Exam 3: Pituitary Flashcards
Pituitary Adenomas:
- Most are clinically ______
- Most are monoclonal (meaning what?)
- Expanding tumor mass can destroy other parts of pituitary resulting in ____ symptoms
- Negative feedback is _____
- Make up 10-20% of all intracranial tumors
Pituitary Adenomas:
- most are clinically asymptomatic
- most are monoclonal: derived from single cell genetic mutation
- exanding tumor mass can destroy other parts of the pituitary resulting in “hypohormone” symptoms
- negative feedback only partially or not at all effective (can get partial negative feedback if HUGE dose of exogenous peripheral hormone given)
- make up 10-30% of all intracranial tumors
Clinical Manifestations of Expanding cranial mass:
Tumor can extand superior and lateral into the brain (______-) also can extend lateral into sphenoid bone or down into sphenoid sinus
Clinical Symptoms:
1.
2.
3.
Clinical manifestations of expanding cranial mass:
tumor can extend superior and laterally into brain (most common), can also extend lateral into sphenoid bone or down into sphenoid sinus
Clinical Symptoms
- Headaches (stretching of dura)
- Visual field defects (compression of optic chiasm)
- Cranial nerve palsies and temporal lobe epilepsy (lateral extension of mass)
Classification of Pituitary Adenomas:
No system is clinically validated
Morphorlogical features do not always correlate with clinical symptoms
Morphological features cannot differetiate between ____ and ____
_____ is the only conclusive evidence for malignancy (carcinoma)
Classification of Pituitary Adenomas:
No system is clinically validated
Morphological features do not always correlated with clinical symptoms
Morphological features cannot differentiate between benign and malignant
Metastasis is only conclusive evidence for carcinoma (malignancy)
Classification of Pituitary Adenomas
Explain invasiveness vs agressiveness and how to test for both
Explain Hardy vs Knosp system (generally)
Agressiveness: how fast is it growing, tested using histological mitotic markers like Ki67, as well as mitotic p53 levels
Invasiveness: where is it going, expansion of tumor into surrounding sinus
Hardy: no acess to MRI
Knosp: using MRI, looks at relationship of tumor to carotid artery
Hardy Classification of Pituitary Adenomas:
Explain Grade 0 - IV
HARDY: can’t determine aggressiveness
Grade 0: intact, normal
Grade 1: intact, bulging floor
Grade II, intact, enlarged fossa
Grade III, localized sellar destruction
Grad IV: diffuse bone destruction
Grade 0 and 1: noninvasive
Grade 2-4: invasive
Hardy Classification of Pituitary Tumors:
Supracellar extension is _____ critieria of invasiveness
What qualifies as invasive?
Hardy Classification:
Supracellar extension is NOT a criteria of invasiveness (aka going upwards does not mean invasive as it’s the only place it can go)
Only bone destruction qualifies as invasive
Knosp Classification of Pituitary Adenoma:
What does it look at?
Explain grades 0, 1, 2, 3, 4
Knosp: relationship of tumor to carotid artery to check invasiveness
Grade 0, 1: no invasion, doesn’t extend past median line
Grade 2: extends beyond median but not past lateral line (sometimes invasive)
Grade 3: extends beyond lateral line, always considered invasive
Grade 4: wraps around intracavernous carotid artery - always considered invasive
Explain the incidence and also what the following mean:
Prolactinoma
Somatotrope tumor
Corticotrope tumor
Thyrotrope or Gonadotrope tumor
Prolactinoma: most common, 40% of all pituitary tumors
- most patients are asymptomatic
- adenomas most discovered during autopsy
Somatotrope Tumor - excess GH (acromegaly)
Corticotrope Tumor - excess ACTH
- cushing disease
Thyrotrope or Gonadotrope tumor- VERY rare
- most have no clinical symptoms
Pituitary Adenoma Treatment:
-Treatment depends on tumor type
Explain what the following drugs do:
- bromocriptine
- octreotide acetate
Surgical resection
Pituitary Adenoma Treatment:
- Treatment depends on tumor type
- Bromocriptine: dopamine agonist, inhibits prolactin and reduces tumor size
- Ostreotide acetate: somatostatin anagog (inhibits GH)
Explain Cushing Disease vs Cushing Syndrome
Give some examples of cushing syndrome
Cushing Disease: excessive cortisol secretion due to ACTH secreting PITUITARY TUMOR
Cushing syndrome: symptoms of cushing disease due to causes other than a pituitary tumor
- Exogenous glucocorticoid therapy
- small lung cell carcinoma (ACTH)
- Adrenal tumor (of zona fasicularis secreting excess cortisol)
Cushing Diease: Symptoms:
What does it do to body fat?
What does it do to intestinal calcium absorption?
What does it do to blood pressure?
What does it due to insulin’s ability to clear glucose?
What does it cause on the stomach?
