Medicine 3B: Endocrinology MEDISINA

2020
DISORDERS OF THE Thyroid Gland
Lecturer: Gherald Bermudez, M.D. (February 21, 2019)

THYROID GLAND
ANATOMY AND PHYSIOLOGY
" Consists of right and left pear-shaped lobes connected by an
isthmus
" Located anterior to the trachea between the cricoid cartilage
and the suprasternal notch
" Usually weighs around 15-25 g (Caucasians) or 15-20 g
(Asians)
" Produces two related hormones: thyroxine (T4) and
triiodothyronine (T3)
o 80% of the hormones produced by the thyroid gland
is T4
o The biologically active/potent form, T3, is converted
peripherally by the enzyme, deiodinase

o Hypothalamic TRH stimulates pituitary production of

o Thyroid follicles are formed by thyroid epithelial cells
surrounding proteinaceous colloid, which contains
thyroglobulin
o Follicular cells, which are polarized, synthesize
thyroglobulin and carry out thyroid hormone
biosynthesis through series of organification and
oxidation reactions
o TSH regulates thyroid gland function through the
TSH-R, a seven-transmembrane G protein–coupled
receptor (GPCR)
- The TSH-R is coupled to the α subunit of
stimulatory G protein (GSα), which activates
adenylyl cyclase à increased cAMP
o Thyroid hormones bind with high affinity to nuclear
thyroid hormone receptors (TRs) α and β
- TRα is particularly abundant in brain, kidneys,
gonads, muscle, and heart
- TRβ expression is relatively high in the
pituitary and liver
- The TRβ2 isoform, which has a unique amino
terminus (more specific), is selectively
expressed in the hypothalamus and pituitary,
where it plays a role in feedback control of the
thyroid axis
TSH, which, in turn, stimulates thyroid hormone
synthesis and secretion
- TRH is the major positive regulator of TSH
synthesis and secretion
- T4 and T3 feedback to inhibit hypothalamic
production of TRH and pituitary production of
TSH (Classic example of an endocrine
feedback loop)
THYROID HORMONE ACTION
" Thyroid hormones are essential to life as they play a role in
cellular differentiation during development
o That’s why we can observe short stature and mental
retardation in patients with congenital
hypothyroidism
" Thyroid hormones are also responsible for thermogenic and
metabolic homeostasis in adults (in relation to the basal
metabolic rate)
o Therefore, in patients with over or underproduction
of the thyroid hormones, we see imbalance (either
weight loss and heat intolerance or weight gain and
cold intolerance respectively)
" Hormonal problems arising from the thyroid now depend on
hyposecretion or hypersecretion or resistance

