Endocrine system

Bagian -1

DR.WELLY HARTONO, SPPA

0877-41593378
DEPT. PATOLOGI ANATOMI
FK UNTAR
2016
 Endocrine gland

 secrete hormone directly to the blood stream

to reach target cells distant from their site of
synthesis  body function & metabolism.
 Hormone categories

 Trigger biochemical signals upon interacting

with cell-surface receptors
 Peptide hormone : eg. Growth hormone,
insulin
 Small molecules : eg. epinephrine
 Diffuse across the plasma membrane and
interact with intracellular receptors.
 Lipid soluble hormones : eg. Steroid
(estrogen, progesterone & glucocorticoid)
Left: a steroid (lipid) hormone (1) enters a cell (2) binds to a receptor protein (3)
causes mRNA synthesis, the first step of protein synthesis.
Right: protein hormones (1) bind with receptors which (2) trigger a transduction
pathway. (3) transcription factors are activated in the nucleus: protein synthesis
starts. In both diagrams, a is the hormone, b is the cell membrane, c is the
cytoplasm, and d is the nucleus
 Endocrine pathology

1. Impaired synthesis :
 Underproduction/overproduction of hormones

2. Disease associated with mass lesions

 Nonfunctional/underproduction/overproductio
n
Pituitary
 Pituitary

 Pituitary gland is a small structure that lies at

the base of the brain, confines of the sella
turcica
 Along with the hypothalamus, the pituitary has
a central role in the regulation of most other
endocrine glands
 Composed of 2 morphologically & functionally
distinct component :
 Anterior  adenohypophysis
 Posterior  neurohypophysis
In situations of glucocorticoid excess, human corticotrophs
(arrows) undergo accumulation of keratin filaments in the
cytoplasm, resulting in a glassy hyaline appearance; the PAS-
positive secretory material is trapped in the juxtanuclear region or
at the plasma membrane. This is known as 'Crooke's hyaline
change'
Thyrotrophs are angular chromophobic
cells with multiple elongated
cytoplasmic processes that are well seen
on immunostaining for β-TSH.

Gonadotrophs are scattered round to

oval cells that contain strong
cytoplasmic reactivity for α-subunit, β-
FSH and β-LH (β-FSH shown).
 Somatotrophs exhibit diffuse cytoplasmic positivity for GH.
They are most numerous in the lateral wings of the anterior
pituitary (a) but are scattered throughout the gland including
the median wedge (b).

Lactotrophs are polygonal cells that

wrap cell processes around adjacent
cells, usually gonadotrophs; there is
some variation in the intensity of
staining for PRL.
 Neurohypophysis

 Terdiri dari modifikasi sel2 glial  pituicytes

 Menghasilkan 2 hormon peptida: anti-diuretic

hormone (ADH/vasopressin) dan oxytocin
 Symptoms of pituitary disease

 Hyperpituitarism
 Anterior pituitary adenoma
 Hypopituitarism
 Destructive processes : ischemic, surgery/radiation &
inflammatory
 Non fuctional pituitary adenoma
 Local mass effect
 Optic nerve & chiasm : visual field abnormalities 
bitemporal hemianopsia
 Elevated intracranial pressure
 Seizure
 Obstructive hydrocephalus
 Cranial nerve palsy
 Pituitary apoplexy
Pituitary adenoma and Hyperpituarism

 10% intracranial neoplasm

 Usually found in adults, peak 30-50 y
 Most common arising in the anterior lobe as
isolated lesion
 Less common : carcinoma
 Functional & silent : usually composed of
single cell type & produce single hormone
Classification of pituitary adenoma

Lloyd RV, Kovacs K, Young WF, Farrel WE, Asa SL. Pituitary tumour. In : DeLellis
RA, Lloyd RV, Heitz PU, Eng C, editors. Pathology and genetics of tumours of
endocrine organs. France: Llyon; 2004.
 Pituitary adenoma

 Well circumscribed
 30% unencapsulated, infiltrate bone, dura and brain
 invasive adenoma
 Microscopically :
 Uniform polygonal cells arrange in sheets, cord or papilae
 Nuclei : uniform/pleomorphic
 Mitotic activity scanty
 This cellular monomorphism and absence of a
significant reticulin network distinguish adenoma from
non neoplastic lesion
 Adenohypophysis adenoma

Tipe

Prolactin cell (lactotroph) adenomas (chromophobe or weakly acidophilic)

 galactorrhea, amenorrhea, sexual disfunction, infertility.

