Size - Large
Hydrophilic - circulates unbound
Serum half-life - minutes
Receptor location - cell surface
Mechanism of action - second messengers (cAMP)
Examples - LH, FSH, catecholamines, ACTH, TSH, Prolactin, GH, GHRH, CRH, glucagon, insulin, somatostatin
Size - Small
Hydrophobic - circulates bound to proteins
Serum half-life - hours
Receptor location - cytoplasm and nucleus
Mechanism of action - direct nuclear action
Examples - testosterone, E2, progesterone, T4, T3, cortisol, aldosterone, vitamin D, thyroxine
Which ones? What do you have to think about when looking at those lab values?
Steroids, shouldn't have any circulating freely
A negative feedback system?
High levels of a hormone DECREASE hormone synthesis and secretion, low levels STIMULATE
What is difference between primary, secondary and ectopic hyperfunction?
Primary - alteration in fxn of hormone-secreting gland
Secondary - alteration in pituitary or hypothalamic fxn
Ectopic - hormone secretion from tissue other than its usual source
What is difference between primary, secondary and resistance in terms of hypofunction?
Primary - same as previous
Secondary - same as previous
Resistance - inability of a target tissue to recognize a hormone
Know definition of terms: adenoma, neoplasm, hyperplasia so that you could explain results to a patient.
Adenoma - benign enlargement of a cluster of CELLS
Neoplasm - abnormal new growth of tissue; generally considered malignant
Hyperplasia - benign enlargement of entire GLAND
Where does it act?
Acts on renal tubules (increasing permeability at collecting ducts) to cause water reabsorption that results in urinary concentration
How and where and what regulates the release?
Release of ADH is coordinated with activation of the thirst center in the brain
Regulators of ADH secretion:
1. Osmoreceptors in the hypothalamus (detect osmolality of the blood)
2. Atrial and carotid baroreceptors (detects circulating volume)
What are symptoms and signs of DI and why?
1. Excess urine volume with LOW specific gravity (decreased osmolality)
2. Intense polydipsia (thirsty)
3. Hypernatremia, dehydration, hypotension
Why? - Water conservation in the distal collecting tubules cannot occur because ADH is not present or inactive
If a pt presented with all/any of the symptoms, what would be your differential diagnosis?
Glucocorticoid therapy (corticosteroid use)
What lab work would you order if you suspected DI?
Use the plasma and urine osmolality
Water deprivation test
**24-hour urine: measure volume, osmolality glucose, creatinine
-Urine volume <2 liter/24 hrs = rules out DI
What happens to plasma and urine osmolality with central DI, nephrogenic DI and psychogenic water drinkers?
1. Central DI - Plasma is increased, Urine osmolality is decreased
2. Nephrogenic DI - Plasma is increased, Urine osmolality is decreased
3. Psychogenic water drinkers - Plasma and urine osmolality is decreased
What happens to plasma and urine osmol for central DI, nephrogenic DI and psychogenic water drinkers during a water deprivation test?
1. Central DI - no change
2. Nephrogenic DI - No change
3. Psychogenic water drinkers - Increased
What is the expected plasma ADH level in central DI, nephrogenic DI and psychogenic water drinkers and why?
1. Central DI - Low (pituitary doesn't produce)
2. Nephrogenic DI - Normal to High (kidneys don't recognize)
3. Psychogenic water drinkers - Low
What test will be used to differentiate central DI from nephrogenic DI? And how is it administered?
Vasopressin Challenge Test
- Measure urine volume 12 hrs prior to giving desmopressin acetate (dDAVP) - should bring urine back to normal
- If pt has Central DI, you'll see decreased thirst and decreased urine output (increased urine osmolality)
- Imaging - MRI of pituitary and hypothalamus
Test for Nephrogenic DI (kidney resistant to ADH)
- Measure ADH (serum vasopressin) during modest fluid restriction
- Vasopressin level is usually elevated - negative feedback
What are the causes of central and nephrogenic DI? (What in the pt's hx should make you suspicious for DI?)
1. Central DI - Deficiency of ADH secretion from the posterior pituitary
-Surgery, trauma, infection, tumor
2. Nephrogenic DI - Renal insensitivity to ADH
-Medications, Chronic renal disease, pyelonephritis
3. Partial DI - Symptoms less intense.
-Suspect in pts with persistant urinary incontinence/bedwetting
How is central DI treated and why does that work?
*Desmopressin acetate - use lowest effective dose
Central DI is a deficiency of ADH secretion, Desmopressin acetate acts just like ADH
How is nephrogenic DI treated and why does that work?
1. Acutely: *Indomethiacin - NSAIDs increases ADH action at renal tubules (makes renal tubules more sensitive)
2. *Indomethiacin combined with HCTZ, desmopressin or amiloride
- Last 3 are diuretics that produce a hyperosmolar urine while decreasing urine output
- Decreases reabsorption of sodium and chloride in the tubular fluid - helps aid in sodium excretion (stops compensatory loss of water when sodium retained)
What are the causes of SIADH? (What in the pt's hx should make you suspicious for SIADH?)
Normal regulation of ADH release occurs from the central nervous system (osmoreceptors in hypothalamus) and the chest (baroreceptors)
- disorders of the CNS and chest may cause SIADH
1) Tumors secreting ectopic ADH - small cell or oat cell lung cancer *most common*
2) Medication/Drug induced - Antidepressants (increase ADH)
3) Lesions in the pathway of receptors
CNS disorders - stroke, trauma, brain tumor, etc
Pulmonary disease - TB, bacterial pneumonia
How are both mild and severe central SIADH treated and why does that work?
If hyponatremia occurs quickly, pt is symptomatic → treat quickly
If hyponatremia occurs over time and pt is asympomatic → correct slowly with water restriction over time
Euvolemic pts - water restriction
*Demeclocycline - for pts that can't adhere to water restriction (inhibits effect of ADH on distal renal tubules)