Transcript Endocrine – Thyroid and Parathyroid Glands

Endocrine – Thyroid
and Parathyroid
Glands
Dr. Geoffrey Pollack
October 10, 2007
Endocrine - Thyroid
 Embryology
 Median thyroid anlage forms at base of tongue in
region of foramen cecum during 3rd week of
gestation
 Endodermal pocket
 Originates from primitive alimentary tract protruding
between first pair of pharyngeal pouches
 Subsequently descends in the midline to reach its
normal anatomic location developing into a bi-lobed
organ
Endocrine - Thyroid
 Embryology
 Iodine trapping occurs as thyroid hormones are first seen
in the 3rd month of gestation
 The principle cells of the thyroid form thyroid follicles and
produce thyroglobulin
 Lateral anlagen develop from the 4th pharyngeal pouch
and fuse with the median anlagen at about the 7th week
of gestation
 Ultimobranchial bodies which may orignate from the 4th
pharyngeal pouch may give rise to parafollicular or C
cells
 C cells secrete calcitonin
 C cells originate from neural crest and are of ectodermal
origin
Endocrine - Thyroid
 Embryology – Thyroglossal Duct Cyst (TGDC)
 TGDC are the most common non-odontogenic
cysts occurring in the neck
 TGDC are second only to benign
lymphadenopathy of all cervical masses in
children (70% of all congenital neck cysts)
 TGD represents the original attachment of the
thyroid mass to the oropharynx
 TGD is normally resorbed by the 6th week of
gestation
 Distal end of duct may be retained as the
pyramidal lobe of thyroid
Endocrine - Thyroid
 Embryology – Thyroglossal Duct Cyst (TGDC)
 TGDC are located at or near midline between base of
tongue and suprasternal notch
 75% of TGDC are located just inferior to the hyoid bone
 The importance of TGDC is related to
 High incidence of infection
 Recurrence after inadequate surgery
 Possible neoplastic change
 One-third are detected in first year of life; 50% are
detected by age 10
 They present as painless midline lesions that grow
slowly
 They can increase in size after a URI
Endocrine - Thyroid
 Embryology – Thyroglossal Duct Cyst (TGDC)
 TGDC contains thyroid tissue (and perhaps only
functioning thyroid tissue in body – obtain sonogram
in an adult prior to OR)
 Rarely a source of thyroid carcinoma (usually
papillary)
 Treatment: surgery via Sistrunk procedure
 This includes midportion of hyoid bone
 Must excise entire cyst/tract/fistula up to base of tongue
 Recurrence rate with Sistrunk procedure is low (less than
4% compared with 50% when not done using this
procedure)
Endocrine - Thyroid
 Embryology – Thyroglossal Duct Cyst
(TGDC)
Endocrine - Thyroid
 Embryology – Thyroglossal Duct Cyst
(TGDC)
Endocrine - Thyroid
 Embryology – Lingual Tonsil
 Failure of thyroid anlage to migrate can
result in persistence of a functional lingual
thyroid gland
 May represent only functional thyroid tissue
 Excision may be necessary for airway
obstruction, swallowing difficulty, or hemorrhage
Endocrine - Thyroid
 Anatomy
 Normal gland weights between 20-30 grams
 Thyroid lobes lie subadjacent to thyroid cartilage, anterior to
larynx and trachea
 2 lobes connected by the isthmus
 Midline pyramidal process, distal remnant of TGD is present in
40-50% of adults
 Anterior aspect covered by strap muscles
 Posterolaterally lie common carotid arteries, internal jugular
veins and Vagus nerves
 Gland is covered by connective tissue layer derived from pretracheal fascia
 Fascia connects thyroid to upper tracheal rings and cricoid
posteromedially (Berry’s ligament)
Endocrine - Thyroid
 Anatomy
Endocrine - Thyroid
Endocrine - Thyroid
 Anatomy - Recurrent laryngeal nerve (RLN)
 Arises in the chest as a branch of the Vagus nerve
 The right nerve loops under the right subclavian
artery
 The left nerve loops under the aortic arch
 The right can be non-recurrent in a small number of
cases
 As it ascends in the neck from the chest, the
recurrent nerve usually runs just under Berry’s
ligament before entering the larynx (posterior to the
thyroid at the level of the cricothyroid junction)
Endocrine - Thyroid
 Anatomy - RLN
 Motor nerve to intrinsic muscles of larynx except
cricothyroid
 Sensory to mucosa below vocal cords
 Unilateral injury to the nerve can result in a
weakened voice and can lead to shortness of breath
 Bilateral injury is a devastating complication causing
airway obstruction
 RLN must be identified by a surgeon during any
procedure performed on the thyroid gland
Endocrine - Thyroid
 RLN
Endocrine - Thyroid
 Anatomy – Superior laryngeal nerve (SLN)
 Arises from the Vagus nerve at the skull base and
descends along the carotid artery in the neck
 2 branches
 Internal branch is sensory to the larynx above the vocal
cords. It enters the larynx at the level of the thyrohyoid
membrane
 External branch is motor to the cricothyroid muscle (tenses
the vocal cord) and inferior constrictor muscle. It enters the
larynx behind the cricothyroid muscle. Injury to this nerve
will produce hoarseness. Injury can be devastating to
professional singers
Endocrine - Thyroid
 SLN
Internal branch
External branch
Endocrine - Thyroid
 Anatomy
 4 parathyroid glands are associated with the
thyroid gland
 2 superior
 2 inferior
 The parathyroid glands must be
identified by the surgeon during any
procedure performed on the thyroid
gland
Endocrine - Thyroid
 Anatomy
 Thyroid gland supplied by 4 main arteries
 2 superior thyroid arteries (branches of external carotid)
 2 inferior thyroid arteries (branches of thyrocervical trunk)
 Superior, middle and inferior thyroid veins drain
blood into internal jugular vein and brachiocephalic
veins
 Lymphatic drainage
 Intraglandular – travels through isthmus (accounts for
relative frequency of multifocal tumors)
 Central compartment (from hyoid to innominate artery)
 Jugular chain (especially levels II, III, IV, V)
Endocrine - Thyroid
 Physiology





