DISEASES OF THE THYROID

and PARATHYROID
Dr. Ramos
Surgical Pathology
THYROID
develops as a tubular evagination
from foramen caecum at the root of
the tongue
grows downward anterior to trachea
and thyroid cartilage
Abnormal descent leads to aberrant
lingual or substernal thyroid

weighs 20-25 gms

T3 and T4 synthesized by thyroid
and released into blood bound to
TBG, albumin and prealbumin
T3 and T4 modulate cell growth
and functional activity
Undergoes hyperplasia during stress

more common in females,

hyperfunctioning gland
S/Sx: nervousness, palpitations,
rapid pulse, fatigability, weakness,
weight loss, good appetite, diarrhea,
heat intolerance, warm skin, excess
perspiration, emotional lability,
menstrual changes, fine tremors,
eye changes and thyroid
enlargement
Morphology:
eye changes - wide-eyed
stare, proptosis
skin changes peripheral
vasodilatation
cardiac changes
arrhythmias, mild
lymphocytic/eosinophilic
infiltrates, mild fibrosis, fatty
changes in myofiber
Others: fatty infiltration in skeletal
muscle, liver osteoporosis,
lymphadenopathies
Most common cause:
Graves disease diffuse
hyperplasia
Toxic Multinodular goiter
Toxic adenoma

Hypothyroidism

Goitrogens inhibits thyroid gland

function suppress T3T4 synthesis
TSH increases gland enlarges
Examples:
a. Anti thyroid agents
b. Iodide

Cretinism
During development and infancy.
Mental and physical growth
retardation, dry rough skin, wide set
eyes, periorbital puffiness, flat broad
nose, large protuberant tongue.
Endemic or sporadic cretin

Thyrotoxicosis (Hyperthyroidism)
hypermetabolic state, elevated T3
and T4

Myxedema
Slow physical and mental activity,
fatigue, lethargy, cold intolerance,
general listlessness and apathy,
Periorbital edema, thick dry coarse
skin, tongue enlarges, peripheral
edema, constipation, flabby heart and
enlarged with dilated chambers with
myofiber

most common cause of goitrous

hypothyroidism in region sufficient
with iodine
major cause of non-endemic goiter in
children
an organ-specific autoimmune
disease
o F:M (5:1), middle age
ETIOLOGY:
o defect in function of thyroidspecific suppressor T cells,
autosomal dominant
o associations with HLA-DR5
and DR3
o autoantibodies against thyroid
peroxidases, thyroglobulin
colloid Ag, TSH receptor, etc.
o patients may suffer from other
autoimmune disease like sle,
sjogren syndrome, ra, pa,
graves
MORPHOLOGY
o with atrophic and goitrous
variant
o enlarged nodular gland,
rubbery
o replacement of parenchyma
by lymphocytes, plasma cells,
immunoblasts, macrophages,
with germinal centers
o hurtle cell follicles (oncocytes)
o atrophic variant small gland
with fibrosis

CAUSES OF DISTURBED THYROID

FUNCTION
A. THYROIDITIS
1. Hashimotos Thyroiditis
(Struma lymphomatosa)
2. Subacute granulomatous
Thyroiditis (De Quevains)
3. Subacute lymphocytic
(Painless) Thyroiditis
4. Infectious Thyroiditis
5. Riedels Fibrous
Thyroiditis (Riedels
Struma)
Hashimotos Thyroiditis (Struma
lymphomatosa)

SIGNS AND SYMPTOMS

o thyroid enlargement,
hypothyroid
o increase TSH and decrease
T3T4 levels

demonstrate autoantibodies,
increase risk to lymphoma

SUBACUTE GRANULOMATOUS
THYROIDITIS (DE QUEVAINS)
self-limited granulomatous
thyroiditis
second to fifth decade, F:M (3:1)
HLA-B35 association probable viral
etiology
MORPHOLOGY
o enlarged gland, aggregation
of cells around damaged
follicles admixed with
multinucleated giant cells
enclosing naked pools of
colloid granulomatous
o later CI infiltrates and fibrosis

SIGNS AND SYMPTOMS

o acute febrile reaction
o painful enlargement of thyroid
o hyperthyroidism
o self-limited in 6-8 weeks

SUBACUTE LYMPHOCYTIC THYROIDITIS

(Painless Thyroiditis)
in female, post partum period
15% of hyperthyroidism
enlargement of gland, foci of
lymphocytic infiltrates with
occasional interstitial fibrosis

self-limited, T3&T4 levels increased

INFECTIOUS THYROIDITIS
from microbial seeding
Staphyloccocus, Streptococcus,
Salmonella, TB and fungi
RIEDELS FIBROUS THYROIDITIS
(Riedels Struma)
glandular atrophy, hypothyroidism,
fibrosis and adhesions to
surrounding structures
mistaken for malignancy

