• ENDOCRINE PATHOLOGY
binding globulin which causes an increased
• Case 1: Enlarging neck (Grave’s disease)
• A 43 year old female noted gradual neck enlargement every
time she got pregnant. She had occasional irritability &
palpitations, excessive sweating & easy fatigability. Since 1
year ago, she lost 15 kg despite eating adequately. Later, the
patient developed exopthalmos, prompting consult.
• On physical examination, PR 105/minute, regular; RR 24/
minute; BP: 130/80; BW: 52.7 kg. Thyroid lobes are easily
palpable, moves with deglutition, soft, nontender, no nodules
noted. Chest & abdominal findings are normal
• Explain the signs & symptoms of the patient. Discuss the
etipathogenesis of exopthalmos & weight loss.
o Signs & symptoms are due to excessive secretion
of thyroid hormones
o Thyroid hormones increase basal metabolic rate
o Increased basal metabolic rate & increase in
uncoupling protein levels → Increased oxygen
consumption, decreased ATP production, increased
heat production → Activation of heat losing
mechanism of the body → excessive sweating
o Palpitations: increased cardiac rate due to
increased thyroid hormones & effects of increased
oxygen requirement
o Exopthalmos
 T cells are sensitized to antigens shared
by thyroid follicles & orbital fibroblasts,
accumulate around the eye, where they
secrete cytokines that activate
fibroblasts.
 Enlargement of the extraocular muscles
around the orbit. The muscles are normal
but they are swollen by mucionous
edeme & accumulation of fibroblasts &
infiltration by lymphocytes. The increased
orbital contents caused forward
displacement of the eye
o Weight loss: Increased metabolic rate with
subsequent loss of subcutaneous fat
o Pregnancy: Stimulation of human chorionic
gonadotropin on thyroid
• She has been diagnosed with diffuse toxic goiter
o Colloid goiter
o Goiter:
 Any enlargement of the thyroid
 Graves disease
 Iodine deficiency
 Tumor
• Which laboratory ancillary procedures are necessary to
evaluate patient’s condition? What would be the expected
results?
o Thyroid function tests: Free T3, Free T4, TSH
levels
o Expected results: Increased free T3 & T$,
decreased TSH levels
• Slide A: Normal thyroid gland
o Lining epithelium: Cuboidal
o Colloid: Acidophilic intraluminal deposit: thyroid
globulin
o Physiologic enlargement of thyroid due to
pregnancy
o Early in pregnancy: Increase renal blood flow &
glomerular filtration which increased iodine
clearance from plasma. This results in a fall in
plasma iodine concentration & an increase in the
iodide requirements in the diet
o Near the end of 1st trimester: Direct stimulatory
effects of hCG on the thyroid induces a small &
transient increase in the free thryoxine levels & in
turn a partial decrease in TSH secretion
o First half of gestation: Marked increase in thyroid
increase in total serum thyroid levels. Patient may
develop transient hyperthyroid state
• Slide B: Multinodular Goiter
o Gross: Enlarged nodular gland
o Microscopic
 Flattened squamous to cuboidal
epithelium
 Varisized glands with enlarged glands
 Distention of the follicles filled with colloid
 Cystic follicles/ Colloid cyst
o Cyclical variations in the need for thyroid hormones
& alternating episodes of stimulation & involution.