Cushing Disease Symptoms:
- Change in body fat distribution: moon face, buffalo hump, abdominal obesity, thin skin
- Inhibition of intestinal calcium absorption - osteoporosis
- Hypertension
- Glucose Intolerance - antagonism of insulin action
- Purple Striae: fragile skin stretches over increased abdominal fat, vessels hemmorhage into striae
Glucocorticoid Therapy:
What is it used for in medical emergencies?
How is it used for chronic conditions?
Glucocorticoid Therapy:
Medical Emergencies: high acute dose to treat septic shock, severe asthma, severe autoimmune disease flare…. usually no long term side effects when used acutely
Chronic: anti-inflammatory, immunosupressive, preterm infants to improve lung function
Lots of exogenous cortisol causes LOTS of negative feedback on HPA axis, causing an atrophied zona fasiculata
What kind of glucocorticoid therapy is the strongest?
Which one would you give for addison’s disease?
Glucocorticoid Therapy:
Dexamethasone is strongest, has 20x potency on GR receptors, only 0.5 x potency on MR receptors
Give fludrocortisone for addision’s disease, targets MR receptors more
Diabetis Insipidus:
What are the two main causes of diabetes insipidus?
Explain central vs nephrogenic
Diabetes Insipidus
Central: Decreased AVP release, hypothalamic or pituitary defect “central” due to AVP gene mutation, trauma, surgery, cancer, infectious disease
Nephrogenic: Decreased renal responsiveness to AVP, genetic X linked mutation in AVP receptor, happens with people on lithium drugs (for bipolar disorder)… AVP levels are usually normal in these patients
Diabetes Insipidus:
Genetic:
Mutation in AVP gene:
- usually within _____ sequence or ______ sequence
- Lack of normal peptide cleavage causes misfolding, ER stress, cell death
Diabetes Insipidus:
Genetic:
Mutation in AVP Gene:
Usually in signal peptide sequence of neurophysin sequence
Lack of normal peptide cleavage causes misfolding, ER stress, cell death
Diabetes Insipidus: Clinical Presentation:
Poly___
Poly___
Hyper______
(Serum osmdolality _____ than urine osmolality)
Diabetes Insipidus Clinical Presentation:
Polyuria - lack of water reabsorption from kidneys (AQ2 doesn’t relocate)
Polydipsia: high plasma osmolality triggers thirst response in hypothalamus
Hypernatremia: high plasma sodium content
Serum osmolality persistently higher than urine osmolatiry (this is not normal)
Diabetes Insipidus: Differential Diagnosis
Urine Glucose?
Plasma AVP?
Plasma Osmolality?
Diabetes Insipidus:
first have to rule out other types of diabetes, in diabetes insipidus there will be NO glucose in the urine
Plasma AVP: low avp is central DI, whereas normal to high AVP levels means nephrogenic DI
Plasma Osmolality: you can artificially alter osmolality to measure AVP response (inject with saline, in a central DI patient, the AVP level won’t change because it can’t be produced, where as in a nephrogenic DI patient, the AVP level will increase)
What is the primary clinical presentation of SIADH?
SIADH:
hyponatremia (low sodium plasma levels) in the absence of edema
these patients usually have salt cravings
SIADH: hyponatremia in absence of edema
Etiology:
Only 33% of SIADH cases are from _______
The rest are all other causes such as:
CNS disorders
lung infections
extrapituitary tumors secreting AVP
Aldosterone deficiency (explain this one)
SIADH: hyponatremia in absence of edema
Etiology:
only 33% are from central pituitary disorders (pituitary secreting too much AVP)
Rest are from:
CNS disorders
Lung infections
Extra-pituitary tumors secreting AVP
Aldosterone deficiency: low aldosterone levels will have hypovolemia, AVP is triggered by severe blood volume loss, and will be secreted despite decrease in plasma osmolality
Explain the following symptoms in Cushing pts:
Weakness
Easy bruising
Purple Striae
Cushing
Weakness: catabolic effects of glucocorticoids on skeletal muscle causes breakdown and weakness
Easy bruising: loss of subcutanous fat, skin is fragile and prone to bruising
Purple Striae: central obesity causes skin to stretch in abdominal region, veins are prone to hemorrhage
Explain elevated fasting blood sugar concentration in Cushing patients
Primary action of cortisol is to increase plasma glucose
Stimulate gluconeogenesis and mobolize energy stores
anti-insulin actions
How does a doctor evaluate suspected case of Cushings?
How do you distinguish between pituitary dependent, ectopic, primary adrenal or exogenous hypercortisolism?
First, you can do a high dexomethasone test
In a pituitary dependent case of Cushings’, the dexomethasone will supress ACTH somewhat. MRI to detect pituitary tumor
Ectopic: not responsive to dexamethosone because tumor not in pituitary
In order to see if it’s primary adrenal or iatrogenic… measure ACTH levels:
Primary adrenal: ACTH will be low, this is because it is caused by excess adrenal secretion of cortisol NOT in response to ACTH
Iatrogenic: exogenous hypoercorticolism (most common cause due to treatment with glucocorticoids), zona fasiculata will atrophy: no CRH or ACTH production
