The Thyroid Gland

1. Evaluation of the Neck:
The Thyroid Gland
Frederick Untalan MD

2.  Common clinical finding – NECK MASS
 All age groups
 Very complex differential
diagnosis!
 Systematic approach essential

4.  Prominent
landmarks
 Triangles of
the neck
 Carotid bulb
 Lymphatic
levels

5.  Prominent
landmarks
 Triangles of the
neck
 Carotid bulb
 Lymphatic levels

6.  Prominent
landmarks
 Triangles of the
neck
 Carotid bulb
 Lymphatic levels

9.  Patient age
 Pediatric (0 – 15 years): 90% benign
 Young adult (16 – 40 years): similar to pediatric
 Late adult (>40 years): “rule of 80s”
 Location
 Congenital masses: consistent in location
 Metastatic masses: key to primary lesion

10. Metastasis Location according
to Various Primary Lesions

11.  History
 Developmental time course
 Associated symptoms (dysphagia, otalgia, voice)
 Personal habits (tobacco, alcohol)
 Previous irradiation or surgery
 Physical Examination
 Complete head and neck exam (visualize & palpate)
 Emphasis on location, mobility and consistency

12.  Inflammatory mass suspected
 Two week trial of antibiotics
 Follow-up for further investigation

13.  Fine needle aspiration biopsy (FNAB)
 Computed tomography (CT)
 Magnetic resonance imaging (MRI)
 Ultrasonography
 Radionucleotide scanning

14.  Standard of diagnosis
 Indications
 Any neck mass that is not an obvious
abscess
 Persistence after a 2 week course of
antibiotics
 Small gauge needle
 Reduces bleeding
 Seeding of tumor – not a concern
 No contraindications (vascular ?)

16.  Distinguish cystic from
solid
 Extent of lesion
 Vascularity (with contrast)
 Detection of unknown
primary (metastatic)
 Pathologic node (lucent,
>1.5cm, loss of shape)
 Avoid contrast in thyroid
lesions

17.  Similar
informati
on as CT
 Better for
upper
neck and
skull
base
 Vascular
delineati
on with
infusion

18.  Less important
now with FNAB
 Solid versus cystic
masses
 Congenital cysts
from solid
nodes/tumors
 Noninvasive
(pediatric)

19.  Salivary and thyroid
masses
 Location – glandular
versus extra-glandular
 Functional information
 FNAB now preferred for
for thyroid nodules
 Solitary nodules
 Multinodular goiter
with new increasing
nodule
 Hashimoto’s with new
nodule

20.  Any solid asymmetric mass MUST
be
considered a metastatic neoplastic
lesion until proven otherwise
 Asymptomatic cervical mass
 12% of cancer
 ~ 80% of these are SCCa

21.  Ipsilateral otalgia with normal otoscopy –
direct attention to tonsil, tongue base,
supraglottis and hypopharynx
 Unilateral serous otitis – direct examination
of nasopharynx

22.  Panendoscopy
 FNAB positive with no primary on repeat exam
 FNAB equivocal/negative in high risk patient
 Directed Biopsy
 All suspicious mucosal lesions
 Areas of concern on CT/MRI
 None observed – nasopharynx, tonsil
(ipsilateral tonsillectomy for jugulodigastric
nodes), base of tongue and piriforms
 Synchronous primaries (10 to 20%)

23.  Unknown primary
 University of Florida (August, 2001)
 Detected primary in 40%
 Without suggestive findings on CT or panendoscopy
yield dropped to 20%
 Tonsillar fossa in 80%

24.  Open excisional biopsy
 Only if complete workup negative
 Occurs in ~5% of patients
 Be prepared for a complete neck dissection
 Frozen section results (complete node
excision)
 Inflammatory or granulomatous – culture
 Lymphoma or adenocarcinoma – close
wound

25.  Congenital masses
 Benign lesions
 Vascular and lymphatic malformations
 Infectious and inflammatory conditions
 Malignant lesions

26.  Thyroid mass  Carotid body
 Lymphoma and glomus
 Salivary tumors tumors
 Lipoma  Neurogenic
tumors

27.  Leading cause of anterior
neck masses
 Children
 Most common neoplastic
condition
 Male predominance
 Higher incidence of
malignancy
 Adults
 Female predominance
 Mostly benign

28.  Lymph node metastasis
 Initial symptom in 15% of papillary
carcinomas
 40% with malignant nodules
 Histologically (microscopic) in >90%
 FNAB has replaced USG and radionucleotide
scanning
 Decreases # of patients with surgery
 Increased # of malignant tumors found at
surgery
 Doubled the # of cases followed up
 Unsatisfactory aspirate – repeat in 1 month

