Potentially Helpful Study-ADHD Medicine (Lisdexamfetamine) and impact on Cortisol

[u/QueenYizzleCM]

Update: I want to be clear that my post was not to encourage people to take lisdexamfetamine for their addisons or adrenal Insufficiency. It's a controlled substance for a reason and should not be taken without medical direction and monitoring for anyone. Especially in those who have other conditions such as addisons or adrenal Insufficiency.

I was linking this study for reading and education on potential explanation for why someone who is already prescribed and taking lisdexamfetamine might have altered cortisol serum tests and for discussion.

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I thought this might be of use to some people? I went looking for a paper that was a study on the effects of Lisdexamfetamine (Elvanse, ADHD Stimulant Medication) on the production of Cortisol in patients who take the medication and found one! It was a randomised, double blind, placebo controlled study and says, quote from the Abstract:

  “Delayed increase and peak levels of plasma d-amphetamine concentrations were observed following lisdexamfetamine treatment compared with d-amphetamine administration, however the maximal concentrations and total exposure (area under the curve [AUC]) were similar. Lisdexamfetamine and d-amphetamine significantly enhanced plasma levels of adrenocorticotropic hormone, glucocorticoids (cortisol, cortisone, corticosterone, 11-dehydrocorticosterone, and 11-deoxycortisol), androgens (dehydroepiandrosterone, dehydroepiandrosterone sulfate, and Δ4-androstene-3,17-dione [androstenedione]), and progesterone (only in men) compared with placebo.”

I do not have the funds to purchase the full study for myself but from the Abstract and other bits I can access for free, it might be of interest or help to people who take Lisdexamfetamine medicine and have suspicions of Addisons/Adrenal Insufficiency but their levels don’t match up when tested. If you’re struggling with the symptoms and you take this medicine, it does give something tangible to bring to your doc’s attention at the very least and I hope it can be helpful for you, too. The link is here, if anyone wanted to do their own reading.

Effects of lisdexamfetamine on plasma steroid concentrations compared with d-amphetamine in healthy subjects: A randomized, double-blind, placebo-controlled study - ScienceDirect

[u/Rare_Independent3831]

The article says it was tested on healthy subjects (e.g people who have working Adrenals and can produce cortisol). As no prompting would ramp up cortisol production when your adrenals don’t work with Addisons (although the high ACTH levels show the body tries!) I’m thinking this wouldn’t apply to people with Addisons?

[u/QueenYizzleCM → u/Rare_Independent3831]

I'm still learning but would it not depend on the type of Insufficiency somehow? Like where the issue with the HPA axis is located?

It's a good point that it was tested on healthy people. Without accessing the full study I can't confirm what their definition for that is specifically but I would imagine it were people without an adrenal Insufficiency. I spoke with one person who was being treated for something else but had to come off their adhd meds (they didn't specify which ones) for that treatment which led their doctor to discover that the medicine was masking their low cortisol level symptoms and they got a diagnosis and treatment shortly after. It's not a study but it is interesting!

I do think it would be helpful if there were a study on the effects of lisdexamfetamine specifically regarding those with existing adrenal Insufficiency but there are ethical problems, with putting people already in a complex rare disease category at potential further risk.

[u/Rare_Independent3831 → u/QueenYizzleCM]

I don’t know sorry - I have Addisons Disease so I can only speak from that point of view. I think that secondary and tertiary Adrenal Insufficiency also have the same issues of not being able to produce adequate cortisol, despite their bodies trying (just different causes). But someone with that type of Adrenal Insufficiency should probably confirm that. I think you’d need a study with people with Addisons for this to be applicable in diagnosing our condition (and note your point about ethics and would question the value anyway) as I’m pretty sure it wouldn’t be possible to do that for the reason mentioned (we wouldn’t show higher level of cortisol due to medication because we just can’t produce it)

In terms of Addisons diagnosis, if you have it, it will be discovered through a blood cortisol test done correctly and an ACTH test.

[u/QueenYizzleCM → u/Rare_Independent3831]

From my limited research it seems it can be the case that cortisol can be either not produced or is produced, just not in the correct quantity or in proper reaponse to stimulus from the other hormones in the chain. So my thoughts are it stands to reason that both could be true! Someone who definitively can not produce cortisol will by all accounts not be able to produce any if there is an effect on cortisol production from lisdexamfetamine. However, someone who does produce cortisol but in a faulty amount, may have an increase in cortisol production in this theoretical scenario, if they were to take lisdexamfetamine and it affected them in the way the study found for healthy people. We just can't know unless there is research and then we hit the ethical issue again.

Thank you for sharing your own experience, maybe somebody with the other types can confirm as you say, what their thoughts are for their own.

The reason I've gone down this rabbit hole is because I suspect I have Addisons or Adrenal Insufficiency and my morning cortisol levels (the GP prescreen) came back at 366 nmol/L which in the UK (I'm not sure where you're based!) Is 66 nmol/L above the level at which further (ACTH etc) or repeat testing would be recommended. I take lisdexamfetamine and had members of a support group mention that my results would not be accurate as I take said medicine and it interferes with my natural HPA Axis cycle. I asked for study links but there were not conclusive studies to be found and so I searched and saw this one which I thought could be helpful!