CAUSES OF DISTURBED THYROID

FUNCTION
B. GRAVES DISEASE
TRIAD:
o hyperthyroidism
diffuse hyperplasia
o ophthalmopathy lid
lag, stare, proptosis,
upper lid retraction,
periorbital edema
o dermopathy localized
edema at dorsa of legs
and feet
INCIDENCE:
o 1-2% of female, HLADR3 and B8
o between Graves and
other autoimmune
diseases

 ETIOLOGY:
o autoantibodies to TSH
receptor leading to
hyperfunction of gland:
o Thyroid stimulating Ab
o Thyrotropin-binding inhibitor
Ig inhibits TSH binding
o Ophthalmopathy due to
lymphocytic infiltrates in EOM
and retro-orbital fibrofatty
tissue, glycosaminoglycans in
orbital fat
o T cell-mediated action with
local release of cytokines and
growth factors
MORPHOLOGY:
o enlarged, meaty parenchyma
o tall columnar epithelium,
increase number of cells
(pseudopapilla buds)
o eaten-up colloid
o increase lymphoid tissue
o morphology may be altered
by medications

SIGNS AND SYMPTOMS:

o young female
o thyrotoxicosis
o ophthalmopathy
o dermopathy
o thyroid enlargement
o increase RAIU, decrease TSH,
increase T3 & T4
CAUSES OF DISTURBED THYROID
FUNCTION

C. DIFFUSE NON-TOXIC GOITER

(COLLOID GOITER)
diffuse thyroid enlargement
without hypo- or
hyperfunction endemic goiter
deficient intake of iodine
decrease T3 & T4, increase
TSH
follicle hyperplasia
euthyroid state
GOITROGENS
o Calcium
o Fluorides
o Cabbage
o Cassava
o Cauliflower
o Turnips
o Brussel sprouts
o Brassica and Crucifera
plants
Non-endemic/Sporadic
Goiter
o F:M (8:1), puberty or
young adult
o either physiologic
superimposed on or
hereditary defect in
thyroxine synthesis

Signs and Symptoms

o enlarged gland
o euthyroid state
MORPHOLOGY:
a. Hyperplastic Stage
enlarged,
hyperemic follicles
lined by columnar
epithelium with
scanty colloid
b. Colloid Stage
colloid
accumulation,
markedly enlarged
gland (up to 500
gms or more)
distended follicles
lined by flattened
epithelium filled
with colloid
irregular
distribution of small
and distended
follicles,

hyperplastic foci
may persist

CAUSES OF DISTURBED THYROID

FUNCTION
D. MULTINODULAR GOITER (MCAG)
from simple goiters
with sporadic and endemic
forms
toxic or non-toxic
extreme enlargement
F>M
MORPHOLOGY:
o nodular, enlarged
gland up to 2 kg,
asymmetric
o nodularity created by
islands of colloid-filled
or hyperplastic follicles
o random irregular
scarring
o focal hemorrhage and
hemosiderin deposition
o focal calcifications
o miocrocysts formation

CAUSES OF DISTURBED THYROID

FUNCTION
E. TUMORS: Thyroid Nodules
GENERALIZATIONS:
1. A solitary nodule is more likely to be
neoplastic than multiple nodules.
2. Functioning hot nodules are more
likely to be benign than malignant.
3. The younger the patient (<40), the
greater the likelihood of neoplasia
4. A nodule in a male is more ominous
then one in a female

I.

ADENOMAS
MORPHOLOGY:
discrete, completely
encapsulated masses with
parenchyma different from that
outside the capsule, compress
surrounding non-neoplastic
thyroid tissue
approximately 3-10 cms
soft, fleshy, may be
hemorrhagic
composed of well or poorly
developed follicles; fetal,
colloid or trabecular type,
spindle cell (atypical), Hurthle
cell adenomas (oncocytic type)

SIGNS AND SYMTPOMS:

o enlarged thyroid causing
cosmetic and functional
impairment
o dysphagia, choking sensation,
inspiratory stridor, SVC
syndrome
o signs of thyrotoxicosis - RAIU
& T3&T4
o cardiac manifestations

