SM_178b: Thyroid Pathophysiology & Nodules / Cancer Flashcards
Describe the hypothalamus-pituitary-thyroid negative feedback loop
Hypothalamus-pituitary-thyroid negative feedback loop
- Hypothalamus secretes TRH
- Pituitary secretes TSH
- Thyroid secretes T4, T3
- Peripheral cell and T4, T3 negatively feedback onto pituitary and hypothalamus
In hypothyroidism, TSH is ____, T4 is ____, and T3 is ____
In hypothyroidism, TSH is high, T4 is low, and T3 is low
In hyperthyroidism, TSH is ____, T4 is ____, and T3 is ____
In hyperthyroidism, TSH is low, T4 is high, and T3 is high
Hypothyroidism can be ____, ____, or ____
Hypothyroidism can be primary, surgical, or central
- Primary: autoimmune destruction (Hashimoto’s) in iodine-sufficient population, iodine deficiency is most common worldwide, radiation induced
- Central hypothyroidism: primary pituitary, TBI
24 yo woman with fatigue, constipation, and weight gain over past 7 months and family Hx of thyroid disease. Next step is to ___
24 yo woman with fatigue, constipation, and weight gain over past 7 months and family Hx of thyroid disease. Next step is to check TSH
Low TSH. low fT4, and high TPO antibody indicates ____
Low TSH. low fT4, and high TPO antibody indicates Hashimoto’s thyroiditis
- Treat with levothyroxine, TSH monitoring
Hashimoto’s thyroiditis ultrasound shows ____
Hashimoto’s thyroiditis ultrasound shows heterogeneous (hypoechoic) echotexture
Hypothyroidism often presents with ____ such as ____, ____, ____, and ____
Hypothyroidism often presents with nonspecific symptoms such as fatigue, weight gain, constipation, and hair/skin changes
Subclinical hypothyroidism is ____
Subclinical hypothyroidism is elevated TSH with normal T4
- Always treat if TSH > 10
- Treat TSH > 7 if age < 65, possible prevention of CV outcomes and improvement in lipids
- Always treat in pregnancy
Mechanism of levothyroxine for treating hypothyroidism is ___
Mechanism of levothyroxine for treating hypothyroidism is conversion of T3 by mono-deiodinases which helps normalize TSJ
Overt hypothyroidism is ____
Overt hypothyroidism is high TSH and low fT4
____ treats hypothyroidism
Levothyroxine treats hypothyroidism
Hyperthyroidism is when ____
Hyperthyroidism is when elevated T3 and T4 cause decreased TSH
_____, _____, and _____ are the most common causes of thyrotoxicosis and hyperthyroidism
Graves disease, toxic multinoudlar goiter, and thyroiditis are the most common causes of thyrotoxicosis and hyperthyroidism
Describe presentation of hyperthyroidism
Hyperthyroidism
- Weight loss despite increase in appetite
- Heat intolerance
- Hyperactivity
- Fatigue
- Irritability
- Tremor
- Anxiety
- Insomnia
- Menstrual disturbances
- SOB
- Palpitations
- Pelvic and pectoral girdle muscle weakness
- Sleep disturbance
- Weakness
- Eye pain, tearing, gritty feeling
- Tachycardia, wide pulse pressure, systolic HTN, dynamic precordium, brisk reflexes, tremor of outstretched hands
____ and ____ confirm diagnosis of Graves disease
Ultrasound and antibodies confirm diagnosis of Graves disease
Hyperthryoidism treatment involves ____ and ____
Hyperthryoidism treatment involves beta blockers for rapid amelioration of adrenergic symptoms (cardiac exam) and methimazole
Methimazole is commonly used to treat ____
Methimazole is commonly used to treat hyperthyroidism
- First line anti-thyroid drug
- Short term: to cool the patient down prior to RAI or surgery
- Long-term: generally continued for 12-18 months then stopped to assess for remission
- Side effects: agranulocytosis (major), rash / urticaria / pruritis / fever / GI (minor)
- Recheck TSH, fT4 and T3 in 4 weeks and TSI every other lab check
Propylthiouracil can cause side effect of ____
Propylthiouracil can cause side effect of severe liver injury (fulminant hepatic necrosis)
____ is an option to treat hyperthyroidism for patients with large toxic nodular goiters and compressive symptoms, pregnant women with large anti-thyroid drug doses, pre-pregnancy, and patients with severe drug-related adverse effect
Total thyroidectomy is an option to treat hyperthyroidism for patients with large toxic nodular goiters and compressive symptoms, pregnant women with large anti-thyroid drug doses, pre-pregnancy, and patients with severe drug-related adverse effect
