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Flashcards in Thyroid Deck (25):
1

Histology of the Thyroid Gland

Organized into follicles filled with colloid and lined by follicular cells and parafollicular c cells

C CELLS --> Make CALCITONIN which ANTAGONIZES the function of PTH

FOLLICULAR CELLS --> Make T3 or T4

Complicated biosynthetic pathway that involves IODINE as an essential component --> 99.5% bound in peripheral blood, Iodine functions in up-regulating carbohydrate and lipid metabolism as well as stimulating hormone synthesis, resulting in a net effect of INCREASED basal metabolic rate

2

3 conditions that cause 99% of HYPERthyroid?

DIFFUSE TOXIC HYPERPLASIA

TOXIC MULTINODULAR GOITER

TOXIC ADENOMA

LABS = Increased T3, Increased T4, LOW TSH (neg. feedback)

Other causes = hyper functioning thyroid carcinoma, acute/subacute thyroiditis, neonatal thyrotoxicosis, struma ovarii (ectopic functioning thyroid tissue in the ovary), Iatrogenic (exogenous thyroid hormone), TSH secreting pituitary adenoma

3

Goiter vs. Toxic Thyroid

GOITER = Enlargement of the thyroid gland - can be HYPO, HYPER, or EUTHYROID

TOXIC Thyroid = HYPERFUNCTIONING thyroid gland

4

****SYMPTOMS OF HYPERTHYROIDISM****

INCREASED METABOLIC RATE
TACHYCARDIA
ARRHYTHMIAS (A-fib)
WEIGHT LOSS w/ CONCURRENT INCREASED APPETITE
HEAT INTOLERANCE
Nervousness
Warm skin
Fine hand tremor
Menstrual changes
Emotional lability
Insomnia
Eye changes (EXOPTHALMUS w/ Grave's)
Muscular weakness/atrophy
Neck thickening

5

MYXEDEMA

Hypothyroid in adults

Occurs with INADEQUATE levels of thyroid hormone

F > M

LABS = DECREASE T3, T4 with INCREASED TSH

Causes -- HASHIMOTO'S THYROIDITIS (15-60%)

Iodine deficiency (developing countries), infiltrating disease that takes over thyroid (amyloidosis, sarcoidosis), end stage toxic goiter, carcinoma, anti-thyroid drugs, iatrogenic, pituitary/hypothalamic derangement (secondary hypothyroidism)

With excessive stimulation due to excess TRH and TSH, THYROID MAY ENLARGE, but it remains non-functional

6

Symptoms of MYXEDEMA/HYPOTHYROID

DECREASED METABOLIC RATE (including slowed physical activity and apathy)
COLD intolerance
Weight GAIN
Decreased exercise capacity
Shortness of breath
Constipation
Cool and pale skin
Decreased sweating
Enlargement of the tongue
Deepening of the voice

7

CRETINISM

Hypothyroid in KIDS

Can cause IRREVERSIBLE, SEVERE MENTAL/GROWTH RETARDATION (impaired skeletal growth)

Rarely apparent at birth, noticed over WEEKS to MONTHS so it is important to screen infants failing to thrive because it can be prevented if caught early

CONGENITAL causes --> biosynthetic defect in T4 synthesis or agenesis of the thyroid; endemic goiters from LACK OF IODINE and dietary problems

8

SYMPTOMS of Cretinism

MENTAL RETARDATION
IMPAIRED SKELETAL GROWTH
Coarse facial features
Protruding tongue
Umbilical hernia

9

Causes of DIFFUSE enlargement of the Thyroid

DIFFUSE GOITERS (multinodular or familial)

DIFFUSE TOXIC GOITER (Grave's Disease)

THYROIDITIS

10

Multinodular Goiter

Multinodular --> presents usually EUTHYROID (normal) with COMPRESSIVE symptoms or COSMETIC issues

Possible for the goiter to turn TOXIC!! This is called Plummer Syndrome (same as Grave's, just no exopathalmus or dermopathy)

Generally idiopathic
Thyroid EXTREMELY ENLARGED and can often be MISINTERPRETTED as neoplastic

Multilobulated, nodular, asymmetrical involving one or both lobes

Histology --> nodules NOT encapsulated and surrounded by FIBROSIS; dilated follicles, colloid-rich, inactive epithelium and hyperplasia; follicles CAN have surrounding normal thyroid tissue

11

Familial Goiter

Known as DYSHORMONOGENETIC GOITER

Occurs due to an ENZYMATIC DEFECT in the SYNTHESIS OF THYROID HORMONES

so patients present HYPOTHYROID, but sometimes eythyroid if it's mild

Goiter may become NODULAR, but it is ALWAYS non-toxic!!