Page 1 of 10
DISCLAIMER: I only placed what was emphasized in the lecture. Use at your own risk!
 MED 3B (ENDO): DISORDERS OF THE THYROID GLAND
GHERALD BERMUDEZ, M.D. (FEB 21, 2019)
HYPOTHYROIDISM
" Characterized as a disorder with multiple causes in which the
thyroid fails to produce the thyroid hormone
o Iodine deficiency remains a common cause of
hypothyroidism worldwide
o In areas of iodine sufficiency, autoimmune disease
(Hashimoto’s thyroiditis) and iatrogenic causes
(treatment of hyperthyroidism) are most common
CAUSES
§ In Primary Hypothyroidism, the main culprit is the thyroid gland
o Cellular infiltration of the thyroid (as seen in infiltrative
disorders such as amyloidosis, sarcoidosis,
hemochromatosis) can cause failure and eventually alter
the production of T3 and T4
o Consumptive hypothyroidism due to overexpression of
type 3 deiodinase
- Type 3 deiodinase converts T4 and T3 to the
inactive form à Hypothyroidism
§ Secondary Hypothyroidism involves the pituitary gland (Central)
§ Transient Hypothyroidism is common in cases of inflammation
(thyroiditis) because sometimes patients will not manifest with
symptoms of permanent hypothyroidism
o Patients will revert back to normal after several months
or years
o Subacute thyroiditis usually occurs after viral infections
(granulomatous thyroiditis)
- Acute cases arise from bacterial infections
NOTE: PRIMARY vs SECONDARY HYPOTHYROIDISM
- Primary: Dec T3 & T4, Inc TSH (due to the compensatory
response of the pituitary gland)
- Secondary: Dec T3 & T4, Dec TSH
o If N TSH but Dec T3, T4 à Inappropriate response
REFERENCES: Lecture notes & handouts + Harrison’s, 20th ed
PRIMARY HYPOTHYROIDISM
" Development of this disease is highly dependent on the iodine
content in the diet and in the soil
" Iodine deficiency is prevalent in many mountainous regions
and in central Africa, central South America, and northern
Asia
From: The Philippine Thyroid Diseases Study (PhilTiDeS 1): Prevalence
of Thyroid Disorders Among Adults in the Philippines by Josephine
Carlos-Raboca, et.al.
CONGENITAL HYPOTHYROIDISM
" Occurs in about 1 in 4000 newborns and neonatal screening is
performed in most industrialized countries
" Neonatal hypothyroidism may be due to:
o Thyroid gland dysgenesis (80–85%)
o Inborn errors of thyroid hormone synthesis (10–15%)
o TSH-R antibody-mediated (5%)
AUTOIMMUNE HYPOTHYROIDISM
" Types:
v Hashimoto’s/Goitrous thyroiditis
- Associated with goiter
v Atrophic thyroiditis
- Characterized by absence of goiter
- With minimal residual thyroid tissue at the later
stages of Hashimoto’s (ultimate product of
fibrosis and destruction of cells)
Page 2 of 10
 MED 3B (ENDO): DISORDERS OF THE THYROID GLAND
GHERALD BERMUDEZ, M.D. (FEB 21, 2019)
" The mean annual incidence rate of autoimmune CLINICAL MANIFESTATIONS
hypothyroidism is up to 4 per 1000 women and 1 per 1000
men
o Men obtaining this disorder signifies poor prognosis
" The mean age at diagnosis is 60 years, and the prevalence of
overt hypothyroidism increases with age
" Subclinical hypothyroidism is found in 6–8% of women (10%
over the age of 60) and 3% of men
o Subclinical/Mild hypothyroidism is characterized as N
T3 & T4 but dec TSH
PATHOGENESIS
v Hashimoto’s/Goitrous thyroiditis
" Characterized by marked lymphocytic infiltration of the
thyroid with germinal center formation, atrophy of the
thyroid follicles accompanied by oxyphil metaplasia,
absence of colloid, and mild to moderate fibrosis
v Atrophic thyroiditis
" Fibrosis is much more extensive, lymphocyte infiltration LABORATORY EVALUATION
is less pronounced, and thyroid follicles are almost " Recently, there has been dissociation of clinical and laboratory
completely absent diagnosis in hypothyroidism
v Susceptibility is determined by a combination of genetic and o Therefore, we should not only rely on the signs and
environmental factors symptoms but perform biochemical and laboratory
o HLA-DR polymorphisms are the best documented testing to confirm the diagnosis
genetic risk factors for autoimmune hypothyroidism, o Only 20% are truly hypothyroid when we base on
especially HLA-DR3, DR4, and DR5 in Caucasians symptoms alone
v Environmental susceptibility factors are poorly defined at o 50% were euthyroid and may be related with other
present causes (eg. adrenal insufficiency)
o A high iodine or low selenium intake and decreased o 30% are inconclusive
exposure to microorganisms in childhood increase the " There are certain conditions with compelling evidence to
risk of autoimmune hypothyroidism support case finding/screening:
o Smoking cessation transiently increases incidence o We do not perform screening tests in all populations
whereas alcohol intake seems protective o Screening is recommended in the following:
v Antibodies to TPO (more common) and thyroglobulin (Tg) are § Autoimmune diseases (eg. Type 1 DM) à May
clinically useful markers of thyroid autoimmunity, but any be accompanied with other autoimmune
pathogenic effect is restricted to a secondary role in amplifying disorders as well
an ongoing autoimmune response § If with family history of autoimmune diseases
o Almost all patients have antibodies to TPO and Tg § Prior history of thyroid surgery
v Up to 20% of patients with autoimmune hypothyroidism have § Psychiatric disorders
antibodies against TSH-R § Amiodarone & Lithium intake
o More commonly encountered in hyperthyroidism § Thyroiditis
(Graves’ disease) but may still occur in cases of
hypothyroidism
IATROGENIC HYPOTHYROIDISM
" Common cause of hypothyroidism and can often be detected
by screening before symptoms develop
" In the first 3–4 months after radioiodine treatment for Graves’
disease, transient hypothyroidism may occur due to reversible
radiation damage

