Posterior Pituitary Flashcards
Describe the pathway of ADH/Oxytocin release
1) Hypothalamic neurons synthesize oxytocin or ADH
2) Transported down axons of hypothalamic-hypophyseal tract to posterior pituitary
3) Oxytocin/ADH are stored in axon terminals in posterior pituitary
4) Hypothalamic neurons firing causing releasing of oxytocin/ADH to blood
What is the function of oxytocin?
Releases milk and uterus muscle contractions during labor, dilation of cervix
What are the actions of vasopressin?
Adjust water permeability of collecting duct in kidneys
Electrolyte handling: mild increase in reabsorption of Na and secretion of K
Vascular resistance: increase vascular resistance —> increase BP
Association with cortisol: cortisol has inhibitory effect on CRH and ADH, adrenal insufficiency leads to a persistent rise in ADH
Factor VIII and vWF release from vascular endothelium
What are the major stimuli for ADH secretion?
Hyper osmolality and effective circulating volume depletion
How is osmolality and volume sensed to release ADH?
Osmoreceptors in the hypothalamus sense sodium concentration or glucose in uncontrolled diabetes
Baroreceptors also sense volume in aortic arch and carotid sinus
Cause release of ADH —> increased water reabsorption —> increased blood volume and pressure
What factors can increase circulating ADH?
Nausea (500 fold rise)
Surgery (elevated ADH for several days after operation due to stress response)
What is the action of ADH on the kidneys?
Adds aquaporins to the collecting duct leading to dilute blood (concentrated urine)
What happens to ADH when you drink a glass of water?
Water is absorbed into blood, plasma osmolality drops—> hypothalamus sees drop and signals pituitary gland to slow release of ADH —> low ADH leads to diluted urine —> plasma osmolality is back to normal
When extracellular fluid sodium concentration rises, plasma osmolality will ___
Increase
When plasma osmolality increases, all of the following occur except:
Thirst mechanism in hypothalamus is activated, anterior pituitary decreases release of ADH, ADH causes increased water absorption in collecting ducts, ADH causes vasoconstriction to increase BP
Anterior pituitary decreases release of ADH
Based on what you know about ADH, high levels of ADH will cause
Large Volume of dilute urine, small volume of concentrated urine
Small volume of concentrated urine
Based on what you know about ADH, high levels of ADH will cause
Large volume of dilute urine, small volume of concentrated urine
Small volume of concentrated urine (high urine osmolality)
Condition defined by hyponatremia and hypo-osmolality resulting from continued secretion or action of ADH despite normal or increased plasma volume
Syndrome of Inappropriate Antidiuretic Hormone secretion
What is the most common cause of euvolemic hyponatremia in hospitalized patients?
Syndrome of Inappropriate Antidiuretic Hormone secretion
SIADH consists of __________
Hyponatremia, inappropriately elevated urine osmolality, and decreased serum osmolality in a euvolemic patient, urine sodium >30-40 mmol/L (normal is 20 on random sample)
What setting does SIADH need to be diagnosed in?
Setting of otherwise normal cardiac, renal, adrenal, hepatic, and thyroid function in absence of diuretic therapy
What is the etiology of SIADH?
Inappropriate hypersecretion from hypothalamus/pituitary or ectopic production
4 categories that stimulate ADH release, potentiate ADH action, or have uncertain mechanism:
-nervous system disorders: acute psychosis, hemorrhage, inflammatory and demyelinating diseases, mass lesions, stroke, trauma
-Neoplasms: extra thoracic, mediastinal, pulmonary
-Pulmonary diseases: hypercapnia can stimulate ADH release
Drug-induced: can stimulate release of ADH or potentiate
What is the general clinical presentation of SIADH/early symptoms?
Based on severity of hyponatremia and rate of progression (slower=less symptoms)
Anorexia, nausea, and malaise are early symptoms and may be seen when serum Na is less than 125
Further decrease in Na: headache, muscle cramps, irritability, drowsiness, confusion, weakness, seizures, and coma as osmotic fluid shift results in cerebral edema and increased ICP
What are the 3 key mild-moderate symptoms of SIADH?
Headache, disorientation/confusion, impaired memory
What are the 5 advanced symptoms of SIADH?
Confusion, disorientation, somnolence, hallucinations, acute psychosis
What are the 3 key symptoms of grave SIADH?
Seizures, severe somnolence, coma
In SIADH, the patient is normally ____ and _____ presenting as
Euvolemic, normotensive; peripheral and pulmonary edema, dry mucous membranes, reduced skin turgor, and orthostatic hypotension are usually absent
Edema in a hyponatremia patient warrants consideration of CHF, cirrhosis, or CKD
What is diagnostic criteria for SIADH?
Hyponatremia with corresponding serum hypo osmolality
Continued renal excretion of Na
Urine osmolality is increased
Absence of clinical evidence of volume depletion- normal skin turgor, blood pressure
Absence of other causes of hyponatremia ie adrenal insufficiency, hypothyroidism, cardiac failure, pituitary insufficiency, renal disease with salt wastage, hepatic disease, or drugs that impair renal water excretion
Correction of hyponatremia by fluid restriction
What labs should be ordered to diagnose SIADH and rule out other causes?