Thyroid gland converts inorganic iodine into thyroid hormone (TH)
Iodine enters thyroid and is trapped by follicular cells
TH synthesis takes place at interface of cell and thyroglobulin (THG)
THG is a glycoprotein (colloid)
Iodine oxidized by thyroid peroxidases to an activated form of iodine
that binds the amino acid tyrosine forming T3 and T4 (TH)
 The newly formed TH is stored in THG
 Thyroid gland releases T3 and T4 into the circulation
 20% of all T3 and the majority of T4
 99% of TH is protein-bound (thyroxin binding globulin,
prealbumin, albumin)
 80% of T3 is formed from T4 in peripheral tissue
 Thyroid hormone release is regulated by TSH (thyrotropin stimulating
hormone) from the pituitary
Endocrine - Thyroid
 Physiology
Endocrine - Thyroid
 Physiology
Endocrine - Thyroid
 Physiology
 Thyroid function tests
 Direct tests
 Radioactive iodine uptake (RAIU)
 Tests of hormone concentration and binding





T4
T3
T3 resin uptake
T4 index (Totally T4 + T3 resin uptake)
T7
 Tests of hypothalamic – pituitary – thyroid axis
 TSH
 Other tests
 Anti-thyroid peroxidase
 Anti-thyroglobulin
Endocrine - Thyroid
Endocrine - Thyroid
 1. Operations on the thyroid account for the
largest number of procedures performed for
tumors of the head and neck
 2. Thyroid carcinoma is unique because of the
low-grade nature of the majority of lesions
 3. The major problem for surgeons
 Correct diagnosis of the small number of malignant
tumors from the large number of benign growths
 Selecting the optimal surgical treatment using a safe
effective technique
Endocrine - Thyroid
 Benign conditions
 Benign diseases are common and affect
women 5 times more than men
 About 1% of women develop hypo or
hyperthyroidism
 Benign conditions can be categorized as
 Toxic [toxic multinodular goiter, toxic solitary
nodule, diffuse toxic goiter (Graves’ disease)]
 Non-toxic [diffuse and nodular (solitary or
multiple goiter)]
 Inflammatory diseases consisting of thyroiditis
Endocrine - Thyroid
 Benign conditions
 With the exception of hyperthyroidism, benign
thyroid diseases are of significance to the surgeon
either because of mechanical constraint on the
upper aerodigestive tract or because it is not
possible to rule out carcinoma within a nodular or
diffuse lesion
 Nodular increase may be indistinguishable from goiter or
cancer
 Autoimmune disease may cause firm nodular enlargement
difficult to distinguish from carcinoma
 Follicular adenoma is a true neoplasm that may be
indistinguishable from follicular carcinoma except by
permanent histologic exam after surgery (vascular or
capsule invasion)
Endocrine - Thyroid
 Benign conditions – Hyperthyroidism
 Hyperthyroidism – an excess of production and
secretion of thyroid hormone with a characteristic
hypermetabolism result
 Thyrotoxicosis – hypermetabolic state that can be
caused by hyperthyroidism (or can occur without
hyperthyroidism)
 Lab tests
 Elevated T4 or T3
 Suppressed TSH
 Normal RAIU
Endocrine –
Thyroid
 Hyperthyroidism
Endocrine - Thyroid
 Benign conditions – Hyperthyroidism
 Treatment
 Usually medical but surgery may be required if
medical treatment has failed or is contraindicated
in 3 conditions
 Graves’ disease
 Toxic multinodular goiter (TMNG)
 Toxic solitary nodule (TSN)
Endocrine - Thyroid
 Benign conditions – Hyperthyroidism
 Graves’ disease
 Autoimmune toxic diffuse goiter
 Antibodies against TSH receptor
 6-7 times more common in women
 Genetic factors play a role
 Triad
 Diffuse toxic goiter
 Infiltrative opthalmopathy
 Infiltrative dermopathy (pre-tibial myxedema)
Endocrine - Thyroid
 Benign conditions – Hyperthyroidism
 Graves’ disease – Treatment
 Antithyroid drugs
 Thionamides (PTU, Tapazole)
 Inhibits organification of iodine and coupling of iodothyronine
 Must be used for long duration; recurrence can occur if meds
discontinued
 Success correlates inversely with gland size
 May cause agranulocytosis
 Beta-blockers – usually in adjuvant setting if patient is symptomatic
or pre-surgery
 Radioactive Iodine
 Most commonly chosen therapy
 Hypothyroidism expected complication
Endocrine - Thyroid
 Benign conditions – Hyperthyroidism
 Graves’ disease – Treatment: Surgery
 10% of patients require surgery
 Pregnancy (131-I contraindicated)
 Failure of drug therapy
 Concurrent nodular disease with positive FNA
 Pre-op preparation to attain euthyroid state
increases safety (PTU, Tapazole, Beta-blockers,
Iodine)
 Controls hypermetabolic state
 Decreases risk of thyroid storm
 May decrease vasularity
Endocrine - Thyroid
 Benign conditions – Hyperthyroidism
 Graves’ disease – Treatment: Surgery
 Total vs. Subtotal thyroidectomy
 Total
 Hypothyroidism expected
 Risks to nerves and parathyroids
 Recurrence of hyperthyroidism approaches 0%
 Subtotal – purposefully leaving tissue behind at poles or
laterally