" A normal TSH level excludes primary (but not secondary)

hypothyroidism
" If the TSH is elevated, an unbound T4 level is needed to
confirm the presence of clinical
Page 3 of 10
REFERENCES: Lecture notes & handouts + Harrison’s, 20th ed
 MED 3B (ENDO): DISORDERS OF THE THYROID GLAND
GHERALD BERMUDEZ, M.D. (FEB 21, 2019)
hypothyroidism, but T4 is inferior to TSH when used as a
screening test, because it will not detect subclinical
hypothyroidism
" Circulating unbound T3 levels are normal in about 25% of
patients, reflecting adaptive deiodinase responses to
hypothyroidism
o T3 measurements are, therefore, not indicated
" Once clinical or subclinical hypothyroidism is confirmed, the
etiology is usually easily established by demonstrating the
presence of TPO and Tg antibodies, which are present in
>95% of patients with autoimmune hypothyroidism
" TBII can be found in 10–20% of patients, but measurement is
not needed routinely
TREATMENT
v Levothyroxine
" Daily replacement dose, usually 1.6 μg/kg body
weight (typically 100–150 μg; use ideal body mass),
ideally taken at least 30 min before breakfast (In
patients with no residual thyroid function)
o No coffee, no milk (impairs absorption of LT4)
" Goals:
o Resolve signs and symptoms
o Normalize TSH levels
o Avoid overtreatment (Monitor patients
periodically)
" Dose may need to be increased by up to 45% during
pregnancy
o The only source of the baby’s thyroid
hormones during the 1st trimester would be
maternal T4 (Hypothalamic-Thyroid axis of the
patient is not yet developed at this time)
o Women should increase levothyroxine from
once daily dosing to nine doses per week as
soon as pregnancy is confirmed, to anticipate
this change
" Elderly patients may require 20% less thyroxine than
younger patients
o In the elderly, especially patients with known
coronary artery disease, the starting dose is
12.5–25 μg/d with similar increments every 2–
3 months until TSH is normalized
" Adult patients under 60 years old without evidence
of heart disease may be started on 50–100 μg daily
o In patients with heart disease, especially with
known coronary artery disease, starting dose
is 12.5-25 μg/d (regardless of the weight of
the patient)
" Should be separated from other potentially
interfering medications (eg. Calcium carbonate and
Ferrous sulfate); at least 4 hours apart from your
thyroid hormone
" Other medications that may interfere:
o Aluminum hydroxide and Sucralfate
(insufficient absorption of your thyroid
hormones)
" Side effects:
o Inadequate replacement: Increased total
cholesterol level à Progression of CVD
o Atrial fibrillation à Thrombosis
o Osteoporosis (administer calcium
supplements; taken at lunch or dinner)
REFERENCES: Lecture notes & handouts + Harrison’s, 20th ed
SUBCLINICAL HYPOTHYROIDISM
" Refers to biochemical evidence of thyroid hormone deficiency
in patients who have few or no apparent clinical features of
hypothyroidism
" Levothyroxine is recommended if the patient is a woman who
wishes to conceive or is pregnant, or when TSH levels are above
10 mIU/L
" When TSH levels are below 10 mIU/L, a trial of treatment may
be considered when patients have suggestive symptoms of
hypothyroidism, positive TPO antibodies, or any evidence of
heart disease
o Treatment must be individualized
o It is important to confirm that any elevation of TSH is
sustained over a 3-month period before treatment is
given
MATERNAL HYPOTHYROIDISM
" Affects fetal neural development
" May be associated with adverse gestational outcomes
(miscarriage, preterm delivery)
" Prior to conception, levothyroxine therapy should be targeted
to maintain a serum TSH in the normal range but <2.5 mIU/L
for hypothyroid women
o After delivery, levothyroxine doses typically return to
prepregnancy levels
MYXEDEMA COMA
" Characterized by exaggeration of hypothyroidism
