175. Thyroid pathophysiology Flashcards

1
Q

Neuroendocrine tumor of the parafollicular C cells

Produce calcitonin and CEA

~2% of all thyroid carcinomas

~75% sporadic, ~25% hereditary in the context of MEN2

A

MTC

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2
Q

Occurrence of hyperthyroidism and/or hypothyroidism during the postpartum period in women who were euthyroid during pregnancy
- gland is partially destroyed

At highest risk:

  • pts w/ Type 1 DM
  • previous history of other autoimmune diseases like Hashimoto’s or Graves’

Goes from hyperthyroidism to hypothyroidism to euthyroid if the pt is able to remit

A

Postpartum Thyroiditis (PPT)

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3
Q

Causes a decrease in TT4 and TT3

Can be caused by:

  • androgens
  • gluococorticoids
  • l-asparaginase
  • cirrhosis
  • nephrotic syndrome
  • acromegaly
A

TBG decrease

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4
Q

Signs: can wax and wane, can be one or the other or both

  • chemosis - conjunctival irritation
  • lid edema
  • proptosis (exopthalmos)
  • double vision
  • keratitis - when lids aren’t fully closing
  • optic nerve involvement (extreme cases)
A

Graves’ Ophthalmopathy

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5
Q

Combination of transglobulin-measurement with imaging

  • US of neck
  • Whole body scan with radioiodine
  • PET-scan
  • CT
  • MRI
A

Long-term management of thyroid cancer

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6
Q

Should expect what kind of levels of TSH during pregnancy

A

Low levels

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7
Q

Etiology:

  • Graves’
  • Hyperfunctioning nodules
  • Early pregnancy
  • Post partum thyroiditis
  • Congenital
A

Hyperthyroidism

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8
Q

Bilateral, multifocal MTC lesions points more towards

A

Familial MTC/MEN2

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9
Q

Autoimmune disease with stimulatory antibodies against the TSH receptor

Associated w/ eye disease

Treated with methimazole and propranolol

A

Graves’ Disease

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10
Q

Unilateral MTC lesion points more towards..

A

Sporadic MTC

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11
Q

Mutation in RET proto-oncogene associated w/:

  • MTC
  • Pheochromocytoma
  • Hyperparathyroidism
  • Hirschsprung’s
A

MEN2A

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12
Q

Metastasis of __ is primarily through the bloodstream and typical locations include the lungs and bone.

A

FTC (follicular thyroid cancer)

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13
Q

This protein increases during pregnancy, thus causing lower amounts of T3/T4 activity

Hypothyroidism pts will need to increase levothyroxine dose

A

TBG

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14
Q

The __ is one of the most sensitive organs to the neoplastic effects of radiation

A

Thyroid

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15
Q

Elevated TSH

Normal FT4, T4

Patients often have few specific clinical symptoms or signs

Sympatoms are ordinary and nonspecific

Specific age and sex-related presentations

A

Subclinical hypothyroidism (Mild Thyroid Failure)

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16
Q

Signs:

  • Goiter
  • Weight loss
  • Tachycardia
  • Diastolic HTN
  • Arrythmias - A-Fib
  • Hyperreflexia
  • Eye signs like exopthalmos
  • Irregular menses and infertility in women
A

Hyperthyroidism

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17
Q

Signs:

  • goiter
  • weight gain
  • bradycardia
  • diastolic hypertension
  • swollen face
  • hyporeflexia
  • global edema
  • irregular menses and infertility in women
A

Hypothyroidism

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18
Q

Metastasis of __ is primarily lymphatic and can involve the locoregional lymph nodes and lungs

A

PTC (papillary thyroid cancer)

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19
Q

Before removing the thyroids d/t MTC, one must always check for

A

Pheochromocytoma

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20
Q

Staging of thyroid cancers is based mostly on what?

A

Age

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21
Q

Treatment for Graves’ ophthalmopathy

A

Steroid infusions

Orbital decompression

Rituximab - IL-6 inhibitor
- used if steroid resistant

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22
Q

Well-differentiated types of thyroid cancer

A

Papillary
Follicular
Hurthle

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23
Q

Type of tumor found in the thyroid gland that makes a lot of thyroid hormone

Rest of gland will be quiet on radioiodine uptake d/t decrease of TSH activity

Treat w/ I-131
- normal tissue should not be destroyed bc it is not active

A

Toxic adenoma

24
Q
  1. Total thyroidectomy
    - remove the thyroid with all cancerous tissue
  2. Radioactive iodine treatment
    - destroy any microscopic residual thyroid tissue
  3. Without any or very little thyroid tissue
    - completely dependent on administration of levothyroxine
A