Bilateral subtotal
Unilateral total with contralateral subtotal
50-60% recurrence rate
Recurrence can occur 1-30 years after surgery
Re-op much more difficult
Endocrine - Thyroid
 Benign conditions – Hyperthyroidism
 Toxic multinodular goiter (TMG)
 “Hot” nodules take up radioactive tracer at higher than
normal levels
 “Hot” nodules can be
 Autonomous (not responsive to TSH suppression)
 Not autonomous (responsive to TSH suppression)
 Autonomous nodules can be
 Toxic (thyroid hormone in excess clinically hyperthyroid)
 Non-toxic
 Rate of cancer in “hot” nodules is low
Endocrine - Thyroid
 Benign conditions – Hyperthyroidism
 Toxic multinodular goiter (TMG)
 Over age 50 in setting of longstanding nontoxic
multinodular goiter
 Nodules become autonomous and toxic (clinically
hyperthyroid) - cannot be suppressed
 Treatment:
 Same as Graves’ disease (thionamides, radioiodine, surgery)
 Radioiodine treatment of choice
 Surgery performed for large goiters and compressive
symptoms after patient made euthyroid. Remove all nodules
Endocrine - Thyroid
 Benign conditions – Hyperthyroidism
 Toxic solitary nodule (TSN)
 Most are follicular adenomas that can have
spontaneous infarction
 Less than 1% are carcinoma
 Life cycle (“hot” nodule  autonomous “hot”
hodules  autonomous TSN)
 More worrisome in nodules greater than 2.5-3cm
 Surgery for worrisome nodules otherwise 131-I
therapy
Endocrine - Thyroid
 Benign conditions – Hyperthyroidism
Endocrine - Thyroid
 Benign conditions – Thyroiditis
 Includes heterogeneous mixture of diseases
with variable etiologies, presentation and
treatment
 Can result in diffusely enlarged, nodular and
even normal gland in appearance
 May be euthyroid, hypo or hyper
 Often preceding triggers (partuition, viruses,
medication)
Endocrine - Thyroid
 Benign conditions – Thyroiditis
 Classified by
 Descriptive, subjective history (painful or not
painful)
 Temporal course (acute, subacute, chronic)
 Histopathology (hyperplastic, lymphocytic,
granulomatous or fibrosis)
 Doctor’s name (Graves, Hashimoto, DeQuervain,
Reidel)
Endocrine - Thyroid
 Thyroiditis
Endocrine - Thyroid
 Thyroiditis
Endocrine - Thyroid
 1. Operations on the thyroid account for the
largest number of procedures performed for
tumors of the head and neck
 2. Thyroid carcinoma is unique because of the
low-grade nature of the majority of lesions
 3. The major problem for surgeons
 Correct diagnosis of the small number of malignant
tumors from the large number of benign growths
 Selecting the optimal surgical treatment using a safe
effective technique
Endocrine - Thyroid
 Benign conditions
 Benign diseases are common and affect
women 5 times more than men
 About 1% of women develop hypo or
hyperthyroidism
 Benign conditions can be categorized as
 Toxic [toxic multinodular goiter, toxic solitary
nodule, diffuse toxic goiter (Graves’ disease)]
 Non-toxic [diffuse and nodular (solitary or
multiple goiter)]
 Inflammatory diseases consisting of thyroiditis
Endocrine - Thyroid
 Benign conditions
 With the exception of hyperthyroidism, benign
thyroid diseases are of significance to the surgeon
either because of mechanical constraint on the
upper aerodigestive tract or because it is not
possible to rule out carcinoma within a nodular or
diffuse lesion
 Nodular increase may be indistinguishable from goiter or
cancer
 Autoimmune disease may cause firm nodular enlargement
difficult to distinguish from carcinoma
 Follicular adenoma is a true neoplasm that may be
indistinguishable from follicular carcinoma except by
permanent histologic exam after surgery (vascular or
capsule invasion)
Endocrine - Thyroid
 Thyroid Nodule
 Range of disease for thyroid nodule
 Benign cyst
 Lethal malignancy
 Need strategy to identify malignant vs.
benign
Endocrine - Thyroid
 Thyroid Nodule
 Prevalence
 5% of adults by palpation (greater than 1.5cm)
 30% of adults by sonography
 Increased risk




Female
Age
History of XRT
Endemic iodine deficiency
Endocrine - Thyroid
 Thyroid Nodule
 Risk of cancer
 New thyroid nodules 275,000 per year
 1:20 new nodules are malignant (This represents
5%; however in some studies it can approach
15%)
 Death from thyroid carcinoma 1,100 per year
 1:200 new nodules are lethal cancer
Endocrine - Thyroid
 Thyroid Nodule – Differential Diagnosis