GH cell (somatotroph) adenomas (eosinofililik)

 gigantism, acromegaly

ACTH-cell (corticotroph) adenoma (basofilik)

 Cushing syndrom

Lainnya: TSH-cells (Thyrotroph) adenomas, Nonfunctioning pituitary

adenomas (null cell adenomas)
 Prolactinoma (lactotroph adenoma)

 The most common hyperfunctioning pituitary

adenoma.
 F>M, between 20-40 y.o
 Hyperprolactinemia : amenorrhea, galactorrhea,
loss of libido and infertility
 Can cause by pregnancy, high dose estrogen
therapy, renal failure, hypothyroidism,
hypothalamic lesions & dopamine-inhibiting
drug (eg. Reserpine)
Other adenoma producing hormone

 Growth hormone producing adenoma :

 If occur before epiphyses close  gigantism
 If occur after epiphyses close  acromegaly

 Other disturbances : abnormal glucose tolerance, DM,

muscle weakness, hypertension, arthritis, osteoporosis &
CHF
 Corticotroph cell adenoma
 Cushing syndrome
 Pituitary carcinoma

 Rare, 0.2% of all pituitary tumors

 Pituitary carcinoma requires evidence of metastatic
disease
 outside the central nervous system (CNS)/separate
noncontiguous foci within the CNS
 malignant nature is not usually obvious in
microscopic appearance and reliable distinction
between carcinoma and adenoma is impossible on
the basis of standard histological criteria
 Hypercellularity, nuclear pleomorphism, occasional
mitotic figures, necrosis, hemorrhage, and even
invasion are not reliable indicators of the malignant
nature of the tumor
A. Acinar or organoid architecture replaced by sheets of cells (low power magnification)
B. Population of pleomorphic nuclei in this area of tumor, including multinucleated
giant cells; the tumor cell nuclei have clumped chromatin, huge nucleoli; there is no
necrosis (high power magnification)
C. Sheets of cells with pleomorphic nuclei, mitoses are difficult to identify (medium
power)
D. Tumor cells are diffusely positive for prolactin
E. High labeling index; 23% of nuclei are positive for Ki-67
F. Diffuse nuclear labeling with p53
Thyroid
 Thyroid disease

 Hyperthyroidism : excessive release of thyroid

hormones
 Hypothyroidism : thyroid hormone deficiency
 Mass lesion of the thyroid
 Hyperthyroidism

 Thyrotoxicosis is a hypermetabolic state cause by

elevated circulating levels of free T3 and T4
 Clinical manifestation : hypermetabolic state related
to overactivity of the sympathetic nervous system:
 Constitutional symptoms : warm, flushed, heat
intoleranced & excessive sweating
 GI : hypermotility, malabsorption, diarrhea

 Cardiac : palpitation, tachycardia, cardiomegaly

 Neuromuscular : tremor, irritability, nervousness

 Hyperthyroidism

 Ocular : staring gaze & lid lag

 Thyroid storm : abrupt onset of hyperthyroidism,
occur most common in Graves disease  medical
emergency (untreated patients die of cardiac
arrhytmia)
 Apathetic hyperthyroidism : occuring in elderly, may
blunt the typical features of thyroid hormon excess
seen in younger patients
Disorder assc with thyrotoxicosis

Associated with hyperthyroidism

 Primary:
• Diffuse toxic hyperplasia (Graves disease)
• Hyperfunctioning (toxic) multinodular goiter
• Hyperfunctioning (toxic) adenoma
 Secondary:
• TSH-secreting pituitary adenoma (rare)
 Not associated with hyperthyroidism:
• Granulomatous thyroiditis (painful)
• Subacute lymphocytic thyroiditis (painless)
• Struma ovarii (ovarian teratoma with ectopic
thyroid)
• Factitious thyrotoxicosis (exogenous thyroxine
intake)
 Hypothyroidism

 Primary : thyroid abnormality

 Secondary : result from hypothalamic or pituitary
disease
 Clinical manifestation :
 Cretinism : in infancy/early childhood

 Myxedema : in older children & adult

 Cretinism

 Endemic : Himalaya, China, Africa &

mountain area
 Sporadic cretinism : result from inborn error
of metabolism  interfere biosynthesis of
thyroid hormone
 Clinical features : impaired development of
skeletal system & central nervous system,
mental retardation, short stature, coarse facial
features, protruding tongue & umbilical
hernia
 Myxedema

 = Gulls disease
 Clinical feature :
 Apathy and mental sluggishness  mimic
depression in the early stage
 Listless, cold intolerant, obese.

