variegated appearance; normal
homogeneous parenchymal structure is
deformed by nodules.
Adenomatous (Nodular) Goiter
• The nodules frequently degenerate and
form cysts; with old or recent
hemorrhage, and a calcified cyst wall.
• There is extensive fibrosis. Areas of
normal thyroid tissue are seen
between the nodules, which also show
lymphocytic infiltration.
Nodular Goiter
The nodules vary:
• size (from a few mm to
several cm);
• outline (from sharp
encapsulation in adenomas to
poorly defined margins;
• architecture (from solid
follicular adenomas to colloid-
rich gelatinous nodules or
degenerative cysts.
vari-size acini
focal hyperplasia
Thyroid Tumors
• 95% primary
• 5%: malignant lymphomas, mesenchymal tumors,
and metastatic tumors
• Primary epithelial tumors:
1) Follicular cell differentiation: 80% benign
2) C-cell differentiation
• 60-70% in females
• Most present as painless “cold” nodules
Follicular Adenoma
• Round to oval nodule surrounded by a complete
fibrous capsule
• Cut surface is homogeneous and more fleshy
the rest of the thyroid
• Secondary changes: hemorrhage, calcification
or cystic degeneration
• Hyperplastic changes: papillary or
pseudopapillary
• Diagnostic features: a single encapsulated
nodule that appears different from the rest of
the thyroid
Follicular
adenoma
bisected single encapsulated nodule
Follicular Adenoma
hemorrhage
increased capsule
vascularity cystic change
Follicular adenoma
intact capsule and

no vascular invasion
Hurthle-cell adenoma
Large granular
acidophilic cells
Intact capsule
Algorithm for Thyroid Mass
Types of Carcinomas
• Well differentiated
 Papillary carcinoma and follicular variant
 Follicular carcinoma
 Oncocytic (Hurthle cell) carcinoma
• Undifferentiated: (anaplastic) large or small
cell carcinoma
• Medullary (“C" cell) carcinoma
• Others: Nonepithelial malignancies
Clinical Staging:
• Stage I. Intrathyroid.
• Stage II. Positive nodes, no fixation
• Stage III. Fixed cancer or fixed nodes
• Stage IV. Distant metastasis
Follicular Carcinoma
• 30% of thyroid cancers; with a greater rate of
recurrence and metastasis than papillary CA.
• Single nodule that is “cold” on scintigrams
• Most often seen in middle-aged females
• More aggressive than papillary carcinoma.
70% mortality in 5 years.
• Types: a) minimally invasive
b) widely invasive
capsular invasion
vascular invasion
widely invasive
• in minimally invasive, tumor is seen outside of
thick capsule and/or has invaded blood vessels
near capsule; 1% show metastasis if only
capsular invasion, 5% if with vascular invasion
• in widely invasive, the unencapsulated tumor
shows widespread infiltration of the gland and
blood vessels. Extrathyroid extension common
and distant metastasis (lungs and bone) seen
in 80% of cases
Hurthle Cell Carcinoma
• Histologically distinct
from other follicular
tumors.
• Has oxyphil features
• Invade and metastasize
locally and recur. The
course tends to be
prolonged.
Papillary Carcinoma
• Most common type of thyroid cancer and seen
in both adults and children
• Many childhood cases are associated with
previous head and neck irradiation
• Presents as an asymptomatic nodule; 20% as a
cervical lymph node enlargement
• Usually solitary but multicentric in 20%
• 95% 10-year-survival in those <40 and 75% in
those > 40 years of age
• About 10% of patients die of the malignancy
Histologic Features
• Architectural hallmark: true papillae with
fibrovascular cores
• Psammoma bodies, from L. psammos sand, are
calcific deposits with distinct concentric
laminations and are virtually diagnostic
• Types: a) follicular variant: cells with
characteristic nuclear features arranged as
acini, b) diffuse sclerosing variant: heavy
fibrosis and lymphocytic infiltration, numerous
psammoma bodies
longitudinal
nuclear groove
nuclear inclusion papillae
FNAB, Papillary Carcinoma