Some patients have thyroid growth
immunoglobulins that promote thyroid growth
without activating hormone production
o Signs & symptoms: Asymptomatic thyroid
enlargement
o Complications:
 Dysphagia & stridor: Large goiter
compressing the esophagus & trachea
 Venous congestion of head & face:
Pressure on neck veins
 Hoarseness: Compression of recurrent
laryngeal nerves
 Local pain: Hemorrhage into a nodule or
cysts
• Slide C: Grave’s disease
o Gross: Diffuse, symmetrically enlarged
o Microscopic
 Diffusely hyperplastic
 Tall columnar epithelial cells
 Papillae that project into lumen
 Depleted colloid (scalloped or moth eaten
appearance)
o IgG antibodies are present which are directed
against components of thyroid follicular epithelium,
stimulating TSH receptor & increasing thyroid
hormone secretion
o Most frequent cause of hyperthyroidism in patient
younger than 40
o Signs & symptoms:
 Enlarged thyroid gland
 Hyperthyroid state: Nervousness,
irritability, weight loss, exopthalmus,
tremor, excessive sweating
o Complication: Progressive thyroid failure
• Slide D: Hashimoto’s thyroiditis
o Gross: Diffusely enlarged gland
o Microscopic:
 Infiltration by mononuclear cells &
lymphocytes
 Presence of germinal centers
 Destruction & atrophy of follicles
 Hurthle cell change: Oxyphilic metaplasia
of follicular cells
o Autoimmune process: Activation of CD4 T cells that
have been sensitized by to thyroid follicles. The
activated T cells recruit both autoreactive B cells &
cytotoxic CD 8 T cells
o More common during the 4th to 5th decade of life;
women more affected than men
o Signs & symptoms: Gradual onset of goiter; initially
euthyroid becoming hypothyroid
o Complications: Overt hyperthyroid state
• Slide E: De Quervain’s thyroditis (Subacute)
o Gross: Enlarged gland
o Microscopic
 Patchy leukocytic infiltrate, plasma cells
& macrophages
  Destruction of follicles allow release of
colloid that elicits granulomatous reaction
 Numerous foreign body type
Multinucleated giant cells
o A self-limiting viral infection characterized by
granulomatous inflammation.
o Typically occurs after an upper respiratory tract
infection caused by influenze virus, adenovirus,
echovirus & coxsackie virus
o Affects women between 30 to 50 years
o Signs & symptoms
 Pain in anterior neck
 Fever
 Tender thyroid gland
• Case II: Firm mass on neck (Papillary carcinoma
• A 34 year old female noted slight swelling of the neck during
pregnancy. After giving birth, the swelling persisted on one
side. Consult revealed a palpable, non-tender, firm, nodule on
the swollen side that moves with deglutition. Aside from the
swollen neck, the patient is apparently normal
o Recent growth: mass with tenderness &
hoarseness, with radiation to head & neck →
thyroid cancer
o Significance of palpable nodule: Enlarged cervical
lymph nodule
o Diagnostic work up could be done to evaluate
patient’s condition? What will be the expected
results?
 Fine needle aspiration biopsy:
Lymphocytes & psamomma bodies
 Radionuclide scan:
(Hyperthyroidism)
• Slide A: Papillary Carcinoma
o Gross
 Solitary, with fibrosis & calcifications
 Firm, hard gritty nodule with pale cut
surfaces
o Microscopic
 Branching papillae
 Fibrovascular core with single row of
stratified cuboidal to columnar epithelium
 Nuclear atypia
 Ground glass appearance
 Orphan annie eye nuclei
 Eosinophilic pseudoinclusion & nuclear
grooves
o Malignant neoplasm associated with iodine excess,
radiation & genetic factors
o Most common form of thyroid cancer
o More common in women between ages 20 to 50
o Signs & symptoms
 Painless, palpable nodule
 Enlarged cervical lymph nodes
 Cervical lymphadenopathy without
palpable nodule
o Complications
 Hoarseness, dysphonia, cough
dyspnea: Obstruction to trachea &