" Has a 20–40% mortality rate, despite intensive treatment
o Considered as endocrine emergency
" Outcomes are independent of the T4 and TSH levels
" Clinical manifestations include reduced level of consciousness,
sometimes associated with seizures, as well as the other
features of hypothyroidism
" Almost always occurs in the elderly and is usually precipitated
by factors that impair respiration (requires ventilatory support
in the ER):
o Drugs (especially sedatives, anesthetics, and
antidepressants)
o Pneumonia
o Congestive heart failure
o Myocardial infarction
o Gastrointestinal bleeding
o Cerebrovascular accidents
" Treatment:
o Levothyroxine can initially be administered as a single
IV bolus of 200–400 μg, which serves as a loading dose,
followed by a daily oral dose of 1.6 μg/kg/d, reduced by
25% if administered IV
CASE:
- 55 y/o female complained of weight gain, daytime
sleepiness and constipation
- No known previous thyroid disorder, no neck irradiation
o What is the initial screening test? TSH
- TSH: 75 (NV 0.4-4.0 IU/L); FT4: 8 (NV 12-22 IU/L)
o Diagnosis? Primary hypothyroidism (Inc TSH, Dec
FT4)
o Treatment? Levothyroxine
Page 4 of 10
 MED 3B (ENDO): DISORDERS OF THE THYROID GLAND
GHERALD BERMUDEZ, M.D. (FEB 21, 2019)
HYPERTHYROIDISM
THYROTOXICOSIS
" State of thyroid hormone excess
" Not synonymous with hyperthyroidism, which is the result of
excessive thyroid function
" Major etiologies are hyperthyroidism caused by Graves’
disease, toxic multinodular goiter (MNG), and toxic
adenomas
§ In Primary Hyperthyroidism, the most commonly encountered
condition is Graves’ disease
o Classic Triad:
- Hyperthyroidism
- Proptosis/Exophthalmos
- Goiter
o Mutations are less common
o Drugs (eg. Amiodarone) can elicit:
§ Jod-Basedow phenomenon (Inc T3, T4)
- Thyroid hormone synthesis becomes
excessive as a result of increased iodine
exposure
§ Wolff-Chaikoff phenomenon (Dec T3, T4)
- The initiation of amiodarone treatment
is associated with a transient decrease of
T4 levels, reflecting the inhibitory effect
of iodine on T4 release
- Most individuals escape from iodide-
dependent suppression (shutting down of
inhibitory processes) of the thyroid (Wolff-
Chaikoff effect), and the inhibitory effects
on deiodinase activity and thyroid
hormone receptor action become
predominant
REFERENCES: Lecture notes & handouts + Harrison’s, 20th ed
§ Thyrotoxicosis without hyperthyroidism
o Viral infections (Subacute thyroiditis)
o Silent thyroiditis
" Highly triphasic:
" (1) Inflammation causes destruction of follicles à
Patient will initially secrete T3, T4 à
Hyperthyroidism
" (2) Once follicles are totally destroyed à T3, T4
production becomes decreased à
Hypothyroidism
" (3) If patient is able to recover à Euthyroidism
NOTE: PRIMARY vs SECONDARY HYPERTHYROIDISM
- Primary: Inc T3 & T4, Dec/N TSH (due to the
compensatory response of the pituitary gland)
- Secondary: Inc T3 & T4, Inc TSH
o (+) Presence of tumor in the pituitary gland that
secretes high levels of TSH
o Rare; <5% of pituitary tumors
GRAVES’ DISEASE
" Accounts for 60–80% of thyrotoxicosis
" Occurs in up to 2% of women but is one-tenth as frequent in
men
" Rarely begins before adolescence
" Typically occurs between 20-50 years of age (during
reproductive age of females)
PATHOGENESIS
" Caused by thyroid-stimulating immunoglobulin (TSI) that are
synthesized in the thyroid gland as well as in bone marrow and
lymph nodes
o Such antibodies can be detected by bioassays or by
using the more widely available thyrotropin-binding
inhibitory immunoglobulin (TBII) assays
o The presence of TBII in a patient with thyrotoxicosis
implies the existence of TSI, and these assays are useful
in monitoring pregnant Graves’ patients in whom high
levels of TSI can cross the placenta and cause neonatal
thyrotoxicosis (Not commonly requested among non-
pregnant patients)
" Thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies
occur in up to 80% of cases
" Involves combination of environmental and genetic factors
including polymorphisms in:
o HLA-DR
o Immunoregulatory genes CTLA-4, CD25, PTPN22,
FCRL3, and CD226
o Gene encoding the thyroid-stimulating hormone
receptor (TSH-R)
" Smoking is a minor risk factor for Graves’ disease and a major
risk factor for the development of ophthalmopathy
" There is a threefold increase in the postpartum period
o Pregnancy is characterized as a state of
immunosuppression à Patients do not experience
hyperthyroidism
o During the postpartum period, rebound
hyperthyroidism occurs
Page 5 of 10
 MED 3B (ENDO): DISORDERS OF THE THYROID GLAND
GHERALD BERMUDEZ, M.D. (FEB 21, 2019)
CLINICAL MANIFESTATIONS
" The clinical presentation depends on:
o Severity of thyrotoxicosis (Mild = Less or no S/S)
o Duration of disease (Longer duration = More S/S)
o Individual susceptibility to excess thyroid hormone
o Patient’s age
" Apathetic Thyrotoxicosis
- Occurs in the elderly
- Features of thyrotoxicosis may be subtle or masked
- Patients may present mainly with fatigue and weight
loss
" Thyroid is usually diffusely enlarged to 2-3x its normal size due
to hyperactivity à Hyperplastic follicular cells
o The consistency is firm, but not nodular
o There may be a thrill or bruit, best detected at the
inferolateral margins of the thyroid lobes, due to the
increased vascularity of the gland and the
hyperdynamic circulation
SALIENT FEATURES
§ Graves’ ophthalmopathy
- aka Thyroid-associated ophthalmopathy (occurs in the
absence of hyperthyroidism in 10% of patients
- Onset occurs within th eyear before or after the
diagnosis of thyrotoxicosis in 75% of patients
- Mechanism: Fibroblast activation and increased
synthesis of glycosaminoglycans à Proteins are able to
hold water à Fluid retention remains at the posterior
of the eye à Proptosis
REFERENCES: Lecture notes & handouts + Harrison’s, 20th ed
§ Thyroid dermopathy
- Occurs in <5% of patients, almost always in the
presence of moderate or severe ophthalmopathy
- Most frequent over the anterior and lateral aspects of
the lower leg (pretibial myxedema)
- Characterized as noninflamed, indurated plaque with a
deep pink or purple color and an “orange skin”
appearance
- Nodular involvement can occur, and the condition can
rarely extend over the whole lower leg and foot,
mimicking elephantiasis
§ Thyroid acropachy
- Refers to a form of clubbing found in <1% of patients
- It is so strongly associated with thyroid dermopathy
that an alternative cause of clubbing should be sought
in a Graves’ patient without coincident skin and orbital
involvement
NOTE: CLUBBING IN GRAVES’ DISEASE VS COPD/Anemia
- Graves’: Tender upon palpation
- COPD/Anemia: Nontender on palpation
CLINICAL COURSE
§ Clinical features generally worsen without treatment
§ Mortality was 10–30% before the introduction of satisfactory
therapy
§ Some patients with mild Graves’ disease experience
spontaneous relapses and remissions
§ About 15% of patients who enter remission after treatment
develop hypothyroidism 10–15 years later as a result of the
destructive autoimmune process
LABORATORY EVALUATION
" In Graves’ disease (Primary): Inc T3 & T4, Dec TSH
" In 2–5% of patients (and more in areas of borderline iodine
intake), only T3 is increased (T3 toxicosis)
Page 6 of 10
 MED 3B (ENDO): DISORDERS OF THE THYROID GLAND
GHERALD BERMUDEZ, M.D. (FEB 21, 2019)
TREATMENT
v Antithyroid drugs
" Predominant therapy in many centers in Europe, Latin
America, and Japan
" Main drugs: Thionamides
o Propylthiouracil
- Also inhibits deiodination of T4 → T3
- Indications:
§ First trimester of pregnancy
(Crosses the placenta and cause
embryopathies less likely)
§ Thyroid storm (Due to additional
benefit of deiodination)
§ Minor adverse reactions to
