where does the anterior pituitary originate from? what is its function?
originates from Rathke pouch
responsible for the synthesis and release of hormones
portal blood flow system with hypothalamus for realizing or inhibiting hormones
where does the posterior pituitary originate from? what is its function?
originates from the third ventricle outpuching
it’s axonal projections from supraoptic and paraventricular nuclei in the hypothalamus
it’s responsible for storage of hormones like oxytocin and ADH that were made in the hypothalamus
what is posterior pituitary syndrome?
usually due to hypothalamic lesions!!
what stimulates the thyroid gland? what is the chain of hormones in involved?
TRH from the hypothalamus goes to the pituitary to release TSH which then goes to the thyroid which releases T4/T3
what type of disease are most thyroid disease?
usually primary
primary disease is the endocrine gland, secondary disease is the pituitary, tertiary disease is the hypothalamus
what does the thyroid mostly secrete?
T4
most T3 (3 x potent) is produced by peripheral conversion of T4 in tissues
what are the 2 main functions of thyroid hormones?
- regulate BMR in tissues
- fetal brain development
calcitonin is also produced in the thyroid, helps regulate serum calcium
what are TSH levels like in primary hypo vs. hyperthyroidism? what is the best screen to differentiate the two?
primary hyperthyroidism: TSH undetectable (except rare TSH-secreting tumor)
primary hypothyroidis: TSH high
so TSH is the best screen for hyper or hypothyroidism in PRIMARY disease!!! for secondary/tertiary hypothyroidism do TRH stimulation test
what lab results are seen with primary hyperthyroidism?
low serum TSH because the thyroid is already putting out a lot of T3/T4
increased free T4 and/or T3
what is the clinical presentation of primary hyperthyroidism?
- hypermetablism
- nervousness
- arrhythmias/cardiomegaly
- rapid pulse
- weight loss
- diarrhea
- weakness
- heat intolerance/sweating
- emotional lability
- hand tremors
what is thyroid storms?
refers to abrupt onset of severe hyperthyroidism, elevated catacholamine levels
this is a medical emergency because it can result in death from arrhythmia
what is apathetic hyperthyroidism?
hyperthyroidism with blunted symptoms in elderly patients
what can cause primary hyperthyroidism?
- Grave’s disease aka diffuse toxic hyperplasia (85%) – gland is uniformly enlarged and is smooth
- toxic multinodular goiter – lots of nodules
- toxic adenoma – only one nodule and the rest of the thyroid looks normal
4.
what is Grave’s disease?
autoimmune disease so common in females 20-40 years old
there are antibodies to TSH receptors in the hypothalamus and they’re called TSI thryoid-stimulating immunoglobulins
triad of symptoms:
1. hyperthyroidism
- opthalmopathy
- dermopathy (pretrial leg edema)
what causes the opthalmopathy in Grave’s disease?
retro-orbital T-lymph infiltration, edema and mucopolysaccharide deposition
what is infant hypothyroidism?
aka cretinism
- mental retardataion
- large protuberant tongue
- short stature
usually caused by dietary iodine deficiency or inborn errors of synthesis
what is adult hypothyroidism?
aka myxedema
there is mucopolysaccharides in soft tissues resulting in non-pitting edema
autoimmune etiology or iatrogenic
what is the clinical presentation of hypothyroidism?
- fatigue
- cold intolerance
- overweight
- poriorbital edema
- thick dry skin
- constipation
- flabby enlarged heart
- mental slowness
- sometimes psychosis aka myxedema madness
what are the lab results in hypothyroidism
high TSH with low free T4
if TSH is low but you really suspect hypothyroidism, do a TRH stimulation test to determine if it’s primary or tertiary hypothyroidism
TSH will be low if secondary, but will be increased in tertiary
what is the most common cause of hypothyrdoisim?
Hashimoto’s thyroiditis
what is Hashimoto’s thyroiditis?
most common cause of hypothyroidism!
autoimmune disease where destruction is caused by CD8 cytotoxic T-cells (associated with cytotoxic T-lymphocyte-associated antigen-4 (CTLA4)) and cytokines from CD4 T-cells as well as antibodies (ADCC)
presents with hypothydoidism, painless diffuse enlargement goiter, other autoimmune associations
increased risk in DS patients
what are the labs associated with Hashimoto’s thyroiditis?
- high TSH with low T4
- antimicrosomal antibodies (Ab to thyroid peroxidase)
- antithyroglobulin antibodies
what is the pathology of Hashimoto’s thyroiditis?
lymphocytic infiltrate with germinal centers and Hurthle cell hyperplasia, maybe fibrosis
small increased risk of B cell lymphoma
which diseases can cause hyper or hypothyroidism?
- subacute lymphocytic thyroiditis
- deQuervain’s granulomatous thyroiditis
- Riedel ligneous thyroiditis
what is subacute lymphocytic thyroiditis?
painless enlargement of thyroid gland with lymphocytes invading thyroid but no follicles with germinal centers like in Hashimoto
hyperfunction is usually the presentation but may become hypo
sometimes occurs postpartum
antibodies may be present but not always
what is deQuervain’s granulomatous thyroiditis?
giant cells/granulomas
may be due to viral etiology because it peaks in the summer
patients present with fever, painful thyroid enlargement
usually hyperthyroidism but you never know so run the TSH test
what is Riedel ligneous thyroiditis?
rare, dense, fibrosis of the thyroid
feels hard and fixes the thyroid to the trachea mimicking carcinoma
what is a goiter?
any enlarged thyroid gland
it doesn’t matter the pathology that’s causing it
what is the etiology of Graves disease?
