Thyroid Pathophysiology

Frank Vuitch, MD

Thyroid Pathophysiology
Learning Objectives
Discuss useful laboratory tests to evaluate thyroid function
List major causes of hyperthyroidism and hypothyroidism
Describe clinicopathologic findings and pathogenesis of
(a) Graves disease as a prototype of hyperthyroidism, and
(b) Hashimoto thyroiditis as a prototype of hypothyroidism
Describe clinical and pathologic findings and pathogenesis
of multinodular goiter
List four clinical features favoring carcinoma over a goitrous
nodule in a patient with a solitary thyroid nodule
List major thyroid neoplasms and describe their gross and
microscopic appearances and clinical features,
including oncogene associations, multifocality,
metastatic patterns, relative incidences, and prognosis
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Thyroid Function Tests

Reference range = normal value for population
95% of individuals fall in reference range
Individuals have narrower personal normal range
Pituitary response to small fluctuations in free T4
and free T3 will be prompt opposite TSH change
Best screening test is TSH, now highly sensitive
Free T4 is biologically active component in serum
Most of total T4 is bound to TBG
Thyroid autoantibodies elevated in Hashimoto
thyroiditis and Graves disease
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Hyperthyroidism and
Hypothyroidism
Hyperthyroidism (thyrotoxicosis): hypermetabolic
state caused by elevated free T3 and T4 levels,
manifested by nervousness, palpitations, rapid
pulse, muscular weakness, weight loss despite
good appetite, heat intolerance, fine tremor, eye
changes... Graves, toxic goiter, toxic adenoma.
Hypothyroidism: structural or functional thyroid
derangement interferes with production of
adequate levels of thyroid hormones. High TSH
- primary thyroid failure. Low TSH - pituitary or
hypothalamic failure. Hashimoto thyroiditis,
iodine deficiency, congenital errors, iatrogenic.
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Forms of Hypothyroidism
Cretinism:

Hypothyroidism developing in
infancy or early childhood. Features include:
Mental retardation: Severity depends on how
early thyroid deficiency occurs in utero
Growth retardation: Short stature
Myxedema: Hypothyroidism developing in older
child or adult. Features include slowing of
mental and physical activity. Patients may have
apathy, fatigue, listlessness (mimic depression
or dementia), cold intolerance, constipation,
weight gain, and myxedema (brawny edema)
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Radioactive Iodine Scan

Identify in the Scans:
Normal Scan
Graves Disease
Goiter
Cold Nodule
Hot Nodule

Thyroid Mass Lesions

Most non-neoplastic thyroid diseases can present
as mass - 2 to 4% of US population have thyroid
nodules
0.004% of population/year have thyroid cancer
Adenomas:
Follicular
Carcinomas:
Papillary:
75-85%
Follicular:
10-20%
Medullary:
5%
Anaplastic: <5%
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Clinical features favoring carcinoma

over solitary goitrous nodule
Fixed

to skin, deep structures, nerve

Presence of cervical lymphadenopathy
Nodule in child or elderly patient, or man woman in child-bearing years favors goiter
History of head and neck radiation
True solitary nodule - ultrasound shows
cysts, additional nonpalpable nodules
Cold on radioactive iodine scan
Suspicious fine needle aspiration cytology
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Follicular Adenoma
Gross: Solitary circumscribed
homogeneous encapsulated
solid mass in otherwise normal
thyroid lobe
Histology: This neoplastic tissue
is very well-differentiated,
showing follicles containing
colloid. Nuclei are uniform and
round, with small nucleoli and
no mitotic figures, and polarity
of the cuboidal cells toward
follicular lumens is preserved
Question: Cold or hot ?
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Papillary Carcinoma
Gross: Thyroid lobectomy, 2
cm irregular expansile
mass. No discernible
papillae on cut surface.
Neoplasm not
encapsulated, but welldemarcated from normal
thyroid parenchyma.
Distends and distorts
thyroid capsule without
penetrating through.
Histology: Into clear spaces,
numerous papillary fronds
protrude, showing a
delicate branching
architecture with central
fibrovascular cores.
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Papillary CA vs Follicular CA
Clear irregular nuclei, papillae
Psammoma bodies
+/- follicles, capsular/vascular
All ages, including children
Related to previous radiation
Multifocal in gland
Lymph node metastases 50%
Distant metastases
uncommon
Prognosis excellent

Capsular and/or blood vessel

invasion
Lack papillary Ca nuclear
features
Middle-aged and older
Surrounding gland normal
Unifocal
Nodal metastases uncommon
Visceral metastases common
- lung and bone
Significant mortality at 10 y
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Thyroid Carcinomas
Papillary and Follicular

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Medullary Thyroid Carcinoma

C-cell neoplasm
Secrete calcitonin - amyloid
stroma is procalcitonin
Sporadic - solitary
Familial (MEN) - multifocal
RET protooncogene
Metastasize both to lymph
nodes and viscera
Mortality 50%

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