175. Thyroid pathophysiology Flashcards
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
MTC
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
Postpartum Thyroiditis (PPT)
Causes a decrease in TT4 and TT3
Can be caused by:
- androgens
- gluococorticoids
- l-asparaginase
- cirrhosis
- nephrotic syndrome
- acromegaly
TBG decrease
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)
Graves’ Ophthalmopathy
Combination of transglobulin-measurement with imaging
- US of neck
- Whole body scan with radioiodine
- PET-scan
- CT
- MRI
Long-term management of thyroid cancer
Should expect what kind of levels of TSH during pregnancy
Low levels
Etiology:
- Graves’
- Hyperfunctioning nodules
- Early pregnancy
- Post partum thyroiditis
- Congenital
Hyperthyroidism
Bilateral, multifocal MTC lesions points more towards
Familial MTC/MEN2
Autoimmune disease with stimulatory antibodies against the TSH receptor
Associated w/ eye disease
Treated with methimazole and propranolol
Graves’ Disease
Unilateral MTC lesion points more towards..
Sporadic MTC
Mutation in RET proto-oncogene associated w/:
- MTC
- Pheochromocytoma
- Hyperparathyroidism
- Hirschsprung’s
MEN2A
Metastasis of __ is primarily through the bloodstream and typical locations include the lungs and bone.
FTC (follicular thyroid cancer)
This protein increases during pregnancy, thus causing lower amounts of T3/T4 activity
Hypothyroidism pts will need to increase levothyroxine dose
TBG
The __ is one of the most sensitive organs to the neoplastic effects of radiation
Thyroid
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
Subclinical hypothyroidism (Mild Thyroid Failure)
Signs:
- Goiter
- Weight loss
- Tachycardia
- Diastolic HTN
- Arrythmias - A-Fib
- Hyperreflexia
- Eye signs like exopthalmos
- Irregular menses and infertility in women
Hyperthyroidism
Signs:
- goiter
- weight gain
- bradycardia
- diastolic hypertension
- swollen face
- hyporeflexia
- global edema
- irregular menses and infertility in women
Hypothyroidism
Metastasis of __ is primarily lymphatic and can involve the locoregional lymph nodes and lungs
PTC (papillary thyroid cancer)
Before removing the thyroids d/t MTC, one must always check for
Pheochromocytoma
Staging of thyroid cancers is based mostly on what?
Age
Treatment for Graves’ ophthalmopathy
Steroid infusions
Orbital decompression
Rituximab - IL-6 inhibitor
- used if steroid resistant
Well-differentiated types of thyroid cancer
Papillary
Follicular
Hurthle
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
Toxic adenoma
- Total thyroidectomy
- remove the thyroid with all cancerous tissue - Radioactive iodine treatment
- destroy any microscopic residual thyroid tissue - Without any or very little thyroid tissue
- completely dependent on administration of levothyroxine
Initial treatment of thyroid cancer
Indications:
- very large goiters
- allergies to thionamides
- lesions suspicious for malignancy
Complications:
- hypothyroidism
- hypoparathyroidism
- vocal cord injury - recurrent laryngeal nerve damage
Thyroidectomy
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
Tyrosine kinase inhibitors FDA approved for medullary thyroid cancer
Vandetanib
Cabozantinib
Undifferentiated thyroid cancer
Rare, extremely malignant
Anaplastic cancer
Skin condition that can be associated with Graves’
- shows that autoimmune conditions often present together
Vitiligo
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
Autoimmune disease w/ antibodies against the thyroid
- against TPO
Progressive destruction of the gland
- gradual or rapid
Hashimoto’s Thyroiditis
With increasing suppression of TSH after cancer treatment, pts are at an increased risk for:
A-Fib
Postmenopausal osteoporosis
Signs/symptoms of thyrotoxicosis
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
Hispanics > whites»_space; 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
Mutation in RET proto-oncogene associated w/:
- MTC
- Pheochromocytoma
- Ganglioneuromas
- Marfanoid habitus
MEN2B
Preferred thionamide to be prescribed to pregnant women in the first trimester of their pregnancy
Side effect: fulminant hepatic failure in children
PTU
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
If you are under what age then your papillary or follicular thyroid cancer is only staged to I or II
45yo
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
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
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
Causes an increase in TT4 and TT3
Can be caused by:
- estrogens
- fluoroacils
- clofibrate
- opiates
- hepatitis
- porphyria
TBG elevation
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
Preferred thionamide to be prescribed for patients who are suffering from hyperthyroidism
Methimazole
Metastasizes to the liver (most common), lungs, bone, and brain
Spread to locoregional lymph nodes is common
MTC
Side effects:
- Maculopapular or urticarial skin rash
- Pruritis
- Hepatotoxicity (esp. PTU)
- Arthralgias
- Agranulocytosis (inhibiting bone marrow –> no WBCs)
Thionamides
Thyroid cancer originating from parafollicular cells (C-cells)
Calcitonin-producing
- marker along w/ CEA
- can also make a ton of amyloid
Medullary thyroid cancer
Tyrosine kinase inhibitors FDA approved for papillary, follicular, and hurthle cancer
Sorafenib
Lenvatinib
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
Thyroid cancer originating from follicular thyroid cell
- well-differentiated
Thyroglobulin producing
Papillary - 80%
Follicular - 18%
Symptoms:
- fatigue
- depression
- cold intolerance
- constipation
- decreased appetite
- paresthesias
- hair and skin changes
Hypothyroidism
Biggest risk factor for pts w/ Graves’ to develop eye issues
Smoking
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
What do papillary and follicular thyroid cancer cells produce that can be measured as a marker?
Thyroglobulin
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