Histology --> large, colloid-less follicles and NO normal thyroid tissue

12

GRAVE'S DISEASE

Occurs with a diffuse hyperplastic goiter with hyperthyroidism

TRIAD --> DIFFUSE GOITER, HYPERTHYROIDISM, INFILTRATIVE PATHOLOGY OF EYES and/or PRE-TIBIAL REGION presenting as EXOPTHALMOS or PRE-TIBIAL MYXEDEMA (waxy, discolored indentation of the skin, orange-peel)

AUTOIMMUNE

F > M, 20-40 y.o.

Increased incidence of the disease among family members with a strong MHC association, especially with HLA-B8, HLA-DR3

Autoantibodies present may be the thyroid stimulating immunoglobulin (TSI) which binds to the TSH receptor to continuously stimulate the gland, thyroid growth stimulating immunoglobulin, and TSH-binding inhibitor immunoglobulin

ENTIRE gland is involved --> marked hyperplasia, tall columnar follicular cells and papillary infoldings lining the follicle, PERIPHERAL SCALLOPING of the colloid, increased vascularity, lymphocytic thyroiditis

LABS = Increased Free T3/T4 and Decreased TSH

Tx = propyl thiouracil, radioactive iodine ablation, surgery if all else fails

13

HASHIMOTO'S THYROIDITIS

Most common single cause of HYPOthyroidism

Thyroid failure from AUTOIMMUNE destruction of the thyroid gland

Primary T cell defect, but B cells also activated to produce autoantibodies to THRYOGLOBULIN, THYROID PEROXIDASE, TSH and IODINE TRANSPORTER (first step in thyroid hormone synthesis)

F > M, 45-65 (slightly older than Grave's)
HLD-DR5 associated, sometimes HLA-DR3

Frequency of OTHER autoimmune diseases INCREASES!

Symptoms --> PAINLESS enlargement of the thyroid, usually with SOME degree of hypothyroidism; also possible to get TRANSIENT HYPERthryoidism from follicular disruption (hashitoxicosis)

These patients are at INCREASED RISK OF B-CELL LYMPHOMA

Histo -- Lymphocyte and Plasma cell infiltration, forming well-developed GERMINAL CENTERS

Follicular epithelium has oxyphilic cells characterized by abundant eosinophilic, granular cytoplasm with increased interstitial connective tissue with fibrosis

Disruption of the follicles with NO follicle invasion

14

SUBACUTE THYROIDITIS

De Quervian's or Granulomatous Thyroiditis
F > M, 30-50
Associated with HLA-B35

Unknown but POTENTIALLY VIRAL ETIOLOGY --> often preceded by an UPPER RESPIRATORY TRACT infection

BILATERAL or UNILATERAL ENLARGEMENT of the thyroid that is ****PAINFUL****

Patients may have TRANSIENT HYPERthyroidism and subsequent asymptomatic hypothyorid and recover after 6-8 weeks

Histo --> PATCHY changes that depend on stage (early = disrupted follicles with neutrophils and micro abscesses; later = mixed inflammatory cells forming granulomas; END = chronic inflammation and FIBROSIS)

15

REIDEL'S THYROIDITIS

Unknown, potentially autoimmune etiology
F > M

Presents as a ****ROCK HARD THYROID**** GLAND that is DENSELY FIBROTIC AND ADHERENT TO SURROUNDING STRUCTURES

Histo - FIBROUS connective tissue scarring with visible chronic inflammation, follicular atrophy, vasculitis -- completely abnormal thyroid tissue!!

Presents SIMILARLY to ANAPLASTIC CARCINOMA (horrible prognosis, so better differentiate)

16

What can caused LOCALIZED enlargement of the thyroid?