Papillary Carcinoma
partial encapsulation
orphan Annie nuclei microcarcinoma
< 1.0 cm
fronds with
fibrovascular core psammoma body
Papillary CA, Follicular variant
• Follicular architecture
with nuclear features of
papillary CA
• Usually unencapsulated
and infiltrative
• Prognosis is similar to that
of regular type of papillary
cancer
Adverse Factors in Papillary CA
• patient is more than 40 years of age

• nodule larger than 5 cm
• tumor extends beyond thyroid capsule
• symptomatic (dysphagia or hoarseness)
• distant metastasis
• subtotal thyroidectomy when tumor >1.5 cm
• residual tumor (post-op) fails to take up I131
Medullary Carcinoma
• The cause is unknown
• Risk factors: family history of MEN, prior history
of mucosal neuromas, pheochromocytoma,
or hyperparathyroidism.
•The average age at diagnosis is the mid-40s;
earlier in patients with inherited cancer
syndromes.
• Usually presents as a hard mass, and is often
accompanied by blood vessel invasion.
Medullary Carcinoma
• Occurs in 2 forms: sporadic and familial;
unilateral when sporadic and almost always
bilateral in the familial form.
• Metastases to regional lymph nodes are
found in 50% of cases. Prognosis depends on
extent at presentation, regional lymph node
metastases and completeness of surgical
resection.
Medullary Carcinoma
FNA H&E
Medullary Carcinoma
amyloid +ve
Congo Red Calcitonin

Undifferentiated Tumors
• Usually in an older age group

• Half of the cases arise in a long-standing benign
lesion or differentiated cancers
• Spindle cell, and most giant-cell cancers of the
thyroid grow rapidly and are very invasive.
• Metastasize to lymph nodes both locally and
widely, but not characteristically to bone.
Pulmonary metastases are frequent.
Undifferentiated CA
• All are considered stage IV disease.
• Are highly malignant cancers:
1) small cell or 2) large cell carcinomas. Both
grow rapidly and extend beyond the thyroid.
Both present as hard, ill-defined masses.
• 5-year survival is poor. Death from uncontrolled

local spread in the neck usually occurs within
months of diagnosis.
Anaplastic Giant Cell CA
FNA Tissue
Undifferentiated Tumors
• Prognosis is poor. When diagnosed, tumors have
spread and most patients die in 6-12 months.
• Behavior is similar to that of any highly
malignant tumor elsewhere.
• Course of epidermoid carcinoma and sarcoma
of the thyroid is essentially the same as
elsewhere.
• Small cell anaplastic carcinomas are probably
lymphomas.
Malignant Lymphoma
Recurrent Thyroid Cancer
• Recurrence and/or metastases develop in

