Low Vasopressin In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2025, Huhmar/Bragée/Polo

[N_Dina]

I stumbled upon this paper because I'm experiencing a severe crash and had some private blood work done. As usual (and frustratingly) all seemed normal except Copeptin (2,36) and serum osmolality (330). High osmolality suggests dehydration but than Copeptin should be way higher as a compensation mechanism. ChatGTP claims this is highly suggestive (95-100% specificity and sensitivity) of central diabetes inspidus. A friend endocrinologist agreed but had some reservations about the accuracy of the tests as the blood was send by mail.

I'm now getting a retest including urine osmolality and then probably a copeptin stimulation test at the hospital.

After a 20 year struggle I hope to have finally found the silver bullet.!It does make sense. As long as I remember I've been drinking 5-10 liter water per day, it all started with orthostatic symptoms, never had the myalgia aspect always pee in 0,5-1l increments and since this crash I've been experiencing extremely dry skin and a huge increase in orthostatic symptoms.

These researchers might be on to something, at least in a subset of patients!

Hi @Fancymyblood!
Was diabetes insipidus confirmed in your case?

 

[SNT Gatchaman]

Low Vasopressin In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Spoiler: Authors

Helena M Huhmar; Lauri S Soinne; Bo Christer Bertilson; Per Hamid Ghatan; Björn A Bragée; Olli J Polo

OBJECTIVE
The complex clinical picture of ME/CFS includes orthostatic intolerance with symptoms and signs suggesting abnormal water homeostasis and hypovolemia. Since many ME/CFS patients report polyuria-polydipsia, we conducted an observational study based on series of plasma and urine osmolality (P-Osm and U-Osm) as well as plasma levels of vasopressin (P-VP) or copeptin in consecutive patients diagnosed with ME/CFS according to the International Consensus Criteria.

METHODS
P-VP as well as P-Osm and U-Osm were measured in 111 patients after 10 hour overnight fasting and fluid deprivation. Additional 13 patients were assessed for copeptin, when P-VP measurements were no longer available. The clinical routine also included brain MRI and blood chemistry.

RESULTS
P-Osm was abnormally high (>292 mOsm/kg) in 71/124 (57.3%) and U-Osm below the reference interval (< 750 mOsm/kg) in 82/124 (66.1%) patients. P-VP was below the level of detection (<1.6 pg/mL) in 91/111 (82.0%) patients. A normal P-VP level compared with their P-Osm was found in 11/111 (9.9%) patients. Copeptin levels were all within the given reference range, albeit in the lower end in most patients. No indication of relevant pathology in either hypothalamus or hypophysis was present.

CONCLUSIONS
Our findings suggest that chronic down-regulation of VP mimicking central diabetes insipidus is an important measurable part of the disease mechanism that potentially contributes to criterial symptoms of ME/CFS.

HIGHLIGHTS
• orthostatic intolerance and polyuria-polydipsia typify disabling forms of ME/CFS

• in a consecutive series of ME-CFS patients, majority had very low vasopressin levels, relatively high plasma osmolality and low urine osmolality, in absence of overt hypothalamic or hypophyseal pathology

• chronic down-regulation of vasopressin mimicking central diabetes insipidus may contribute to the core symptoms of ME/CFS

Web | DOI | PDF | Endocrine Practice | Open Access

 

[SNT Gatchaman]

Our results reveal a high prevalence of low P-VP, low urine osmolality and high plasma osmolality after overnight water restriction. These findings are in line with polydipsia polyuria (PP), which is a common complaint when specifically asked about during the clinical interview. PP often appears at the beginning of illness, and the manifestations may be constant and monophasic, transient, or intermittent, and it seems to be often overlooked in the patientphysician communication. The combination of high P-Osm with low P-VP excludes both psychogenic polydipsia and renal resistance to VP. Instead, it indicates a central VP deficiency resembling central diabetes insipidus (cDI)

This all rings many bells for me. Here are some comments from the saline infusion thread discussion.

In PEM my fluid intake goes up a lot, and in the catastrophic crashes I had before I was diagnosed, it was bizarre. I needed 10 to 12 litres of water a day, and my skin still looked dehydrated. Last time round I even asked our stage manager to get me rehydration salts to add to it, because I was worried about washing out too many nutrients. I don't know whether it made any difference, and the only thing that reduced the need for fluids was when I began to recover.

Although I had no idea what was going on then, I had a warning moderate PEM crash six months before I crashed out to severe, but the second crash was astonishingly dramatic. One of its features was a sudden massive diuresis and I simply could not keep up with the losses. I would drink water but I would pee it out within 15-20 minutes - faster than I would expect one could absorb, but maybe it was the previous glass. This was much more than I'd ever experienced with bog standard past viral illnesses. Eventually this stabilised but it seemed obvious to me that I was now intravascularly depleted in status quo. That improved at around 6 months, either just with time +/- helped along by supplements. Renal function in terms of eGFR has remained normal.

Dehydration and polyuria has been a common PEM symptom for me. One year I had nocturia as well, and got up once or twice every night to pee. But that only occured for one year nearly on the mark. Since it was a new symptom I had it checked out and nothing was found. Since I had the history of polyuria with PEM I have assumed there was a connection

@MelbME I'm probably jumping the gun, but I'd be interested on your thoughts on this paper. I would need to read up about copeptin which I'd never heard about before now. They felt the copeptin assay that replaced the vasopressin (radionuclide) assay for the last few of the cohort suffered from too few numbers so no inferences could be drawn. But the results on that assay seemed to be pretty normal in that subgroup. Could that be a clue? Any chance in your saline study that both VP and copeptin be measured to see if there's a mismatch?

I was naively wondering if there was a potential biochemical explanation where the vasopressin is not being produced (or not properly functional) while copeptin still is secreted at normal levels. Some limitation on arginine for VP production eg if there were wider issues with nitrogen metabolism?? Ie I'm wondering if it's possible for the propeptide to be inadequately produced, while the copeptin end is complete and able to be cleaved, and then measured as normal.

 

[forestglip]

They say high electrolyte content due to low vasopressin might lead to over-excitability of neurons.

Furthermore, hyperosmolality may even contribute to sensitization of neurons, an essential feature in ME/CFS pathophysiology, since influx of cations into shrinking neurons might shift the resting potential closer to the threshold of action potential. The resulting excessive irritability of different types of neurons could explain a wide range of neurological symptoms such as spontaneous pain and oversensitivity to light and sound.

 

[hotblack]

It may be wildly off but the experiences of drinking/peeing/etc that many of us talk about is one of the things that made me interested in the idea of involvement of chemoreceptors in the kidneys