Vasopressin (antidiuretic hormone) abnormalities in ME/CFS

[forestglip]

Since there are several studies that reported low vasopressin in ME/CFS, it seemed worth a thread.

Vasopressin (VP) is also known as arginine vasopressin (AVP) and antidiuretic hormone (ADH).

Here are the studies I know of that tested vasopressin in ME/CFS or similar phenotypes. [Edit: I added one study that is just a test of response to desmopressin, so this table is not purely studies that tested VP values.]

Year	Title	Authors	Cohort	Findings	Links
1992	Hypothalamic Dysfunction and Neutrotransmitter Abnormalities in the Postviral Fatigue Syndrome [Thesis]	A. M. O. Bakheit	[Reports same data as next study.]		Article | S4ME
1993	Abnormal arginine-vasopressin secretion and water metabolism in patients with postviral fatigue syndrome	A. M. O. Bakheit, P. O. Behan, W. S. Watson, J. J. Morton	9 postviral fatigue syndrome 8 age/sex-matched controls	Low plasma VP VP correlated with serum and urine osmolality only in controls, not cases.	Article | S4ME
1999	Desmopressin augments pituitary–adrenal responsivity to corticotropin-releasing hormone in subjects with chronic fatigue syndrome and in healthy volunteers	Lucinda V Scott, Sami Medbak, Timothy G Dinan	For desmopressin tests: 12 ME/CFS (Fukuda criteria) 11 healthy controls	Normal ACTH response to desmopressin Normal cortisol response to desmopressin	Article
2001	Abnormalities in response to vasopressin infusion in chronic fatigue syndrome	Margaret Altemus, Janet K Dale, David Michelson, Mark A Demitrack, Philip W Gold, Stephen E Straus	19 ME/CFS (Fukuda criteria) 19 age/sex-matched healthy controls	No significant difference in plasma VP, though values were at or close to detection limit in both groups. Reduced ACTH response to VP infusion. Faster cortisol response to VP infusion.	Article
2010	Hormonal alterations in adolescent chronic fatigue syndrome	Vegard Bruun Wyller, Johan Arild Evang, Kristin Godang, Kari K. Solhjell, Jens Bollerslev	67 patients with 3 consecutive months of disabling fatigue 55 healthy controls	Low plasma VP High serum osmolality	Article | S4ME
2017	Down-regulation of renin–aldosterone and antidiuretic hormone systems in patients with myalgic encephalomyelitis/chronic fatigue syndrome	Kunihisa Miwa	18 ME/CFS (ICC criteria) 15 age/sex-matched controls	Low plasma VP	Article | S4ME
2025	Low Vasopressin in Myalgic Encephalomyelitise/Chronic Fatigue Syndrome	Helena M Huhmar, Lauri S Soinne, Bo Christer Bertilson, Per Hamid Ghatan, Björn A Bragée, Olli J Polo	Retrospective study on 111 patients with ME/CFS (ICC criteria) Copeptin tested in additional 13 patients No control group	(Compared to reference ranges) High plasma osmolality in 57.3%. Low urine osmolality in 66.1%. Plasma VP below limit of detection in 77.5%. Copeptin (surrogate for VP) levels normal, but at the low end in most of 13 patients.	Article | S4ME

Edit: Added Scott et al. 1999 and Altemus et al. 2001

 

[Turtle]

Thanks for this thread @forestglip , really helpful.
Has been talked about since the nineties of the last century, why has nothing been done about it in the form of treatment?

 

[Jonathan Edwards]

Interesting to see that. Vasopressin has been discussed here from the start - of interest to MeSci in particular. There does not seem to be a consistent major shift in levels but maybe there is a fluctuating functional mismatch that sometimes contributes to clinical problems.

The opposite of vasopressin lack/diabetes insipidus is interesting - inappropriate vasopressin/ADH production occurs secondary to diseases like TB and cancer. It is particularly evident in people who are terminally ill with cancer and progresses rapidly over a few days.

Perhaps there is some situation that does the opposite - produces a functional vasopressin deficit.

 

[ME/CFS Science Blog]

Useful overview, thanks.

I'm not aware that polyuria (high urine output) is a common or notable problem in ME/CFS. Does anyone know any survey data on this? Perhaps it's easily overlooked given the many other symptoms and problems ME/CFS patients have.