Dominant adenomatoid nodules

Primary thyroid neoplasms

Metastatic disease

17

Dominant adenomatoid nodules

Occur in the setting of multilobular goiters, in which a SINGLE LOBE is larger than the other so that the thyroid is ASYMMETRICAL and appears as if it has a locally enlarged nodule

18

What makes a nodule MORE LIKELY to be neoplastic?

Solitary
Younger patients
Males
Cold Nodules (hypo functioning)
Radiation

19

Follicular ADENOMA

Makes up 70% of solitary nodules

RARELY hyperfunctional

Benign, COLD nodules (10% of the cold nodules are malignant)

Autonomous growth, CANNOT be suppressed with thyroid hormone administration

Surgically resected

20% of these patients have a POINT MUTATION IN THE RAS ONCOGENE FAMILY, so there is POTENTIAL FOR PROGRESSION TO CARCINOMA

Gross -- solitary, encapsulated nodules with well-formed fibrous capsules, that creates a distinct boundary between internal/external tissue ****WITHOUT capsular or vascular invasion**** <--- this is what makes it different from CARCINOMA (they look identical)

20

Follicular CARCINOMA

Super similar histologically/morphologically to adenoma!

10-20% of all thyroid carcinomas; F > M; 40-50 y.o.

Incidence higher in IODINE DEFICIENT REGIONS (goiters may predispose)

Typically COLD (less Iodine uptake, less active)

Gross - encapsulated nodule (90% 10 yr survival); infiltrative (30-50% 10 yr), hemorrhagic (ruh roh)

Histo -- CAPSULAR AND/OR VASCULAR INVASION (distinguishing feature!!!!)

Metastasis via HEMATOGENOUS SPREAD

40-50% have RAS FAMILY MUTATIONS

Treatment -- THYROIDECTOMY (can be lobar or subtotal if not widely invasive) with EXOGENOUS THYROID HORMONE to remove stimulation of the tumor cells by TSH

21

Papillary CARCINOMA

MOST COMMON TYPE OF THYROID CARCINOMA

70-80%, F > M, 30-39 (younger)

Presents as a COLD, PAINLESS NODULE; can be encapsulated or invasive

Histo - paipillary (finger-like processes, PSAMMOMA BODIES), ORPHAN ANNIE NUCLEI

LYMPHATIC SPREAD in 50% of cases, but if confied to LOCAL NODES, there is a 90% 20 year survival!

Genetics --> RET/PTC fusion gene (20%), BRAF mutations (45%)

Several types -- microscopic, follicular variant (looks like follicular carcinoma), diffuse sclerosing (more aggressive), tall cell/columnar cell (worse prognosis)

Overall, TRADITIONAL papillary has a 98% 10 year survival!!!

22

MEDULLARY CARCINOMA

10-15%
Arise from the CACLITONIN PRODUCING PARAFOLLICULAR C CELLS OF THE THYROID

80% sporadic, 20% associated with MEN IIA and IIB or Familial Syndromes --> so DON'T take to OR right away because there could be a pheochromocytoma too!!!

Presents as SOLITARY (sporadic) or MULTIPLE LESIONS if familial

Histology --> looks neuroendocrine --> small cells arranged in nests which stain POSITIVE FOR CALCITONIN, chromogranin, CEA, serotonin, synaptophysin; lack of colloid, throglobulin negative; these DO NOT arise from regular thyroid tissue

Lymphatic spread

RET proto-oncogene plays role!

23

ANAPLASTIC CARCINOMA

100% mortality within 6 months

RARE (less than 5% of thyroid carcinomas)

OLDER; half with a history of multinodular goiter;

BILATERAL, invasive, rapidly growing; could COMPRESS LARYNX; metastases already present frequently on presentation

Histo - cells very differentiated and can be LARGE, SMALL, SPINDLES; potential islands of follicular/papillary differentiation

24

Lateral Aberrant Thyroid

Tissue found lateral to the JUGULAR VEIN outside of the lymph nodes in that area

Looks like lymphatic spread or metastases, but luckily it is just normal tissue without features of thyroid neoplasm

25

Thyroglossal Duct Cyst

Patients of any age will sometimes present with a LARGE MASS ALONG THE ROUTE OF MIGRATION OF THE THYROID (thyroglossal duct!)

Cyst is caused by a FAILURE OF THE INVOLUTION OF THE DUCT, and will have a LYMPHOCYTIC INFILTRATE potentially with thyroid follicles in the walls