Colloid nodule – multinodular goiter
Adenoma
Cyst
Focal thyroiditis
Carcinoma
95%
Endocrine - Thyroid
 Thyroid Nodule – Differential Diagnosis
 Metastasis to thyroid
 Lobar hypertrophy status post hemithyroidectomy
 Non-thyroid






Lymph node
Laryngeal, esophageal tumor
TGDC
Cystic hygroma, dermoid, teratoma
Laryngocele
Nerve sheath tumor
Endocrine - Thyroid
 Thyroid Nodule – History
 Age <20 or >60
 Male (nodular disease is more common in women, but risk of cancer
is 2 times greater in men)
 History of XRT
 Family history (MTC)
 Size >4cm
 Rapid growth
 Invasion/compression
 Trachea/larynx: airway, vocal cord paralysis, cough
 Esophagus: dysphasia
 Pain (subacute thyroiditis or hemorrhage)
 Thyroid functional status




Hashimoto’s
MTNG
STN
Remember most cancers are euthyroid that is, no functional deficiency
Endocrine - Thyroid
 Thyroid Nodule – History
 Low dose ionizing radiation
 Tonsils/thymus, acne, tinea (ended approx.
1955), Hodgkin’s, scatter from breast
 20-30% develop nodules
 Patients presenting with such a history have a 30-50%
chance of developing cancer
Endocrine - Thyroid
 Thyroid Nodule – Physical Exam






Solitary, dominant
Consistency, fixed
Trachea, larynx shift
Lymph nodes
Vocal cord motion
Retrosternal/Pemburton’s sign
Endocrine - Thyroid
 Thyroid Nodule – Degree of clinical
concern for carcinoma based on history
and physical exam
 Less concern
 Stable exam
 Evidence of functional disorder
 Multinodular gland without dominant nodule
Endocrine - Thyroid
 Thyroid Nodule – Degree of clinical concern for
carcinoma based on history and physical exam
 More concern