esophagus
 Metastasis to regional lymph nodes,
lungs & brain
• Slide B: Follicular adenoma
o Gross
 Solitary, spherical well demarcated
 Area of hemorrhage
 Encapsulated
o Microscopic
 Proliferating epithelium with fibrous
capsule without invasion (Usually not
demonstrated in fine needle aspiration
biopsy)
 No vascular invasion
o Signs & symptoms
 Unilateral painless mass
 Cold nodule: Takes up less iodine
o Benign thyroid neoplasm
o Complications: Compression of contiguous
structures (Trachea & esophagus)
o Common in young women but occurs in all ages
• Slide C: Follicular carcinoma
o Gross: Solitary encapsulated nodule
o Microscopic
 Proliferating thyroid epithelial cells
 Variable nuclear pleomorphism
 Definitive fibrous capsule with capsular
invasion (arrow)
o 2nd most common thyroid carcinoma
o More common in 40 to 50
o Signs & symptoms: Palpable thyroid nodule (Cold)
o Complications: Metastasis (Hematogenous) to
bone & lungs
• Slide D: Medullary carcinoma
o Gross
 Hemorrhage, necrosis
 Tends to arise in the superior portion of
the thyroid where it is richest in C cells
o Microscopic
 Polygonal granular cells separated by a
distinct vascular stroma
 Upper inset: Acellular stromal amyloid
Hot
(deposition of procalcitonin)
 Lower inset: Positive reaction with
calcitonin marker
o Signs & symptoms
 Increased vasoactive peptide: Might
manifests as diarrhea
 Carcinoid syndrome: Serotonin
o Tumor derived from the parafollicular or C cells of
the thyroid which are distinguished by their
secretion of calcium lowering calcitonin
o Mean age: 50, more in female
o Complications: Widespread metastasis
• Case III: Body weakness: Parathyroid adenoma
• A 65 year old female complained of bone pains, recurrent
abdominal cramps & constipation. She is also often lethargic
& weak
• She had recurrent UTI due to presence of calcium oxalate
stones in urine. She had been told of possible parathyroid
pathology
o Hyperparathyroidism
 Increase bone resorption (activation of
osteoclasts, which makes the bone
weak)
 Increase gastric absorption of calcium
 Increase excretion of phosphates
&  Increase renal absorption of calcium
o Renal stones: Increased resorption from renal
tubules, urinary retention
o Laboratory/ ancillary procedures
 Increased serum ionized calcium
 Increased chlorine
 Decreased phosphate
• Slide A: Parathyroid hyperplasia
o Microscopic
 Normal adipose tissue is replaced by
hyperplastic chief cells arranged as
sheets
 Small foci of adipose tissue is still
noticeable
 o Non specific proliferation of parathyroid chief cells
leading to excessive secretion of parathyroid
hormone
o Gross: all 4 parathyroid glands are enlarged
o Signs & symptoms: Asymptomatic hypercalcemia to
systemic renal & skeletal disease
o Complications
 Chondrocalcinosis
 Pathological fracture
 Renal failure secondary to
nephrocalcinosis
 Chronic pancreatitis
 Gastrointestinal disturbances
 Lethargy, depression, seizures
 Aortic & mitral valve calcifications
• Slide B: Parathyroid Adenoma
o Gross: Solitary circumscribed mass
o Microscopic
 Sheets of neoplastic chief cells
embedded in rich capillary network
o 80% of all cases
• Case IV: Galactorrhea: Pituitary adenoma (Prolactinoma)
• A tall voluptuous 24 year old female experienced double
vision upon waking up. Since adolescence, her menses were
irregular but she had been amenorrheic for the past 3 months
• Physical examination revealed large breasts, with minimal
white secretions expressed from the nipples
o Tumor cells secrete prolactin
o Double vision
 Increase in the size impinges on the optic
chiasm
 Cranial nerves 3,4 & 6: Weakness of
ocular muscles
o Amenorrhea: Increase in prolactin exerts
antagonistic effect on FSH & LH
o Laboratory/ Ancillary procedures
 Serum prolactin elevation
