My apologize for not getting back to you sooner. I had a busy few weeks and many sick days
Wow! 40 years! That's awful. My heart goes out to you. I find it difficult to imagine living with this condition for another year, let alone another 30. I'm happy to hear that you're getting at least some relief from the hydrocortisone.
I think one of the biggest problems with this condition is that it's under-reported in the literature. The avg physician can't even reference any reports of similar cases for comparison and diagnosis. Once they check off common possible causes of generalized edema such as hereditary angioedema, mastocytosis/mast cell activation disorder, allergies, kidney, heart, liver issues, etc, you're on your own more or less, as a patient.
Even in it's "classic" acute form, the SCLS is still a very poorly defined and under-researched condition, which is why they still refer to it as a syndrome rather than a disease. I've read just about every publicly available published paper and still don't see a clearly defined consensus as to what what SCLS actually is. They describe a constellation of symptoms and abnormal labs but offer no definitive diagnostic markers or underlying cause. I've read a few published reports about cancer patients who develop generalized edema and what sounds like a systemic inflammatory response after receiving chemotherapy agents (Interleukin 2 primarily). They refer to this syndrome as "secondary SCLS". Now, is this the same syndrome that's occurring in the idiopathic acute cases? Nobody knows. Also, there are scattered reports of idiopathic cyclical edema, primarily effecting women during their menstrual cycles. These women develop generalized edema but without the hypovolemia and low blood pressure that characterizes SCLS. Are these women suffering from a similar underlying pathology as SCLS patients? Again, nobody seems to know. It would be helpful if we had a registry of some kind where our physicians could submit reports and possibly share information in order to help others struggling with similar symptoms.
Most (90%) of the published papers on SCLS are simply case studies and reports. There's very little actual research aimed at studying underlying biological mechanisms responsible for the syndrome. The only person I am aware of who has done a fair amount of study in this area is Dr Druey but his research is probably limited by funding.
I'm obviously not a doctor, but I suspect that SCLS is spectrum disease involving varying degrees of abnormal capillary permeability resulting in fluid shifts. The key term here being fluid shifts. It's the loss of vascular fluid along with the edema that distinguishes SCLS from other generalized swelling conditions far as I can tell. That's why SCLS patients are full of edema yet paradoxically dehydrated. There's too much fluid outside the blood vessels and too little fluid inside. Blood vessels even in healthy folks are always permeable to a degree but in the case SCLS the vessels become abnormally permeable which leads to massive fluid loss and edema. On the one end of the spectrum, you've got the classic acute life-threatening cases and on the other end you've got more chronic and difficult to treat cases-- and still other folks who fall somewhere in the middle of the spectrum in terms of their symptoms.
I also think that cytokines and perhaps some other unknown chemical messengers are the main culprits behind the syndrome. If researchers could positively identify these culprits, they could probably get a better handle on managing the condition and possibly develop more definitive diagnostic tests, rather than relying on clinical signs and symptoms. Hemoconcentration, for example, isn't a maker for SCLS but rather a marker of decreased plasma volume (low blood volume). It just means that the blood is concentrated due to fluid loss into tissues. It's not specific for SCLS or any other condition. But that's the best diagnostic test for SCLS that we have at the moment. It would be nice if we had some more definitive and exact blood tests, which would likely lead to more definitive and exact treatments. As it stands now, the best they have to offer in terms of diagnosis are CBC reports, albumin levels and BP monitoring, in addition to clinical signs and symptoms. Patients like myself and perhaps you as well who don't match exactly with the currently proposed diagnostic criteria can easily fly under the radar, IMO. Half the time when I'd show up to ER during an attack, I'd already be urinating off some of the fluid and deflating, so my labs would look normal or near normal.
What they're calling SCLS seems to me like a deranged immune response of some kind, perhaps similar to the biochemical derangement that occur during sepsis and anaphylaxis. For whatever reason, folks who suffer from SCLS seem to develop an inappropriate immune response to normal everyday stimuli that results in abnormal amounts of fluid escaping from the small vessels. If it's severe, it can be lethal; and if it's chronic, it can be very debilitating and possibly lethal as well in the long term. I think this is why it's so difficult to pin down triggers. I'm not sure there are any. I suspect that folks who suffer from SCLS are experiencing an immune reaction to otherwise harmless stimuli, possibly similar to an autoimmune type reaction. The immune system mistakes ordinary stimuli for a life-threatening pathogen and overreacts....Perhaps this is why steroids and the T&T combo work for some patients. Those drugs inhibit the inflammatory response and prevent the vessels from dilating and becoming too permeable...... I have no medical background to back up my theory, though, so my opinion on this matter is basically worthless.
When I first got sick, one of the first symptoms I noticed, in addition to flu-like symptoms and the rapid weight gains and losses, was dehydration and inability to perspire. I'd always sweat quite profusely when active but that stopped after I started swelling. Despite the fluid everywhere else in my body, my mouth was bone dry and the skin on the back of my hands was wrinkled, dry and had the pale complexion of a corpse. Urine output diminished greatly as well and of course blood pressure would drop from my normal 120/80 to 90/50 or thereabouts. My CBC reports showed a total white blood cell count that ranged anywhere from 15k-25k with elevated neutrophils and monocytes as well. This was a consisted abnormality for 8 years but docs at the time never paid attention. They'd always look at the isolated reports and blame it on something transient like an infection, which never made sense to me because I wasn't suffering from any infection that I was aware of. It wasn't until I got fed up with years of misdiagnosis and misdirection that I stapled all the reports together myself and brought them to my GI doc who flipped through the thick stack of abnormal CBC reports lying on her table and immediately referred me to an immunologist. It was only then that I started getting some answers.
I've also had idiopathic pancreatitis and the whole slew of idiopathic inflammatory conditions I mentioned above. My testosterone was very low at one time as well, when I was very sick and swollen, but the levels have returned to low-normal as the swelling has diminished somewhat over the past year. I've had very low early-morning cortisol reading like yourself but they weren't abnormal during ACTH test. These endocrine abnormalities led to misdiagnosis of possible pituitary tumor, which was dismissed after a clean MRI. This was years ago when I was being sent to multiple specialists and getting misdiagnosed repeatedly.
At any rate, thanks for sharing, Annmarie! I believe that the more info we share about this condition the better for both patients and physicians alike.
BTW, here's a published case report of a 64 year old male SCLS patient who presented with multiple endocrine abnormalities like yours which reversed after he was treated with IVIG. His hormone levels returned to normal after his physicians got the SCLS under control. The authors speculate that the hormone abnormalities were a consequence rather than cause of his SCLS. See here : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313677/
Additionally, here's another very recently published paper (2019) on the chronic form of capillary leak syndrome. It's the only published paper and review of the literature I am aware of that focuses exclusively on the handful of reported cases of chronic SCLS . It's just an abstract, unfortunately. I wish I could get my hands on the full paper. See here: https://www.ncbi.nlm.nih.gov/pubmed/30431430?dopt=Abstract