SIADH/hypogonad/aldosteronism Flashcards
Dorwart Chalmers Formula -
Serum Osmolality = (1.86(Na)) + (Glucose/18) + (Bun/2.8) + 9
Normal Serum Osmolality ranges from approximately
275mOsm/kg water - 295mOsm/kg water
Smithline and Gardner -
Serum osmolality = 2(Na) + glucose/18 + BUN/2.8
The Normal Response to Water Deprivation
The Normal Response to Drinking Water
Effects of ADH (3)
Increase H20 permeability in late distal tubule Collecting Duct
Increase activity of Na K 2CL transporter enhancing counter current multiplication.
Increase urea permeability in inner medullary collecting ducts
Regulation of ADH
Normal? ADH levels are almost entirely controlled by plasma osmolarity
Only a volume change of 10% or greater causes significant shifts in ADH levels
Shock (Severe Volume loss) triggers ADH secretion to maintain volume
Syndrome of inappropriate ADH
serum vs urine
serum in hypOnatremic
urine is hypertonic.
water is being retained in blood despite hydration.
beerporomania
general
beer doesnt have Na so it dilutes blood
low osmalality urine and blood,
don’t break the seal!
SIADH
general
ADH is secreted independently of osmoreceptors
Produces Hyperosmotic urine, Hypoosmotic Plasma, and Abnormally High levels of ADH
SIADH
etiology
ADH is secreted from areas that don’t respond to the feedback mechanism. Lung Tumors, Head Injuries (neuro is important exam) , Some Drugs can cause this.
(typical and atypical psychotic meds)
SIADH
Tx
- Treat the Hyponatremia first, the root cause second. Do NOT correct the sodium rapidly.- can cause locked in syndrome.
- First Line treatment - Fluid restriction. for 24-48 hours
- Second Line Treatment - Vaptons (Vasopressin receptor antagonists) if fluid restriction ineffective after 24 to 48 hours.
- Finally, treat the root cause. (cancer?)
male hypogonadism
HPG axis
anterior pituitary
leydig cells and sertoli cells in testes.
HPG
Sertoli cells
Sertoli cells are a type of sustentacular “nurse” cell found in human testes which contribute to the process of spermatogenesis
HPG
Leydig cells
produec testosterone in the presence of LH
HPG
primary hypogonadism
f the condition is “Primary” the problem you will see is with the gonads themselves. In other words, the gonads do not produce enough sex hormone to suppress the Pituitary’s secretion of FSH and LH. In this condition you will see an increased FSH and LH in an attempt to stimulate the gonads.
problem in the gonads (leydig not producing enough testosterone.) will see elevated FSH and LH with low testoserone
HPG
Secondary hypogonadism
If the condition is “Secondary” the problem lies either with the Hypothalamus not producing enough GnRH or failure of the Pituitary to respond to the secretion of LSH or FSH. This type of hypogonadism will commonly be observed as one of many Pituitary deficiencies.
hypogonadism
So what’s the primary thing we measure first?
- We measure the FSH and LH. These tests are routine and inexpensive.
- If the LH and FSH are high - Hypergonadotropic Hypogonadism (the condition is “Primary”)
- If the LH and FSH are low - Hypogonadotropic Hypogonadism (the condition is “Secondary”)
hypogonadism
what do we do with pt who comes in asking for testosterone saying hes depressed and has low energy and sexdrive
. First, we absolutely do check FSH, LH, TSH, DHEA, GH, SBHG, Cortisol, Estradiol and Testosterone (Free and total) levels. Testosterone levels, to be measured appropriately, must be done between 8:00am and 10:30 am.
checking additional hormones to differential between hypothalamus and pituitary
hypogonadism
A 35 year old male presents to his Primary Care Physician’s office. He has very low muscle density, a high pitched voice, and is very child like in his appearance and actions. Physical examination reveals that he is Tanner Stage 1.
Social Hx - Currently lives with his mother. Does not drink or Smoke.
Occupation - Unemployed.
What’s the difference between these two cases?
- We still do the same things for patient 1 that we did for patient 2 - check FSH, LH, TSH, DHEA, GH, SBHG, Cortisol, Estradiol and Testosterone (Free and total) levels. However, with this patient we are going to get an MRI.
hypogonadism
S/Sx if onset before puberty
Males who develop hypogonadism before the onset of puberty and are not treated do not develop body hair and a beard characteristic of other men in the family, temporal hair recession, full male musculature, or deep voice.
Men who develop hypogonadism after puberty may lose these characteristics if the hypogonadism is severe enough and/or ofsufficient duration, usually years.
Males who develop hypogonadism before the onset of puberty have small testes (< 20 mL) and a small phallus.
hypogonadism
S/Sx if onset after puberty
If hypogonadism develops after puberty, the testes usually decrease in size if the hypogonadism is primary, which preferentially damages the seminiferous tubules, but they usually do not decrease to a recognizabledegree if it is secondary. The phallus does not decrease in size.
hypogonadism
In adult men, several common but nonspecific symptoms begin within a few weeks of the onset of testosterone deficiency
decreased vigor and libido and depressed mood. Decreased muscle mass and body hair are less common but do not occur for a year or many years. Hot flashes occur only when the degree of hypogonadism is severe and especially when the rate of fall is rapid. Gynecomastia, tender or not, is more likely to occur in primary than secondary hypogonadism, as is infertility.
hypogonadism
Tx (3)
- Transdermal - Testim, Androgel, Fortesta
- Pellets - 2 to 6 Testosterone pellets placed in Subdermal fat
- Injections - Once every 1-2 weeks.
hypogonadism
Things that will lower T
- obesity - adipose tissue produces and secretes sexbinding hormone globulin (SBHG) which binds and takes up testosterone, reducing free testosetrone. losing weight will help, so will weight lifting!