- iodine deficiency
- goitrogens like broccoli, Brussel sprouts, cabbage, cauliflower, cassava
- Hashimoto’s
decreased T4 output leads to increased TSH ultimately resulting in enlargement of the thyroid gland
what are the effects of a goiter on the surrounding structures?
- dysphagia
- tracheal compression
- SVC syndrome
what are the types of goiters?
- diffuse non-toxic goiter
- multi nodular goiter
- substernal goiter
- other: surgery, radiation, drugs, gene mutations
how do thyroid neoplasms usually present clinically?
- unilateral
- painless
- solitary nodules
- younger female patients
- history of radiation exposure usually malignant
what is a benign thyroid adenoma?
if the nodule takes up radioactive iodine, then it’s almost always benign and it’s called a hot nodule
if it doesn’t take up iodine it’s a cold nodule and it’s still probably benign but the risk for cancer goes up
either way, surgically remove ALL suspect lesions!
90% of the benign adenomas are surrounded by an intact capsule!!!
what is the etiology of benign adenomas?
mutations lead to cAMP activation which lead to formation of a nodule
sometimes the cells in the nodule have bright eosinophilic cytoplasm and they’re called Hurthle cell adenomas
what do thyroid adenomas lok like histologically?
most adenomas look like normal thyroid parenchyma…
with Hurthle cell adenomas there’s a lot of eosinohoplhilic cytoplasm
what does thyroid cancer look like?
usually asymtomatic cold nodules are what lead to thyroid cancer
malignant follicular lesions show capsular or vascular invasion or metastasis…these things are what a cold nodule malignant
how do you follow up if a thyroid removal of a cancerous lesion was successful?
serum thyroglobulin can be useful to follow post thyroidectomy
what are the 2 main thyroid carcinomas?
- papillary carcinoma
2. follicular carcinoma
which genetic mutations are most associated with papillary carcinomas of the thyroid?
- RET/PTC
- BRAF in mitogen-activated protein (MAP) kinase pathway
BRAF is a worse prognosis
which genetic mutations are most associated with follicular and anaplastic carcinomas of the thyroid?
- RAS
2. PI3K/AKT pathway (phosphatidyl inositol-3-kinase)
what are papillary carcinomas of the thyroid?
most common; 85%
- local lymphatic spread*
- good prognosis
how do you diagnose papillary carcincomas?
- papillary architecture
- Orphan Annie nuclei
- nuclear grooves
- psammoma bodies are diagnostic!!
if you don’t have papillary architecture and it looks more follicular but still has 2-4 characteristics then it’s a papillary carcinoma
what is a follicular carcinoma?
less common; 5-15%
metastasizes via the blood!!
worse prognosis because metastasis can be widespread unlike papillary which usually just goes to the neck lymph nodes
how do you diagnose follicular carcinoma?
- follicular architecture
- NO orphan annie nuclei, nuclear grooves or psammomma bodies
- capsular or vascular invasion or distant blood-born mets to bones/lung/liver
what is anaplastic carcinoma?
large masses with giant cells and spindle sarcoma like cells
aggressive, poor prognosis; looks horrible
p53 mutation
what is a medullary carcinoma?
tumor of C cells derivation aka the cells between the follicles – it’s a neuroendocrine tumor production calcitonin!!!
NO hypocalcemia! serum calcium doesn’t go down even though the cells contain calcitonin; so calcitonin is used as a biomarker
calcitonin can crystalize and become amyloid storm which is commonly seen around these tumor cells; stain amyloid with congo red and green biofringence when polarized
what is the clinical presentation of medullary carcinoma?
neck mass or weird presentation due to tumor production of VIP (diarrhea) or ACTH (Cushing syndrome)
what is the genetic mutation associated with medullary carcinoma?
RET mutation!!!
30% of people with MEN2 syndrome have an assocaition with the RET mutation and it’s a germline mutations it’s in EVERY cell int he body!! so they end up with multi-nodular medullary carcinoma so younger patients who have MEN2 syndrome you should consider a prophylactic total thyroidectomy
what genetic mutations are associated with papillary, follicular, medullary and anaplastic carcinomas?
papillary: RET/PTC translocation or BRAF mutation in the MAPK pathway
follicular: RAS mutation or PI3K mutation
medullayr: RET mutation
anaplastic: p53 mutation
what is a common congenital anomaly of the thyroid?
thryoglossal duct cyst that can sometimes reform after the descent of the thyroid
midline mass anterior to the trachea
may become infected and painful
note: branchial cleft cysts are similar but usually in the lateral neck
why do you have multiple endocrine tumors?
germline mutations!!
what is MEN syndrome?
tumors in younger age group with multiple endocrine sites
more aggressive
MEN = multiple endocrine neoplasia –> there is MEN1 and MEN2 syndrome
what is MEN1?
P lesions:
- Parathyroid
- Pituitary
- Pancreatic islets
- Peptic ulcers
MEN1 genetuation which is atumor suppresion gene
what is MEN2 syndrome?
tumors that can present are:
1. medullary carcinoma of the thyroid
- pheochromocytoma
- parathyroid hyperplasia
due to mutation of RET protooncogene – screen family members and get prophylactic total thyroidectomy if there is a RET mutation present
there’s MEN2a and MEN2b and the only different is W2 is without parathyroid hyperplasia