10% to 30% of patients treated for
differentiated thyroid cancer.
• 80% recur with disease in the neck alone and
20% with distant metastases (most
common site is the lung).
• Up to 25% will not show I-131 uptake.
Parathyroid Glands
Parathyroid Glands
• Derived from the 3rd and 4th branchial
pouches (endoderm)
• Adult dimensions: 30 mg each (6 x 4 x 2 cm)
• 4 glands in 90 to 97% of population
• Location: behind middle 3rd and lower pole of
thyroid
• Ectopic locations: anterior mediastinum,
thymus, thyroid, retroesophageal space
Parathyroid Glands
• Histology: cell types
1) chief cell: spheroidal cells
in cords, sheets, nests and
pseudofollicles; cytoplasm
contains much glycogen;
intracellular fat droplets
2) oxyphil cell: homogeneous,
granular, eosinophilic
cytoplasm (? proliferation of
mitochondria in chief cells) normal gland
Parathyroid Gland
• Calcium homeostasis:
1) age: growth phase positive calcium balance;
equilibrium during young adulthood;
negative balance in later life 2)
integration: GIT (intake), kidneys and sweat
glands (excretion), bones (storage)
3) forms in serum: total and ionized
4) 1000 to 1200 g (adults); 99% in bone as
crystalline hydroxyapatite, 1% exchanged with
intracellular and serum calcium
Parathyroid Hormone
• Synthesized ONLY by chief cells
• Gene for PTH found on the short arm of
chromosome 11
• Synthesis in controlled by vitamin D (inverse)
and calcium (Ca++)
• Primary hyperparathyroidism: unregulated
secretion of excessive levels of PTH due to
intrinsic disease
• Secondary hyperparathyroidism: most
common disease of parathyroid gland
Primary Hyperparathryoidism
• Causes: adenoma, carcinoma, primary
hyperplasia
• Effects: hypercalcemia and hypo-phosphatemia
• Incidence: 100 to 350 per 100 000
• Age at diagnosis: 50; younger for carcinomas
(3-7 years )
• Female-to-male ratio is 3:2; 1:1 for CA
• Laboratory diagnosis: high Ca++, low inorganic
phosphorus, high PTH
Primary Hyperparathyroidism
• Presentations:
1) adenoma in one gland
2) hyperplasia of all 4 glands
3) carcinoma in one gland
• Incidence:
1) adenoma: 83%
2) hyperplasia: 15% 3)
carcinoma: 2%
Parathyroid Adenoma
• Usually functional
• Usually sporadic (rarely hereditary)
• Usually one gland (rarely two)
• Are monoclonal neoplasms
• Most frequent cause: accumulation of multiple
successive mutations to different genes
(proto-oncogenes and tumor-suppressor genes)
Parathyroid Adenoma
• Related facts:
1) ionizing radiation
2) higher incidence after menopause 3) high
adenoma to carcinoma ratio 4) no
premalignant precursor 5)
abnormal response to vitamin D
and Ca++ as to PTH secretion
Parathyroid Adenoma: Gross
• Weight :1 to 1.5 gms. When <100 mg,
diagnosis must be supported by surgical
cure.
• Color: orange to dark brown (darker when
made up of oxyphil cells)
• Surface: thin capsule; smooth or nodular
• Cut-section: orange-tan to red-tan with
areas of hemorrhage and/or fibrosis; may
have cysts
Parathyroid Adenoma: Histology
• Architecture: cellular sheets; occasional
pseudogland formation, especially around blood
vessels (rosette-like); may look like thyroid
tumor if entirely of pseudofollicles; giant cells
common
• Cytology: chief cells with nuclei that are larger
and darker than normal; crowded cells with
nuclear overlapping
• Capsule: thin and delicate
• Stroma: sparse with prominent vascularity
• Intratumoral fat: not prominent
Parathyroid Adenoma
Normal tissue
Capsule
Parathyroid Hyperplasia
• Clinically, presents like adenoma

• Related to familial hyperparathyroidism and
MEN syndromes
• Gross: identical to adenoma
• Size: 150 mg to 10 gm
• Symmetrical growth in 50% of cases
• Histologic: proliferation of chief cells with
incomplete capsule around growth
Parathyroid Carcinoma
• Mean age: 44 years (13 to 84)
• Presentation: bone disease in 67%, palpable
neck mass, urolithiasis, renal parenchymal
disease
• Behavior: locally invasive; metastasizes to
regional lymph nodes
• Gross: tumor size of 12 gm (0.8 to 42)
• Histology: trabecular pattern with thick
acellular fibrous bands; cells larger than in
adenoma; capsular and vascular invasion
Adrenal Glands
Normal Adrenal Cortex
Glomerulosa
Fasciculata
Reticularis
Adrenal Hyperplasia-- Bilateral
Adrenocortical Hyperplasia
• Congenital hyperplasia is seen at birth and
when severe presents with life-threatening salt
loss and adrenal crisis (aldosterone and cortisol
deficiency).
• Most common defect: lack of 21-hydroxylase
enzyme that leads to impaired cortisol
synthesis. The decreased negative feedback
leads to elevated ACTH, which causes a buildup
of androgenic metabolites and enzyme
precursors resulting in the masculinization of
the external genitalia of the female fetus.
Adrenogenital Syndrome
masculinization of the
external genitalia of
the female fetus
Adrenocortical Hyperplasia
• Raarely, a less severe, late-onset form of
congenital adrenal hyperplasia is seen in
adolescent girls, who present with acne,
hirsuitism or menstrual irregularity.
• The most common cause in adults is an
ACTH-producing (basophilic) pituitary
adenoma (Cushing’s disease).
• Most patients are in their third and fourth
decades with a 3 to 1 female-to-male ratio.
• The glands are bilaterally enlarged.
Atrophy
Normal
Bilateral
Hyperplasia
Adrenal Insufficiency
• Acute adrenal insufficiency may be a
complication of anticoagulant therapy or to
rapid withdrawal of steroids from patients
under chronic steroid treatment.
• Patients with chronic adrenal insufficiency
who suffer acute stresses, such as trauma or
surgery, may also develop this condition.
Acute Adrenal Insufficiency
• Life-threatening in septic shock and endotoxemia
due to meningococcus and pneumococcus, which
lead to acute hemorrhagic adrenal infarction (DIC).
• Waterhouse-Friderichsen syndrome: patients
manifest high fever,
purpuric rash, and
hypotension, which
can lead to vascular
collapse and irrever-
sible shock.
Adrenal Insufficiency
• Secondary when due to a low ACTH secretion
by the pituitary gland. Not seen in the
secondary form are hyperpigmentation (due
to high melanocyte-stimulating hormone)
and hyperkalemia (aldosterone secretion is
not compromised).
• Tertiary adrenal insufficiency develops in
chronic high dose steroid treatment, which