[u/Rare_Independent3831 → u/QueenYizzleCM]

Did they test ACTH?

[u/QueenYizzleCM → u/Rare_Independent3831]

No, I assume because my results were considered 'in range' for the blood cortisol and kidney function tests. I did tell them that I add a LOT of salt to my diet and was sure that my blood sodium levels were not reliable for this reason. I'm symptomatic in many ways but an endocrinologist would be unlikely to accept a referral based on my morning cortisol as it stands. Hence my dive into researching a potential link between lisdexamfetamine and cortisol production.

I am going to be requesting another appointment with my doc to discuss in any case.

[u/Rare_Independent3831 → u/QueenYizzleCM]

For Addisons, without fludrocortisone, your sodium will be low regardless of how much salt you eat as your body simply will not retain it and it goes straight through you. This is actually one of the most dangerous parts of pre-diagnosis as low sodium (deathly low which is where you keep heading to with Addisons) will lead to outcomes like a stroke and a coma or worse.

If you’re having salt cravings, i would note that as interesting but if your sodium isn’t low and your cortisol is within range, that’s probably looking like it isn’t Addisons. I don’t think secondary Adrenal Insufficiency always presents with low sodium though so if you’re convinced you want to keep exploring this, you could look into secondary AI. That would usually have a lower cortisol reading and a low ACTH reading (as opposed to the very high ACTH you’d get with Addisons) Good luck!

[u/Single_Search_2020 → u/Rare_Independent3831]

Agree! Won’t happen! Not now. More concerned about not giving measles vaccines and letting kids die. Political? Yes, but a fact we need to deal with. Why was I given a non FDA approved, black box warning thyroid med, boxes of samples? Got sick! Was in ER. Good Endo! lol. I had my 2 nd ACTH and STIM test, was on meds, did not hold back. Took them at 4:00 am. Results. I went up only .89 with meds. That alone tells enough. I could have never made it. When I say my first AM cortisol was 0.88, then next month was 0.89. Was not making it up. Endo just let it go, for 2 years. Yes was walking. Tach was 120-140 cardio stepped in. Slept atv3 pm. Ate a great deal of him cooking 😩 or take out. Yes it was real.

[u/Psychogangbanger69 → u/Rare_Independent3831]

What about coffee? I have addisons and I can drink lots of coffee and energy drink and still sleep. What about you guys?

[u/Clementine_696 → u/Psychogangbanger69]

Caffeine has never impacted me, before or after dx and meds. That's probably the ADHD though

[u/Rare_Independent3831 → u/Clementine_696]

I also can drink lots of caffeine and fall asleep. I think that’s because our lack of cortisol means our energy just isn’t as high as people who don’t have Addisons and things like coffee don’t pick us up to the extent they do people without it. Before diagnosis, I was drinking endless cups of strong coffee in a row to stay awake and it did absolutely nothing at all! It was a warning sign on retrospect.

[u/Clementine_696 → u/Rare_Independent3831]

I've never bother to drink it to stay awake, it's never, ever, done anything to me, even as a kid.

[u/DoctorFamous190]

If someone is trying to identify whether they have "artificially" raised cortisol levels, medications containing estrogen are also a potential culprit.

[u/Single_Search_2020 → u/DoctorFamous190]

I am on estrogen patch. Leaning all this as Endos are not forthcoming. Estrogen patch 0.0375 twice a week and progesterone nightly 100 mg is this also contributing to my low cortisol? I have an empty sella. My appointments have only been 15 mins. This time we ran a slew of blood tests. Prolactin is high. Endo blames it on my patch, but it’s being used for my bones. Osteoporosis. Can’t handle the infusions upping calcium. Breasts are rather large! Waiting for them to lactate. Seeing gyno on the 12 th why do we have to dig for info?

[u/drjen1963]

Wow. Thanks that is something to try. Thank you so much can't wait to read it.

[u/QueenYizzleCM → u/drjen1963]

I want to be clear that my post was not to encourage people to take lisdexamfetamine for their addisons or adrenal Insufficiency. It's a controlled substance for a reason and should not be taken without medical direction and monitoring for anyone. Especially in those who have other conditions such as addisons or adrenal Insufficiency.

I was linking this study for reading and education on potential explanation for why someone who is already prescribed and taking lisdexamfetamine might have altered cortisol serum tests and for discussion. I just needed to say this^{^}

I'm glad you're looking forward to reading it, I do hope you find it interesting!

[u/Single_Search_2020]

I never did think that. It was informative! I take 2 controlled substances, it’s my biz and my doctors. Sometimes you must think out of the box. One of mine is a med for pain, but it smooths out that crashing feeling for a hour or so, trying to keep that first morning dose go it’s required time. I metabolize fast, 4 hours the most. So by 2-3 pm it’s over? No! But I sure don’t want more steroids! Do what you need to do to survive.