Term
| What is the etiology of Hashimoto's hypothyroidism that occurs primarily in females? Name the antibodies and genetic predisposition... |
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Definition
Autoimmune:
Anti-TPO (microsomal) and anti-Tg Abs
Intrathyroidal CD8 (cytotoxic) T cells
Increased incidence of HLA-DR5
Increased risk of other autoimmune diseases
Type 1 diabetes mellitus
Addison’s disease (adrenal insufficiency)
Pernicious anemia
Etc. |
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Term
| Name some symptoms of Hashimoto's: |
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Definition
Fatigue
Lethargy
Weakness
Cold intolerance
Mental slowness
Depression
Dry skin
Constipation
Muscle cramps
Irregular menses – also HEAVY PERIOD!
Infertility
Mild weight gain
Fluid retention
Hoarseness |
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Term
| Hypothyroidism: Clinical Signs |
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Definition
Goiter (primary hypothyroidism only)
Bradycardia
Nonpitting edema (b/c pitting is CHF)
Dry skin
Delayed DTR relaxation
Hypertension
Slow speech
Slow movements
hoarseness |
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Term
| T/F: Goiter is a positive sign for hashimoto's |
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Definition
F: goiter can be in either hyper/hypothryoidism
Usually but not always present
Generally firm, non-tender
May be irregular or asymmetric |
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Term
| What lab findings do you find in Hashimoto's: TSH, T4, FT3, Abs |
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Definition
Increased TSH is the most sensitive test
Primary hypothyroidism only
Always measure unless you know the patient has defective TSH secretion
Decreased free T4
probably should measure at diagnosis if TSH high
Decreased FT3
Less sensitive and less specific than decreased FT4 (don’t measure)
Used in pituitary secretion dysfunction!
Anti-TPO and anti-Tg Abs (Hashimoto’s) |
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Term
| When would you try and use F-T3 to dx Hashimoto's? |
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Definition
| Used in pituitary secretion dysfunction! |
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Term
| What the goals and agent for treatment of hypothyroidism? |
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Definition
L-Thyroxine (levothyroxine; T4)
Goals
Alleviate symptoms
Normalize TSH (primary hypothyroidism) or free T4 (secondary and tertiary hypothyroidism) |
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Term
Armour and natural thyroid risk what complication in humans?
What are other T4 and T3 medicines? |
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Definition
Hyperthyroidism from excess T3 in
T4: levothyroxine, Synthroid® , Levoxyl®, Unithroid®, Levothroid®
T3: liothyronine, Cytomel® |
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Term
| The differential diagnosis is large, but the most important thing is to distinguish benign from malignant causes of thyroid nodules. What percent are benign? |
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Definition
~5% of adults have thyroid nodules, with a 5:1 female:male ratio
~95% of thyroid nodules are benign |
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Term
| Key triggers in history for thyroid nodules: |
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Definition
Childhood Irradiation
Age
Gender (malignancy more likely in males)
Duration and Growth (thyroid cancer can be very slow growing)
Local symptoms (hoarseness worrisome)
Hyper- or hypothyroidism (suggest benign)
Family history (MEN2) |
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Term
| High TSH vs. Low TSH in thyroid nodules...What do they mean? |
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Definition
A low TSH suggests the nodule is “hot”, which would indicate it is benign but causing hyperthyroidism.
A high TSH suggests hypothyroidism due to Hashimoto’s thyroiditis. The nodule may disappear with levothyroxine Rx to normalize TSH.
However, TSH will be normal in most cases. |
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Term
| T/F: a radionuclide scan is an effective way of sizing the nodule and ruling out malignancy |
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Definition
| F: you should only scan if the nodule is small and TSH is normal. otherwise most nodules are cold and only a small number a malignant so you need a fine needle biopsy to distinguish between a follicular carcinoma and follicular adenoma. >1.0-1.5 cm need to biopsied. |
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Term
| Thyroid Nodules: Therapy for benign vs. malignant |
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Definition
Benign nodules:
Generally nothing
Sometimes T4
Occasionally surgery
Malignant nodules
Surgery
T4 to suppress TSH
Radioiodine (I-131) |
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Term
| What is a good marker for the most common tumor, that has an excellent prognosis but first initially spreads to the local cervical lymph nodes. |
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Definition
Papillary Thyroid Cancer
Most common type
Excellent prognosis
Spreads first to local cervical lymph nodes; also can spread to lung and bone
Therapy: surgery, T4, radioiodine
Thyroglobulin is an excellent tumor marker |
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Term
| In Papillary thyroid cancer, what's the pathway being activated and where're the mutationsS? |
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Definition
Ras-MAPK pathway
BRAF V600E mutation in ~50% of cases
RET/PTC chromosomal translocation in ~20% of cases
Ras mutations in ~15% of cases |
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Term
| You perform a PCR of the biopsy specimen and find a BRAF V600E mutation. What does this mean for treatment? |
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Definition
Prognosis: tumors tend to be more aggressive than other papillary cancers.