 SIGNS AND SYMPTOMS:

o must be differentiated from
malignancy
o may be cold or hot
o mass may suddenly enlarge
due to intralesional
hemorrhage
II.
MALIGNANT TUMORS:
PAPILLARY Ca
75 85% Welldifferentiated
tumors
FOLLICULAR Ca
10 20%
MEDULLARY Ca
5%
ANAPLASTIC Ca
rare
PATHOGENESIS:
o Irradiation to head and neck
area
o Japanese survivors to atomic
bombs
(7% developed thyroid
CA)
o Hashimotos Thyroiditis
o Non-toxic nodular goiter
o Oncogene PTC present in 2030% of tumors
1. PAPILLARY CARCINOMA
most common
3rd to 5th decade
F:M (2-3:1)
MORPHOLOGY:
from small to large lesions,
often multifocal
gray white, firm, calcified
areas and cystic change
Composed of papillae and or
follicles lined by single or
several layers of columnar
epithelium, papillae with
fibrovascular core
orphan-Annie nuclei

Nuclear grooves, eosinophilic

intranuclear inclusions,
psammoma bodies
Encapsulated variant 10% of
tumors
Follicular variant mostly
follicular structures devoid of
papilla but nuclear detail that
of Papillary
SIGNS AND SYMPTOMS:
Young female, mild to
moderate thyrotoxicosis
50% neck node metastasis at
time of diagnosis 90%
survival at 20 yrs.
Favorable prognostic factors
include:
Female sex
Less than 20 y/o
Confinement to thyroid gland

 Well-differentiated cytologic
morphology
2. FOLLICULAR CARCINOMA
10-20% of thyroid CA
5th-6th decade
F:M (3:1)
SIGNS AND SYMPTOMS:
Slow growing, painless
masses
30% 5-year survival for large
lesions
MORPHOLOGY:
encapsulated, difficult to
distinguish from adenoma
composed of uniform
microfollicular architecture of
orderly cuboidal lining cells
capsular and/or vascular
invasion
little propensity for lymphatic
invasion
vascular invasion is common
distant metastasis

MYC:
1. secrete calcitonin
2. Amyloid stroma
3. 20-25% occur with MEN
Syndrome IIa and II
MORPHOLOGY:
discrete tumors in one lobe or
numerous nodules throughout
gray tan parenchyma,
infiltrative, calcification
polygonal and spindle shaped
cells in organoid nests and
trabeculae, separated by
fibrovascular stroma with
amyloid

SIGNS AND SYMPTOMS:

Mass with associated pressure
symptoms or asymptomatic
Paraneoplastic syndrome
(diarrhea)
Prognosis: familial form 90%
10-year survival
MEN form 30-50% 10-year
survival

3. MEDULLARY THYROID
CARCINOMA
Neuroendocrine neoplasm of
parafollicular C cell origin
5th-6th decade of life, in 3rd
decade if associated with MEN

4. ANAPLASTIC CARCIOMA
5% of carcinomas
Rapid growth, large tumors
Aggressive, metastasize widely
Variants:
1. Spindle cell
2. Giant cell
3. Small cell

DISEASES OF THE PARATHYROID

PARATHYROID GLANDS
4 glands derived from pharyngeal
pouches
36-40 mg
Chief cells
- predominant cell
- secrete PTH

F. MISCELLANEOUS LESIONS
THYROGLOSSAL DUCT CYST

2-3 cm midline cyst

from remnants of foramen

caecum

may occur at any age

cyst with numerous secretion,

lined by squamous or columnar
epithelium with trapped thyroid
follicles in adjacent wall
PTH FUNCTIONS:
Mobilizes calcium from bone.
Increases renal production of
1,25(OH)2D3, active in intestinal Ca
absorption.
Increases renal tubular reabsorption of
Ca thereby conserving it.
Lowers serum phosphate level by
enhancing phosphaturia.
I.

PRIMARY
HYPERPARATHYROIDISM
Result to hypercalcemia
Causes:
1. Adenoma 75-80%
2. Hyperplasia 10-15%
3. Carcinoma - <5%
Incidence:
1. F:M (3:1), 6th decade of
life

2. 25 cases/100,000
Major effects of
hyperparathyroidism:
o Increase bone resorption
and calcium mobilization
from skeleton.
o Increase renal tubular
reabsorption and
retention of Ca
o Increase renal synthesis
of 1,25(OH) 2D3
enhancing GIT calcium
absorption
SIGNS AND SYMPTOMS:
o Vague symptoms
o Weakness and easy
fatigability
o Affective dysfunctions
o Urinary complaints
o Hypercalciuria
1. Adenoma
Solitary, 0.5 to 5.0
gms, encapsulated, no
intervening stromal fat
Usually inferior glands
are affected
Composed mostly of
normal-looking,
enlarged chief cells in
sheets, trabeculae,
follicles

2. Primary Hyperplasia
Sporadic or in MEN I and
IIa
All 4 glands are enlarged,
asymmetric

Diffuse or nodular
hyperplasia composed
predominantly of chief
cells, clear cells, oxyphil
cells in sheets, nests,
trabeculae and follicles
Interspersed fat within
hyperplastic area

3. CARCINOMA
Very similar to adenoma but
with features of local invasion
and metastasis
SIGNS AND SYMPTOMS:
o Renal recurrent stones,
nephrocalcinosis
o Skeletal loss of bone,
osteoporosis, OFC
o GIT peptic ulcer,
pancreatitis
o CNS HA, depression,
memory loss, seizures
o Muscular generalized
weakness
o Others: skin & eye
changes, hyperCa,
hypoPO4, elevated PTH

c
Polypepti
de
DIABETES MELLITUS
TYPE I
SYNONYMS
II.

