SIADH/hypogonad/aldosteronism

Question 1

Dorwart Chalmers Formula -

Answer 1

Serum Osmolality = (1.86(Na)) + (Glucose/18) + (Bun/2.8) + 9

Question 2

Normal Serum Osmolality ranges from approximately

Answer 2

275mOsm/kg water - 295mOsm/kg water

Question 3

Smithline and Gardner -

Answer 3

Serum osmolality = 2(Na) + glucose/18 + BUN/2.8

Question 4

The Normal Response to Water Deprivation

Question 5

The Normal Response to Drinking Water

Question 6

Effects of ADH (3)

Answer 6

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

Question 7

Regulation of ADH

Answer 7

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

Question 8

Syndrome of inappropriate ADH

serum vs urine

Answer 8

serum in hypOnatremic

urine is hypertonic.

water is being retained in blood despite hydration.

Question 9

beerporomania

general

Answer 9

beer doesnt have Na so it dilutes blood

low osmalality urine and blood,

don’t break the seal!

Question 10

SIADH

general

Answer 10

ADH is secreted independently of osmoreceptors
Produces Hyperosmotic urine, Hypoosmotic Plasma, and Abnormally High levels of ADH

Question 11

SIADH

etiology

Answer 11

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)

Question 12

SIADH

Tx

Answer 12

1. Treat the Hyponatremia first, the root cause second. Do NOT correct the sodium rapidly.- can cause locked in syndrome.
2. First Line treatment - Fluid restriction. for 24-48 hours
3. Second Line Treatment - Vaptons (Vasopressin receptor antagonists) if fluid restriction ineffective after 24 to 48 hours.
4. Finally, treat the root cause. (cancer?)

Question 13

male hypogonadism

HPG axis

Answer 13

anterior pituitary
leydig cells and sertoli cells in testes.

Question 14

HPG

Sertoli cells

Answer 14

Sertoli cells are a type of sustentacular “nurse” cell found in human testes which contribute to the process of spermatogenesis

Question 15

HPG

Leydig cells

Answer 15

produec testosterone in the presence of LH

Question 16

HPG

primary hypogonadism

Answer 16

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

Question 17

HPG

Secondary hypogonadism

Answer 17

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.

Question 18

hypogonadism

So what’s the primary thing we measure first?

Answer 18

1. We measure the FSH and LH. These tests are routine and inexpensive.
2. If the LH and FSH are high - Hypergonadotropic Hypogonadism (the condition is “Primary”)
3. If the LH and FSH are low - Hypogonadotropic Hypogonadism (the condition is “Secondary”)

Question 19

hypogonadism

what do we do with pt who comes in asking for testosterone saying hes depressed and has low energy and sexdrive

Answer 19

. 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

Question 20

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?

Answer 20

1. 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.

Question 21

hypogonadism

S/Sx if onset before puberty

Answer 21

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.

Question 22

hypogonadism

S/Sx if onset after puberty

Answer 22

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.

Question 23

hypogonadism

In adult men, several common but nonspecific symptoms begin within a few weeks of the onset of testosterone deficiency

Answer 23

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.

Question 24

hypogonadism

Tx (3)

Answer 24

1. Transdermal - Testim, Androgel, Fortesta
2. Pellets - 2 to 6 Testosterone pellets placed in Subdermal fat
3. Injections - Once every 1-2 weeks.

Question 25

# hypogonadism Things that will lower T

Answer 25

1. 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! 2. narcotic use - reducing methodone/suboxan will help increase T 3. Sleep issues - will see increased cortisol. will see low T with sleep apnea bc disturbing circadian rhythm.

Question 26

# aldosterone system purpose

Answer 26

to maintain BP ## Footnote designed to keep you from going too low

Question 27

# hyperaldosteronism juxtaglomerular cells

Answer 27

secrete renin when you have a decrease in pressure

Question 28

Question 29

# hyperaldosteronism (3) reasons for renin release

Answer 29

1. drop in BP 2.decrease of sodium in blood- from DCT 3.sympathetic nervous system

Question 30

Answer 30

Question 31

Question 32

# hyperaldosteronism Functions of zona Glomerulosa/Fasciculata/Reticularis

Answer 32

## Footnote the deeper you go, the sweeter it gets

Question 33

eating ____ will increase your cholesterol

Answer 33

saturated fats ## Footnote NOT eating cholesterol, its about the building blocks

Question 34

Answer 34

Aldosterone is regulated by the renin-angiotensin system

Question 35

Primary hyperaldosteronism is also called

Answer 35

Also known as Conn Syndrome

Question 36

# hyperaldosteronism Who should be screened?

Answer 36

* 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)

Question 37

# hyperaldosteronism Significance

Answer 37

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

Question 38

# Hyperaldosteronism Etiology

Answer 38

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)

Question 39

# hyperaldosteronism Plasma aldosterone/renin ratio (ARR)

Answer 39

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

Question 40

# hyperaldosteronism Tx

Answer 40

**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

Question 41

# hyperaldosteronism Diagnosis

Answer 41

**Start with CT** to exclude large masses that may represent adrenocortical carcinoma, can also help interventional radiology before adrenal venous sampling (AVS)

Question 42

# hyperaldosteronism pre and post-operative Management

Answer 42

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

Question 43

# hyperaldosteronism Medical Management of FH-I/GRA | genetic

Answer 43

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