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ENDOCRINE > 176b/177b/178b - Thyroid Physio, Path, Pathopys, Nodules, Cancer > Flashcards

176b/177b/178b - Thyroid Physio, Path, Pathopys, Nodules, Cancer Flashcards

1
Q

What are the imaging modalities of choice for evaluating thyroid structure?

A

Ultrasound = first line

CT if there is intrathoracic extension of large goiters

Use iodine isotopes for thyroid function

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2
Q

Which thyroid neoplasm is derived from C-cells?

A

Medullary carcinoma of the thyroid

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3
Q

Which type of thyroid cancer is associated with a history of radiation exposure?

A

Papillary carcinoma of the thyroid

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4
Q

Which thyroid neoplasm is most likely to have a hereditary component?

A

Medullary thyroid carcinoma

  • Association with MEN-2
    • Mutation in RET oncogene
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5
Q

What is the most common cause of thyroid disease worldwide?

A

Iodine deficiency

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6
Q

A patient presents with bilateral pheochromocytoma

What organ will you check next to evaluate for neoplasm?

A

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

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7
Q

What is the most common congenital thyroid nodule?

A

Thyroglossal duct cyst

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8
Q

How does biotin supplementation affect thyroid lab values?

(TSH, T3, T4)

Why?

A
  • 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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9
Q

What is organification? (in the context of TH synthesis)

What enzyme is responsible?

A

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

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10
Q

Describe the histologic features of non-invasive follicular thyroid neoplasm (NIFTP)

What is the treatment?

A
  • 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
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11
Q

Which 3 proteins bind thyroid hormone in the blood?

A
  • Thyroid binding globulin (TBG)
  • Transthyretin
  • Albumin

Affinity: TBG > Transthyretin > Albumin

Note: only very small percentages of T4 and T3 are unbound

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12
Q

Describe the 24h iodine uptake pattern that is pathognomonic for Graves’ disease

A

Diffuse, homogenous uptake

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13
Q

What is the role of molecular testing in the evaluation of thyroid nodules?

A

Test intermediate-suspicion nodules for characteristic mutations

Most useful as rule-out tests for specific pathologies

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14
Q

Where in the body is the thyroid hormone receptor alpha (TR-alpha) found?

What about thyroid TR-beta?

A
  • TR-alpha
    • Brain
    • Skeletal tissues
    • Intestines
    • Heart
  • TR-beta
    • Liver
    • Heart
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15
Q

Describe the findings associated with Grave’s Disease

  • Gross:
  • Histology:
A
  • Gross:
    • Diffuse, symmetric enlargement
  • Histology:
    • Papillary hyperplasia
    • Tall follicular cells
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16
Q

What neoplasms are associated with MEN-2? (both 2A and 2B)

Which neoplasms are specific to 2A and 2B respectively?

A
  • All MEN-2
    • Medullary thyroic carcinoma
    • Pheochromocytoma (medulla of adrenal gland)
  • MEN-2A
      • Parathyroid hyperplasia
  • MEN-2B
      • Marfanoid appearance
      • Mucosal neuroma/ganglioneuroma
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17
Q

What is the histological hallmark of thyroid papillary caricinoma?

A

Atypical nuclear morphology

  • Nuclear grooves
  • Orphan Annie eye inclusions
  • Hypochromasia
  • Psamoma bodies
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18
Q

Describe the thyroid findings of Hashimoto’s thyroiditis

  • Gross:
  • Histology:
  • Cytology:
A
  • Gross:
    • Diffusely enlarged
  • Histology:
    • Lymphocytes and plasma celsl infitrate parenchyma
    • Atrophic follicles
  • Cytology:
    • Hurthle cells + heterogeneous lymphocytes
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19
Q

What is the classic histological finding of a follicular adenoma of the thyroid?

A

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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20
Q

What is the first line medication for anti-thyroid drug therapy?

Are there exceptions?

A

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

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21
Q

List 3 substances that negatively regulate TRH secretion from the hypothalamus

A

Somatostatin

Dopamine

T3 (negative feedback)

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22
Q

What supplement may interfere with TSH, T3, T4 assays?

A

Biotin!

Will cause falsely low TSH, falsely high T3, T4

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23
Q

What etiology of hyperthyroidism will have bilateral increased iodine uptake?

A

Graves’ disease

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24
Q

What percentage of medullary thyroid carcinomas are hereditary?

What gene is likely mutated?

Which syndrome is associated?

A

20-25% are hereditary

RET proto-oncogene

  • MEN-2 (2A or 2B)
    • Association with mutations in
  • Also can just be familial tumors
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25
Q

What (general) lab values are associated with subclinical hyperthyroidism?

When should it be treated?

A

Low TSH, normal free T3/T4

Treat if TSH <0.1 to avoid atrial fibrillation, osteoporosis

26
Q

What is the vertebral level of the thyroid?

A

C5 - T1

27
Q

Which micronutrient is essential for the synthesis of thyroid hormone?

