Flashcards in Module 5: Endocrine: Follicular Carcinoma, Papillary and Medullary and Cushings Deck (44):
Now moving on to the rest of the thyroid lesions, Follicular Carcinoma. What is the origin??
Thyroid follicle epithelial cells
-second most aggressive
What is the etiology and risk factor for follicular carcinoma?
More common in women and most begin de novo
---Risk Factor: Iodine Deficiency (africa, asia)
What is the presentation for follicular carcinoma?
Invasion of the capsule and neighboring organs
--dyspnea, dysphagia, and hoaresness
Always Cold Nodule (so normal thyroid levels)
Euthyroid (just means normal thyroid levels)
Decreased radio iodine uptake compared to the rest of the thyroid
What are the complications with follicular carcinoma?
--liver, lungs, brain ,bones and kidneys
Of course mass effect
What is the histological and gross appearance of follicular carcinoma?
Excisional Biopsy (most accurate): capsule has been breached
Histology: malignant follicular cells invading the capsule
Next in the thyroid lesions is the most common thyroid carcinoma, Papillary Carcinoma. What is the gross and histology?
Gross: Papillary carcinoma lesion within the thyroid. On cut surface, granular and papillary foci
Histology: Papillary projections with fibrovascular core and psamomma bodies and lined by clear orphan annie eye nuclei (optically dispersed nuclear chromatin with clear space in the nucleus) (Also may say ground glass appearance)
--hypercellular stroma and features of aptica
What is the etiology for papillary carcinoma?
Most common thyroid cancer (rare)
Etiology: BRAF and RET point mutation (Activation of the MAP kinase pathway)
Origin: thyroid follicle epithelial cells
What is the pathogenesis for papillary carcinoma?
Pre-disposing factor: long standing ionizing radiation (ex. Hodgkin's lymphoma on radiotherapy for 8 years, dysgerminoma, seminoma or medullary carcinoma of the breast)
What are signs and symptoms associated with papillary carcinoma?
Non-functional Tumor: painless mass in the neck, either within the thyroid or as metastasis in a cervical lymph node
What investigations can be done for papillary carcinoma of the thyroid?
Excisional biopsy: most accurate
Radioactive iodine uptake: always cold nodule aka does not secrete thyroid hormone (normal T3,T4 and TSH)
FNAC: can be used for dx -- look for orphan annie eye nuclei
What are complications associated with Papillary Carcinomas?
1. Invasion of trachea, esophagus, recurrent laryngeal nerve (mass effect)
2. Metastasis to cervical lymph nodes: liver, lung and bones
What is the prognosis for papillary carcinoma?
Good prognosis because they are slow growing
What other cancers have psammomma bodies?
Papillary Renal Cell and Papillary Carcinoma of the thyroid
Mesothelioma and Meningioma
Serous Ovarian Tumors and Serous Type Endometrial Carcinoma
The last thyroid abnormality to discuss is Medullary Carcinoma of the thyroid. What is the origin and tumor marker?
Origin: Parafollicular C cells
--calcitonin is tumor marker: calcium slightly low to normal
What is the etiology for medullary carcinoma?
RET (proto-oncogene = 1 hit)
---familial (bilateral): younger patients and multifocal, MEN2A or MEN2B
--- sporadic (unilateral); sporadic is more common: older patients and just one mass
What is the pathogenesis for medullary carcinoma?
Malignant parafollicular (C cells) secreting localized amyloid (similar to type 2 diabetes)
What are the MEN2A mutations?
MEN2A: only time you see hypercalcemia with medullary carcinoma
--medullary carcinoma of the thyroid: increased calcitonin but normal Ca2+ b/c PTH drives calcium
--parathyroid adenoma/hyperplasia: only time you will see hypercalcemia due to the increased PTH: nephrogenic diabetes insipidus (aquaporin channels in collecting duct insensitive to ADH)
What are the MEN2B mutations?
--medullary carcinoma of the thyroid (increased calcitonin)
--marfanoid habitus (look like Marfan's patients and mucosal neuromas: benign tumors of mucosal nerves)
NO PARATHYROID HYPERPLASIA: NO HYPERCALCEMIA (slightly low calcium)
What is the presentation for medullary carcinoma?
Invasion (mass effect)
What is the treatment for medullary carcinoma?
--if patients have a history of MEN2A or MEN2B mutations
What is the most accurate test for medullary carcinoma?
Excisional Biopsy: invasion of the capsule, hemorrhage, necrosis
Histo: malignant parafollicular C cells secreting amyloid -- calcitonin derived amyloidosis (localized to thyroid) and eosinophilic appearance
--tumor marker is calcitonin
What is the metastasis of medullary carcinoma?
To cervical lymph nodes to blood (liver, lungs and bone)
What paraneoplastic syndromes are seen in medullary carcinoma?
ACTH: cushings syndrome
VIP (vasoactive intestinal polypeptide)
--secretory diarrhea ---- hypokalemia: cardiac arrhythmias, nephrogenic diabetes insipidus (aquaporin channels in collecting duct insensitive to ADH)
Serotonin: leads to carcinoid syndrome
In MEN2A mutations you see hypercalcemia, what are the complications of this?