 Intelectual function and speech  slowed

 Mucopolysaccharide-rich edema accumulates in

skin, subcutaneous tissue & visceral sites
 Chronic lymphocytic thyroiditis
(Hashimoto)

 The most common cause of hypothyroidism in area

of the world where iodine levels are sufficient
 45-65 y, F:M = 10-20:1
 Autoimmune disease  progressive depletion of
thyroid epithelial cells  replaced by mononuclear
cell infiltration & fibrosis
 Clinical feature :
 Painless enlargement
 Hypothyroid
 May preceded by transient thyrotoxicosis
(hashitoxicosis)  ec disruption of thyroid follicles.
 Chronic lymphocytic thyroiditis
(Hashimoto)

 Gross : thyroid usually diffuse & symmetrically

enlarged, capsul intact
 Microscopic :
 infiltration of parenchyma by mononuclear
inflammatory infiltrate
 Thyroid follicles are atrophic

 Hϋrthle/oxyphil cells
 Subacute (granulomatous) thyroidits
(de Quervain)

 40-50 y, F:M = 4:1

 Caused by viral infection/postviral
inflammatory process, majority have history
upper respiratory infection
 Clinical feature :
 Pain (particularly when swallowing), fever, malaise
& enlargement of thyroid
 The inflamation and hyperthyroidism are transient,
usually disminishing in 2-6 weeks, even if not
treated.
 Self limited (return to euthyroid 6-8 wk)
 Subacute granulomatous thyroiditis
(de Quervain)

 Gross : gland firm, intact capsule,

unilateral/bilateral enlarged
 Microscopic :
 Disruption of thyroid follicle  extravasation of
colloid  granulomatous reaction
 PMN infiltrate, replaced over time by lymphocytes,
plasma cells & macrophages
 Riedel thyroiditis

 Rare, unknown etiology characterized by

extensive fibrosis involving in the thyroid &
contiguous neck structures
 Hard, fixed thyroid mass clinically stimulates
thyroid neoplasm
 Suggest autoimune etiology : presence
circulating antithyroid antibodies
 Grave’s disease

 The most common cause of endogenous

hyperthyroidism
 Triad of manifestations :
 Thyrotoxicosis
 Infiltrative ophthalmopathy  exophthalmus
 Infiltrative dermopathy/pretibial myxedema
 Peak incidence : 20-40 y, F:M=10:1
 Genetic factors are important
 Autoimune disorder, antibodies to :
 TSH receptor (specific)

 Thyroid peroxisomes

 Thyroglobulin
 Grave’s disease

 Infiltrative ophthalmopathy :
 Marked infiltration of the retroorbital space by mononuclear
cells, predominantly T cells
 Inflammatory edema & swelling of extra-ocular muscles

 Accumulation of extracellular matrix, specifically hydrophilic

glycosaminoglycans such as hyaluronic acid & chondroitin
sulfate
 Increase number of adipocytes
 Grave’s disease

 Clinical feature:
 Thyrotoxicosis

 Diffuse hyperplasia of thyroid

 Ophtalmopathy

 Dermatopathy

 Thyroid enlargement usually smooth & symmetric, but

sometimes asymmetric
 Increase blood flow to the thyroid  audible bruit

 Increase serum free T4&T3, depressed serum TSH

 Radioactive iodine uptake is increased

 Radioiodine scan show diffuse uptake of iodine

 Grave’s disease

 Diffuse hypertrophy & hyperplasia of thyroid

follicular epithelial cells
 Morphology :
 The thyroid usually symmetrically enlarge ec diffuse
hypertrophy and hyperplasia follicular epithelial cells
 Untreated case : follicular epithelial cells are tall, columnar &
more crowded than usual
 Follicular lumen with scalloped margin
 Lymphoid infiltrate, predominantly T-cells
 Treated case : accumulation of colloid by blocking
thyroglobulin secretion
 Diffuse & multinodular goiter