- narcotic use - reducing methodone/suboxan will help increase T
- Sleep issues - will see increased cortisol. will see low T with sleep apnea bc disturbing circadian rhythm.
aldosterone system
purpose
to maintain BP
designed to keep you from going too low
hyperaldosteronism
juxtaglomerular cells
secrete renin when you have a decrease in pressure
hyperaldosteronism
(3) reasons for renin release
- drop in BP
2.decrease of sodium in blood- from DCT
3.sympathetic nervous system
hyperaldosteronism
Functions of zona Glomerulosa/Fasciculata/Reticularis
the deeper you go, the sweeter it gets
eating ____ will increase your cholesterol
saturated fats
NOT eating cholesterol, its about the building blocks
Aldosterone is regulated by the renin-angiotensin system
Primary hyperaldosteronism is also called
Also known as Conn Syndrome
hyperaldosteronism
Who should be screened?
- Sustained BP >150/100 mmHg on each of three measurements obtained on different days
- Hypertension (BP >140/90) resistant to 3 conventional antihypertensive drugs (including a diuretic)
- Controlled BP (< 140/90) on 4+ antihypertensive agents
Hypertension plus:
Spontaneous or diuretic-induced hypokalemia
Adrenal incidentaloma
Sleep apnea(high cortisol and aldosterone)
Family history of early onset hypertension or cerebrovascular accident at a young age (<40 years)
First-degree relatives of patients with primary aldosteronism (PA)
hyperaldosteronism
Significance
Inappropriately high aldosterone production, autonomous of major regulators of secretion (angiotensin II, potassium)
Causes hypertension, cardiovascular damage, sodium retention, suppression of plasma renin, increased potassium excretion (hypokalemia 9-37%)
Increasingly recognized, >5% and possibly >10% of hypertensive patients
Higher cardiovascular morbidity and mortality than age and sex matched patients with essential hypertension and same degree of BP elevation
Hyperaldosteronism
Etiology
Adrenal adenoma (most common)
Unilateral or bilateral adrenal hyperplasia
Adrenal carcinoma
Inherited conditions of familial hyperaldosteronism
Familial hyperaldosteronism type 1 (FH-I), aka glucocorticoid remediable aldosteronism
Recombination between 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2)
Expression of mutant form of CYP11B2 drives transcription under control of ACTH
There also exists FH-II and FH-III
-if at thispoint send them for genetic testing)
hyperaldosteronism
Plasma aldosterone/renin ratio (ARR)
Collect samples in the morning after patients out of bed for at least 2 hours, usually after they have been seated for 5-15 minutes
Unrestricted dietary salt intake, ideally potassium-replete
Mineralocorticoid receptor antagonists withdrawn for at least 4 weeks
Complete cessation of all interfering antihypertensives is usually not necessary
hyperaldosteronism
Tx
Mineralocorticoid receptor antagonists
Spironolactone (1st generation)
Starting dose 12.5-25 mg/d, once daily
Reduces SBP 25%, DBP 22%
Half of patients can manage with spironolactone monotherapy
Non-selective, has anti-androgen and progesterone agonist effects
Eplerenone (2nd generation)
Shorter half life and lower MR affinity, compared to spironolactone
Starting dose 25 mg BID
Newer agent, more expensive
Selective MR antagonist
Third generation MR antagonists and aldosterone synthase inhibitors are new to market/in development
hyperaldosteronism
Diagnosis
Start with CT to exclude large masses that may represent adrenocortical carcinoma, can also help interventional radiology before adrenal venous sampling (AVS)
hyperaldosteronism
pre and post-operative Management
Pre-operative
Hypertension and hypokalemia should be well controlled
Post-operative
Measure plasma aldosterone and renin activity shortly after surgery
Day 1 – discontinue potassium supplementation and spironolactone, and reduce antihypertensive therapy, if appropriate
Generous sodium diet to avoid hyperkalemia that can develop from hypoaldosteronism due to chronic contralateral adrenal glands suppression
BP normalizes or shows improvement in 1-6 months, but can continue to fall for up to 1 year
hyperaldosteronism
Medical Management of FH-I/GRA
genetic
Use glucocorticoid to partially suppress pituitary ACTH secretion
Long-acting glucocorticoids preferred
Starting dose in adults:
Dexamethasone 0.125-0.25 mg/d
Prednisone 2.5-5 mg/d
Glucocorticoid doses in children vary by age and body weight
Taken at bedtime to suppress the early morning ACTH surge
Use the lowest possible dose to normalize BP and/or serum potassium
Avoid overtreatment/iatrogenic Cushing syndrome