methimazole (If major, do not give
PTU because it may cross react;
Advise definitive therapy such as
surgery/radioactive therapy)
o Carbimazole
- Not available in the US
- Eventually converted to Methimazole in
the circulation (Inactive form)
- 6 mg Methimazole: 10 mg Carbimazole
o Methimazole
- Recommended first line of treatment in
Graves’ disease
- Can cross the placenta and cause
embryopathies
" Mode of action: All inhibit the function of TPO, reducing
oxidation and organification of iodide à Dec T3, T4
synthesis
" Enhances spontaneous rate of remission
" Also reduce thyroid antibody levels by mechanisms that
remain unclear
" Thyroid function tests and clinical manifestations are
reviewed 4–6 weeks after starting treatment, and the
dose is titrated based on unbound T4 levels
o Most patients do not achieve euthyroidism until
6–8 weeks after treatment is initiated
o Maximum remission rates (up to 30–60% in some
populations) are achieved by 12–18 months
" Minor side effects:
o Rash
o Urticaria
o Fever
o Arthralgia (1-5% of patients)
" Rare but major side effects:
o Hepatitis (especially with PTU; Avoid use in
children
- Monitor AST and ALT levels
- If > 3x elevated: Discontinue the drug à
RAI/Surgery
o Cholestasis (Methimazole and Carbimazole)
- Monitor Bilirubin levels
o Vasculitis
o Agranulocytosis (<1%)
REFERENCES: Lecture notes & handouts + Harrison’s, 20th ed
v Supportive Treatment
o Propranolol (20–40 mg every 6 h) or longer-acting
selective β1 receptor blockers such as atenolol
" May be helpful to control adrenergic symptoms,
especially in the early stages before antithyroid
drugs take effect
" Also useful in patients with thyrotoxic periodic
paralysis, pending correction of thyrotoxicosis
o Anticoagulation with warfarin
" Should be considered in all patients with atrial
fibrillation
o Digoxin
" Increased doses are often needed in the
thyrotoxic state
v Radioiodine (131I) treatment
" More often the first line of treatment in North America
" Causes progressive destruction of thyroid cells
" Can be used as initial treatment or for relapses after a
trial of antithyroid drugs
" Absolute contraindications:
o Pregnancy (Patients can conceive safely 6
months after treatment)
o Lactation
" In general, patients need to avoid close, prolonged
contact with children and pregnant women for 5–7
days because of possible transmission of residual
isotope and exposure to radiation emanating from the
gland
v Total or Near-Total Thyroidectomy
" Option for patients who relapse after antithyroid drugs
and prefer this treatment to radioiodine
" Careful control of thyrotoxicosis with antithyroid drugs,
followed by potassium iodide (1–2 drops SSKI orally tid
for 10 days), is needed prior to surgery to avoid
thyrotoxic crisis and to reduce the vascularity of the
gland
" Major complications:
o Bleeding
o Laryngeal edema
o Hypoparathyroidism (Due to removal of
parathyroid glands)
o Damage to the recurrent laryngeal nerve à
Hoarseness
THYROID STORM/THYROTOXIC CRISIS
" Rare and presents as a life-threatening exacerbation of
hyperthyroidism (Endocrine emergency)
" Accompanied by fever, delirium, seizures, coma, vomiting,
diarrhea, and jaundice
" The mortality rate due to cardiac failure, arrhythmia, or
hyperthermia is as high as 30%, even with treatment
" Thyrotoxic crisis is usually precipitated by:
o Acute illness (e.g., stroke, infection, trauma, diabetic
ketoacidosis)
o Surgery (especially on the thyroid)
o Radioiodine treatment of a patient with partially
treated or untreated hyperthyroidism
o Most common cause: Uncontrolled hyperthyroidism
" Management requires intensive monitoring and supportive
care, identification and treatment of the precipitating cause,
and measures that reduce thyroid hormone synthesis
Page 7 of 10
 MED 3B (ENDO): DISORDERS OF THE THYROID GLAND
GHERALD BERMUDEZ, M.D. (FEB 21, 2019)