Age <20 >60
Males
Rapid growth, pain
History of radiation therapy
Family history of thyroid carcinoma
Hard fixed lesion
Lymphadenopathy
Vocal cord paralysis
Size >4cm
Aerodigestive tract compromise (e.g., stridor, dysphagia)
Cyst recurrence after aspiration
Endocrine - Thyroid
 Thyroid Nodule – Lab Work up
 Thyroid function tests
 TSH, T4, Total T3, resin uptake, T4 index, T7
 Hashimoto’s: TPO
 Malignancy: No effective markers
 Thyroglobulin
 Extensive overlap benign vs. malignant
 Hampered by anti-thyroglobulin autoantibodies
 Useful in long-term follow-up in patients with
thyroid carcinoma
Endocrine - Thyroid
 Thyroid Nodule – Hashimoto’s Thyroiditis
 Can present with small, firm thyroid lobes which can
be mistaken for thyroid nodules on exam
 Common cause of hypothyroidism in females
 Development of progressively enlarging mass within
Hashimoto’s should trigger concern for lymphoma
 FNA can give false positive findings (microfollicles,
Hurthle cells, lymphocytes)
Endocrine - Thyroid
 Thyroid Nodule – Toxic Nodule
 Decreased TSH (rationale for checking TSH
prior to FNA)
 Very low incidence of malignancy
 High risk of microfollicle false positive FNA
Endocrine - Thyroid
 Thyroid Nodule – Multinodular Goiter
 Dominant nodule is considered as a solitary
nodule in terms of malignancy risk
Endocrine - Thyroid
 Thyroid Nodule – Radiographic Work up
 CXR – tracheal deviation, substernal extension,
metastasis
 CT – impact on adjacent cervical viscera,
retrosternal extension, adenopathy (cervical or
mediastinal), tracheal invasion; caution with use of
iodine in multinodular goiter where patient may be
subclinically hyperthyroid
 MR – Retrosternal mediastinal vascular relationship
Endocrine - Thyroid
 Thyroid Nodule – I123 Scan
 95% cold: cold solid nodule, cyst, focal thyroiditis;
only 10-15% malignant
 5% hot: <4% hot nodules are malignant
 When to scan:
 Identification of a functional solitary thyroid nodule when
TSH is decreased
 If an FNA is reported as a follicular neoplasm or suspicious,
the finding of a “hot” nodule may decrease the suspicion of
a cancer
 Detecting neck metastasis
Endocrine - Thyroid
 Thyroid Nodule – Sonography
 Does not distinguish between benign vs. malignant
 Provides a sensitive and objective measure of nodule size
prior to FNA, surgery, suppression
 Provides clear-cut baseline
 Finds contralateral nodules, lymph nodes which can be helpful
at surgery
 Nonpalpable or difficult to palpate nodules for US-guided FNA
 Follow-up imaging for solitary nodules that are managed
medically or by observation
 Nondiagnostic fine needle aspirate (as an adjunct to repeat
FNA)
Endocrine - Thyroid
 Thyroid Nodule – Sonography
 Studies show
 70% of nodules are solid  20% are malignant
 19% are cystic  7% are malignant
 11% are mixed  12% are malignant
Endocrine - Thyroid
 Thyroid Nodule – Sonography
 US features suggesting malignancy
 Absent “halo” sign
 Solid or hypoechogenicity
 Heterogeneous echo structure
 Irregular margin
 Fine calcifications
 Extraglandular extension
Endocrine - Thyroid
 Thyroid Nodule – Fine Needle Aspiration (FNA)
 All palpable lesions of the thyroid require FNA
 Decreased the percent of patients brought to
surgery by 20-50%
 Increased the percent of carcinoma found in
surgical specimens by 10-15%
 Overall decreases cost of care by 25%
Endocrine - Thyroid
 FNA
Endocrine - Thyroid
 Thyroid Nodule – FNA Diagnostic Categories
Endocrine - Thyroid
 Thyroid Nodule – Fine Needle Aspiration (FNA)
“Suspicious”
Endocrine - Thyroid
 Thyroid Nodules - Management of the Thyroid Cyst
Endocrine - Thyroid
 Thyroid Nodule Suppression
 Exogenous T4 suppresses TSH and withdraws
stimulatory influence on the thyroid and nodules
within it
 Goal and length of treatment are unclear
 Controversy regarding whether suppressive therapy
is superior to placebo
 Risks
 Suppressive therapy promotes osteoporosis and in an
elderly population increases atrial fibrillation
Endocrine - Thyroid
 Thyroid Nodule Algorithm
Endocrine - Thyroid
 Nontoxic Goiter
 Goiter is defined as any benign enlargement
of the thyroid gland
 Iodine deficiency is most common cause
(endemic goiter)
 In response to iodine deficiency  increase TSH
 Epithelial hyperplagia of thyroid gland followed by focal
nodular hyperplagia
 Can grow extremely large
 In US, most goiters are nonendemic
 3-4% of US population
 Cause unknown
Endocrine - Thyroid
 Nontoxic Goiter – Indications for Surgery
 Symptoms of airway, esophageal, or superior vena
caval obstruction
 Thyroid enlargement despite nonoperative
treatment
 FNA biopsy positive or suspicious for malignancy
 Radiologic finding of tracheal deviation or
compression
 Susternal goiter
 Cosmetic deformity/patient preference
Endocrine - Thyroid
 Nontoxic Goiter – Surgery: Controversy
 Patients with unilateral thyroid enlargement
lobectomy and isthmusectomy
 Patients with diffuse or multinodule goiter
 Total on one side and subtotal on the other
 Total
 Bilateral subtotal
 High recurrence rate (up to 25%)
 Need for reoperation
Endocrine - Thyroid
 Thyroid Cancer – Statistics
 1.5% of all cancers in the US
 Most common endocrine malignancy (95%
of all endocrine cancers)
 Approx. 22,000 new cases each year
 74% occur in women
Endocrine - Thyroid
 Thyroid Cancer – Pathology
Endocrine - Thyroid
 Thyroid Cancer – Papillary Carcinoma
 75-80% of all thyroid cancers
 Consists of pure papillary, follicular, tall cell*,
columnar cell*, oxyphilic*, diffuse sclerosing, and
encapsulated variants
 Accounts for 90% of radiation-induced thyroid ca.
 Familial in 3% of patients (Cowden’s syndrome and
Gardner’s syndrome)
* Aggressive forms of papillary carcinoma
Endocrine - Thyroid
 Thyroid Cancer – Papillary Carcinoma
 Histological features
 Psammoma bodies
 Intranuclear grooves
 Cytoplasmic inclusions
 Multicentric in 30-50% of tumors
 Spreads via lymphatics
 Cervical metastasis is not uncommon on initial
presentation (in one study, microscopic mets
present in 90% of elective neck dissection
specimens)
Endocrine - Thyroid
 Thyroid Cancer – Papillary Carcinoma
 Treatment
 Papillary carcinoma <1cm in size “microcarcinoma” 
lobectomy and isthmusectomy
 Papillary carcinoma >1cm in low-risk group  lobectomy
and isthmusectomy (low-risk have recurrence rate of 511%; mortality rate .07-5%)
 Papillary carcinoma >1cm in high-risk group  total
thyroidectomy (high-risk have recurrence rate of 48%;
mortality rate 48%)
 Patients with history of head and neck irradiation  total
thyroidectomy (high incidence of ca. at sites other than
nodule and increased lifetime risk of developing thyroid
carcinoma)
Endocrine - Thyroid
 Thyroid Cancer – Papillary Carcinoma
Endocrine - Thyroid
 Thyroid Cancer – Papillary Carcinoma
 Treatment
 Total thyroidectomy – Advantages
 Associated with lowest incidence of local and regional
occurrence
 When combined with post-op 131I ablation there is improved
survival
 Allows use of serum thyroglobulin (Tg) and radioiodine for
early detection and treatment of metastatic disease
 Avoids possible future re-op surgery
 Total thyroidectomy – Disadvantages
 Injury to recurrent laryngeal nerves and parathyroid glands
Endocrine - Thyroid
 Thyroid Cancer – Papillary Carcinoma
 Treatment
 Lymph nodes
 Prophylactic lymph node dissection not warranted
 Enlarged lymph nodes in central and lateral neck
should be removed and submitted for frozen section
 If FS+ in central neck  central neck dissection
performed
 If FS+ in lateral neck  modified radical neck
dissection (functional neck) performed
Endocrine - Thyroid
 Thyroid Cancer – Papillary Carcinoma
 Treatment –
Lymph Nodes
Endocrine - Thyroid
 Thyroid Cancer – Follicular Carcinoma