Graves ophthalmopathy (thyroid eye disease) presents with ____, ____, ____, and ____
Graves ophthalmopathy (thyroid eye disease) presents with proptosis, diplopia, optic nerve involvement, and inflammatory changes including conjunctival injection / periorbital edema / chemosis
____ is used to treat Graves ophthalmopathy (thyroid eye disease
Teprotumumab is used to treat Graves ophthalmopathy (thyroid eye disease
(monoclonal Ab that inhibits IGF1R, IGF1R and TSHR both located on orbital fibrocytes)
____ clinical manifestation of excess thyroid hormone action at the tissue level due to inappropriately high circulating thyroid hormone concentrations
Thyrotoxicosis is the clinical manifestation of excess thyroid hormone action at the tissue level due to inappropriately high circulating thyroid hormone concentrations
(hyperthyroidism is a subset)
Describe different thyroid scans in thyrotoxicosis
Thyroid scans in thyrotoxicosis
These thyroid scans represent ____
These thyroid scans represent Graves disease
This thyroid scan represents a ____
This thyroid scan represents a toxic adenoma
This thyroid scan represents a ____
This thyroid scan represents a toxic multinodular goiter
____ supplementation for hair and nails can lead to low TSH and high T4 and T3
Biotin supplementation for hair and nails can lead to low TSH and high T4 and T3
- Biotin can lead to false results by capturing monoclonal antibodies
Low TSH and presenting with hair loss postpartum and stress might be ____
Low TSH and presenting with hair loss postpartum and stress might be biotin supplementation
Low TSH, neck tenderness to palpation, and recent URI is ____
Low TSH, neck tenderness to palpation, and recent URI is painful thyroiditis
- Ultrasound is chaotic if patient lets you image
- I-123 scan shows no uptake
- ESR high
- Low grade fever
- TSH suppressed, fT4 high, total T3 less elevated
- NSAIDs, prednosine (often)
Thyroiditis is ___
Thyroiditis is damage to thyroid gland
- Leakage of stored thyroid hormone causing thyrotoxicosis: lasts 6-8 weeks until stored thyroid hormone is depleted
- Return to euthyroid state orwing to transient hypothyroidism (damaged follicular cells need to recover)
Low TSH and postpartum may be ___
Low TSH and postpartum may be postpartum thyroiditis
Gestational thyrotoxicosis is ___
Gestational thyrotoxicosis is hCG-mediated increase in thyroid hormone production
- Occurs in late 1st and early 2nd trimesters with improvement as hCG decreases
Gestational thyrotoxicosis has ____ and ____
Gestational thyrotoxicosis has no goiter and negative TSH receptor antibody
Subclinical hyperthyroidism is ____ TSH, ____ fT4, and ____ T3
Subclinical hyperthyroidism is persistently low TSH, normal fT4, and normal T3
- Cardiac (Afib, heart failure), bone, mortality
Incidence of atrial fibrillation ____ with decreasing serum TSH
Incidence of atrial fibrillation increases with decreasing serum TSH
High risk of fracture is subclinical hyperthyroidism with TSH ___ or endogenous cause
High risk of fracture is subclinical hyperthyroidism with TSH < 0.1 mIU/L or endogenous cause
TSI, TBII, and TRAb are for ___
TSI, TBII, and TRAb are for Graves disease
Up to ____ of people have thyroid nodules but risk of cancer in thyroid nodule is ____
Up to 60% of people have thyroid nodules but risk of cancer in thyroid nodule is 10%
- Many more detected on ultrasound than palpation
- Some noted by patient, third party, or other tests
Thyroid neoplasms can be ____ or ____
Thyroid neoplasms can be benign or malignant
Thyroid adenoma requires ___
Thyroid adenoma requires careful evaluation of the capsule
- Benign neoplasm
- Solitary nodule
- Follicular / Hurthle cell
First step in evaluating thyroid nodule is ____
First step in evaluating thyroid nodule is TSH
- If TSH is low, do a thyroid scan
- If TSH is normal / high, do ultrasound
Describe ATA patterns
ATA patterns
- 3 points -> TR3 mildly suspicious -> FNA if ≥ 25 cm, follow if ≥ 1.5 cm
- 4-6 points -> TR4 moderately suspicious -> FNA if ≥ 1.5 cm, follow if ≥ 1 cm
Thyroid nodules are suspicious if ___
Thyroid nodules are suspicious if hypoechoic solid nodule or partially cystic nodule with ≥ 1 of the following suspicious features
- Microcalcifications
- Shape taller than wide
- Irregular margins