Serum Na+, potassium, chloride, and bicarbonate
Plasma osmolality
Serum creatinine
Blood urea nitrogen
Blood glucose
Urine osmolality
Serum cortisol
Thyroid-stimulating hormone
What diagnostic tests should be ordered to help in diagnosis of SIADH and rule out other causes?
Serum Na+, potassium, chloride, bicarbonate
Plasma osmolality
Serum creatinine
Blood urea nitrogen
Blood glucose
Urine osmolality
Serum cortisol
Thyroid-stimulating hormone
How is SIADH treated?
Depends on degree of hyponatremia, symptoms, and whether acute (<48 hours) or chronic
Consult with nephrologist for difficult cases
What can correcting hyponatremia too rapidly in SIADH cause?
Central pontine myelin ply’s is with permanent neurologic deficits
Neurological disease caused by severe damage of the myelin sheath of nerve cells in the brain stem, specifically the pons, and characterized by acute paralysis, dysphagia, and dysarthria, and other neurological symptoms.
Central pontine myelinolysis
What is treatment of SIADH in an emergency setting?
Aggressive management if seizures, stupor, coma, respiratory arrest:
Raise serum Na+ levels (by .5-1 mEq/h and not more than 10-12 mEq in first 24 hours)
3% hypertonic saline = fluid of choice
Neurological symptoms and serum Na+ monitoring
Furosemide increases excretion of free water and has been used along with hypertonic saline
How is SIADH treated in an acute setting?
3% hypertonic saline
Loop diuretics with saline (furosemide)
Vasopressin-2 receptor antagonists (aquaretics, such as conivaptan)
Water restriction
What is the MOA of vasopressin receptor antagonists?
Inhibition of AVP V2 receptor reduces number of aquaporins-2 water channels in the renal collecting duct and decreases water permeability of collecting duct
What are the aquaretics (agents that competitively block ADH action and increase water excretion)?
Vaptans: conivaptan (Vaprisol), IV
Tolvaptan (Samsca), oral
What is the MOA of conivaptan?
Parenteral dual V1a and V2-receptor antagonist
What is the mechanism of action of tolvaptan?
Selective oral V2 receptor antagonist approved for use in hospitalized patients for hypervolemic and euvolemic hyponatremia
What should you keep in mind when using vaptans?
Have profound effect on serum Na
Should be avoided in hypovolemic hyponatremia
Benefit of prompt serum Na correction
Risk of excessively rapid rate of correction of serum Na
More effective than fluid restriction alone
How is SIADH treated in chronic setting?
Fluid restriction and V2 receptor antagonists, referral to nephrologist for chronic vaptan use
Condition characterized by increase in thirst and passage of large quantities of urine of low specific gravity, caused by a deficiency of vasopressin or resistance to vasopressin
Diabetes insipidus
What are the causes of primary central diabetes insipidus
Something is wrong with ADH release: no lesion of pituitary or hypothalamus
Autoimmunity against hypothalamic AVP-secreting cells
Genetic: familial diabetes insipidus -dominant genetic trait
What is the cause of secondary central diabetes insipidus?
Damage to hypothalamus or pituitary stalk by tumor, hypophysitis, infarction, hemorrhage, anoxic encephalopathy, surgical or accidental trauma, infection, or granulomas
What are causes of nephrogenic diabetes insipidus?
Defect in kidney tubules that interferes with water reabsorption
Normal secretion of vasopressin and polyuria is unresponsive to it
Congenital nephrogenic diabetes insipidus is present from birth due to defective expression of renal vasopressin V2 receptors or vasopressin-sensitive water channels (X-linked trait)
Acquired: usually less severe, pyelonephritis, renal amyloidosis, myeloma, Sjogren syndrome
What is the cause of vasopressinase-induced diabetes insipidus?
Last trimester of pregnancy and puerperium, circulating enzyme destroys native vasopressin but synthetic desmopressin unaffected
What is the clinical presentation of diabetes insipidus?
Intense thirst
Craving for ice water
Polyuria: large urine volumes
High volume of ingested fluid: 2 L to 20 L
Partial diabetes insipidus = less intense symptoms, enuresis
May present with hypernatremia and dehydration if no free access to water or altered thirst mechanism
Aggravated by administration of high-dose corticosteroids, which increases renal free water clearance
How is diabetes insipidus diagnosed?
Clinical judgement, no single diagnostic test
24-hour urine collection for volume and creatinine (volume <2 L/24 hr rules out DI)
Serum glucose, urea nitrogen, calcium, potassium, sodium, and uric acid levels
Restrict water intake and pt with central DI = dilute urine
Supervised vasopressin challenge test: desmopressin acetate IN with measurement of urine volume before and after admin —> if central DI, reduction in thirst and polyuria
In nonfamilial central DI, what should be done?
MRI of pituitary and hypothalamus to look for mass lesions
If nephrogenic DI is a diagnostic consideration, what diagnostic test should be done?