10% of all thyroid cancers
Spreads hematogenously (lungs and bones)
Only 10% spread to cervical lymph nodes
FNA cannot distinguish benign from malignant follicular
neoplasm (capsule or vascular invasion are determining
factors)
 FNA report “consistent with follicular neoplasm” has 20%
chance of malignancy
 These patients should undergo lobectomy and isthmusectomy
 If permanent section is positive for carcinoma, then completion
thyroidectomy is done
Endocrine - Thyroid
 Thyroid Cancer – Hurthle Cell Carcinoma
 5% of thyroid cancers
 Similar to follicular carcinoma but more
aggressive tumor
 10-year survival 30%
Endocrine - Thyroid
 Thyroid Cancer – Staging
 Papillary and Follicular carcinoma are
considered well-differentiated thyroid tumors
 Both Papillary and Follicular ca have good
prognoses
 20-year survival rates are 90% and 70%
respectively
 Most important prognostic factor is age
Endocrine - Thyroid
 Thyroid Cancer – Staging
Endocrine - Thyroid
 Thyroid Cancer – Post-op Treatment of WellDifferentiated Thyroid Carcinoma
 Thyroid remnant ablation destroys residual thyroid tissue after
surgery using 131I
 Destroys microscopic disease
 Allows for detection of recurrent disease by radioiodine scanning
 Allows for improved sensitivity of serum thyroglobulin (Tg)
measurements during follow-up
 Used for:
 Papillary ca. >1.5cm
 Papillary ca. with mets
 Invasive follicular or Hurthle Cell ca.
 Patient should be off thyroid hormone for weeks (or T3 for 2
weeks) to allow for maximal TSH levels
Endocrine - Thyroid
 Thyroid Cancer – Post-op Treatment of
Well-Differentiated Thyroid Carcinoma
 Thyroid hormone given post-ablation to
suppress TSH (TSH stimulates tumor
growth, invasion, angiogenesis, Tg
secretion)
 Long-term follow-up using serum Tg and 131I
whole-body scans
Endocrine - Thyroid
 Thyroid Cancer – Medullary Carcinoma (MTC)
 Parafollicular cells of neuroectoderm origin
 5% of all thyroid cancers (75% sporadic; 25% hereditary)
 FNA can be characteristic along with special staining for
calcitonin
 Hereditary
 Part of multiple endocrine neoplasia syndromes type IIA and IIB
(IIA – hyperparathyroidism and pheochromocytoma, lichen planus
amyloidosis, Hirschprung’s disease; IIB – pheochromocytoma,
marfanoid body habitus, mucosal neuromas, ganglioneuromatosis
of the GI tract)
 RET proto-oncogene is currently primary factor implicated
 This allows for screening, early detection and treatment
Endocrine - Thyroid
 Thyroid Cancer – Medullary Carcinoma (MTC)
 Treatment
 Surgery is main modality of treatment
 Total thyroidectomy with central neck dissection
 Modified radical neck dissection is performed for cervical
lymph node metastasis
 These tumors are not amenable to radioiodine therapy or
other adjuvant therapy
 Post-treatment
 Monitor serum calcitonin levels
Endocrine - Thyroid
 Thyroid Cancer – Anaplastic Cancer
 A most aggressive cancer
 Overall 5-year survival; 3.6% with median survival of
4 months
 No adequate therapy known; complete surgical
resection is difficult because of tumor size, extra
thyroid growth and invasion into surrounding
tissues. Besides attempted resection, surgery may
be indicated for airway management (e.g.,
tracheotomy)
 Surgery, radiation therapy, chemotherapy combined
may improve local control
Endocrine - Thyroid
 Thyroid Cancer – Lymphoma








Less than 1% of thyroid cancers
Usually non-Hodgkin’s B-cell type
Associated with Hashimoto’s thyroiditis
Usually in older women
Presents as rapidly enlarging painless neck mass
FNA 80% accurate
Occasional biopsy is necessary for tissue diagnosis
50-70% 5-year survival
Endocrine - Thyroid
 Thyroid Cancer – Surgery: Complications
 2 primary potential complications that must be considered in
performing thyroid surgery are RLN injury and
hypoparathyroidism
 With total thyroidectomy, incidence of temporary
hypoparathyroidism ranges from 5-40%
 With total thyroidectoy, the incidence of permanent
hypoparathyroidism ranges from 1-5% in some studies to 832% in other studies
 The rate of temporary RLN injury is 3-7%
 With total thyroidectomy the incidence of permanent RLN
injury is 0-3% per side in some studies, and up to 11% in other
studies
 Lastly, injury to the superior laryngeal nerve can be a
devastating complication to professional singers
Endocrine - Thyroid
 Thyroid Cancer – Surgery: Complications
 Hypoparathyroidism (hypocalcemia)







