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dr Shintia Christina, SpPA

Pathology anatomy department, Ukrida

Endocrine gland

secrete hormone directly to the blood


stream to reach target cells distant from
their site of synthesis

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/overpro
duction

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 PASpositive 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 -TSH.

Gonadotrophs are scattered round to


oval cells that contain strong
cytoplasmic reactivity for -subunit, FSH and -LH (-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

10% intracranial neoplasm


Usually found in adults, peak 30-50 y
Most common arising in the anterior lobe as
isolated lesion
Less common : hyperplasia & 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
Prolactinoma (lactotroph adenomas) (chromophobe or weakly acidophilic)
GH (somatotroph cell) adenomas (eosinofil)
ACTH-secreting (corticotroph cell) adenoma (basofil)
Lainnya: Thyrotroph (TSH-producing) adenomas, Nonfunctioning
pituitary adenomas (null cell adenomas)

Prolactinoma

The most common hyperfunctioning pituitary


adenoma
Hyperprolactinemia : amenorrhea, galactorrhea,
loss of libido and infertility
Can cause by pregnancy, high dose estrogen
therapy, renal failure, hypothyroidim,
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

Penyakit tiroid

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
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

Causes of 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:
Subacute granulomatous thyroiditis
(painful)
Subacute lymphocytic thyroiditis (painless)
Struma ovarii (ovarian teratoma with
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 early
state mimic depression
Listless, cold intolerant, obese
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)

Chronic lymphocytic thyroiditis


(Hashimoto)

Gross : thyroid usually diffuse &


symmetrically enlarged, capsul intact
Microscopic :
infiltration of parenchyma by
mononuclear inflammatory infiltrate
Thyroid follicles are atrophic
Hrthle/oxyphil cells

Subacute lymphocytic thyroidits


(de Quervain)

30-50 y
Caused by viral infection/postviral inflammatory
process, majority of patients have history upper
respiratory infection
Clinical feature :
Pain (particularly when swallowing), fever,
malaise & enlargement of thyroid
Transient hyperthyroidism, with progression of
disease a transient hypothyroid phase may ensue
Self limited (return to euthyroid 6-8 wk)

Subacute lymphocytic thyroidits


(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

Graves disease

The most common cause of endogenous


hyperthyroidism
Triad of manifestations :

Thyrotoxicosis
Infiltrative ophthalmopathy exophthalmus
Infiltrative dermopathy/pretibial myxedema

Peak incidence : 20-40 y


Genetic factors are important
Autoimune disorder, antibodies to :
TSH receptor (specific)
Thyroid peroxisomes
Thyroglobulin

Graves 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

Graves 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

Graves disease

Diffuse hypertrophy & hyperplasia of thyroid


follicular epithelial cells
Morphology :
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
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 Plummers
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%)

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-PPAR1
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 nodules/multiple, may involving both lobes
Muticentricity is 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 (75-80%)
Primary hyperplasia (10-15%)
Parathyroid carcinoma (<5%)

Clinical feature

F:M = 3:1
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 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

Delta

Somatostatin

Inhibit insulin & glucagon secretion

PP

Pancreatic
polypeptide

Function in humans unknown

Promotes breakdown of glycogen (only


in liver) & gluconeogenesis

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

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

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 :
Insidious onset, except if associated with small cell
carcinoma of the lung
Early manifestation : hypertension & weight gain
Centripetal distribution of adipose tissue truncal
obesity, moon face & buffalo hump
Glucocorticoid gluconeogenesis hyperglycemia,
glucosuria & polydipsia
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 :


Cortical atrophy
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 reponse to activation of reninangiotensin system increased levels of plasma renin
Associated with : decrease renal perfusion, arterial
hypovolemia&edema, pregnancy

Adrenal insufficiency

Primary hypoadrenalism because of primary adrenal


disease
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
(Addisons 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

Acute adrenocortical
insufficiency

Exogenous
corticosteroid

Atrophic
adrenal

Rapid
withdrawal of
steroid

Acute stress

Failure to
increase
steroid

Adrenal crisis

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


(chromaffin cells) & supporting cells (sustentacular
cells)
The most important disease of adrenal medulla are
neoplasms
Neuroblastoma
Pheochromocytoma

Pheochromocytoma

Composed of chromaffin cells synthesize &


release catecholamines hypertension
Rule of 10 :
10% of pheochromocytoma arise in association with
one of several familial syndromes MEN-2A &
MEN-2B, type-1 neurofibromatosis, Von HippelLindau disease, Sturge-Weber syndrome
10% of pheochromocytoma are extra-adrenal
10% are bilateral
10% are biologically malignant

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, if only in one organ
often multifocal
usually preceded by an asymptomatic stage of
endocrine hyperplasia
the tumor usually more aggressive & recur

MEN syndrome (Multiple endocrine neoplasia)

MEN I (MEN1 gene) : parathyroid (95%), pancreas


(40%), pituitary (30%)
Primary hyperparathyroidism from multiglandular
parathyroid hyperplasia
Endocrine tumor of the pancreas (often functional)
The most frequent pituitary tumor in MEN-1 is a
prolactin-secreting macroadenoma. Some individual
develops acromegaly from somatotrophin-secreting
tumor.

MEN syndrome (Multiple endocrine neoplasia)

MEN II (RET gene) : two distinct groups of disorder


that unified by the occurrence of activating
mutations of RET protooncogene
MEN type 2A
Thyroid : medullary carcinoma, tumors commonly
multifocal
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
Unlike MEN-2A, patients with MEN-2B :
Do not develop primary hyperparathyroidism
Develop extraendocrine organism :
ganglioneuroma of mucosal sites
(gastrointestinal tract, lips, tongue) &
marfanoid habitus

MEN syndrome (Multiple endocrine neoplasia)

All persons carrying germ line RET mutations


are
advised
to
have
prophylactic
thyroidectomyto prevent development of
medullary carcinoma.

Thank You

Normal
parathyroid

Parathyroid gland
The four small parathyroid glands are
located in the neck, right next to the
thyroid gland. The parathyroid glands are
endocrine organs producing a hormone
called parathormon (PTH) and are
involved in calcium blood level regulation.
In the low power magnification a round,
encapsulated organ is seen. Within the
gland there is a lot of adipose tissue and
numerous venules, which run through the
gland that are filled with red blood cells.
These are seen either in cross section or
longitudinal section.
The parathyroid gland has two cell types,
chief cells and oxyphil cells. Chief cells are
more numerous and have a round nucleus
surrounded by a small amount of
cytoplasm. Chief cells produce PTH. The
oxyphil cells are seen in scattered groups
among the chief cells. They have a slightly
smaller nucleus and eosinophillic
cytoplasm. The function of the oxyphil
cells is unknown.

Adrenal cortex

Consist of 3 layers :
Z. glomerulosa (beneath the capsule)
Z. fasciculata (75% total cortex)
Z. reticularis (abut the medulla )

Synthesized three different types of steroids :


Mineralocorticoid : produce aldosterone
(z.glomerulosa)
Glucocorticoid : produce cortisol (primarily in the
z.fasciculata)
Sex steroid (estrogen & androgen) : produce largely in
z. reticularis

Adrenal medulla

Composed of chromafin cells synthesize & secrete


cathecholamines (mainly epinephrine)

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