In this paper, approximately 50% of patients reported urinary frequency as a symptom, but perhaps there is other and better data.
A definition‐based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome - De Becker - 2001 - Journal of Internal Medicine - Wiley Online Library

 

[Jonathan Edwards]

I'm not aware that polyuria (high urine output) is a common or notable problem in ME/CFS.

The interest of a shift in vasopressin might not be so much that it affects symptoms but that it is another subtle clue to something happening around the hypothalamus? (Maybe like the prolactin response to buspirone.)

 

[V.R.T.]

m not aware that polyuria (high urine output) is a common or notable problem in ME/CFS.

I'm surprised by that! It's something I deal with and have heard a fair few other people mention too.

 

[Yann04]

I'm surprised by that! It's something I deal with and have heard a fair few other people mention too.

I deal with it as well, but for me i’d say it’s downstream of polydipsia (excessive thirst), which is a major symptom.

 

[V.R.T.]

I deal with it as well, but for me i’d say it’s downstream of polydipsia (excessive thirst), which is a major symptom.

Thats quite probable. For me it started at the beginning of my prodromal phase. I think it is probably is correlated with thirst. But can't be certain.

 

[ME/CFS Science Blog]

The interest of a shift in vasopressin might not be so much that it affects symptoms but that it is another subtle clue to something happening around the hypothalamus? (Maybe like the prolactin response to buspirone.)

The reasoning was more that if vasopressin is reduced, it would likely result in more frequent complaints of polyuria in ME/CFS, and I was wondering if we have any good data on this.

I'm surprised by that! It's something I deal with and have heard a fair few other people mention too.

I know it's reported (think it's mentioned in the ICC also), but it never really stood out to me among the dozens of other symptoms and complaints mentioned under ME/CFS.

Looks like the DSQ-2 asks about "urinary urgency" and "waking up at night because you need to urinate" so there should be a lot of data on this.

https://www.evidencio.com/uploads/files/models/files/11272/07261a-DSQ-2.pdf

 

[ScoutB]

Maybe not ideal for our purposes, but looks like DecodeME had this in question 21:

Automatic body functions
21. In the last 6 months, have you had any of the symptoms below often, repeatedly, or constantly? Please mark any that apply. If none apply, leave all the boxes blank.
 Bladder problems, such as feeling that you suddenly need to pee or pee more often than usual.

If I'm reading the radar chart from here right it looks like it got a similar response rate to the paper you found: around 9000 responded 'yes' out of around 17,000 participants?

chart caption:

Most frequently reported symptoms are furthest from these circles’ centre. Twelve different groups of questions are indicated in separate colours; for each symptom group, the most and least frequently reported symptoms are listed and indicated as unfilled circles. With reference to the DecodeME questionnaire (www.decodeme.org.uk/app/uploads/2022/08/DecodeME-Questionnaire.pdf) the questions (Q) are, clockwise: [...] Autonomic (Q21-3, -6, -11, -10, -9, -4, -2, -1, -5, -7, -12, -8), [...]

(It always takes me 10 minutes and three missteps to read this chart so if there's a normal table somewhere let me know haha)

Personally, I would not be surprised if this is a relatively common issue but just not talked about much. I have this, and it's not usually my first instinct to bring up a more personal-ish problem that has a relatively small impact on my quality of life compared to all the other issues.

 

[Jonathan Edwards]

The reasoning was more that if vasopressin is reduced, it would likely result in more frequent complaints of polyuria in ME/CFS

Yes, it might. But it might present as a tendency to thirst if people with ME/CFS end up not drinking so much because of the effort involved. Most people drink more than they actually need to, so pee more than they need to anyway.

 

[AliceLily]

Increased urine output mainly during/around PEM and I can't recall it happening every time but it really is something that you notice after many repetitions over 30 years.

 

[Holinger]

Having severe thirst as part of my Me/cfs I would probably like to experiment with someone’s guidance but I would not know where to start. Some people have contacted me and said they were put on Desmopressin and felt shocking. Surely if that is a real symptom of Me/Cfs then my non scientist view understands that the hypothalamus must be involved.

