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Flashcards in Thyroid Deck (44):
1

What are follicles lined by?

cuboidal to low columnar follicular cells

2

What do parafollicular or C cells secrete? What origin ar they?

calcitonin-promotes absorption of calcium by the skeletal system and inhibits reabsorption of bone
Neural crest origin

3

What is the mechanism of action and function of thyroid hormones?

1. Stimulation of protein synthesis
2. Up regulation of carbohydrates and lipid catabolism
3. Increase in basal metabolic rate
4. critical role in the development of brain in fetuses and neonates

4

Thyrotoxicosis

Hyper metabolic state due to increased circulating levels of thyroid hormones (T4 and T3)
-most commonly caused by hyper functioning of the thyroid gland but can be not associated with hyperthyroidism

5

Clinical manifestations of hyperthyroidism/ thyrotoxicosis

Excess thyroid hormone and over activity of sympathetic nervous system
1. Increased BMR-soft warm flushed skin
2. Heat intolerance and excess sweating
3. Weight loss despite increased appetite
4. Cardiovascular-increased CO, tachy, palpitaitons, cardiomegaly, arrhythmias especially atrial fibrillation is common in the elderly
5. Development of low output heart failure
6. Neuromuscular-nervousness, emotional lability, insomnia, muscular weakness, fine tremor of the hands
7. proximal muscle weakness and decreased muscle mass
8. Gastrointestinal: hypermotility, malabsorption
9. Wide staring gaze and lid lag
10. Thyroid ophthalmopathy (proptosis) only associated with graves
11. Stimulates bone resorption and osteoporosis
12. THyroid storm-medical emergency

6

Diagnosis of hyperthyroidism

TSH levels-usually decreased-Most sensitive
Free T4-usually increased

7

How do you exclude secondary or pituitary associated hyperthyroidism?

TRH stimulation test
-inject TRH
-if normal rise in TSH then it is not secondary hyperthyroidism

8

What radioactive iodine uptake results indicate Graves, toxic adenoma, or thyroiditis?

graves: diffuse uptake
toxic adenoma: localized
thyroiditis: reduced uptake

9

What is the most common cause of hypothyroidism?

primary hypothyroidism
-can be accompanied by enlargement of the gland(goiter)

10

What is the most common worldwide congenital hypothyroidism due to?

iodine deficiency

11

Cretinism

Hypothyroidism in infants or early childhood
-secondary to iodine deficiency or rarely from inborn errors in metabolism
-impaired development of skeletal muscles and CNS: severity varies to timing of deficiency
-if maternal thyroid hormone deficiency before development of fetal thyroid, mental retardation is sever
-mental retardation, short stature, coarse facial features

12

Hypothyroidism Myxedema

Adult hypothyroidism
Gradual slowing of mental and physical activity
-fatigue, lethargy, apathy, slowed speech
-cold intolerance and reduced sweating
-overweight and constipation
-periorbital edema, thick coarse skin, enlarged tongue (deposition of glycosaminoglycans)
-reduced cardiac output causes shortness of breath and decreased exercise capacity
-promotes an atherogenic profile (increased cholesterol)-adverse cardiovascular mortalities

13

What lab values do you find in hypothyroidism?

Decreased T4
TSH levels-most sensitive for hypothyroidism
Primary-Increased TSH
Secondary-Decreased/normal TSH

14

Thyroiditis
types with Pain and No pain

1. Inflammation with pain, sometimes severe
-Infectious thyroiditis
-subacute granulomatous thyroiditis (De quervain thyroiditis)

2. Relatively little pain
-Subacute lymphocytic thyroiditis
-Riedel's thyroiditis
-Hashimoto's thyroiditis

15

Hashimoto Thyroiditis

most common hypothyroidism in non-iodine deficient areas
-autoimmune destruction of thyroid gland
-45-65
-major cause of non endemic goiter in pediatric age group
-strong genetic component

16

What are the three mechanisms of breakdown in self tolerance and induction of thyroid autoimmunity in Hash?

1. T cell mediated cytotoxicity-CD8
2. Thyrocyte injury-CD4-INF gamma-macrophages
3. Antibody-dependent cell mediated cytotoxicity

17

What antibodies are seen in hashimoto thyroiditis?

1. Thyroglobulin and thyroid peroxidase (TPO)!!!

2. TSH receptor
3. Iodine receptor

18

Hashimoto thyroiditis
Gross
Histology

Gross
Diffusely enlarged gland
Intact Capsule
Well demarcated
Pale, yellow, tan and somewhat nodular and firm

Histology:
1. Thyroid follicles lined by Hurthle cells/oncocytes
-have abundant granular pink cytoplasm (numerous mitochondria)
2. formation of germinal centers
3. Thyroid parenchyma infiltrated by mononuclear inflammatory cells
-blue lymphocytes
-pink cells forming a follicle with colloid in the middle-residual follicular cells

19

Clinical course Hashimoto Thyroiditis

-transient hyperthyroidism due to disruption of thyroid follicles with release of thyroid hormones (hashitoxicosis)
-gradual hypothyroidism

