2/14 Thyroid Nodules/Cancers - Wondisford

Question 1

thyroid growth : thyroid fx

Answer 1

thyroid growth is regulated in parallel to thyroid fx

• hypothal:TRH → pituitary_thyrotrophs:TSH → hits TSH receptor on thyroid epithelial cells → stim thyroid growth and fx
• negative feedback:
  
  • thyroid hormone feeds back negatively on hypothalamic TRH and pituitary TSH secretion

TSH deficiency (hypopit) → thyroid atrophy

TSH excess (hypothyroidism, TSH-secreting tumor, TSHreceptor-stimulating antibodies_Graves) → thyroid growth

Question 2

nuclear med scan results in pt with thyroid enlargement/nodules

1. diffuse enlargement / low TSH
2. single nodule / low TSH
3. multiple nodules / low TSH
4. diffuse enlargement / low TSH

Answer 2

1. Graves Disease
2. toxic adenoma (“hot” → benign)
3. toxic multinodular goiter (“warm”)
4. Graves w “cold” nodule

Question 3

significance of cold nodules on RAI scanning

Answer 3

vast majority of nodules are HYPOfxing (“cold”) or ISOfxing (“warm”)

most are benign

• virtually all thyroid cancers are cold/isofxing
  
  • cold nodule gives no info about cancer risk
• “hot” nodules : suppres TSH and the fx of the rest of the gland effectively excludes thyroid cancer in that nodule

Question 4

physical exam: thyroid nodule

algorithm

Answer 4

ony time you DONT do a fine needle aspiration → hot nodule (benign)

Question 5

overview of thyroid cancer types

Answer 5

• papillary 85
• follicular 10
  
  • Hurthle
• medullary 4
• anaplastic 1

papillary & follicular are differentiated thyroid cancers

• derived from follicular epithelium
• features:
  
  • TSH receptor
  • iodine uptake
  • thyroglobulin secretion
  • thyroid hormone synthesis (rare)

medullary

• derived from parafollicular C cells
• lack differentiated features
• secrete calcitonin

anaplastic

• undifferentiated
• origin: pre-existing DTC
• highly aggressive

Question 6

somatic mutations in thyroid follicular cell

Answer 6

cause neoplasia!

• hot nodules : up to 80% have constitutively active mutant TSH receptor
• papillary carcinoma : RET/PTC, Ras, BRAF
• follicular carcinoma : Ras, PI3KCA
• anaplastic carcinoma : p53, beta-cat/Wnt

Question 7

thyroid cancers

biochemical markers

Answer 7

• differentiated (papillary, follicular) → thyroglobulin
• medullary → calcitonin
• anaplastic → none

Question 8

thyroid cancers

metastatic patterns

Answer 8

• papillary : nodes, lung (infreq)
• follucular : lung, bone
• medullary : nodes, lung, liver, bone
• anaplastic : locally aggressive, lung

Question 9

papillary follicular cancer tx

Answer 9

• surgery
• radioactive iodine
• thyroid hormone
  
  • tx of surgical hypothyroidism
  • suppress TSH to prevent thyroid growth

Question 10

MTC

MEN2

Answer 10

medullary thyroid cancer derived from cancitonin-producing parafollicular cells

• hereditary in 25% of cases : Multiple Endocrine Neoplasia type2 ft. germline RET mutations
  
  • MEN2A → MTC, pheochromocytoma, hyperparathyroidism
  • MEN2B → aggressive MTC, pheo, Marfanoid body habitus, intestinal gangliomas
  • FMTC → familial MTC

Question 11

summary

Answer 11