Circumoralparasthesia
Mental status change
Carpopedal spasm
Seizures
QT interval prolongation
Cardiac arrest
Most common after total thyroidectomy but can occur in
patients with hyperparathyroidism who undergo parathyroid
surgery, especially when the calcium is extremely elevated
preoperatively, with significant bone disease (hungry bone
syndrome)
 Should be treated as a general rule when serum calcium
falls below 7 and / or patient is symptomatic
Endocrine - Thyroid
 Surgery –
Technique
Endocrine - Thyroid
 Surgery –
Technique
Endocrine - Thyroid
 Surgery –
Technique
Endocrine – Parathyroid
-84%
-84%of
ofadults
adultshave
have44parathyroids
parathyroids
-Autopsy
-Autopsyresults
resultsreveal
reveal13%
13%have
havegreater
greaterthan
than44and
and3%
3%have
have
less
lessthan
than44
Endocrine - Parathyroid
Endocrine - Parathyroid
 Anatomy and Embryology
 Inferior glands are derived from the 3rd
branchial pouch and migrate caudally with
the thymus. They then separate at the level
of the inferior thyroid pole
 Superior glands are derived from the 4th
branchial pouch and follow the migration of
the ultimobranchial bodies at the lateral part
of the thyroid anlage
Endocrine - Parathyroid
 Anatomy and Embryology
 The inferior glands vary more in their
location than the superior glands
 The superior glands are generally located
superior to the inferior thyroid artery and
posterior to the recurrent laryngeal nerve
(classically described as lying 1cm above
the intersection of the RLN and inferior
thyroid artery
Endocrine - Parathyroid
 Anatomy and Embryology
 Common ectopic location for the superior gland
includes paraesophageal or retroesophageal areas
(superior posterior mediastinum) and intrathyroid
 The inferior glands usually lie near the inferior pole
of the thyroid and are inferior to the inferior thyroid
artery and anterior to the RLN
 The inferior glands are more variable in location.
Ectopic locations include in or around the thymus
(anterior mediastinum)
Endocrine - Parathyroid
 Anatomy
and
Embryology:
Ectopic
locations
Endocrine - Parathyroid
 Anatomy





Glands are usually oval, bean-shaped or oblong
Weigh 30-65mg
Average 5x3x2mm
Light yellow to caramel color
Blood supply to the superior and inferior glands is
from the inferior thyroid artery in 86% of patients. In
the remainder, both glands are supplied by the
superior thyroid artery or by anastomotic arch from
both vessels
Endocrine - Parathyroid
 Anatomy
Endocrine - Parathyroid
 Physiology
 Parathyroid hormone (PTH) is an 84-amino acid
peptide with the biologic activity residing at its amino
terminal
 PTH regulates serum calcium concentration and
bone metabolism (affects bone, kidney and intestine
particularly)
 Serum calcium concentration in turn regulates PTH
secretion
high calcium  PTH secretion
low calcium  PTH secretion
Endocrine - Parathyroid
 Physiology

PTH
 Increase in renal calcium absorption
 Increase in enzyme activity converting Vitamin D
to its active form and thereby increasing intestinal
absorption of calcium
 Increases osteoclast activity which increases
bone resorption and bone remodeling
 Decreased phosphorous excretion, mild
metabolic acidosis and decrease in GFR also
occur
Endocrine - Parathyroid
 Physiology
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
 Syndrome of inappropriate secretion of PTH by one
or more abnormal glands
 Most cases are sporadic with female to male 4:1
 Familial syndrome are relatively rare and include:
MEN Types I and II
Familial isolated HPT
Hereditary HPT jaw tumor syndrome
 85-90% are caused by a single adenoma
 Multiple gland disease either as multiple adenomas
or hyperplasia of all 4 glands 10-15%
 <1% parathyroid carcinoma
Endocrine - Parathyroid
 Parathyroid Adenoma – Right inferior
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
 Classic presentation: “renal stones, painful bones,
abdominal groans, psychic moans and fatigue
overtones”
 Severe symptoms which are uncommon include:
osteitis fibrosis cystica, osteoclastomas (Brown
tumors) and nephrocalcinosis
 Most patients today are “asymptomatic” with
increased calcium found in routine blood tests
 “Asymptomatic” patients may have subtle symptoms
such as neuropsych disorders, dyspepsia,
constipation and high blood pressure
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
 Diagnosis made by blood test of increased
calcium and increased circulating intact PTH
 Other causes of hypercalcemia should be
ruled out
 Familial hypocalciuric hypercalcemia (FHH)




