Mutation in RET Inherited autosomal dominant

Proto-Oncogene mutations in RET Proto-Oncogene

RET activation of RET-signaling

pathway

Dysregulation of MAPK and

P13K/AKT pathways

Uncontrolled cell growth

Proliferation in Thyroid
C-cells

Formation of tumor

Tumor grows

Palpable lump/nodules
in the neck

Compresses nearby structures

including muscles, nerves, blood Exerts pressure on surrounding
vessels, and adjacent tissues in Tumor expands
structures of the neck
the neck

Exerts pressure in the Exerts pressure to the Tumor induced Affects Nearby vocal
dyspnea trachea esophagus angiogenesis cords and laryngeal

Airway becomes Exerts pressure to the

obstructed esophagus Supply nutrients and Disrupt normal nerve
oxygen to the rapidly function
dividing cancer cells

Interferes with the Lumen of esophagus

normal airflow narrows Affects motor control of
MTC cells invade the vocal cords
surrounding tissues
(lymph nodes, blood
Leads to difficulty in Partially obstructed by
vessels) Infiltration of laryngeal
breathing tumor
nerves

Cancer progresses
dyspnea Impedes the smooth
passage of food and Partial paralysis of one or
liquids both vocal cords
MTC cells metastasize

Changes in voice quality

Leads to difficulty in
swallowing MTC Cells release
excessive amount of
calcitonin Voice hoarseness
dysphagia

Elevated Calcitonin Levels

HYPOCALCEMIA

Less Ca+2 outside

cells, positive
charges inside the
cells (no changes)

Intracellular is
positively charged
(related to
depolarization)

Stimulation of neuron Altered Ion

and cardiac myocyte Permeability: Na+
influx
 Delayed repolarization

Increased neuronal Increased Cardiac

activity: excitability depolarization/ action

Inability to fire action

potentials frequently QT prolongation

Delayed neurotransmitter Abnormal rapid

release contraction: Premature
impulses occur

Disrupts synaptic
Increased Cardiac
transmission
depolarization/ action

Altered sensory ability Neuromuscular

Premature impulses
Hyperexcitability
occur

Tingling sensations in the Rare cases:

lips, tongue, fingers, and Tetany arrhythmia
or feet Fatigue Torsades de Pointes
Cramps

Laryngospasm Tetany Ventricular

tachycardia
 Trousseau
sign
 Chvostek sign
Respiratory Distress
 Mutation in RET Inherited autosomal dominant
Proto-Oncogene mutations in RET Proto-Oncogene

RET activation of RET-signaling

pathway

Dysfunction of tumor suppressor

Excessive catecholamine production

Uncontrolled proliferation

Formation of a mass or
tumor

Excessive
epi/norepinephrine
production

Activation of Sympathetic
Nervous System

Signals sent to release

catecholamines into Stimulation of cholinergic
the bloodstream

Activation of eccrine sweat

Persistent and Catecholamines bind glands
Sustains heightened excessive to adrenergic and
sympathetic flow release of alpha- adrenergic
catecholamine receptors Hyper-activty of SNS

Affects tissues including Constricts blood vessels

skeletal muscles Increased production of
watery sweat
Enhances cardiac output vasoconstriction
Muscle Tremors
Diaphoresis

Increased heart rate

Elevated blood pressure

Reduced blood flow to the

skin and peripheral tissues Affects cerebral blood
vessels

Pallor
Increased intracranial
pressure

Disrupts cerebral blood flow

Nociceptor stimulation
headache
 Helicase
Malfunction

Incomplete
Separation of
DNA strands

Anomalies occur
in base pairing

Disrupt normal
hydrogen
bonding process

Incomplete correction of
replication by DNA errors

Persistent
mutations

Errors during
translation
synthesis

Specialized polymerase
bypass damaged site

Mutations

Unequal crossing over

during meiotic
recombination

Duplications or deletions
of genetic material

Inadequate telomere
maintenance by telomerase

Chromosomal
Instability

Cumulative errors in DNA

Replication processes

Cumulative errors in DNA

Replication processes

Genetic Mutations
\