30. Nodular goiter
Goiter displacing the trachea

31.  Benign Nontoxic Conditions
 Diffuse and Nodular Goiter
 Benign Toxic Conditions
 Toxic Multinodular Goiter
 Graves’ Disease
 Toxic Adenoma
 Inflammatory Conditions
 Chronic (Hashimoto’s) Thyroiditis
 Subacute (De Quervain’s) Thyroiditis
 Riedel’s Thyroiditis

32.  Usually picked up on routine physical exam or
as incidental finding
 Patients may have clinical or subclinical
thyrotoxicosis
 Patients may have compressive symptoms:
tracheal, vascular, esophageal, recurrent
laryngeal nerve

33.  Suppressive Therapy
 Antithyroid Medications: Propylthiouracil and
Methimazole
 I-131
 Surgical Therapy

34.  Antithyroid Drugs
 May require prolonged therapy
 Radioactive iodine
 May worsen ophthalmopathy unless
followed by steroids
 Surgery
 Make patient euthyroid prior to surgery
 Potassium iodide two weeks prior to surgery
can decrease the vascularity of the gland

35.  Autonomously functioning thyroid nodule
hypersecreting T3 and T4 resulting in
thyrotoxicosis (Plummer’s disease)
 Almost never malignant
 Manage with antithyroid drugs followed by
either I-131 or surgery

36.  Also known as Hashimoto’s disease
 Probably the most common cause of
hypothyroidism
 Autoantibodies include: thyroglobulin
antibody, thyroid peroxidase antibody, TSH
receptor blocking antibody

37.  Painless goiter in a patient who is either
euthyroid or mildly hypothyroid
 Low incidence of permanent hypothyroidism
 May have periods of thyrotoxicosis
 Treat with levothyroxine

38.  Also known as De Quervain's
thyroiditis
 Most common cause of thyroid pain and
tenderness
 Acute inflammatory disease most likely due to
viral infection
 Transient hyperthyroidism followed by
transient hypothyroidism; permanent
hypothyroidism or relapses are uncommon

39.  Symptomatic: NSAIDS or a
glucocorticoid
 Beta-blockers indicated if there are
signs of thyrotoxicosis
 Levothyroxine may be given during
hypothyroid phase

40.  Rare disorder usually affecting middle-aged
women
 Likely autoimmune etiology
 Fibrous tissue replaces thyroid gland
 Patients present with a rapidly
enlarging hard neck mass

41.  1.0%-1.5% of all new cancer cases
 tenfold less than that of lung,
breast, or colorectal cancer
 8,000-14,000 new cases diagnosed each year
(Sessions, 1993, Geopfert, 1998)
 3% of patients who die of other causes have
occult thyroid cancer and 10% have microscopic
cancers (Robbins, 1991)
 35% of thyroid gland at autopsy in some studies
have papillary carcinomas (<1.0cm) (Mazzaferri,
1993)

42.  1,000-1,200 patients in the U.S. die each year of
thyroid cancer (Goldman, 1996)
 4%-7% of adults in North America have
palpable thyroid nodules (Mazzaferri, 1993, Vander,
1968)
 4:1 women to men (Mazzaferri, 1993)
 Overall, fewer than 5% of nodules are malignant
(Mazzaferri, 1988)

43.  Symptoms
 The most common presentation of a thyroid
nodule, benign or malignant, is a painless mass
in the region of the thyroid gland (Goldman, 1996).
 Symptoms consistent with malignancy
 Pain
 dysphagia
 Stridor
 hemoptysis
 rapid enlargement
 hoarseness

44.  Risk factors
 Thyroid exposure to irradiation
 low or high dose external irradiation (40-50 Gy
[4000-5000 rad])
 especially in childhood for:
 large thymus, acne, enlarged tonsils, cervical
adenitis, sinusitis, and malignancies
 30%-50% chance of a thyroid nodule to be
malignant (Goldman, 1996)
 Schneider and co-workers (1986) studied, with
long term F/U, 3000 patients who underwent
childhood irradiation.
 1145 had thyroid nodules
 318/1145 had thyroid cancer (mostly papillary)

45.  Family History
 History of family member with medullary
thyroid carcinoma
 History of family member with other endocrine
abnormalities (parathyroid, adrenals)
 History of familial polyposis (Gardner’s
syndrome)

46.  Examination of the thyroid nodule:
 consistency - hard vs. soft
 size - < 4.0 cm
 Multinodular vs. solitary nodule
 multi nodular - 3% chance of malignancy
(Goldman, 1996)
 solitary nodule - 5%-12% chance of
malignancy (Goldman, 1996)
 Mobility with swallowing
 Mobility with respect to surrounding tissues
 Well circumscribed vs. ill defined borders