 CT scan, MRI
 Enlarged sella turcica
 Tumor enlargement
o Causes
 Physiologic: Pregnancy, stress, nipple
stimulation
 Patholgic: Dopamine antagonists &
antihypertensives (Reserpine)
o More common in men between 20 to 50 years
• Slide A
o Acidophiles or chromophobe hypersecreting
prolactin
o Gross: Usually a macroadenoma
o Signs & symptoms: Galactorrhea, infertility,
decreased libido & erectile dysfunction
o Complications: Expansile growth of the tumor into
sphenoid sinus, cavernous sinus & optic chiasm
may damage optic nerves & grow into brain &
disrupt morphology & function of hypothalamus
• Slide B: Corticotroph adenoma
o Tumor cells secrete corticotrophin which induces
adrenal cortical hypersecretion to produce Cushing
disease
o Gross: Usually a microadenoma
o Microscopic: Intensely basophilic tumor cells
o Signs & symptoms: Due to excessive corticosteroid
 Obesity: Face, neck, trunk, abdomen
 Atrophic skin
 Hirsuitism
 Hyperpigmentation
 Osteoporosis
 Hypertension
 Glucose intolerance
 Virilized female
 Erectile dysfunction
• Case V: Uncontrolled hypertension: Pheochromocytoma
• A 53 year old male, experienced episodes of “headiness” &
nape discomfort, increasing frequency & severity. His
symptoms were relieved upon intake of antihypertensive
medication. In between attacks, he is apparently normal
• During the last attack, BP was 190/110, PR 102/minute, RR
26/minute, temp 36.8°C. Initial workup revealed slight
tachycardia on ECG, normal chest x ray, & elevated 24 hour
VMA
• He was informed of possible pathology in adrenal gland
causing hypertension
o Vanylylmandellic acid
 Metabolite of epinephrine
 Mediates systemic actions of epinephrine
• Laboratory/ ancillary procedures
o Plasma catecholamines
o CT scan
o MRI
o Tumor related metabolite for diagnosis, adequacy
of excision & follow up (Elevation:
recurrence/metastasis)
• Slide A: Cortical Adenoma
o Benign tumor of adrenal cortex
o Gross
 Solitary lesion
 Well circumscribed with delicate capsule
 Firm yellow lobulated mass
 Thin rim of compressed adrenal cortex
surrounds tumor
o Microscopic
 Brown oval nuclei with clear cytoplasm
 Clear, lipid laden cells arranged in sheets
& nests
• Slide B: Adrenal cortical adenoma
o Gross: Encapsulated lobulated bulky tumor with
yellow cut surfaces
o Microscopic: Clear & compact cells with varying
degrees of nuclear pleomorphism
o Malignant neoplasm of the adrenal cortex
• Slide C: pheochromocytoma
o Tumor of chromaffin cells of the adrenal medullar
that secretes cathecholamines
o Gross: Sharply circumscribed, reddish brown mass
occupying adrenal medulla, adrenal cortex
compressed
o Microscopic
 Membrane bound vesicles with
catecholamine
 Polyhedral to fusiform tumor cells
exhibiting marked pleomorphism
o Signs & symptoms: sustained or episodic
hypertension
o Complications
 Angina & myocardial infarction: due to
myocardial necrosis caused by elevated
catecholamine
• Slide D: Neuroblastoma
o Malignant tumor of neural crest origin that is
composed of neoplastic neuroblasts & originates in
adrenal medulla & sympathetic ganglia
o Neuroblasts: from primitive sympathogonia
represents intermediate stage of development of
sympathetic ganglionic neurons
o Persistence & transformation of this embryonal
structure
o Gross
 demarcated with fibrous pseudocapsule
  Large lobulated hemorrhagic mass
adherent to upper pole of the kidney
o Microscopic
 Small cells with dark nucleus & scanty
cytoplasm
 Dense sheets of small round to fusiform
cells with hyperchromatic nuclei & scanty
cytoplasm
o Signs & symptoms
 Enlarging abdomen
 Firm, irregular non-tender mass
 Marked irritability: Due to pain from bony
metastasis
 Gait disturbance: Due to spinal cord
compression
• Complications: Widespread metastasis (Bone, liver, thorax)