Acute pancreatitis: activation of enzymes
Nephrogenic Diabetes Insipidus: ADH insensitivity in aquaporin channels due to the hypokalcemia
Stimulate gastric acid release: duodenal ulcers
--Anaplastic is most aggressive thyroid cancer
Finally Cushing's Syndrome, what is the most common cause?
Exogenous Steroids: Iatrogenic (aka the doctor prescribes them to you), bilateral adrenal atrophy due to negative feedback suppressing ACTH
What is the most endogenous reason for Cushing's Syndrome?
Endogenous: Anterior Pituitary Adenoma
--aka Cushing's disease
causes Bilateral Adrenal Hyperplasia because the body is making ATCH from zona fasciulata
What are other reasons for Cushing's Syndrome?
Adrenal Cortical Adenoma producing cortisol
--suppresses ACTH: contralateral atrophy of the adrenal glands (b.c the one making cortisol is big)
What are the paraneoplastic syndromes associated with ectopic source of ACTH?
Bilateral Adrenal Hyperplasia
Small Cell lung Cancer (most common)
Renal Cell Carcinoma (2nd most common)
Medullary Carcinoma of the Thyroid
The etiology of Cushing's Syndrome can be either ACTH dependent or independent. What is the etiology of Cushing's in regards to ACTH dependent (aka pituitary or non pituitary ACTH secreting tumor)?
1. Anterior Pituitary Adenoma (Cushing's disease/MEN1 mutation): does not respond to negative feedback but will respond to feedback from high dose dexamethosone --- bilateral hyperplasia of adrenal glands
2. Ectopic ACTH: due to small cell carcinoma of lungs or renal cell carcinoma ---- bilateral hyperplasia of adrenal glands and skin hyperpigmentation (palmer creases)
What are the ACTH independent (aka an adrenal gland source) causes of Cushing's Disease?
1. Unilateral adrenal cortical adenoma: makes cortisol: contralateral atrophy of adrenal gland (b/c cortisol produced by the overproductive gland has negative feedback on AP)
2. Exogenous Steroids: bilateral atrophy of adrenal glands due to negative feedback on AP ---- decreased ACTH and no hyperpigmentation (giving steroids aka cortisol so therefore ACTH is inhibited and therefore the gland atrophies)
--most common cause is exogenous steroids
What is the presentation for Cushing's Syndrome?
Moon Facies and Buffalo Hump
Abdominal Striae -- purple because cortisol leads to defective collagen synthesis (blood vessels are prone to rupture)
DM2 (b/c cortisol is catabolic and gluconeogenic -- antagonizes insulin -- gluconeogenesis --- hyperglycemia)
Osteoporosis: b/c cortisol is catabolic
What is the HTN mechanism in Cushings?
HTN: b/c cortisol is a weak mineralocorticoid (aldosterone)
--results in reabsorption of Na and H20 --- leads to HTN and increased intravascular volume but no hypernatremia
--secretion of K in exchange --- hypokalemia -- increased pH --- metabolic alkalosis
--upregulation of alpha 1 receptors: allows permissive action of catecholamines --- vasoconstriction -- HTN
What is the recurrent infections mechanism in Recurrent infections in Cushing's patients?
B/C cortisol is immunosuppressant
--decreased margination of WBCs: decreased cell mediated immunity (more susceptible to opportunistic fungal infections)
--decreased production of cytokines: decreased humoral immunity
What are the complications for Cushing's Syndrome?
Hypokalemia: arrhythmia and nephrogenic DI
Recurrent Infections: cortisol suppression of immune system
Type 2 DM
Bitemporal Hemianopia: only in anterior pituitary adenoma
What is the most common cause of death in Cushing's Syndrome?
Atherosclerosis + HTN: MI and arrhythmias due to hypokalemia
What is the screening test for Cushing's Syndrome?
Elevated 24 hour urinary cortisol
---highest concentration of ACTH and cortisol in the morning and lowest at midnight
Exogenous is the easiest to diagnosis, why?
Because the patient brings in the script and tells you they have been taking this drug for a prolonged period of time
How do you rule in pseudo-cushings?
Giving patient low Dose dexamethasone 4mg (2mg a day for 2 days): and monitor cortisol levels
--if urinary cortisol drops over 2 days than this is pseudo-cushings, because the dex is suppressing ACTH which is causing the urinary cortisol to drop
Dexamethasone inhibits secretion of ACTH (similar to the action of cortisol through negative feedback)
How do you rule in anterior pituitary adenoma (ACTH dependent) ?
Give patient high dose dexamethasone 8mg: if cortisol levels decrease then this is anterior pituitary adenoma (cushings syndrome)
--so dex is inhibiting secretion of ACTH which is in turn suppressing levels of cortisol
Once you get a positive high dose dexamethasone test, what is the next step?
MRI of the brain and try and find this tumor
What do you do next if the MRI does not find an anterior pituitary adenoma?
Inferior Petrosal Sinus Test sampling ACTH levels
If after the high dose dexamethasone test, there is no suppression of the urinary cortisol levels, what now?
That just means just excluded cushings disease so you do plasma ACTH
-basically you are giving cortisol and there is not negative feedback on ACTH so cortisol is being produced.
If you conduct a plasma ACTH level and its high now what?
Chest xray because most common ectopic source is small cell carcinoma of the lung
--then CT (kidney) and CT of neck (medullary carcinoma of the thyroid)