47.  Examine for ectopic thyroid tissue
 Indirect or fiberoptic laryngoscopy
 vocal cord mobility
 evaluate airway
 preoperative documentation of any
unrelated abnormalities
 Systematic palpation of the neck
 Metastatic adenopathy commonly found:
 in the central compartment (level VI)
 along middle and lower portion of the
jugular vein (regions III and IV) and
 Attempt to elicit Chvostek’s sign

48.  Thyroid function tests
 thyroxine (T4)
 triiodothyronin (T3)
 thyroid stimulating hormone (TSH)
 Serum Calcium
 Thyroglobulin (TG)
 Calcitonin

49.  Advantages
 Most sensitive procedure or identifying lesions
in the thyroid (2-3mm)
 90% accuracy in categorizing nodules as solid,
cystic, or mixed (Rojeski, 1985)
 Best method of determining the volume of a
nodule (Rojeski, 1985)
 Can detect the presence of lymph node
enlargement and calcifications
 Noninvasive and inexpensive

50.  Currently considered to be the best first-line
diagnostic procedure in the evaluation of the thyroid
nodule:
 Advantages:
 Safe
 Cost-effective
 Minimally invasive
 Leads to better selection of patients for
surgery than any other test (Rojeski, 1985)

51.  Mechanism/Rationale
 Exogenous thyroid hormone feeds back to
the pituitary to decrease the production of
TSH
 Cancer is autonomous and does not require
TSH for growth whereas benign processes do
 Thyroid masses that shrink with suppression
therapy are more likely to be benign
 Thyroid masses that continue to enlarge are
likely to be malignant

52. Limitations:
 16% of malignant nodules are suppressible
 Only 21% of benign nodules are suppressible
 Provides little use in distinguishing benign from
malignant nodules
(Geopfert, 1998)

53.  Uses:
 Preoperative
 patients with nonoxyphilic follicular neoplasms
 patients with solitary benign nodules that are
nontoxic (particularly men and premenopausal
women)
 women with repeated nondiagnostic tests
 Postoperative
 Use in follicular, papillary and Hurthle cell
carcinomas
(Geopfert, 1998, Mazzaferri, 1993)

54.  How to use thyroid suppression
 administer levothyroxine
 maintain TSH levels at <0.1 mIU/L
 use ultrasound to monitor size of nodule
 if the nodule shrinks, continue L-thyroxine
maintaining TSH at low-normal levels
 if the nodule has remained the same size after 3
months, reaspirate
 if the nodule has increased in size, excise it
(Geopfert, 1998,)

55.  Papillary carcinoma  Medullary Carcinoma
 Follicular variant  Miscellaneous
 Sarcoma
 Tall cell
 Lymphoma
 Diffuse sclerosing  Squamous cell carcinoma
 Encapsulated  Mucoepidermoid
 Follicular carcinoma carcinoma
 Overtly invasive  Clear cell tumors
 Pasma cell tumors
 Minimally invasive
 Metastatic
 Hurthle cell carcinoma
 Direct extention
 Anaplastic carcinoma
 Kidney
 Giant cell  Colon
 Small cell  Melanoma

56.  Pathogenesis - unknown
 Papillary has been associated with the RET proto-
oncogene but no definitive link has been proven
(Geopfert, 1998)
 Certain clinical factors increase the likelihood of
developing thyroid cancer
 Irradiation - papillary carcinoma
 Prolonged elevation of TSH (iodine deficiency) -
follicular carcinoma (Goldman, 1996)
 relationship not seen with papillary carcinoma
 mechanism is not known

57.  60%-80% of all thyroid cancers (Geopfert, 1998, Merino, 1991)
 Histologic subtypes
 Follicular variant
 Tall cell
 Columnar cell
 Diffuse sclerosing
 Encapsulated
 Prognosis is 80% survival at 10 years (Goldman, 1996)
 Females > Males
 Mean age of 35 years (Mazzaferri, 1994)

58.  Lymph node involvement is common
 Major route of metastasis is lymphatic
 46%-90% of patients have lymph node involvement
(Goepfert, 1998, Scheumann, 1984, De Jong, 1993)
 Clinically undetectable lymph node involvement does not
worsen prognosis (Harwood, 1978)

59.  20% of all thyroid malignancies
 Women > Men (2:1 - 4:1) (Davis, 1992, De Souza, 1993)
 Mean age of 39 years (Mazzaferri, 1994)
 Prognosis - 60% survive to 10 years (Geopfert, 1994)
 Metastasis - angioinvasion and hematogenous
spread
 15% present with distant metastases to bone and lung
 Lymphatic involvement is seen in 13% (Goldman,
1996)

60.  Variant of follicular carcinoma
 First described by Askanazy
 “Large, polygonal, eosinophilic thyroid follicular cells
with abundant granular cytoplasm and numerous
mitochondria” (Goldman, 1996)
 Definition (Hurthle cell neoplasm) - an
encapsulated group of follicular cells with at least
a 75% Hurthle cell component
 Carcinoma requires evidence of vascular and
capsular invasion
 4%-10% of all thyroid malignancies (Sessions, 1993)

