Thyroid Pathology Flashcards
Thyroglobulin is synthesized and stored in ______
______ is transported into the cell, and incorporated into TG
Thyroglobulin is endocytosed and cleaved to release free T3 and T4
Colloid
Iodide
Differentiate causes of primary vs. secondary hyperthyroidism
Primary (more common) = Diffuse hyperplasia (graves disease), hyperfunctioning multinodular goiter, hyperfunctioning thyroid adenoma
Secondary hyperthyroidism = pituitary adenoma
What will diagnostic labs show in primary vs. secondary hyperthyroidism?
Hyperthyroidism is confirmed by elevated T3 and/or T4
To differentiate primary vs. secondary, measure TSH. If TSH is low, it is primary hyperthyroidism. If TSH is high, it is secondary hyperthyroidism
Signs/symptoms of hyperthyroidism
Perspiration Facial flushing Nervousness Excitability Restlessness Emotional instability Insomnia Palpitations Tachycardia Increased appetite Diarrhea Tremor Muscle wasting Weight loss
In terms of all types of hyperthyroidism, what physical finding is unique to Grave’s disease?
Exophthalmos
What is a thyroid storm?
Hyperthyroid “crisis” — sudden and severe onset of thyrotoxic manifestations
A thyroid storm is characterized by the Burch Wartofsky score. What are some criteria associated?
Fever
Cardiac manifestations (tachycardia, CHF)
GI symptoms (diarrhea, jaundice)
Precipitating history (pregnancy/postpartum, hemithyroidectomy, drugs: amiodarone)
[fever and precipitating hx are really how you distinguish thyroid storm from typical long-term hyperthyroid]
Tx of hyperthyroidism
High doses of iodide (Wolff-Chiakoff effect)
Thionamide
Radioiodine ablation
Surgery
To tx manifestations:
Beta blockers
NSAIDs
Most common etiology of hyperthyroidism
Graves disease
Classic diagnostic triad of Graves disease
Hyperthyroidism with gland enlargement
Infiltrative ophthalmopathy
Pretibial myxedema
[note that this triad is not always present and not all features must be present for dx of Graves]
Pathogenesis of Graves disease affecting the orbit
- Lymphocytes invade preorbital space
- Fibroblasts have TSH receptor
- EOM swelling
- Matrix accumulates
- Adipocytes expand
Infiltrative dermopathy with scaly, indurated skin on the anterior shins that is often seen in hyperthyroidism
Pretibial myxedema
Lab test results in graves disease
T3/T4 high
TSH low
TSI (thyroid-stimulating Ig) high [this confirms graves as etiology]
Primary etiologies of hypothyroid
Hashimoto thyroiditis
Iodine deficiency
Drugs (lithium, iodides, p-aminosalicylic acid)
Postablative (surgery, radioiodine therapy, external irradiation)
Thyroid hormone resistance syndrome (THRB)
Genetic defects in thyroid development (PAX8, FOXE1, TSH receptor mutations)
Congenital biosynthetic defect (dyshormonogenetic goiter)
Secondary etiologies of hypothyroid
Pituitary failure
Hypothalamic failure
Congenital hypothyroidism is also known as ______
Cretinism
Early infancy/childhood manifestations of cretinism
Mental retardation
Growth retardation
Coarse facial features
Umbilical hernias
Cretinism is endemic in areas without ____ supplementation
Iodine
[can also be a result of genetic alterations in normal thyroid metabolic pathways]
Cretinism is congenital hypothyroidism and manifestations are dependent upon maternal age of onset.
______ is hypothyroidism in the adult/older child characterized by mental and physical sluggishness, weight gain, cold intolerance, decreased cardiac output, and hypercholesterolemia
Myxedema
4 types of thyroiditis
Hashimoto thyroiditis
Granulomatous (de Quervain)
Subacute lymphocytic thyroiditis
Reidel
Most common cause of hypothyroidism in iodide-sufficient areas
Hashimoto thyroiditis
Hashimoto thyroiditis is autoimmune hypothyroidism characterized by autoantibodies against ____ and _____
Thyroglobulin; thyroid peroxidase (TPO)
Morphologically, Hashimoto thyroiditis is characterized by lymphocytic infiltrate with germinal centers, as well as atrophic follicle cells with eosinophilic change known as __________
Hurthle cell metaplasia
Antibody prevalence in Hashimoto vs. Graves
Hashimoto:
TSHR-Ab (TSI) — 10-20%
hTg-Ab — 80-90%
hTPO-Ab — 90-100%
Graves:
TSHR-Ab (TSI) — 80-95%
hTg-Ab — 50-70%
hTPO-Ab — 50-80%
Type of thyroiditis in which the patient is typically euthyroid, but they present with very painful thyroid gland
Granulomatous thyroiditis (aka de Quervain’s thyroiditis)
Fibrosing type of thyroiditis in which fibrotic tissue extends from thyroid into adjacent tissue (i.e., skeletal m.)
