176b/177b/178b - Thyroid Physio, Path, Pathopys, Nodules, Cancer Flashcards
What are the imaging modalities of choice for evaluating thyroid structure?
Ultrasound = first line
CT if there is intrathoracic extension of large goiters
Use iodine isotopes for thyroid function
Which thyroid neoplasm is derived from C-cells?
Medullary carcinoma of the thyroid
Which type of thyroid cancer is associated with a history of radiation exposure?
Papillary carcinoma of the thyroid
Which thyroid neoplasm is most likely to have a hereditary component?
Medullary thyroid carcinoma
- Association with MEN-2
- Mutation in RET oncogene
What is the most common cause of thyroid disease worldwide?
Iodine deficiency
A patient presents with bilateral pheochromocytoma
What organ will you check next to evaluate for neoplasm?
Thyroid
- Bilateral pheo = high suspicion for MEN-2
- MEN-2A and MEN-2B both have increased risk of medullary thyroid carcinoma in addition to pheochromocytoma
- In addition:*
- MEN-2A: look for parathyroid hyperplasia*
MEN-2B: look for marfinoid appearance, ganglioneuroma
What is the most common congenital thyroid nodule?
Thyroglossal duct cyst
How does biotin supplementation affect thyroid lab values?
(TSH, T3, T4)
Why?
- Falsely low TSH
- Falsely high T4, T3
Will lead to false diagnosis of Graves’ disease!
Biotin cleaves the assay antibody (something like this)
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What is organification? (in the context of TH synthesis)
What enzyme is responsible?
Organification via TPO
- Oxidation of I- to I2
- Iodination: Attach I2 to tyrosine residues on thyroglobulin
Result = Thyroglobulin with MIT and DIT
Will be coupled by TPO as well: Combine MIT and DIT
Describe the histologic features of non-invasive follicular thyroid neoplasm (NIFTP)
What is the treatment?
-
Nuclear features of papillary thyroid carcinoma
- Nuclear grooves
- Psamoma bodies
- Orphan Annie eye inclusions
-
Well encapsulated like follicular adenoma
- Well-encapsulated (uniform, continuous, fibrous capsule)
- Tumors are well-behavied
- Act like follicular adenomas
- Tx = lobecctomy
Which 3 proteins bind thyroid hormone in the blood?
- Thyroid binding globulin (TBG)
- Transthyretin
- Albumin
Affinity: TBG > Transthyretin > Albumin
Note: only very small percentages of T4 and T3 are unbound
Describe the 24h iodine uptake pattern that is pathognomonic for Graves’ disease
Diffuse, homogenous uptake
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What is the role of molecular testing in the evaluation of thyroid nodules?
Test intermediate-suspicion nodules for characteristic mutations
Most useful as rule-out tests for specific pathologies
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Where in the body is the thyroid hormone receptor alpha (TR-alpha) found?
What about thyroid TR-beta?
- TR-alpha
- Brain
- Skeletal tissues
- Intestines
- Heart
- TR-beta
- Liver
- Heart
Describe the findings associated with Grave’s Disease
- Gross:
- Histology:
- Gross:
- Diffuse, symmetric enlargement
- Histology:
- Papillary hyperplasia
- Tall follicular cells
What neoplasms are associated with MEN-2? (both 2A and 2B)
Which neoplasms are specific to 2A and 2B respectively?
- All MEN-2
- Medullary thyroic carcinoma
- Pheochromocytoma (medulla of adrenal gland)
- MEN-2A
- Parathyroid hyperplasia
- MEN-2B
- Marfanoid appearance
- Mucosal neuroma/ganglioneuroma
What is the histological hallmark of thyroid papillary caricinoma?
Atypical nuclear morphology
- Nuclear grooves
- Orphan Annie eye inclusions
- Hypochromasia
- Psamoma bodies
Describe the thyroid findings of Hashimoto’s thyroiditis
- Gross:
- Histology:
- Cytology:
- Gross:
- Diffusely enlarged
- Histology:
- Lymphocytes and plasma celsl infitrate parenchyma
- Atrophic follicles
- Cytology:
- Hurthle cells + heterogeneous lymphocytes
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What is the classic histological finding of a follicular adenoma of the thyroid?
Normal-looking thyroid cells surrounded by a continous fibrous capsule
Note: FNA cannot distinguish between adenoma and carcinoma, but histologically, the carcinoma capsule will invade
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What is the first line medication for anti-thyroid drug therapy?
Are there exceptions?
Methimazole
- Use acutely to cool the pt down prior to radioiodine or surgery
- Use long term for 12-18 months, then stop to assess remission
Exception = 1st trimester of pregnancy; use propylthiouracil (PTU) instead
List 3 substances that negatively regulate TRH secretion from the hypothalamus
Somatostatin
Dopamine
T3 (negative feedback)
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What supplement may interfere with TSH, T3, T4 assays?
Biotin!
Will cause falsely low TSH, falsely high T3, T4
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What etiology of hyperthyroidism will have bilateral increased iodine uptake?
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Graves’ disease
What percentage of medullary thyroid carcinomas are hereditary?
What gene is likely mutated?
Which syndrome is associated?
20-25% are hereditary
RET proto-oncogene
- MEN-2 (2A or 2B)
- Association with mutations in
- Also can just be familial tumors
What (general) lab values are associated with subclinical hyperthyroidism?
When should it be treated?
Low TSH, normal free T3/T4
Treat if TSH <0.1 to avoid atrial fibrillation, osteoporosis
What is the vertebral level of the thyroid?
C5 - T1
Which micronutrient is essential for the synthesis of thyroid hormone?
What is the recommended daily allowance?