Autosomal dominant
<1% of patients with hypercalcemia
PTH usually normal or slightly elevated
Urinary calcium secretion NOT usually elevated (in
contrast to PHPT) so the fasting urinary calcium to
creatnine ratio is less than 0.01
Endocrine - Parathyroid
 Differential diagnosis of hypercalcemia
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
 Indications for surgery
 Virtually all patients with symptomatic PHPT and selected
patients with asymptomatic PHPT should undergo surgery
 Guidelines have been liberalized over the years; that is,
more people who are asymptomatic now come to surgery
(in one study, 25% of asymptomatic patients develop some
form of metabolic complication within 5 years of diagnosis
 Asymptomatic patients not meeting criteria for surgery
should have serum calcium checked twice a year and bone
densitometry and serum creatnine checked yearly
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
 Conventional parathyroidectomy
 Bilateral neck exploration with identification of all
4 glands
 Removal of enlarged gland(s) (+ / - biopsy of
normal glands)
 95% success rate
 This operation is indicated when localization
studies fail; when diagnosis of hyperplasia is
suspected; and for cases of secondary and
tertiary hyperparathyroidism
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
 New approaches to surgery
 Localization studies
 Technetium-99 –labeled sestamibi
 Absorbed and retained by parathyroid disease but
rapidly washed out from thyroid
 Accuracy enhanced by combining it with single
photon emission CT (SPECT)
 Picks up 85% of adenomas
 Sensitivity decreases with multiple gland disease
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
 New approaches to surgery
 Localization studies
 Cervical USG – 60-70% of abnormal glands
 MRI / CT 75% sensitivity but usually reserved for
reoperation
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
 New approaches to surgery
 Directed parathyroidectomy
 Makes use of localization studies to allow for unilateral
neck dissection on the side of the positive localization
 Methylene blue, when used preoperatively, can
enhance success of localization intraoperatively.
Abnormal tissue turns dark blue in color
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
 New approaches to surgery
 Directed parathyroidectomy
 Intraoperative PTH monitoring
 iPTH has short half-life
 Serial measurement of serum iPTH before, during
and at 5 and 10 minutes after removal of enlarged
gland will show fall in iPTH
 Reduction in iPTH greater than of equal to 50% of
pre-surgery level indicates success
 Absolute level of iPTH should fall to normal
 Success exceeds 90%
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
 New approaches to surgery
 Directed parathyroidectomy
 Radioguided parathyroidectomy
 Employs injection of 99-Tc sestamibi immediately
before OR
 Using gamma probe to detect area of greatest
radioactivity
 Can combine techniques
 Minimally invasive parathyroidectomy – requires
proper localization studies
 Open minimal access parathyroidectomy
 Endoscopic parathyroidectomy
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
 Results
 Parathyroidectomy is curative in 95% of cases of
PHPT
 Persistent PHPT usually results from a missed
adenoma
 Recurrent PHPT (occurs 6 months or more postop) may develop 5-10% of time, probably due to
a second adenoma or hyperplasia of remaining
glands
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
 Complications
 Temporary hypocalcemia (20-30%)
 Cervical hematoma (less than 1%)
 Recurrent nerve palsy (1-2%)
 Recurrent nerve injury (less than 1%)
Endocrine - Parathyroid
 Primary hyperparathyroidism (PHPT)
 Parathyroid hyperplasia
 Consider this diagnosis when localization studies are not
helpful
 15% of all PHPT
 Diagnosis in 37% of patients undergoing re-op
 Pathology found in secondary and tertiary
hyperparathyroidism and MEN syndromes
 Requires bilateral neck exploration
 In PHPT – perform either 3 ½ gland resection making sure
remnant left is viable and marking remnant with vascular
clip in case of need for re-exploration or total
parathyroidectomy with autotransplantation
Endocrine - Parathyroid
 Secondary and Tertiary Hyperparathyroidism
 Secondary hyperparathyroidism
 Result of chronic overstimulation leading to hyper
secretion and hyperplasia of normal parathyroid
glands, i.e., chronic hypocalcemic stimulation
 Seen most commonly in chronic renal failure
 Surgery is associated with end-stage renal failure,
only 1% usually require surgery
 Bilateral exploration either performing subtotal
parathyroidectomy or total parathyroidectomy with
immediate autotransplantation
Endocrine - Parathyroid
 Secondary and Tertiary Hyperparathyroidism
 Tertiary hyperparathyroidism
 Occurs in setting of longstanding 2HPT
 Longstanding parathyroid hyperplasia leads to
autonomous function
 Bilateral exploration either performing subtotal
parathyroidectomy or total parathyroidectomy with
immediate autotransplantation
Endocrine - Parathyroid
 Secondary and Tertiary Hyperparathyroidism
 Indications for surgery
 Bone and joint pain
 Intractable pruritis
 Muscle weakness
 Malaise
 X-ray signs of renal osteodystrophy
 Uncontrolled hypercalcemia
 Uncontrolled hyperphosphatemia
 Extraskeletal nonvascular calcifications
 calciphylaxis
Endocrine - Parathyroid
 Secondary and Tertiary Hyperparathyroidism
Endocrine - Parathyroid
 Persistent or Recurrent Hyperparathyroidism
 Re-operation surgery includes surgery for
persistent HPT when the previous operation has
failed, and recurrent HPT following initially
successful surgery
 Main causes of recurrent or persistent PHT is
missing an adenoma on initial surgery (e.g.,
failure to locate an ectopic gland), multiglandular
disease, multiple adenomas or hyperplasia of
the remaining glands, or transplanted
parathyroid tissue
Endocrine - Parathyroid
 Persistent or Recurrent Hyperparathyroidism
Bibliography
Bibliography
Bibliography











Kreisel, D. et al. The Surgical Review: An integrated basic and clinical science
study guide. Lippincott, 2001.
Randolph, G. Management of the Thyroid Nodule. American Academy of
Otolaryngology – Head and Neck Surgery Foundation, Inc., 1999.
Silver, C. and Rubin, J. Atlas of Head and Neck Surgery. Churchill Livingston,
1999.
Cummings, C. et al. Otolaryngology Head and Neck Surgery. Mosby, 1993.
Bailey. Head and Neck Surgery – Otolaryngology. Lippincott
Greenfield. Surgery – Scientific Principles and Practice. Lippincott
Harvey, H. The Otolaryngologic Clinics of North America: Disorders of the thyroid
and parathyroid. Vol I. April 1990.
Harvey, H. The Otolaryngologic Clinics of North America: Disorders of the thyroid
and parathyroid. Vol II. June 1990.
Shindo, M., and Singer, P. The Otolaryngologic Clinics of North America: Current
concepts in the management of thyroid and parathyroid disorders. August 1996.
Miller, F., and Otto, R. The Otolaryngologic Clinics of North America: Disorders of
the thyroid. February 2003.
Stack, B. The Otolaryngologic Clinics of North America: Parathyroids. August 2004