THYROID NODULAR DISEASE THYROID NODULAR DISEASE

GOITER " Characterized by the disordered growth of thyroid cells,
" Refers to an enlarged thyroid gland which can be either hyperplastic or neoplastic in the
" Causes: background of fibrosis
o Biosynthetic defects (compensatory) " Normally, it occurs around 3-7% of adults and assessed by
o Iodine deficiency physical examination
o Autoimmune disease " May be an incidental finding and is only present on the neck
o Nodular diseases (may or may not cause S/S)
" Biosynthetic defects and iodine deficiency are associated " >25% of adults will show nodules in the presence of
with reduced efficiency of thyroid hormone synthesis, ultrasound
leading to increased thyroid-stimulating hormone (TSH), " May be solitary or multiple
which stimulates thyroid growth as a compensatory " May be functional or non-functional hypersecretion
mechanism to overcome the block in hormone synthesis TOXIC ADENOMA
DIFFUSE NONTOXIC (SIMPLE) GOITER " A solitary, autonomously functioning thyroid nodule
" There is diffuse enlargement of the thyroid that occurs in the " Thyrotoxicosis is usually mild and is generally only detected
absence of nodules and hyperthyroidism when a nodule is >3 cm
" More common in women than men, probably because of the " A thyroid scan provides a definitive diagnostic test,
greater prevalence of underlying autoimmune disease and demonstrating focal uptake in the hyperfunctioning nodule
the increased iodine demands associated with pregnancy and diminished uptake in the remainder of the gland, as
activity of the normal thyroid is suppressed
TERMS:
§ Simple goiter
- Absence of nodules
§ Colloid goiter
- Presence of uniform follicles that are filled with
colloid
§ Endemic goiter
- Most commonly caused by iodine deficiency
- Affects >5% of the population
§ Sporadic goiter
- Occurs in nonendemic regions
- Cause is usually unknown
§ Juvenile goiter " Radioiodine ablation is usually the treatment of choice.
- Thyroid enlargement in teenagers o Patients are highly resistant to antithyroid drugs
§ Substernal goiter o Because normal thyroid function is suppressed, 131I
- Thyroid mass that has 50% or more of its volume is concentrated in the hyperfunctioning nodule with
located below the thoracic inlet minimal uptake and damage to normal thyroid tissue
- May cause obstruction " Surgical resection is also effective and is usually limited to
- Pemberton’s sign lobectomy, thereby preserving thyroid function and
Ø Refers to facial and neck congestion due to minimizing risk of hypoparathyroidism or damage to the
jugular venous obstruction when the arms are recurrent laryngeal nerves
raised above the head, a maneuver that draws " Medical therapy using antithyroid drugs and beta blockers
the thyroid into the thoracic inlet can normalize thyroid function but is not an optimal long-
DIAGNOSIS term treatment (only administered when S/S of
" Thyroid function tests should be performed in all patients thyrotoxicosis is present)
with goiter to exclude thyrotoxicosis or hypothyroidism THYROID CANCER
" TPO antibodies may be useful to identify patients at increased
" Most common malignancy of the endocrine system
risk of autoimmune thyroid disease
" Malignant tumors derived from the follicular epithelium are
" Thyroid scanning is not generally necessary but will reveal
classified according to histologic features
increased uptake in iodine deficiency and most cases of
" Incidence has increased from 4.9 to 14.3 cases per 100,000
dyshormonogenesis
individuals in the US
o Thyroid Ultrasound
" Request for thyroid ultrasound à confirm with biopsy
- Performed if there are suspicious nodules on PE
" Increases with age
" More common among females
o Male gender is a poor prognostic indicator
o Males harbor the worst classification of thyroid
carcinoma (poorly differentiated)