Iodine
150 mcg/day
What etiology of hyperthyroidism will have unilateral increased uptake?
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Toxic adenoma
- The rest of the thyroid is trying to uptake less
- This is a “hot nodule” = less likely to be malignant
Describe the clinical course of post-partum thyroiditis
Hyperhtyroid -> Hypothyroid -> Euthroid
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Which cells of the thyroid secrete calcitonin?
C cells
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Hurtle cells are associated with which thyroid pathology?
Hashimoto’s thyroiditis
What is the first-line managment for Graves’ opthalmopathy?
Seleinum
Also:
- Artificial tears
- Avoid tobacco exposure
- Even 2nd hand smoke
- Teprotumumab
- Monoclonal antibody that inhibits IGF-1 receptor; cross-reacts with TSH receptor?
Which enzyme converts T4 to reverse T3?
5 (mono)deiodinase
(DIO3)
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What are the characteristics of a solid thyroid nodule on ultrasound? (3)
Many echo reflections
Back wasll indistinct
No acoustic enhancement
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What are the (general) TSH and T4 levels in subclinical hypothyroidism?
When should it be treated?
High TSH with normal free T4
- Treat if TSH > 10 (even if asymptomatic)
- ALWAYS treat if TSH elevated in pregnancy
- Ideally, pre-pregnancy
What is the most common malignant thyroid nodule?
Papillary thyroid carcinoma
Which enzyme converts T4 to T3?
5’ (mono)deiodinase
(Either DIO1 or DIO2)
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Describe the presentaiton of an anaplastic thyroid carcinoma
What is the prognosis?
Suddenly enlarged neck
Poor prognosis - usually extensive metastasis at time of presentation
What is the most common cause of hypothyroidism in the USA?
Worldwide?
USA = Hashimoto’s thyroiditis
World = Iodine deficiency
When a thyroid problem is suspected, which lab should be checked first?
TSH
Then check free T4 and total T3
(Don’t want to only check T4/T3 and miss a central problem)
Why does thyroid gland move when we swallow or speak?
The thyroid gland is attached to the tonge by the thyroglossal duct
What percentage of thyroid noduels are benign?
90%
(VAST majority are benign; many foudn incidentally)
Describe the signaling cascade activated when TSH binds to its receptor:
- Gs:
- Gq:
-
Gs:
- Activates adenylyl cyclase
- Increase cAMP
- Phosphorylation + activation of PKA
- Activation of targets in cytosol and nucleus
-
Gq:
- IP3/CA2+
- Activates PLC
- Iodination, H2O2 production
After a thyroid nodule is found on ultrasound, what is the next diagnostic step?
Fine needle aspiration if the ultrasound is concerning
Which genetic mutations are assoicated with papillary carcinoma of the thyroid?
BRAF
RET
What is the classic histologic finding in follicular carcinoma of the thyroid?
Follicular celsl surrounded by a capsule - will see capsular and vascular invasion
Vs. follicular adenoma - caspule will be uniform and continuous
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What is the best management of a patient with newly dignosed Grave’s disease?
Start methimazole (if not pregnant; PTU if 1st trimester)
+/- propanolol, glucocorticoids
- Re-evaluate in 3 weeks and discuss:
- Continued medical therapy
- Radioiodine ablation
- Surgical ablation
Typically, pts are not thinking super clearly during Graves’ presentation/exacerbation; cool them off first, then discuss long term management
What are the characteristics of a thyroid cyst on ultrasound? (3)
Anechoic center
Smooth black wall
Acoustic enhancement
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What is the main driver of the increase in incidence of thyroid nodules and thyroid cancer?
Increased ultrasound use
What is the imaging modality of choice for thyroid function?
Iodine isotopes
Use ultrasound for thyroid structure
Does a “hot” thyroid nodule need to be biopsied?
No!
Need to cool off nodule before biopsy
Also, most hot nodules are benign
What is the most likely diagnosis of a patient with elevated free T4 and very low iodine uptake in the thyroid gland?
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Thyroiditis
- Thyroid gland is damaged
- -> Not working and pre-stored thyroid hormone is spilling out into the system
- Will eventually get to a hypothyroid state
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What are the symptoms of hypothyroidism? (6)
New symptoms of:
- Menstrual irregularity
- Infertility
- Depression
- Cognitive decline
- Hyperlipidemia
- Hair/skin changes
- Nonspecific
- Fatigue, weight gain, constipation
Antibodies against thyroglobulin and TPO are round in whihc thyroid pathology?
Hashimoto’s thyroiditis
What are the indications for:
- 123I scan:
- 131I scan:
- 99TcO4 scan:
-
123I scan:
- Evaluate thyroid iodine uptake
- Whole body scan; evaluate metastasis
-
131I scan:
- Ablate thyroid cells that uptake 131I via beta decay
-
99TcO4 scan:
- Evaluate thyroid function
What is the functional unit of the thyroid?
Follicle
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What is the treatment of choice for hypothyroidism?
Levothyroxine
What is coupling? (In the context of TH synthesis)
What enzyme is responsible?
Coupling via TPO
Occurs after organification by TPO that results in MIT and DIT bound to thyroglobulin
- MIT and DIT are coupled to form T4 and T3
- T4 = DIT + DIT
- T3 = MIT + DIT
Describe the pathophysiology of gestational thyrotoxiosis
hCG -> increase in thyroid hormone production
- Occurs in late 1st and early 2nd trimester, when hCG is high
- hCG binds to TSH receptor
- -> increased thyroid hormone production
- -> decreased TSH
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What is the embryologic tissue of origin of the thyroid?
Neuroectoderm (1st pharyngeal arch)