Normal Anatomy

• two lobes, one isthmus
• follicular cells – produce thyroid hormones
• C cells – produce calcitonin (parafollicular)
• Colloid – stores thyroid hormone extracellularly

Abnormalities of Development

• agenesis
• Maldescent

Ø  can result in a pyramidal lobe

Ø  ectopic thyroid tissue

Ø  pathway of descent – foramen cecum to thyroid and cricoid cartilage

Ø  can be found in the preaortic, pericardium, and heart tissue

• Lateral aberrant thyroid

Ø  found lateral to jugular vein

Ø  if found within a lymph node – metastatic papillary carcinoma

• Thyroglossal duct cysts
• Midline cysts anterior to the trachea
• May move with movement of the tongue
• Can become infected or give rise to neoplasms

Endocrine Manifestations

• Normal Thyroid Hormones: A nice way to remember the differences between T₃ and T₄ is this: T₃ is 10 times LESS prevalant, but 10 times MORE potent.

Ø  T₄ – thyroxine

1)     99.97% bound to protein; 0.03% free ALWAYS!!

2)     Total T₄- measures all (bound and unbound)

3)     Free T₄ – measures non-bound

• unaffected by changing thyroid binding globulin levels

Ø  T₃ – triiodothyronine

1)     ACTIVE FORM

2)     99.7% bound; 0.3% free

Ø  TSH

1)     stimulates the thyroid to produce both T₄ and T₃

Ø  TRH – thyrotropin releasing hormone

• Hyperthyroidism

Ø  Symptoms

1)     nervousness, palpitations, rapid pulse, fatigability, muscle weakness, unexplained weight loss, diarrhea, heat intolerance, warm skin, sweating, emotional lability, menstrual changes

2)     Those seen in Thyroid Storm: hypermetabolism, fever, tachycardia, cardiac failure, obtundation, and coma

Ø  Clinical Signs

1)     warm, moist skin

2)     flushed appearance

3)     exopthalmus

4)     cardiac changes: tachycardia, palpitations, arrhythmias, and cardiomegaly

Ø  Pathology

1)     myocardial changes: eosinophilic infiltration, interstitial fibrosis, fatty changes in the myofibers. Increase in size and number of mitochondria

2)     fatty infiltration and atrophy of skeletal muscle

Lab tests

1)     decreased TSH, increased free T₄,

2)     TRH stimulation tests

3)     Radioiodine uptake and scan

Ø  most common causes

1)     Graves’ disease

2)     Toxic multinodular goiter

3)     Toxic adenoma

• Hypothyroidism

Ø  Causes

1)     insufficient thyroid parenchyma

2)     interference with thyroid hormone synthesis

3)     suprathyroidal: (ex. Pituitary & Hypothalamic lesions)

Ø  Lab tests

• increased TSH, decreased free T₄

Ø  Consequences

1)     Cretinism – detected as infant, usually

2)     Myxedema

• initial symptoms: fatigue, lethargy, cold intolerance, general listlessness, constipation, carpal tunnel syndrome
• Late manifestations: periorbital edema, thickening, dryness and coarseness of skin, enlargement of the tongue, slowing of motor functions, dec. cardiac output

Thyroiditis

• Infectious thyroiditis

Ø  nonspecific inflammatory change

Ø  usu transient with no long term sequelae

• Hashimoto’s thyroiditis

Ø  General Features

1)     autoimmune with genetic predisposition mostly among middle age women

2)     most common cause of sporadic goitrous hypothyroidism

3)     HLA-DR5

4)     Assoc w/ an increased risk of lymphoma

Ø  pathology

1)     genetically alteration in Ag-specific suppressor T cells

• T_cytotoxic cells attach to follicular cells
• T_Helper cells come in and aid in formation of auto-Abs by B cells
• The auto-Abs are directed against the TSH receptor, thyroid microsomes, thyroglobulinm T₃, T₄, and follicular cell membranes