 

[bobbler]

I’d always been thirsty and drinking more than peers noticeably in the years before I got ill. Taking a lite bottle to sports training , school etc where everyone else had a small 300ml one type thing. And weed more of course

But the what I now know as PEM thing is just a different level and generally was at night so I’d not be able to sleep due to being up and down but it being like the hope that the wee would then settle my body down but it not and it being like a 12hr pergutory where often at some points during it I’d also need to drink and quite often need salt (can tell from body symptoms and in younger years I’d get cramp which I then had to ease by salt).

It’s like spending the night in suffering with a specific leg pain (not restless legs tho I do get that too from iron but a different kings of legs like revving aching almost like they are hot and inflamed - I note it’s sort of like if you had an old desktop computer 20yrs ago and it had been left on for days/weeks and suddenly went into that kind over being noisy overdrive type mode

One of the absolute worst things to do that to me was flying - so it wrecked any chance of holidays. Nb it was always 36hrs after flight it hit, so on the day of travel when everyone else was tired by the night I often seemed ok or was on adrenaline but it was the next night it hit with me up all night (and then led to sleep reversal because after all that I’d then be exhausted and have to sleep for a few days solid).

Strangely I think when I had big nights out and drunk alcohol (which I had a lot of fluid with too - I drank very dilute drinks) then this would sometimes happen on the night itself, maybe I’d wake up after 2hrs needing the loo and that’d be it for the rest of night. Even tho such would normally also give me PEM (delayed symptoms) too - that one is a complex one to think through.

It’s a really distinctive thing even compared to borderline wondering if I had DI when I was younger. Then it going more haywire

 

[AliceLily]

Same here with the thirst especially in my severest years. Felt very dehydrated. The frequent urine thing was odd though because it wasn't tallying up with how much I was drinking all the time. You would think input and output would be the same all the time but the unusual sudden frequency always left an impression that it was different to normal intake output. Having difficulty explaining. Something else was at play.

 

[BrokenBeaktheBrave]

I deal with it as well, but for me i’d say it’s downstream of polydipsia (excessive thirst), which is a major symptom.

I experience polyuria during PEM but not excessive thirst. Like my body is just dumping any fluid it can. Sometimes I'm shocked how much fluid is in me given how little I drink.

 

[JellyBabyKid]

I'm not aware that polyuria (high urine output) is a common or notable problem in ME/CFS

I Googled and it is mentioned on MEpedia, health Rising, and at least 4 threads on Reddit - I'm sure I read it on MEA recently. I was quite surprised how many places it was mentioned as a common symptom.

Also found this:

Low Vasopressin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract Details

Poster presentation

Authors: Helena Huhmar, Lauri S. Soinne, MD, PhD, FAAN, Dr. Soinne, Per Sjögren, Bo Bertilson, Per Hamid Ghatan, Björn Bragée, Olli Polo (Bragée ME/CFS Center)

 

[MeSci]

Interesting to see that. Vasopressin has been discussed here from the start - of interest to MeSci in particular. There does not seem to be a consistent major shift in levels but maybe there is a fluctuating functional mismatch that sometimes contributes to clinical problems.

The opposite of vasopressin lack/diabetes insipidus is interesting - inappropriate vasopressin/ADH production occurs secondary to diseases like TB and cancer. It is particularly evident in people who are terminally ill with cancer and progresses rapidly over a few days.

Perhaps there is some situation that does the opposite - produces a functional vasopressin deficit.

Yes, I needed desmopressin for many years. But (from April 2024):

Post in thread 'Low Vasopressin In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2025, Huhmar/Bragée/Polo'

Apr 14, 2024

I produced too much urine from before 2000, and benefited greatly from desmopressin. Then, recently, a while after having had some dental work including the extraction of an infected tooth, I stopped needing it.

My blood pressure also normalised, when I had been taking the beta blocker Nebivolol since 2014, and an ACE inhibitor before that.

I am almost 71, and have had ME since about 1995. No medication needed now except to help me sleep!

https://www.s4me.info/threads/diarrhoea-caused-by-too-much-desmopressin.36981/#post-521077

• MeSci

• 

 

[Turtle]

Is there a way the body could be "protecting" something by lowering blood volume?

 

[sneyz]

I experience polyuria during PEM but not excessive thirst. Like my body is just dumping any fluid it can. Sometimes I'm shocked how much fluid is in me given how little I drink.

Second this! Though I get thirsty when I start recovering.