Page 8 of 10
REFERENCES: Lecture notes & handouts + Harrison’s, 20th ed
 MED 3B (ENDO): DISORDERS OF THE THYROID GLAND
GHERALD BERMUDEZ, M.D. (FEB 21, 2019)

WELL-DIFFERENTIATED THYROID CANCER

PAPILLARY
" Most common type of thyroid cancer, accounting for 80-85%
" Characteristic cytologic features of PTC help make the
diagnosis by FNA or after surgical resection:
o Large, clear nuclei with powdery chromatin (described
as an “orphan Annie eye” appearance) with nuclear
grooves and prominent nucleoli
" May be multifocal and invade locally within the thyroid gland
as well as through the thyroid capsule and into adjacent
structures in the neck
" It has a propensity to spread via the lymphatic system but can
metastasize hematogenously as well, particularly to bone and
lung
" Most papillary cancers are identified in the early stages (>80%
stages I or II) and have an excellent prognosis, with survival
curves similar to expected survival
" Treatment: Surgery then radioactive iodine
FOLLICULAR
" More common in iodine-deficient regions
" Difficult to diagnose by FNA because the distinction between
benign and malignant follicular neoplasms requires histology
because the nuclear features of follicular adenomas and
carcinomas do not differ
o Diagnosed by the presence of capsular and/or vascular
invasion
" FTC tends to spread by hematogenous routes leading to bone,
lung, and central nervous system metastases
" Mortality rates associated with angioinvasive FTC are less
" >4 cm: Suspect thyroid malignancy favorable than for PTC, in part because a larger proportion of
" Family history of MEN 2: Medullary thyroid carcinoma patients present with stage IV disease
" Poor prognostic features:
o Distant metasteases
o Age >50 years
o Primary tumor size>4 cm
o Hürthle cell histolory
o Presence of marked vascular invasion
TREATMENT
" All well-differentiated thyroid cancers >1cm (T1b or larger)
should be surgically excised although active surveillance may be
an option for small intrathyroidal micropapillary thyroid cancers
(T1a) without metastases
" TSH Suppression Therapy
- Because most tumors are still TSH-responsive,
levothyroxine suppression of TSH is a mainstay of
thyroid cancer treatment
" Radioiodine Treatment
- After near-total thyroidectomy, <1 gm of thyroid tissue
remains in the thyroid bed
- Postsurgical radioablation of the remnant thyroid
eliminates residual normal thyroid, facilitating the use
of Tg determinations
" The degree of TSH suppression should be individualized based on
a patient’s risk of recurrence
o For patients at low risk of recurrence, TSH should be
maintained in the lower normal limit (0.5–2.0 mIU/L)
" Follow-up:
o Whole body scan 6 months post-therapy to check if
there are any metastatic focus

Page 9 of 10
REFERENCES: Lecture notes & handouts + Harrison’s, 20th ed
 MED 3B (ENDO): DISORDERS OF THE THYROID GLAND
GHERALD BERMUDEZ, M.D. (FEB 21, 2019)

POORLY DIFFERENTIATED THYROID CANCER NOTE: HOT VS COLD NODULES

ANAPLASTIC - Hot: Always benign à Treat as Graves’ or multinodular
" Very aggressive cancer; Rare - Cold: Highly suspicious of malignancy
" Prognosis is poor
" Most patients die within 6 months of diagnosis

MEDULLARY
" Can be sporadic or familial
" Accounts for about 5% of thyroid cancers
" There are three familial forms:
o MEN 2A (Pheochromocytoma, MTC, Parathyroid)
o MEN 2B (Pheochromocytoma, MTC,
Neurofibromatosis)
o Familial MTC without other features of MEN
" In general, MTC is more aggressive in MEN 2B than in MEN
2A, and familial MTC is more aggressive than sporadic MTC
" Elevated serum calcitonin provides a marker of residual or
recurrent disease
" Management: Primarily surgical
" Tumors do not take up radioiodine
o External radiation treatment and targeted kinase
inhibitors may provide palliation

Page 10 of 10
REFERENCES: Lecture notes & handouts + Harrison’s, 20th ed