 Goiter = enlargement of the thyroid

 Reflect impaired synthesis of thyroid hormone  ec
iodine deficiency
 Low level serum of thyroid hormone  rise in the
serum TSH  hypertrophy & hyperplasia of thyroid
follicular cells  enlargement of thyroid gland
 Endemic goiter : goiters are present in more than
10% of the population
 Sporadic goiter : ingestion of substances that
interfere with thyroid hormone synthesis, result of
enviromental/genetic factor
 Diffuse & multinodular goiter

 Clinical features :
 Mass effect of enlarged gland
 Airway obstruction

 Dysphagia

 Compression of large vessels in the neck & upper thorax

 Minority : hyperthyroidism without ophthalmopathy &

dermopathy  Plummer’s syndrome
 Thyroid adenoma

 Benign neoplasm, derived from follicular

epithelium
 All thyroid neoplasms usually solitary
 Vast majority are nonfuctional, small portion
produces thyroid hormones (toxic adenoma)
 Clinical feature :
 Painless nodule  difficulty in swallowing

 Preoperative evaluation : USG & FNAB but

definitive diagnosis can only be made after
histologic examination of the resected specimen
 Excellent prognosis, do not recur/metastasize
 Thyroid adenoma

 Solitary, well defined, intact capsule  important

to distinguish from multinodular goiter
 Cells arranged in uniform follicles that contain
colloid.
 Follicular growth pattern usually quite distinct
from adjacent non neoplastic thyroid
(distinguishing feature from multinodular goiter
Here is a surgical excision of a small mass from the thyroid gland that has been cut in
half. A rim of slightly darker rim normal surrounding thyroid parenchyma is seen at the
left. The mass is well-circumscribed.
 Carcinoma thyroid

 <1% of cancer-related deaths

 Female predominance : early & middle adult years
 expression of estrogen receptor on neoplastic
thyroid epithelium
 Subtype :
 Papillary carcinoma (75-85%)
 Follicular carcinoma (10-20%)
 Medullary carcinoma (5%) : derived from C
cells/parafollicular
 Anaplastic carcinoma (<5%)
Endocrine system
Bag-2

DR.WELLY HARTONO, SPPA

0877-41593378
DEPT. PATOLOGI ANATOMI
FK UNTAR
2016
 Carcinoma thyroid

Pathogenesis
 Genetic variables
 Papillary thyroid carcinoma : chromosomal
rearrangement RET gene
 Follicular thyroid carcinoma : mutation in the RAS
family (HRAS, NRAS & KRAS) or PAX8-PPARγ1
fusion
 Medullary thyroid carcinoma : RET proto-oncogene
mutation  activation of receptor
 Anaplastic carcinoma : inactivating point mutation in
the p53 tumor supressor gene
 Enviromental variables
 Ionizing radiation (first 2 decades of life)

 Long standing multinodular goiter

 Papillary carcinoma

 Clinical features
 Nonfunctional tumor : painless mass in the neck

 Minority, hematogenous metastases present at the time

diagnosis, most common in the lung
 Indolent lesion, 10 ysr >95%

 Prognosis less favorable among elderly or with invasion

of extrathyroidal tissue or distant metastases
 Morphology
 Diagnosis based on nuclear features : ground glass,
intranuclear inclusion, groove
 Psammoma bodies
 Follicular carcinoma

 Usually present at an older age, peak incidence

middle adult years
 Incidence increased in area of dietary iodine
deficiency
 Clinical features :
 Solitary, cold thyroid nodules
 Tend metastasize hematogenous to the lungs, bone &
liver
 Morphology :
 May be grossly infiltrative/minimally invasive

 Diagnosis require capsular/vascular invasion

Capsular invasion
Vaskular invasion
 Medullary carcinoma

 Neuroendocrine neoplasm from parafollicular

cells/C cells  secrete calcitonin
 Calcitonin measurement important for
postoperative follow up & diagnosis
 Some cases, tumor cells elaborate polypeptide
hormones (somatostatin, serotonin & vasoactive
intestinal peptide (VIP)
 80% sporadic  adult (fifth to sixth decade)
 20% familial : MEN syndrome 2A/2B or FMTC
 Medullary carcinoma

 Clinical feature
 Mass in the neck  compression effect

 Effect from peptide hormone : diarrhea

 Morphology :
 Solitary nodulel  sporadic.