Secondary
Hyperparathyroidism
In patients with renal failure

phosphate retention and hypocalcemia

secondary hyperparathyroidism
MORPHOLOGY:
Same as primary HP
III.

Hypoparathyroidism
CAUSES:
1. Surgically induced
2. Congenital absence of
all glands
3. Autoimmune disease
4. Familial and metabolic
syndromes
SIGNS AND SYMPTOMS:
1. Increases neuromuscular
excitability
2. Mental changes
3. Intracranial changes
4. Calcification of lens
5. Cardiac conduction
abnormalities

IV.

Pseudohypoparathyroidism
Abnormality in PTH-receptor
complex interaction
Unresponsive to PTH
Increase PTH due to decrease
serum Ca

PATHOGENESIS

Insulin
dependent
DM (IDDM)
Juvenile
onset
Ketosis
prone DM
Absolute
lack of
insulin due
to reduction
of B cell

TYPE II
Non-insulin
dependent
DM
(NIDDM)
Adult onset
Impaired
insulin
release and
end-organ
insensitivity

THE ENDOCRINE PANCREAS

Review of Normal Physiology
CELL SYNONY
%
PRODU
TYPE
M
CTS
B
BETA
70 Insulin
A
ALPHA
20 Glucago
n
D
DELTA
5Somato
10 statin
PP
Pancreati 1

PRODUCT
ACTION
Anabolic
Catabolic
Vs insulin &
glycogen
GY effects

CAUSES: TYPE I
1. Genetic susceptibility
- resides in chromosome 6
(HLA-D), CI II genes
- 50% concordance in twins

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2. Autoimmunity
90% with islet cell antibodies
(ICA)
3. Environmental factors
a. Viruses
b. Chemicals
c. Cows milk
CAUSES: TYPE II
1. Genetic but not HLA-linked
2. No evidence for autoimmunity
3. No evidence of viral-induced injury
4. Premature cell aging
5. Amylase outside cells
6. Decrese number of receptors
7. Impaired post-receptor signaling
INSULITIS IN TYPE 1 DM

ISLET WITH AMYLOID

CHANGE
MECHANISMS LEADING TO
DIABETIC COMPLICATIONS
1. Non-enzymatic glycosylation
advances glycosylation end
products (AGE)
o HbA1c glycosylated
hemoglobin
o measure of blood
glucose level
2. Increased sorbitol and
fructose OSMOSIS
MORPHOLOGY of other organs:
1. Diabetic microangiopathy
2. Atherosclerosis
CAUSES:
a. Hyperlipidemia
b. Decreases HDL
c. Increased platelet
adhesiveness
EFFECTS:
a. Myocardial infarction
b. Cerebral stroke
c. Gangrene of lower extremities
3. Diabetic Nephropathy
Kidneys are the most severely
affected organ
Morphology:
Diffuse glomerulosclerosis

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Nodular glomerulosclerosis
(Kimmelsteil-Wilson)
Exudative lesion
Necrotizing papillitis

NEPHROSCLEROSIS
ISLET CELL TUMORS

PAPILLARY
NECROSIS

A. INSULINOMA
B cell tumor most common of
the islet cell tumors
Clinical Triad: hypoglycemia,
CNS manifestations, relief
with glucose
Morphology:
Majority are solitary
adenomas
Yellow-brown nodules
composed of B cells
5% malignanT

Kimmelsteil-Wilson
Lesion
4. Diabetic Ocular complications
a. Retinopathy
i.
Non-proliferative
(background
retinopathy)
ii.
Proliferative
b. Cataract
c. Glaucoma
5. Diabetic Neuropathy
Due to damage Schwann cells
an axon
Sexual impotence, bladder
and bowel dysfunction

B. GASTRINOMA
Clinical Triad: Zollinger
Ellison Syndrome (peptic
ulcer disease, gastric
hypersecretion, pancreatic
islet cell tumor)
MORPHOLOGY:
Microscopically similar
to insulinomas; need
immunocytochemistry
or electron microscopy
to differentiate the two
Mostly malignant
(60%)

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