Ø  morphology

1)     GROSS: symmetric focal enlargement of the gland w/ intact capsule

2)     MICRO: 1) marked lymphoplasmacytic infiltrate  2) germinal centers   3) loss of thyroid follicles   4) implantation of lymphoid nodules   5) bands of fibrosis

Ø  Clinical features

1)     PAINLESS enlargement

2)     Patients initially euthyroid—progress slowly to hypothyroid

• Subacute granulomatous thyroiditis (De Quervrain’s)

Ø  General

1)     inflammatory disorder

2)     female:male; 3:1 — 2^nd to 5^th decade peak incidence

Ø  Morphology

1)     GROSS: variable enlargement

2)     MICRO:

• early: follicular disruption and neutrophilic infiltrates
• late: macs and MNGC envelope the leaked colloid

Ø  Clinical Features

1)     PAINFUL enlargement

2)     Fever

3)     Transient elevation in T₃ and T₄

• Subacute lymphocytic thyroiditis

Ø  unknown etiology

Ø  common in postpartum period

• Riedel’s thyroiditis (struma)

Ø  unknown etiology

Ø  characteristic: replacement of the parenchyma by dense fibrous tissue penetrating the capsule and extending into neck structures

Ø  can mimic carcinoma

Graves’ Disease

• GROSS:

Ø  mildly and symmetrically enlarged

Ø  intact capsule

Ø  soft parenchyma

• MICRO

Ø  hypertrophy and hyperplasia of follicular epithelium

¨      thiouracil exaggerates the hyperplasia

¨      iodine 131 – promotes devascularization, accumulation of colloid, and involution of the follicles

Ø  decreased colloid

Ø  hyperplastic lymphoid tissue

Ø  hyperplastic thyroid tissue in adjacent tissues of the neck – maybe

Ø  increased fluid, mucopolysaccharides, collagen, and lymphocytes in orbital soft tissues

• Clinical Features

Ø  thyrotoxicosis

Ø  goiter

Ø  exopthalmos -10-15% of patients

Ø  infiltrative dermopathy – minority of patients

Ø  elevated T₃ and T₄

Ø  extremely low TSH (less than 0.02 ultrasensitive)

Goiters

• General

Ø  start as diffuse enlargement and progress to nodular

Ø  compensatory hyperplasia and hypertrophy due to overstimulation or impaired production of T₃ and T₄

Ø  Major types/causes

Ø  endemic

1)     dietary iodine deficiency

2)     specific foods

Ø  sporadic

1)     less common than endemic

2)     biosynthetic defects in thyroid hormone synthesis

3)     sometimes associated with elevated TSH levels

• Diffuse nontoxic (simple) goiter

Ø  gland enlargement with basic morphological features

Ø  usually the patients remain euthyroid

• Multinodular Goiter

Ø  can be mistaken for neoplasms

Ø  can be nontoxic or thyrotoxic

Ø  distinguish from Graves’ by exopthalmos, derm, and hypermetabolic state seen in Grave’s (I say do an Ab test)

Ø  GROSS

1)     huge gland enlargement possible

2)     neoplasms are concern unless you cut or biopsy

Ø  MICRO

1)     increased nodularity

2)     scarring with focal calcification

3)     focal hemorrhages and hemosiderin deposition

Ø  Clinical Features

1)     think big large neck and the goiter pushing on everything nearby.