produces adrenocortical atrophy.
Chronic Adrenal Insufficiency
• Primary when due to the destruction or

impairment of the adrenal cortex by auto-
immune adrenalitis (Addison’s disease) or a
granulomatous disease (tuberculosis).
• Patients complain of weakness, fatigability,
wasting, and cutaneous hyperpigmentation.
The histopathology of the gland reveals an
intact medulla with fibrous replacement of
the cortex.
Adrenocortical Adenoma
• associated with Cushing’s
syndrome or Conn’s
syndrome depending on
the cell type involved;
virilizing tumors are
usually carcinomas
• in Cushing’s syndrome,
the contiguous or
contralateral gland is
atrophic
Adrenocortical Adenoma
usually unilateral and composed of lipid-rich

cells similar to cells of zona fasciculata
Normal Adrenal Medulla
Adrenal Medullary Hyperplasia
• Adrenal medullary hyperplasia is most
commonly seen in multiple endocrine
neoplasia. In these cases, symptoms of
pheochromocytoma are seen without a
discrete tumor.
Pheochromocytoma
• Rare tumor of the adrenal medulla that occur at
any age, but are most common from the 3rd to
5th decade in sporadic cases (90%).
• Tumor cells have strong affinity for chromium
salts. (Gr. pheo dark, chroma color)
• Patients are hypertensive with severe headache,
palpitations, diaphoresis (classic triad), anxiety,
and nervousness.
• Less than 3% are malignant and metastasis is the
only reliable indicator of malignant nature.
Pheochromocytoma
• Grossly, the unilateral tumor (50% bilateral
when familial) is sharply circumscribed with
pseudoencapsulation by compressed normal
tissue.
• Most measure 3-5 cm (must at least be 1.0
cm to qualify as a neoplasm). It is firm, and
gray or reddish.
• Fibrosis, necrosis and cystic degeneration are
seen.
Pheochromocytoma
Large pheochromocytoma
with necrosis and hemorrhage.
Pheochromocytoma
• Microscopically, the
neoplastic cells are
polygonal with lightly
eosinophilic or basophilic
cytoplasm or resemble
normal chromaffin cells
arranged in trabeculae.
Pheochromocytoma
nuclear pleomorphism in a
benign heochromocytoma.

Endocrine Pa Tho Lecture

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Endocrine Pa Tho Lecture

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Pituitary Gland

• Found within the sella turcica,

• Releasing and inhibiting factors from the hypo-

A- acidophil B- basophil D- chromophobe C- capillary

diffuse growth of acidophilic or diffuse growth composed solely

25% of pituitary adenomas; may present as SOL

Single layer, smooth

growth retardation in a sibling

• an autoimmune disease of unknown cause.

bisected single encapsulated nodule

intact capsule and

nuclear inclusion papillae

FNAB, Papillary Carcinoma

• patient is more than 40 years of age

Congo Red Calcitonin

• Usually in an older age group

• 5-year survival is poor. Death from uncontrolled

• Recurrence and/or metastases develop in

• Clinically, presents like adenoma

chronic high dose steroid treatment, which

• Primary when due to the destruction or

usually unilateral and composed of lipid-rich

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