Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Definitions & Key takeaways

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by excessive release of antidiuretic hormone from the posterior pituitary gland or another source. The increase in fluid retention often results in dilutional hyponatremia in which the plasma sodium levels are lowered. SIADH may present with euvolemic hyponatremia with continued urinary sodium excretion. Urine osmolality is usually higher than serum osmolality. Very low serum sodium levels can lead to cerebral edema or seizures. Other symptoms of SIADH include fatigue, confusion, muscle weakness, nausea, vomiting, lack of appetite, and weight loss. Treatment usually involves fluid restriction, salt tablets, IV hypertonic saline, diuretics, and drugs like conivaptan, tolvaptan, or demeclocycline.

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What is SIADH? How does your body know when to retain fluids and when to get rid of them?
It’s not like you just think to yourself “I’ve had too much water, better get rid of some.” (If you do, and it works, call us).
Your body uses chemicals called hormones to send widespread messages, kind of like how the P.A. system at school tells everyone to ignore the smoke billowing out of the science wing.
The antidiuretic hormone, abbreviated as ADH, is the hormone that controls water retention in the body. It also constrict blood vessels, and incidentally the vasoconstrictor drug called vasopressin is just ADH.
Cool! But that’s not what we’re talking about right now.
Anyways, the more ADH floating around in your blood, the more fluid you retain. The less ADH in your blood, the more fluid you excrete.
The nephrons in the kidneys are the structures that physically control how much water is excreted from your body. Nephrons are mostly a series of tubes attached end-to-end that type fluids and wastes towards the bladder.
These tubes though also allow fluids and electrolytes to move through the tube walls and back into the blood if needed. ADH affects the last two-thirds of these tubes, called the distal convoluted tubule and the collecting ducts.
These tubes focus almost exclusively on reabsorbing water back into the blood. The wall of these tubes are unsurprisingly made up of cells, a common trait of living things, but these cells have proteins called aquaporins.
Aquaporins allow water to move quickly in and out of the cells. The more ADH floating around in the blood, the more aquaporins are available to...
ahem...facilitate water movement through the cell (yo, wata, come over here for a sec). So when ADH is low, most of the water flows through the the distal convoluted tubule and the collecting duct, giving us diluted urine.
When ADH is high, aquaporins grab much of the water passing through the these tubes and throws them back into the blood.
When I drink a glass of water and that water is absorbed into my blood, my plasma osmolality drops, which means I’m diluting my blood with the water.
That means there’s more fluid for all those blood cells to bounce around in (wooo parrttayy). The part of my brain called the hypothalamus sees this drop in plasma osmolality and tells the pituitary gland to slow down the release of ADH (that’s enough!).
Low ADH leads to lots of diluted urine (urine with low osmolality), which brings our plasma osmolality back to normal. What a nifty feedback loop.
Now suppose ADH continues to be released even though my plasma osmolality has dropped (stop it! STOP IT!
pituitary gland whistling). We’re going to continue retaining water, and as we drink more and more water, we might expect our plasma osmolality to continue dropping.
However this isn’t exactly the case. As more water is retained, it dilutes the other solutes floating around in our blood, like sodium.
The extra fluid also takes up more space in our blood vessels. This taking up more space issue triggers another mechanism in our body that causes the hormone aldosterone to stop being released.
Less aldosterone floating around in the blood causes the body to start dumping sodium from the blood into the urine. Concentration gradients cause water to follow sodium, so we end up with the excess water being excreted in the urine with the sodium, normalizing the fluid volume in the blood.
So now our body is removing sodium from blood that already has a lower concentration of sodium. Uh oh!
This means the plasma sodium osmolarity is dropping significantly. This whole fiasco we’ve just talked about is called syndrome of inappropriate antidiuretic hormone, often abbreviated as SIADH.
There are four patterns of ADH release in people with SIADH. Type A is completely erratic and is independent of the plasma osmolality.
ADH levels tend to be very high so the maximum amount of fluid is retained, causing urine osmolality to be very high. Type B is a constant release of a moderate amount of ADH.
Type C is the “baseline” plasma sodium concentration level is set lower than normal. It’s like you turned down the thermostat in your house to a new lower level.
This type is particularly unique because the plasma sodium concentration is stable, unlike other SIADH’s where it would continue to fall.
Type D is the least common type of SIADH where ADH secretion is completely normal, yet urine osmolality is still high. The symptoms a person with SIADH experiences is caused by the dilution and loss of sodium in the blood.
When your body has a lower sodium concentration than normal, you experience symptoms similar to dehydration or any other condition where sodium is low.
Symptoms like headaches, nausea, and vomiting are common initially, along with muscle cramps and tremors. As the sodium concentration continues to get lower in your blood, the neurons in your brain begin to swell leading to cerebral edema.
This causes symptoms like confusion, mood swings, and hallucinations. If left untreated it will lead to the common downwards trend in most illnesses of seizure, coma, death.
It’s not too hard to suspect someone might have SIADH. All we have to do is consider your symptoms in addition to your lab results.
Low blood sodium levels and low plasma osmolarity combined with high urine osmolality and high urine sodium is a giant red flag for SIADH.
So what causes SIADH? Pretty much anything that messes with the secretion of ADH.
Conditions like strokes, hemorrhages, or trauma to the brain can mess up the brain’s ability to release ADH. Similarly, some drugs that act on the brain like mood stabilizers or anti-epileptics can change the way ADH is released.
Surgery in general often causes an increase secretion of ADH, although we’re not entirely sure why. Obviously brain surgery, specifically to the pituitary gland also might cause extra ADH to be released.
ADH can also be produced ectopically by tumors, which means the tumors themselves produce ADH outside of the pituitary gland and release ADH into the bloodstream.
Small cell carcinoma in the lungs is the type of cancer most likely to release ADH this way. Infections in the lungs and brain are also linked to increase the risk of ADH secretion.
If some of your family members have had SIADH before, there’s also a possibility you may develop it. The best treatment for SIADH is to figure out what the underlying cause of the excessive ADH is, and treat that problem.
Otherwise we can manage SIADH by restricting your daily intake of fluid. You can also start a high-salt and high-protein diet to help replace the excess loss of sodium.
Drugs that inhibit ADH secretion can also be used in chronic SIADH situations. For people who have really severe acute hyponatremia symptoms, hypertonic IV fluids are usually administered.