Measurement of serum vasopressin during mild fluid restriction
Central diabetes insipidus myst be distinguished from polyuria caused by _______
Psychogenic polydipsia, diabetes mellitus, Cushing syndrome, corticosteroid treatment, lithium, hypercalcemia, hypokalemia, and nocturnal polyuria of Parkinson’s disease
Central diabetes insipidus must be distinguished from polyuria caused by _____
Psychogenic polydipsia, diabetes mellitus, Cushing syndrome, or corticosteroid treatment, lithium, hypercalcemia, hypokalemia, and nocturnal polyuria of Parkinson’s disease
How is DI treated?
Mild: no treatment other than adequate fluid intake
Desmopressin acetate for central and vasopressinase-induced DI
What is the MOA of desmopressin acetate?
Synthetic analogue of vasopressin with prompt onset and longer, more specific Antidiuretic action; increases water permeability in renal tubular cells, which decreases urine volume and increases urine osmolality
What can desmopressin acetate cause?
Agitation, emotional changes, and depression with increased risk of suicide, hyponatremia
A 26 year old female presents with signs and symptoms of diabetes insipidus. After a 24 hour fluid restriction, her urine osmolality normalizes. Which form of DI does this likely represent?
Psychogenic
A 51 year old male presents with signs and symptoms of diabetes insipidus. After a 24 hour fluid restriction period, his urine osmolality remains low. After administration of desmopressin, urine osmolality is still low. Which form of DI does this likely represent?
Nephrogenic
A 33 year old female presents with signs and symptoms of diabetes insipidus. After a 24 hour fluid restriction periods, her urine osmolality remains low. After administration of desmopressin, urine osmolality normalizes. Which form of DI does this likely represent?
Central
Which of the following stimulates the release of ADH? increased plasma volume, decreased plasma osmolarity, hyponatremia, nausea
Nausea
Which of the following lab findings would you expect to find with diabetes insipidus?
Increased plasma osmolarity, increased urine osmolarity, hyponatremia
Increased plasma osmolarity
In a patient with central DI, what happens during water deprivation when ADH is given?
Treatment with ADH with concentrate urine
How common are pituitary adenomas?
One in 6 autopsies
What are symptoms and signs of pituitary adenomas?
Related to expanding intracranial mass (headaches, vision changes) and/or manifestations of excess or deficiency of one or more pituitary hormones
Which type of pituitary adenoma is more likely to present with complaints related to hormone excess?
Micro adenomas
Which type of pituitary adenoma can impinge on the optic chiasm or other structures and may or may not affect hormones?
Macro adenomas
What is the etiology of pituitary adenomas?
Benign tumor of epithelial cell origin
Any cells type undergoes hyperplasia
What are clinical syndromes of lactotrope adenomas?
Hypogonadism, galactorrhea
What are clinical syndromes of gonadotropin adenoma cell origin?
Silent or hypogonadism
What is the clinical syndrome associated with somatotrope adenoma cell origin?
Acromegaly/gigantism
What is the clinical syndrome associated with corticotrope adenoma cell origin?
Cushing’s disease
What is the clinical syndrome associated with mammosomatotrope adenoma cell origin?
Hypogonadism, galactorrhea, acromegaly (PRL, GH product)
What is the clinical syndrome associated with thyrotrope adenoma cell origin?
Thyrotoxicosis
What are clinical features of MEN 1?
Hyperparathyroidism
Pancreatic Neuro endocrine tumors
Foregut carcinoids
Adrenal adenomas
Skin lesions
Pituitary adenomas
What are the clinical features of MEN 4?
Hyperparathyroidism
Pituitary adenomas
Other tumors
What are the clinical features of carney complex?
Pituitary hyperplasia and adenomas
Atrial myxomas
Schwannomas
Adrenal hyperplasia
Lentigines
What is the classic visual field defect in a patient with an expanding pituitary mass?
Bitemporal hemianopia
How is pituitary adenoma diagnosed?
MRI of the brain
Opthalmologic exam
Laboratory studies: presenting clinical features of functional pituitary adenomas should guide studies
What is treatment of pituitary adenoma?
Goals: normalize excess pituitary secretion, amelioration of symptoms and signs, shrinkage or ablation of large tumor masses
Transphenoidal surgery is desired surgical approach
Radiation
Medication, depending on tumor type
What are complications of transphenoidal surgery?
(Mortality rate 1%), transient DI, hypopituitarism, permanent DI, nasal septal perforation, visual disturbances
Less common: carotid artery injury, loss of vision, hypothalamic damage, meningitis
Why would radiation be used for pituitary adenoma treatment?
Primary therapy or adjunct to surgery, usually for post surgical management
What medication is the treatment of choice for prolactinomas?
Dopamine agonists
What is the treatment with medication for acromegaly?
Somatostatin analogues, GH receptor antagonists
What are the treatments for TSH secreting tumors?
Somatostatin analogues and dopamine agonists
What are the medication treatments for ACTH secreting tumors?
Generally not responsive to medications and require surgery and/or irradiation