Treatment: An experimental BRAF inhibitor is in a clinical trial for papillary thyroid cancer. There currently are no effective chemotherapeutic agents to treat thyroid cancers. |
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Term
| _____is a plasma membrane receptor with a cytoplasmic tyrosine kinase domain. |
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Definition
| RET: ~20% of papillary cancers are caused by translocations involving the RET proto-oncogene. |
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Term
| what juxtaposition => RET's inappropriate expression? |
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Definition
RET is not normally expressed in thyroid follicular cells. A chromosomal inversion juxtaposes sequences of another gene (called PTC) with the tyrosine kinase domain of RET, resulting in inappropriate RET expression.
Detection of RET rearrangements by PCR of thyroid biopsies and peripheral blood may become important diagnostic tests. |
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Term
The 1986 Chernobyl accident released a large amount of radioiodine into the atmosphere.
New cases of thyroid cancer began to increase in 1990, and rose 50-fold by 1993.
Which mutation did they have? |
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Definition
| => RET/PTC rearrangements mostly in children <5yo |
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Term
| The American Thyroid Association recommends that nuclear power plants stock _______ for emergency administration to local residents. |
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Definition
| NaI/KI...may be preventable by ingestion of iodide (non-radioactive) |
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Term
| Which tumor also has thyroglobulin as a good marker, but has a large tendency to spread to lung and bone/less to cervical lymph nodes. |
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Definition
Follicular TC: Less common than papillary
Prognosis probably not quite as good as papillary, but still excellent
Greater tendency than papillary to spread to lung and bone, with less to cervical lymph nodes
Therapy: surgery, T4, radioiodine
Thyroglobulin is an excellent tumor marker |
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Term
FTC involves which of the following:
point mutations (gain of function)
frameshift mutations
chromosomal translocations
gene rearrangments
activating kinases |
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Definition
(3, 4)
Often caused by a chromosomal translocation fusing the genes encoding Pax8 and PPARg.
Pax8 is a transcription factor that controls the development of the thyroid and the expression of many thyroid specific genes.
PPARg is a nuclear receptor (it is the target of the insulin sensitizing drugs thiazolidinediones). |
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Term
| Which is an excellent tumor marker for a cancer derived from parafollicular C cells (not follicular cells) |
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Definition
calcitonin is a good marker for Medullary thyroid cancer
Can be sporadic or part of MEN2a or 2b
Therapy - surgery (radioiodine ineffective)
Only ~5% of thyroid cancers |
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Term
| Multiple Endocrine Neoplasia Type I - what is this in? |
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Definition
MEN 1
Pituitary adenoma
Parathyroid (usually 4 gland hyperplasia)
Pancreas (gastrinoma, insulinoma) |
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Term
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Definition
MEN 2A
Medullary carcinoma of the thyroid
Parathyroid (usually 4 gland hyperplasia)
Pheochromocytoma (usually bilateral)
MEN 2B
Medullary carcinoma of the thyroid
Pheochromocytoma (usually bilateral)
Mucosal neuromas, Marfanoid habitus, ganglioneuromas |
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Term
| T/F: MEN I mutations are autosomal dominant |
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Definition
F: RET point mutations (single amino acid changes) cause MEN2A and 2B.
Similar RET mutations also are found in some sporadic medullary cancers. RET translocations cause some papillary cancers.
RET mutations that cause thyroid cancer are gain of function mutations, and hence MEN2A and 2B are autosomal dominant. |
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Term
| Patients with medullary thyroid cancer and family members can be tested for RET mutations. What are the differences between MEN 2A and 2B mutations? |
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Definition
MEN2A - RET mutations occur in extracellular domain cysteines.
Results in intermolecular RET dimerization, leading to inappropriate kinase activation.
MEN2B - RET amino acid 918 is mutated from methionine to cysteine.
Mutation lies within the kinase domain and presumably alters enzyme specificity. |
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Term
| Why is it that amiodarone causes weight gain even though Standard maintenance therapy with 200 mg amiodarone can provide more than 100 times the daily iodine requirement???? |
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Definition
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