Riedel thyroiditis
Riedel thyroiditis is characterized morphologically by a lot of fibrosis, but also lymphocytes and plasma cells. It is considered a ____-related disease
IgG4
[other IgG4-related diseases include autoimmune pancreatitis, inflammatory pseudotumor, Mikulicz’s syndrome, multifocal fibrosclerosis, idiopathic retroperitoneal fibrosis, and inflammatory aortic aneurysm]
_____ goiters are more common in females
Sporadic
Dietary goitrogens
Cassava root (thiocyanate)
Brassicaceae — broccoli, cauliflower, cabbage, radish
Are diffuse goiters more common in younger or older individuals?
Younger; after age 25 tend to be classified as nodular
T/F: diffuse goiters are euthyroid
True — so presenting symptoms are typically due to mass effect: dysphagia, hoarseness, stridor, SVC syndrome
What causes goiters to be multinodular?
Hyperplasia, regression (involution) cycle
Varied response of nodules to stimuli
Neoplastic nature of some nodules (adenomas)
What is the purpose of doing radioisotope scanning for thyroid nodules?
Determines if a specific nodule is responsible for HYPERFUNCTION — if so, it can be treated with excision or ablation
T/F: “Hot” thyroid nodules are more likely to be neoplastic, but ultrasound and fine needle aspiration are more useful in that workup
False; T/F: “cold” thyroid nodules are more likely to be neoplastic, but ultrasound and fine needle aspiration are more useful in that workup
Radioisotope scanning determines if a specific nodule is responsible for hyperfunction.
What test can be used to determine the cellular constituents of a nodule?
Fine needle aspiration
2 types of benign thyroid nodules
Hyperplastic (adenomatoid) nodules
Follicular adenomas
4 types of malignant thyroid nodules
Papillary thyroid carcinoma
Follicular/Hurthle cell carcinoma
Anaplastic carcinoma
Medullary carcinoma
Follicular adenomas are a discrete population of follicular cells with “thyroid autonomy”. What do you need to make sure of in order to confirm they are benign?
Capsule is intact (not invaded), so no growth pattern of follicular carcinoma is present
No nuclear features of papillary carcinoma
What comprises the majority of malignant tumors of the thyroid gland (85%)?
Papillary thyroid carcinoma
Age of onset and sx associated with papillary thyroid carcinoma
Most occur between 25-50 years of age (remember that staging is based on age of onset)
Typically present without symptoms — may discover palpable nodule, or on thyroid ultrasound
How is staging of papillary thyroid carcinoma different based on age?
Under 55 years of age — can only be classified stage I or stage II [major difference is whether or not there is metastasis]
55+ years — can be stage I, II, III, IVA, or IVB [stage IVB = stage II in pts under 55]
Describe morphology and genetic associations of papillary thyroid carcinoma
Papillary architecture
Psammoma bodies
Enlarged nuclei with “clear” appearance: “orphan Annie eye nuclei” — nuclear characteristics are the diagnostic feature allowing for a dx of PTC!!
Associated with RET-PTC mutations, BRAF mutations
Describe follicular variant of papillary carcinoma
Follicular architecture, but nuclear features of papillary carcinoma
[fewer cases have RET-PTC rearrangements or BRAF mutations; MORE cases with RAS mutations]
What variant of papillary carcinoma tends to affect older patients and is aggressive?
Tall cell variant
What variant of papillary carcinoma tends to affect kids and young adults, with greater incidence of distant metastasis to lung, brain, bone, and liver, but is considered very treatable?
Diffuse sclerosing variant of papillary carcinoma
Therapeutic options for thyroid carcinoma
Surgery
Radioactive iodine (I131)
If refractory, can try chemotherapy
Type of thyroid carcinoma that is less common than papillary, but more common in areas with goiter from iodide deficiency
Follicular thyroid carcinoma
Follicular carcinoma is still considered a differentiated thyroid carcinoma, but with invasive properties as manifested through….
Invasion of the capsule (mushroom)
Angioinvasion (allowing for hematogenous metastasis)
Type of thyroid carcinoma that is rare, but tends to occur in elderly patients and is highly aggressive — often presenting with mass effect, and pts typically die within 1 year of local invasion
Anaplastic thyroid carcinoma
The below genetic mutations are associated with what type of thyroid carcinoma:
BRAF gain of function mutations leading to MAP kinase signaling
RET/PTC rearrangements leading to tyrosine kinase activity
Papillary carcinoma
Genetic mutation associated with anaplastic carcinoma
TP53
In terms of thyroid histology, follicular cells predominate, but _______ cells are also present, which are responsible for _____ secretion
Parafollicular “C”; calcitonin
Neuroendocrine thyroid carcinoma derived from C cells
Medullary thyroid carcinoma
Morphology of medullary thyroid carcinoma
Blue cells with dispersed chromatin
Amyloid deposition (apple green birefringence on Congo red stain!)
C-cell hyperplasia
T/F: 70-80% of medullary thyroid carcinomas are sporadic, unifocal, and aggressive with mean age of 50. Familial forms have the BEST prognosis of all forms with 100% 15 year survival, tend to be multifocal and affect mean age of 43
True
Germline mutation identified in association with familial syndromes with medullary thyroid carcinoma
RET
[note that somatic mutations of RET are present in a majority of sporadic tumors as well]