What is the recommended daily allowance?

A

Iodine

150 mcg/day

28
Q

What etiology of hyperthyroidism will have unilateral increased uptake?

A

Toxic adenoma

  • The rest of the thyroid is trying to uptake less
  • This is a “hot nodule” = less likely to be malignant
29
Q

Describe the clinical course of post-partum thyroiditis

A

Hyperhtyroid -> Hypothyroid -> Euthroid

30
Q

Which cells of the thyroid secrete calcitonin?

A

C cells

31
Q

Hurtle cells are associated with which thyroid pathology?

A

Hashimoto’s thyroiditis

32
Q

What is the first-line managment for Graves’ opthalmopathy?

A

Seleinum

Also:

  • Artificial tears
  • Avoid tobacco exposure
    • Even 2nd hand smoke
  • Teprotumumab
    • Monoclonal antibody that inhibits IGF-1 receptor; cross-reacts with TSH receptor?
33
Q

Which enzyme converts T4 to reverse T3?

A

5 (mono)deiodinase

(DIO3)

34
Q

What are the characteristics of a solid thyroid nodule on ultrasound? (3)

A

Many echo reflections

Back wasll indistinct

No acoustic enhancement

35
Q

What are the (general) TSH and T4 levels in subclinical hypothyroidism?

When should it be treated?

A

High TSH with normal free T4

  • Treat if TSH > 10 (even if asymptomatic)
  • ALWAYS treat if TSH elevated in pregnancy
    • Ideally, pre-pregnancy
36
Q

What is the most common malignant thyroid nodule?

A

Papillary thyroid carcinoma

37
Q

Which enzyme converts T4 to T3?

A

5’ (mono)deiodinase

(Either DIO1 or DIO2)

38
Q

Describe the presentaiton of an anaplastic thyroid carcinoma

What is the prognosis?

A

Suddenly enlarged neck

Poor prognosis - usually extensive metastasis at time of presentation

39
Q

What is the most common cause of hypothyroidism in the USA?

Worldwide?

A

USA = Hashimoto’s thyroiditis

World = Iodine deficiency

40
Q

When a thyroid problem is suspected, which lab should be checked first?

A

TSH

Then check free T4 and total T3

(Don’t want to only check T4/T3 and miss a central problem)

41
Q

Why does thyroid gland move when we swallow or speak?

A

The thyroid gland is attached to the tonge by the thyroglossal duct

42
Q

What percentage of thyroid noduels are benign?

A

90%

(VAST majority are benign; many foudn incidentally)

43
Q

Describe the signaling cascade activated when TSH binds to its receptor:

  • Gs:
  • Gq:
A
  • 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
44
Q

After a thyroid nodule is found on ultrasound, what is the next diagnostic step?

A

Fine needle aspiration if the ultrasound is concerning

45
Q

Which genetic mutations are assoicated with papillary carcinoma of the thyroid?

A

BRAF

RET

46
Q

What is the classic histologic finding in follicular carcinoma of the thyroid?

A

Follicular celsl surrounded by a capsule - will see capsular and vascular invasion

Vs. follicular adenoma - caspule will be uniform and continuous

47
Q

What is the best management of a patient with newly dignosed Grave’s disease?

A

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

48
Q

What are the characteristics of a thyroid cyst on ultrasound? (3)

A

Anechoic center

Smooth black wall

Acoustic enhancement

49
Q

What is the main driver of the increase in incidence of thyroid nodules and thyroid cancer?

A

Increased ultrasound use

50
Q

What is the imaging modality of choice for thyroid function?

A

Iodine isotopes

Use ultrasound for thyroid structure

51
Q

Does a “hot” thyroid nodule need to be biopsied?

A

No!

Need to cool off nodule before biopsy

Also, most hot nodules are benign

52
Q

What is the most likely diagnosis of a patient with elevated free T4 and very low iodine uptake in the thyroid gland?

A

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
53
Q

What are the symptoms of hypothyroidism? (6)

A

New symptoms of:

  • Menstrual irregularity
  • Infertility
  • Depression
  • Cognitive decline
  • Hyperlipidemia
    • Hair/skin changes
  • Nonspecific
    • Fatigue, weight gain, constipation
54
Q

Antibodies against thyroglobulin and TPO are round in whihc thyroid pathology?

A

Hashimoto’s thyroiditis

55
Q

What are the indications for:

  • 123I scan:
  • 131I scan:
  • 99TcO4 scan:
A
  • 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
56
Q

What is the functional unit of the thyroid?

A

Follicle

57
Q

What is the treatment of choice for hypothyroidism?

A

Levothyroxine

58
Q

What is coupling? (In the context of TH synthesis)

What enzyme is responsible?

A

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
59
Q

Describe the pathophysiology of gestational thyrotoxiosis

A

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
60
Q

What is the embryologic tissue of origin of the thyroid?

A

Neuroectoderm (1st pharyngeal arch)

ENDOCRINE (17 decks)

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