 Bilateral/Multicentricity are common in familial cases

 Composed of polygonal to spindle shaped cells  nest,

trabeculae & follicles
 Acellular amyloid deposits  distinctive feature
 Anaplastic carcinoma

 The most aggressive human neoplasms

 Mean age 65 y
 20% patients have a history of differentiated
carcinoma
 20-30% have concurrent differentiated tumor,
frequently papillary carcinoma
 Clinical feature :
 Metastases to distant site are common
 Death occur < 1 y
 Anaplastic carcinoma

 Bulky masses that grow rapidly beyond the thyroid

capsule
 Composed of highly anaplastic cells :
 Large, pleomorphic giant cells
 Spindle cells
 Mixed spindle & giant cell
 Small cells
Nikiforov YE. Diagnostic pathology and molecular genetic of the thyroid.
1st ed. 2009. Lippincott Williams & Wilkins.
Nikiforov YE. Diagnostic pathology and molecular genetic of the thyroid.
1st ed. 2009. Lippincott Williams & Wilkins.
Parathyroid
 Hyperparathyroidism

 Most of parathyroid gland composed of chief

cells (light to dark pink, depending on their
glycogen content)  contain PTH
 Activity of parathyroid is controlled by the level
of free calcium
 PTH function :
 Activate osteoclast  mobilizing calcium from bone
 Increase renal tubular reabsorption of calcium
 Increase conversion vitamin D to its active dihydroxy
form in the kidney
 Increase urinary phosphate excretion
 Augments GI calcium absorption
 Primary hyperparathyroidism

 One of the most common endocrine disorder &

important cause of hypercalcemia
 Parathyroid lesion underlying the hyperfunction :
 Adenoma (85-95%)
 Primary hyperplasia (5-10%)
 Parathyroid carcinoma (~1%)
 Clinical feature
 F:M = 4:1

 In the most common cause of clinically silent hypercalcemia

 Symptoms : painful bones, renal stones, abdominal groans &

psychic moans, pain (fracture of bones).
Secondary hyperparathyroidism

 Caused by any condition associated with

chronic depression in the serum calcium
level  compensatory overactivity of
parathyroids
 Renal failure is the most common cause of
secondary hyperparathyroidism
 CRF  decrease phosphate excretion 
hyperphosphatemia  decrease serum calcium
 stimulate parathyroid gland activity
 Morphology

 Adenoma : well circumscribed, soft, tan nodule.

Predominantly composed of chief cells, a rim of
compressed non neoplastic parathyroid tissue
separated by a fibrous capsule.
 Parathyroid hyperplasia : most common is chief cells
hyperplasia  diffuse/multinodular pattern
 Parathyroid carcinoma : larger than adenoma. Two
valid criteria for malignancy are 1) invasion of
surrounding tissue, 2) metastatic dissemination
Parathyroid adenoma
Parathyroid adenoma
Parathyroid hyperplasia
Parathyroid carcinoma
Pancreas
 Pancreas

 Pancreas consist of :
 Exocrine : secrete digestive enzymes into the
duodenum
 Islet of Langerhans : act as endocrine gland

 The islet consist of clusters of compact cells,

contain at least four distinct cell types
according to their hormone content (detected
by immunohistochemistry)
 Cell types in the islets
of Langerhans

Cell type % in islets hormone actions

Beta 70 Insulin Promotes glucose entry to cells, glycogen

synthesis, lipogenesis& protein synthesis

Alpha 20 Glucagon Promotes breakdown of glycogen (only in

liver) & gluconeogenesis

Delta 8 Somatostatin Inhibit insulin & glucagon secretion

PP 2 Pancreatic Function in humans unknown

polypeptide
 Diabetes mellitus

 Abnormal metabolic state characterised by glucose

intolerance due to inadequate insulin action
 Type 1 (juvenile onset) : destruction of beta cells
 Type 2 (maturity onset) : defective of insulin action
 Endocrine pancreas tumor

 Adenoma & carcinoma from islet cells are rare 

hypersecretion of their normal product
 Microscopic :
 Composed of cells resembling normal islet cells