- Extrathyroidal extension
- Interrupted rim calcifications with soft tissue
(risk of malignancy > 70-90%)
Intermediate thyroid nodule suspicion pattern is ___
Intermediate thyroid nodule suspicion pattern is hypoechoic nodules with regular smooth margins
- Papillary carcinoma, benign hyperplastic nodule
Low thyroid nodule suspicion pattern is ___
Low thyroid nodule suspicion pattern is iso- to hyperechoic nodules with regular margins
- Benign Hurthle cell adenoma, PTC foll variant, hyperplastic nodule
Very low thyroid nodule suspicion pattern is ___
Very low thyroid nodule suspicion pattern is mixed cystic / solid nodules (spongiform)
Pure cystic thyroid nodule is most likely ___
Pure cystic thyroid nodule is most likely benign
ACR TI-RADS is ___
ACR TI-RADS is guidelines for thyroid nodules discovered incidentally
If thyroid nodule is suspected to be malignant after fine needle biopsy, patient is treated with ____
If thyroid nodule is suspected to be malignant after fine needle biopsy, patient is treated with thyroidectomy
Describe what to do after fine needle aspiration for thyroid nodule
Fine needle aspiration for thyroid nodule
- Benign (60-70%): follow
- Malignant (10%): surgery
- Inadequate (5%): repeat biopsy
- Suspicious / indeterminate (20%): ultrasound features or molecular markers
Molecular testing is used to inform management of ___ thyroid nodules
Molecular testing is used to inform management of indeterminate nodules
- High sensitivity and NPV
Most common thyroid cancer is ____, which originates from ____
Most common thyroid cancer is papillary cancer, which originates from follicular thyroid cells (well-differentiated)
Describe papillary carcinoma
Papillary carcinoma
- Most common
- Well-differentiated
- Multifocal
- Lymphatic spread
- Excellent prognosis
- Papillae with vascular core
- Optically clear nuclei
- Nuclear pseudoinclusions
- Nuclear grooves
- Rare or absent mitoses
- Psammoma bodies
Follicular carcinoma is ____ or ____
Follicular carcinoma is minimally invasive or widely invasive
- Minimally invasive: vascular or capsular invasion
- Widely invasive: more extensive invasion into the surrounding muscle, vessels, trachea, etc
Describe treatment of thyroid cancer
Thyroid cancer treatment
- Lobectomy or total thyroidectomy
- Radioactive iodine treatment and postop thyroglobulin and ultrasound
- LT4 for TSH suppression
Increasing suppression of TSH leads to ____, ____, and ____
Increasing suppression of TSH leads to increased risk of atrial fibrillation, aggravation of postmenopausal osteoporosis, and increased risk of signs / symptoms of thyrotoxicosis
- The higher risk the cancer history, the lower TSH should be
Anaplastic carcinoma of thyroid has three patterns: ____, ____, and ____
Anaplastic carcinoma of thyroid has three patterns: spindle cell, giant cell, and squamoid cells
- Older age group (poor survival)
- Rapidly growing mass
- Necrosis and hemorrhage
Medullary thyroid carcinoma is a ____ that produces ____ and ____
Medullary thyroid carcinoma is a neuroendocrine tumor of the parafollicular C cells that produces calcitonin or carcinoembryonic antigen
- Most sporadic, others hereditary due to MEN type 2
MEN 2 is an ____ disorder caused by mutations in the ____ proto-oncogene
MEN 2 is an autosomal dominant disorder caused by mutations in the RET proto-oncogene
- Strong genotype-phenoptye correlation
- MEN2A: medullary thyroid cancer, pheochromocytoma, hyperparathyroidism
- MEN2B: medullary thyroid cancer, pheochromocytoma, ganglioneuromas, marfanoid habitus
Once medullary thyroid cancer diagnosis is established, ____, ____, and ____
Once medullary thyroid cancer diagnosis is established
- Screen for pheochromocytoma with 24 hour or plasma free metanephrine measurement
- Determine Ca and PTH if hyperparathyroidism possible
- RET gene analysis
In medullary thyroid cancer, it is not usually possible to localize residual / recurrent disease unless ___
In medullary thyroid cancer, it is not usually possible to localize residual / recurrent disease unless calcitonin > 150 pg/ml
____ are large fleshy masses that often arise in long-standing autoimmune thyroiditis
Lymphomas are large fleshy masses that often arise in long-standing autoimmune thyroiditis
- Usually B cell lymphoma