Initial treatment of thyroid cancer

25
Indications: - very large goiters - allergies to thionamides - lesions suspicious for malignancy Complications: - hypothyroidism - hypoparathyroidism - vocal cord injury - recurrent laryngeal nerve damage
Thyroidectomy
26
From sympathetic overactivity: - stare - lid retraction - lid lag D/t hyperadrenergic states Need to be distinguished separately from eye issues from Graves' specifically
Hyperthyroidism eye problems
27
Tyrosine kinase inhibitors FDA approved for medullary thyroid cancer
Vandetanib | Cabozantinib
28
Undifferentiated thyroid cancer Rare, extremely malignant
Anaplastic cancer
29
Skin condition that can be associated with Graves' | - shows that autoimmune conditions often present together
Vitiligo
30
Hormone that increases in the early weeks of pregnancy When in large amounts, can act on the TSH receptor in early pregnancy causing hyperthyroidism
hCG
31
Autoimmune disease w/ antibodies against the thyroid - against TPO Progressive destruction of the gland - gradual or rapid
Hashimoto's Thyroiditis
32
With increasing suppression of TSH after cancer treatment, pts are at an increased risk for:
A-Fib Postmenopausal osteoporosis Signs/symptoms of thyrotoxicosis
33
This type of thyroiditis can be confirmed by measuring anti-TPO Abs - no uptake on scan Lack of symptoms or signs though Recent pregnancy
Silent thyroiditis
34
Hispanics > whites >> blacks - girls > boys Associated w/ many different genetic defects - 80-90% from development defects of the thyroid gland - 10-15% from thyroid hormone synthesis errors Pts often present with mental retardation, bony changes, global edema Levothyroxine used to treat but will not help with cognitive defects after they have already been established - early treatment is muy importante
Congenital hypothyroidism
35
Mutation in RET proto-oncogene associated w/: - MTC - Pheochromocytoma - Ganglioneuromas - Marfanoid habitus
MEN2B
36
Preferred thionamide to be prescribed to pregnant women in the first trimester of their pregnancy Side effect: fulminant hepatic failure in children
PTU
37
Sporadic MTC somatic mutations in what genes | - one is same as MEN2 that forms a tyrosine kinase that no longer needs to dimerize to be active
RET, KRAS, HRAS, NRAS
38
If you are under what age then your papillary or follicular thyroid cancer is only staged to I or II
45yo
39
Symptoms: - Nervousness - Irritability - Palpitations d/t increased beta receptor activation (usually in evening at rest) - Increased appetite - Frequent bowel movements (not diarrhea necessarily) - Muscle weakness - Hair and skin changes - Feeling warm all the time due to vasodilation
Hyperthyroidism
40
Hypothyroidism therapy T4 will get converted to T3 by Type I and II mono-deiodinases Goal is normalize TSH levels Need to start w/ slower dosing in CAD patients - don't want to give heart too much work from the jump
Levothyroxine
41
When to suspect: - Hypercholesterolemia - Refractory depression - Previous episode of postpartum thyroiditis - Goiter - Family or personal hx of thyroid disease - Over 40 w/ nonspecific complaints - Insidious w/ weight change - Unexplained infertility
Mild thyroid failure
42
Causes an increase in TT4 and TT3 Can be caused by: - estrogens - fluoroacils - clofibrate - opiates - hepatitis - porphyria
TBG elevation
43
Definitive treatment of Graves' Disease - goal: hypothyroidism - can worsen eye disease - need life-long thyroid therapy Definitive treatment of toxic adenoma - goal: euthyroidism Useful for treatment of multinodular goiter - goal: mass reduction and/or euthyroidism Uses beta-particles to obliterate tissue
I-131
44
Preferred thionamide to be prescribed for patients who are suffering from hyperthyroidism
Methimazole
45
Metastasizes to the liver (most common), lungs, bone, and brain Spread to locoregional lymph nodes is common
MTC
46
Side effects: - Maculopapular or urticarial skin rash - Pruritis - Hepatotoxicity (esp. PTU) - Arthralgias - Agranulocytosis (inhibiting bone marrow --> no WBCs)
Thionamides
47
Thyroid cancer originating from parafollicular cells (C-cells) Calcitonin-producing - marker along w/ CEA - can also make a ton of amyloid
Medullary thyroid cancer
48
Tyrosine kinase inhibitors FDA approved for papillary, follicular, and hurthle cancer
Sorafenib | Lenvatinib
49
Inhibit thyroid hormone synthesis First effects in about 2 weeks Euthyroidism achieved in about 6-8 weeks Methimazole is the preferred medication used - PTU also used but can cause fulminant hepatic failure in children Adapt dose continuously based on thyroid function tests
Thionamides
50
Thyroid cancer originating from follicular thyroid cell - well-differentiated Thyroglobulin producing
Papillary - 80% | Follicular - 18%
51
Symptoms: - fatigue - depression - cold intolerance - constipation - decreased appetite - paresthesias - hair and skin changes
Hypothyroidism
52
Biggest risk factor for pts w/ Graves' to develop eye issues
Smoking
53
Inflammation of the thyroid with destruction of thyrocytes Often preceded by a viral infection Painful on the anterior neck Increased ESR Treated w/ steroids and NSAIDs Increased risk for developing hypothyroidism
Subacute thyroiditis
54
What do papillary and follicular thyroid cancer cells produce that can be measured as a marker?
Thyroglobulin
55
Why do you give levothyroxine to cancer patients after they undergo radioiodine therapy?
Want low TSH amounts so that way the tumor has no activity taking place Decreases risk of recurrence of thyroid cancer