 Insulinoma : the most common islet cell tumor 

hypersecretion of insulin
 Glucagonoma : much less common

 Others (somatostatinoma) : very rare

 Gastrinoma
Jain D. Ductal adenocarcinoma NOS. 2012. access from
http://www.pathologyoutlines.com/topic/pancreassuperpagetumor.html
Endocrine system
Bag-3

DR.WELLY HARTONO, SPPA

0877-41593378
DEPT. PATOLOGI ANATOMI
FK UNTAR
2016
Adrenal cortex
 Adrenocortical hyperfunction

 There are three distinctive hyperadreal clinical

syndrome
 Cushing syndrome  excess of cortisol
 Hyperaldosteronism

 Adrenogenital/virilizing syndrome
 Hypercortisolism (Cushing syndrome)

 In clinical practice, most caused by the

administration of exogenous glucocorticoid
 Endogenous cause
 Primary hypothalamic-pituitary diseases assc with
hypersecretion of ACTH
 Primary adrenocortical hyperplasia or neoplasia
 Secretion of ectopic ACTH by neuroendocrine
neoplasm
 F:M = 5:1, 20-30 y
 Hypercortisolism (Cushing syndrome)

Clinical feature :

 Early manifestation : hypertension & weight gain

 Centripetal distribution of adipose tissue  truncal
obesity, moon face & buffalo hump (accumulation of
fat in the post neck and back)
 Glucocorticoid  gluconeogenesis hyperglycemia,
glucosuria & polydipsia  secondary DM.
 Glucocorticoid  supress immune response
 Hypercortisolism (Cushing syndrome)

Morphology
 Pituitary changes : Crooke hyaline change 
glassy hyaline appearance result of the
accumulation of intermediate keratin filamen
in the cytoplasm.
 Hypercortisolism (Cushing syndrome)

Morphology of adrenal glands :

 Diffuse hyperplasia
 Nodular hyperplasia
 Adenoma/carcinoma
Adrenocortical hyperplasia
 Adrenocortical adenoma

 Most cortical adenoma do not cause

hyperfunction
 Gross : yellow represent of lipid within
neoplastic cells
 Microscopic : composed of cells similar to those
normal adrenal cortex. Nuclei tend to be small,
sometimes have pleomorphic nuclei
Adrenocortical adenoma
Adrenocortical adenoma
 Adrenocortical carcinoma
 Rare neoplasm
 Gross : poorly demarcated, contain areas of necrosis,
hemorrhage & cystic change
 Microscopic :
 Well differentiated cells or bizarre, pleomorphic cells
 Adrenal carcinoma has strong tendency to invade
adrenal vein, vena cava & lymphatics
 Bone metastases are unusual
Weiss LM, Bertagna S, Chrousos GP, Kawashima A, Kleihues P, Koch CA,
Giordano TJ, et al. Adrenal cortical carcinoma. In : DeLellis RA, Lloyd RV, Heitz
PU, Eng C, editors. Pathology and genetics of tumours of endocrine organs. France:
Llyon; 2004.
 Hyperaldosteronism

 Excessive levels of aldosterone : sodium retention &

potassium excretion  hypertension & hypokalemia
 Primary hyperaldosteronism
 Adrenocortical neoplasm/hyperplasia
 Overproduction of aldosterone  suppression of the renin-
angiotensin system  decrease plasma renin activity
 Secondary hyperaldosteronism
 Aldosterone release in response to activation of renin-
angiotensin system  increased levels of plasma renin
 Associated with : decrease renal perfusion, arterial
hypovolemia & edema, pregnancy
 ADRENOCORTICAL INSUFF.

 Primary hypoadrenalism/hipofunction because

of primary adrenal disease, or
 Secondary hypoadrenalism because of
deficiency of ACTH  decreased stimulation of
the adrenal
 Pattern of adrenocortical insufficiency :
 Primary acute adrenocortical insufficiency (adrenal
crisis)
 Primary chronic adrenocortical insufficiency (Addison’s
disease)
 Secondary adrenocortical insufficiency
 Causes of adrenal insufficiency

Acute Waterhouse-Friderichsen syndrome

Sudden withdrawal of longterm corticosteroid therapy
Stress in patients with underlying chronic adrenal
insufficiency
Chronic
Major contributors Autoimmune adrenalitis
Tuberculosis
Acquired immunodeficiency syndrome
Metastatic disease
Minor contributors Systemic amyloidosis
Fungal infection
Hemochromatosis
Sarcoidosis
Primary Acute adrenocortical
insufficiency (Adrenal Crisis)