61.  Depending on variables, patients are categorized
in to one of the following three groups:
1) Low risk group - men younger than 40
years and women younger than 50 years
regardless of histologic
type
- recurrence rate -11%
- death rate - 4%
(Cady and Rossi, 1988)

62.  1) Intermediate risk group - Men older than 40
years and women older than 50 years who have
papillary carcinoma
 - recurrence rate - 29%
 - death rate - 21%
 2) High risk group - Men older than 40 years and
women older than 50 years who have follicular
carcinoma
 - recurrence rate - 40%
 - death rate - 36%

63.  10% of all thyroid malignancies
 1000 new cases in the U.S. each year
 Arises from the parafollicular cell or C-cells of the
thyroid gland
 derivatives of neural crest cells of the branchial arches
 secrete calcitonin which plays a role in calcium
metabolism

64.  Familial MTC:
 Autosomal dominant transmission
 Not associated with any other endocrinopathies
 Mean age of 43
 Multifocal and bilateral
 Has the best prognosis of all types of MTC
 100% 15 year survival
(Farndon, 1986)

65.  Multiple endocrine neoplasia IIa (Sipple’s
Syndrome):
 MTC, Pheochromocytoma, parathyroid
hyperplasia
 Autosomal dominant transmission
 Mean age of 27
 100% develop MTC (Cance, 1985)
 85%-90% survival at 15 years (Alexander, 1991,
Brunt, 1987)

66.  Multiple endocrine neoplasia IIb (Wermer’s
Syndrome, MEN III, mucosal syndrome):
 Pheochromocytoma, multiple mucosal
neuromas, marfanoid body habitus
 90% develop MTC by the age of 20
 Most aggressive type of MTC
 15 year survival is <40%-50%
(Carney, 1979)

67.  Highly lethal form of thyroid cancer
 Median survival <8 months (Jereb, 1975, Junor, 1992)
 1%-10% of all thyroid cancers (Leeper, 1985, LiVolsi, 1987)
 Affects the elderly (30% of thyroid cancers in
patients >70 years) (Sou, 1996)
 Mean age of 60 years (Junor, 1992)
 53% have previous benign thyroid disease
(Demeter, 1991)
 47% have previous history of WDTC (Demeter, 1991)

68.  Surgery is the definitive management of thyroid
cancer, excluding most cases of ATC and lymphoma
 Types of operations:
 lobectomy with isthmusectomy - minimal operation
required for a potentially malignant thyroid nodule
 total thyroidectomy - removal of all thyroid tissue
- preservation of the contralateral
parathyroid glands
 subtotal thyroidectomy - anything less than a total
thyroidectomy

69.  Rationale for total thyroidectomy
 1) 30%-87.5% of papillary carcinomas involve
opposite lobe (Hirabayashi, 1961, Russell, 1983)
 2) 7%-10% develop recurrence in the contralateral
lobe (Soh, 1996)
 3) Lower recurrence rates, some studies show
increased survival (Mazzaferri, 1991)
 4) Facilitates earlier detection and tx for recurrent
or metastatic carcinoma with iodine (Soh, 1996)
 5) Residual WDTC has the potential to
dedifferentiate to ATC

70.  Rationale for subtotal thyroidectomy
 1) Lower incidence of complications
 Hypoparathyroidism (1%-29%) (Schroder, 1993)
 Recurrent laryngeal nerve injury (1%-2%)
(Schroder, 1993)
 Superior laryngeal nerve injury
 2) Long term prognosis is not improved by
total thyroidectomy (Grant, 1988)

71.  Indications for total thyroidectomy
 1) Patients older than 40 years with papillary or follicular
carcinoma
 2) Anyone with a thyroid nodule with a history of
irradiation
 3) Patients with bilateral disease

72.  Postoperative therapy/follow-up
 Radioactive iodine (administration)
 Scan at 4-6 weeks postop
 repeat scan at 6-12 months after ablation
 repeat scan at 1 year then...
 every 2 years thereafter

73.  Postoperative therapy/follow-up
 Thyroglobulin (TG) (Gluckman)
 measure serum levels every 6 months
 Level >30 ng/ml are abnormal
 Thyroid hormone suppression (control TSH
dependent cancer) (Goldman, 1996)
 should be done in - 1) all total thyroidectomy
patients
2) all patients who have had
radioactive ablation of any
remaining thyroid tissue

74.  Most have extensive extrathyroidal
involvement at the time of diagnosis
 surgery is limited to biopsy and tracheostomy
 Current standard of care is:
 maximum surgical debulking, possible
 adjuvant radiotherapy and chemotherapy
(Jereb and Sweeney, 1996)