• cosmetic (you think?)
• esophageal compression (how’s that happen?)
• tracheal compression (like the esophagus, it’s in the region)
• whatever else is nearby

2)     abnormal thyroid function

• CV manifestations
• Thyrotoxicosis (less than 50% or as some put it, < ½ )

3)     Labs

• variable T₃ and T₄
• radioactive iodine uptake is either diffuse or into a dominant nodule

Thyroid Neoplasms

General

• nodules are very common (4-7% of adults, 1% of children)
• nodule has to be at least 1 cm in diameter to be able to palpate it
• thyroid cancer occurs in < 5% of nodules (50% MNG, adenomas (34-41%), CA (5-10%))
• neoplasms are usually “cold” nodules – do not take up radioactive iodine in imaging studies (blatant exceptions)
• Increase chances of malignancy

Ø  solitary nodule, age < 40 years, maleness

Follicular Adenomas – Adenomas

• solitary discrete and small nodules
• completely encapsulated
• Clinical

Ø  have to differentiate from CA

Ø  can be assoc with hyperthyroidism

Ø  therapy: removal of lobe

Carcinomas

• General

Ø  7000 deaths in US each year

Ø  female predominance 2-3:1

Ø  associated with radiation, esp. during childhood

Ø  metastasizes to lymph nodes very early

• Staging

Ø  Stage I – intrathyroidal lesion

Ø  Stage II – extra-thyroidal, no fixation

Ø  Stage III – local fixation or fixed cervical metastases

Ø  Stage IV – distant metastases

• Papillary Carcinoma

Ø  GROSS: infiltrative borders, fibrosis, calcification, frequent multifocality

Ø  MICRO: papillary, ground glass appearance, psammoma bodies, thyroglobulin +

Ø  Clinical

1)     MOST FREQUENT FORM OF THYROID CANCER (70-85%)

2)     10 year survival rate – 70-80%

3)     high frequency of local metastases – 10-20%

Ø  Factors to worsen prognosis

1)     extrathyroidal extension

2)     older age

3)     poorly differentiated

4)     long duration of disease

• Follicular Carcinoma

Ø  General

1)     more aggressive than papillary CA

2)     mortality 70% at 5 years

3)     difficult to distinguish from follicular adenomas

Ø  Gross:

1)     fibrosis, hemorrhage, necrosis, and cyst formation

Ø  MICRO

1)     absence of ground glass nuclei, intranuclear pseudoinclusions, papillae, and psammoma bodies.

2)     “CAPSULAR; PARENCHYMA & VASCULAR INVASION”

• Medullary Carcinoma

Ø  General

1)     arises from the C cells (produce Calcitonin)

2)     80-90% of cases elaborate Calcitonin or other peptides which produce systemic symptoms

3)     80-90% sporadic

4)     10-15% of cases autosomal dominant linked to chromosome 10

• assoc. with Multiple Endocrine Neoplasia type IIa and type IIb
• Type IIa – medullary Carcinoma, pheochromocytoma, parathyroid hyperplasia/adenoma
• Type IIb – medullary CA, pheochromocytoma, mucosal neuromas

GROSS

1)     well-circumscribed

2)     unencapsulated

Ø  MICRO

1)     extracellular amyloid

2)     tumor cells arranged in nests, sheets, or trabeculae

3)     composed of “neuroendocrine cells” to spindle shaped sarcomatoid cells

4)     C-cell hyperplasia – in cases of familial transmission

• Undifferentiated CA (anaplastic)

Ø  very few survivors beyond one year

Ø  new treatment: chemotherapy and radiation before removal and after removal has resulted is some prolonged remissions

Ø  extensive local invasion

Ø  7^th 7 8^th decades peak incidence

• Malignant Lymphoma

Ø  can be Hodgkin’s or non-Hodgkin’s

Ø  if non-Hodgkin’s most are high grade B-cell type

• other malignancies

Ø  Sarcomas – rare

Ø  Squamous carcinoma – rare

Tags: ectopic thyroid tissue, Endocrine Manifestations, Hashimoto's thyroiditis, hyperthyroidism, hypothyroidism, metastatic papillary carcinoma, Myxedema, Subacute lymphocytic thyroiditis, Thyroglossal duct cysts, thyroid abnormalities, Thyroiditis, thyroxine

This entry was posted on Friday, July 3rd, 2009 at 5:00 am and is filed under Pathophysiology. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.