Exogenous
corticosteroid

Atrophic
adrenal

Rapid
withdrawal of
steroid Acute stress

Failure to
increase
steroid

Adrenal crisis
 Primary Chronic adrenocortical
insuffiency (Addison disease)

 Uncommon disorder resulting from progressive

destruction of the adrenal cortex
 Autoimmune adrenalitis : 60-70% of cases
 There is autoimmune destruction of steroid-producing cells &
autoantibodies to steroidogenic enzymes
 Infections
 Particularly tuberculosis & fungi

 Metastatic neoplasm
 Fairly common site for metastases

 Ca of the lung & breast are the source of majority of metastases

in adrenal
 Adrenal medulla

 Populated by cells derived from the neural crest ,

termed chromaffin cells & supporting cells
(sustentacular cells)
 The major source cathecolamines.
 The most important disease of adrenal medulla are
neoplasms
 Neuroblastoma
 Pheochromocytoma
 Pheochromocytoma

 Composed of chromaffin cells  synthesize & release

catecholamines.
 Rule of 10 :
 10% of pheochromocytoma arise in association with one of
several familial syndromes  MEN-2A & MEN-2B, type-1
neurofibromatosis, Von Hippel-Lindau disease, Sturge-Weber
syndrome.
 10% of pheochromocytoma are extra-adrenal
 10% are bilateral
 10% are biologically malignant.
 10% are not associated with hypertension.
 Pheochromocytoma

 Range from small, circumscribed lesion to large,

hemorrhagic masses
 Larger lesion tend to be hemorrhagic, necrotic &
cystic
 Microscopic
 Composed of polygonal to spindle shaped chromaffin cells &
their supporting cells, compartmentalized into small
nest/Zellballen
 Nuclei often quite pleomorphic
 Definitive diagnosis of malignancy is based exclusively on the
presence of metastases
MEN syndrome (Multiple endocrine neoplasia)

A group of inherited diseases resulting in

proliferative lesions (hyperplasia, adenomas and
carcinoma) of multiple organs.
 Endocrine tumor arising in MEN syndrome :
 occur at younger age than sporadic
 arise in multiple endocrine organ (syncronously or
metacronously)
 if only in one organ, the tumors are often multifocal
 usually preceded by an asymptomatic stage of endocrine
hyperplasia
 the tumor usually more aggressive & recur
MEN syndrome (Multiple endocrine neoplasia)

 MEN-1 (MEN1 gene) : parathyroid (80-95%),

pancreas (40%), pituitary (30%) Wermer
Syndrom.
 Primary hyperparathyroidism from multiglandular
parathyroid hyperplasia
 Endocrine tumor of the pancreas (often functional)
 The most frequent pituitary tumor in MEN-1 is a
prolactinoma. Some individual develops acromegaly
from somatotrophin-secreting tumor.
MEN syndrome (Multiple endocrine neoplasia)

 MEN-2 (RET gene) : two distinct groups of disorder

that unified by the occurrence of activating
mutations of RET protooncogene

 MEN type 2A (Sipple Syndrom)

 Thyroid : medullary carcinoma, tumors commonly multifocal
(~100% patients)
 Adrenal medulla : 50% patients develop adrenal
pheochromocytoma
 Parathyroid : 1/3 patients develop parathyroid gland
hyperplasia with primary hyperparathyroidism
 MEN syndrome (Multiple endocrine neoplasia)

 MEN, type 2B
 Thyroid and adrenal medulla commonly involved
 Medullarythyroid ca (multifocal, more aggresive)
 pheochromocytoma

 Unlike MEN-2A, patients with MEN-2B :

 Do not develop primary hyperparathyroidism
 In addition, MEN 2B is accompanied by :
ganglioneuroma of mucosal sites (gi-tract, lips, tongue,
skin, eyes, resp-tract) & marfanoid habitus (long axial
skeletal features and hyperextensible joints)
MEN syndrome (Multiple endocrine neoplasia)

 All persons carrying germ line RET mutations are

advised to have prophylactic thyroidectomy to prevent
development of medullary carcinoma.
Thank You
Goodluck