-increased risk of developing other autoimmune
-increased risk of developing Non Hodgkin B cell lymphoma

20

Subacute/Granulomatous (de quervain) thyroiditis

40-50 years of age
-viral or post-viral inflammatory response
-viral antigens or virus induced host tissue damage stimulates formation of cytotoxic T cells which then damage the thyroid follicular cells (process is self limited)


-Most Common cause of thyroid pain
-variable enlargement of thyroid
-history of upper respiratory infection
-transient hyperthyroidism--hypothyroidism--euthyroid
-hyperthyroid phase: T3, T4, decreased TSH, radioactive iodine is diminished
-recovery and normal thyroid function in 6-8 weeks

21

Subacute/Granulomatous (de quervain) thyroiditis
histology

1. unilateral or bilateral enlarged firm with intact capsule
2. changes are patchy
3.
early stage-disruption of follicles with collections of neutrophils forming microabscesses
later stage-aggregates of lymphocytes, plasma cells and activated macrophages around damaged thyroid follicles
-multinucleated giant cells of enclosed fragments of colloid

4. eventually chronic inflammation and fibrosis

22

Riedel thyroiditis

rare disorder of unknown etiology
-extensive fibrosis involving the thyroid and contiguous neck structures
-hard and fixed mass-clinically simulating cancer**
-may be associated with idiopathic fibrosis at other sites like retroperitoneum
-presence of circulating antibodies- autoimmune etiology

23

Graves Disease

Most common cause of hyperthyroidism
1. Hyperthyroidism due to diffuse hyperfunctional enlargement of thyroid
2. infiltrative opthalmo exophthalmo-accumulation of loose connective tissue behind eyeballs-weak extraocular muscles
3. infiltrative dermopathy pretibial myxedema (present in minority of patients)

-20-40 yrs
-30-40% concordance in monozygotic twins as compared to 5% in di

24

What are the autoantibodies seen in graves disease

1. Thyroid stimulating immunoglobulin (TSI)-binds to TSH receptor and mimics its actions (specific for graves)
2. Thyroid growth stimulating immunoglobulin-cause(TGI) proliferation of follicular epithelium
3. TSH-binding inhibitor immunoglobulin (TBII)

25

What does graves look like grossly and histologically

Gross
symmetrically enlarged glands
weigh may be >80 g
soft meaty appearance of the parenchyma

Histological:
Crowded and tall follicular cells
Formation of small papillae filling the lumen of the follicles
Papillae do NOT contain fibrovascular cords
Pale colloid with scalloped margins
-lymphoid infiltrate with germinal centers common

26

What lab findings do you see with graves disease?

Increased serum levels of thyroid hormones
Decreased TSH
Increased radioactive iodine uptake with diffuse uptake on radioiodine scans

27

What are the treatments to graves disease?

1. Beta Blockers- symptomatic treatment of increased adrenergic tone (tachy, palp, tremulousness, anxiety)
2. Propylthiouracil: decreased thyroid hormone synthesis
3. radioiodine ablation
4. surgery

28

Diffuse/ Nontoxic simple goiter
Gross
HIsto
CLinical

Enlargement of the entire glad without producing nodularity
Diffuse symmetric enlargement

Gross
100-150 gm
cut surface-brown, glassy and translucent

Histologically:
2 phases
1. hyperplastic phage-enlarged thyroid gland with crowded follicular cells
2. colloid involution - some follicles are distended and some are small
-entire gland shows flattened epithelium and follicles filled with colloid

Clinical course
-vast majority euthyroid
-mass effect-large thyroid my press on trachea, esophagus and cosmetic disfigurement
-Normal T4 and T3
-Elevated TSH or in the upper limit of normal

29

Multinodular Goiter
Gross
Histology
Clinical

Asymmetric enlargement with numerous nodules
-evolvement from diffuse due to repeated episodes of hyperplasia and involution
-older adults
-both polyclonal and monoclonal nodules occur within the same gland
-toxic or non toxic

Gross
Asymmetric multilobulated
200 gm
irregular nodules containing gelatinous colloid
foci of fibrosis and calcification

Histology
Colloid rich follicles lined by flattened inactive epithelium
-areas of follicular hyperplasia DO NOT have a prominent capsule between the hyperplastic nodule and adjacent parenchyma

30

Multinodular Goiter clinical features? How do you tell if the mass is benign or malignant

-Mass effect with disfigurement or compression
-most patients euthyroid

-minority develop toxic due to development of -
autonomous nodule (plummer's syndrome)
risk of malignancy

31

Nodules more likely to be neoplastic in:

90% 20 year survival
More likely to neoplastic:
-single nodule
-young patients
-male patients
-nonfunctioning "cold" nodule
-history of radiation to the head the neck

32

Follicular Adenoma
Mutation
Gross
Histology

Discrete solitary masses derived from follicular epithelium
Mutation:
RAS or PAX8-PPARG fusion gene
-similar to mutations seen in follicular carcinomas
Gross:
solitary, ENCAPSULATED, spherical mass
-well demarcated, 3cm
-gray-white to red brown mass
-may have areas of hemorrhage, necrosis or calcification
Histology:
neoplastic cells arranged in closely packed follicles
-well defined intact capsule (distinguish from hyperplastic nodules of multinodular goiter)
-uniform small follicles
hurthle cell/oxyphilic/oncocytic adenoma

33

Follicular Adenoma
Clinical features

-Capsule well defined and intact
-NEED ENTIRE NODULE FOR DIAGNOSIS ***

Painless asymptomatic mass
cold on radioactive iodine scan
rarely functioning toxic adenoma
treatment lobectomy
excellent prognosis-do not recur or metastasize

34

Are males or females more likely to get carcinomas of the thyroid in middle adulthood, what about in childhood and late adult life? What type of carcinoma is most common?

