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Flashcards in Thyroid Deck (44)

What are follicles lined by?

cuboidal to low columnar follicular cells


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


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



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


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


Diagnosis of hyperthyroidism

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


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


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

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


What is the most common cause of hypothyroidism?

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


What is the most common worldwide congenital hypothyroidism due to?

iodine deficiency



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


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


What lab values do you find in hypothyroidism?

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


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


Hashimoto Thyroiditis

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


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


What antibodies are seen in hashimoto thyroiditis?

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

2. TSH receptor
3. Iodine receptor


Hashimoto thyroiditis

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

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


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


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


Subacute/Granulomatous (de quervain) thyroiditis

1. unilateral or bilateral enlarged firm with intact capsule
2. changes are patchy
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


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


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


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)


What does graves look like grossly and histologically

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

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


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


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


Diffuse/ Nontoxic simple goiter

Enlargement of the entire glad without producing nodularity
Diffuse symmetric enlargement

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

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


Multinodular Goiter

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

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

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


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


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


Follicular Adenoma

Discrete solitary masses derived from follicular epithelium
RAS or PAX8-PPARG fusion gene
-similar to mutations seen in follicular carcinomas
solitary, ENCAPSULATED, spherical mass
-well demarcated, 3cm
-gray-white to red brown mass
-may have areas of hemorrhage, necrosis or calcification
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


Follicular Adenoma
Clinical features

-Capsule well defined and intact

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


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


Papillary Carcinoma

commonly 25-50yrs
majority associated with radiation exposure

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

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


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


Papillary Carcinoma clinical features

-May be asymptomatic nodule or lymph node metastasis

diagnosed by fine needle aspiration cytology

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


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%


Follicular Carcinoma

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

-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

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


Follicular Carcinoma clinical course/genetics

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

total thyroidectomy with radioactive iodine

Prognosis dependent on metastasis

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


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

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

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


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

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


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

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


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

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