>F early middle adult
M=F childhood and late adult life
Papillary carcinoma

35

Papillary Carcinoma

commonly 25-50yrs
majority associated with radiation exposure

gross:
solitary or multifocal lesion
-may be well circumscribed and encapsulated or may be ill defined and infiltrative
-papillary structures
-foci of fibrosis and calcification

Histology:
Branching papillae with fibrovascular cores lined by multiple layers of cuboidal to columnar epithelium
**Diagnosis based on nuclear features
-longitudinal nuclear grooves
-ground glass or orphan annie eyed nuclei
-psammoma bodies-calcified lamellar concretions usually seen in the cores of the papillae

36

Variants of Papillary carcinoma

1. Follicular variant-based on nuclear features-frequently encapsulated, lower incidence of lymph node and extrathyroidal metastasis and favorable prognosis (no papillae seen)
2. Tall variant-tall columnar cells with intense eosinophilic cytoplasm lining the papillary structures, aggressive behavior
3. Diffuse sclerosis-younger individuals including kids
4. Papillary microcarcinomas-less than 1cm

37

Papillary Carcinoma clinical features

-May be asymptomatic nodule or lymph node metastasis
-cold

Diagnose:
diagnosed by fine needle aspiration cytology

Treat:
Total thyroidectomy with excision of abnormal appearing lymph nodes

Good prognosis>95% ten-year survival
prognosis dependent on: >40 less favorable, extrathyroid extension and distant metastasis (stage), isolated cervical lymph node met does not have effect on prognosis

38

Papillary carcinoma genetic events

1. Rearrangement of RET
10q11 with RET/PTC translocation 20-40%

2. Paracentric inversions or translocations of NTRK1 5-10%

3. BRAF gene-adverse prognostic factors 33-50%

39

Follicular Carcinoma

Second most common thyroid cancer
older age 40-60
Higher incidence in iodine deficient area
-minimally invasive or widely invasive

Gross:
-single well circumscribed nodule largely replacing almost the entire lobe
-nodule has light tan appearance and contain foci of hemorrhage
(may be difficult to distinguish from follicular adenomas grossly)
-may extend beyond capsule to involve adjacent neck structures

Histology:
lacks typical nuclear features of papillary carcinoma
-vascular invasion and/or capsular invasion

40

Follicular Carcinoma clinical course/genetics

-Slowly growing painless nodule
-cold
-hematogenous met to bone, lung, liver

Treatment:
total thyroidectomy with radioactive iodine

Prognosis dependent on metastasis

Genetics:
1/3 to 1/2 PI3K/AKT pathway
1/3 to 1/2 have translocation (2;3)(q13;p25) resulting in PAX8/PPARG fusion product

41

Medullary Carcinoma

Neuroendocrine neoplasm derived from the parafollicular or C cells
-may secrete calcitonin or ACTH or VIP
-70 % sporadic (single), 30% familial or associated with MEN2A or 2B (multiple)
-MEN: first decade
-Familial or sporadic: 4 or 5th decade

Gross:
solid grey tan tumor with NO well defined capsule with infiltration of adjacent thyroid parenchyma
-larger lesions with foci of hemorrhage and necrosis

Histological:
polygonal to spindle shaped cells forming nests, trabeculae and follicles
AMYLOID deposits from calcitonin

42

Medullary carcinoma clinical course

-May be mass or asymptomatic
-may present with paraneoplastic syndrome VIP (diarrhea) and ACTH (cushing)
-MEN2B more aggressive
-hypocalcemia not prominent despite calcitonin

Treatment
total thyroidectomy
MEN-3 with RET mutation are offered prophylactic thyroidectomy as early as possible

43

Anaplastic carcinoma

undifferentiated tumors accounting for 5%
65 years old
mortality approaches 100% with most patients dying in less than 1 year

histology: highly anaplastic cells, spindles, giant cells
-foci or papillary differentiation may suggest their origin from better differentiated tumor

Clinically:
presents as rapidly enlarging bulky mass
-usually spread
-dyspnea, dysphagia, hoarseness and cough de to compression of neck structures


no effective therapy

Genetic: inactivation of p53 or activating mutations of beta catenin

44

Thyroglossal duct/cyst

incomplete atrophy o f the duct
-midline cyst or anterior mass
-lined by benign epithelium with normal thyroid and lymphocytes in the wall
-infection with risk of abscess formation