From the desk of Lewis S. Blevins, Jr. M.D. PWN cofounder – Idiopathic isolated central adrenal insufficiency remains a mystery. I’ve seen several patients with this condition in my career. I first learned about it when I saw my first patient at Hopkins.
Most patients have come to me already taking steroids. Some were on doses that were too high causing Cushingoid features. I have been able to successfully wean some of them from steroid replacement. Others seem to be unable to recover function and remain on long-term treatment even though they have not been on high doses. These tend to be patients who also have postural orthostatic hypotension . Most are also a little overweight. I often wonder if they have a partial POMC deficiency or some other issue with processing of POMC. POMC mutations are a recognized cause of obesity so it always comes to mind. Testing hasn’t been widely available and has mostly been research-related. Perhaps this syndrome is a form of central adrenal insufficiency and autonomic dysfunction with weight gain related to hypothalamic dysfunction.
When evaluating these patients it’s essential to exclude recent or repeated administration of supraphysiologic doses of steroids that can suppress CRH and ACTH release as a potential cause of secondary insufficiency. Also, it’s important to review the medication history as narcotics can also suppress the hypothalamic-pituitary-adrenal axis. Most patients have otherwise normal pituitary functions.
The most severe forms of adrenal crisis occur in patients with primary adrenal failure who have both glucocorticoid and mineralocorticoid deficiency states. It’s the mineralocorticoid deficiency that leads to the high risk of crisis. I’ve seen adrenal crisis in several patients with isolated central adrenal insufficiency and in a few with hypopituitarism. I’m wondering if it’s more common in those with orthostatic hypotension. It would make sense that, if these patients have diminished autonomic outflow, that they might have hyporeninemic hypoaldosteronism leading to mineralocorticoid deficiency thus, increasing their risk for adrenal crisis.
Treatment involves traditional approaches to glucocorticoid replacement. I refer patients to neurology, centers specializing in the autonomic nervous system, or to cardiology for evaluation and management of the postural orthostatic hypotension. Many are treated with compression stockings, alpha-agonists which cause vasoconstriction, and even fludrocortisone which increases salt and water retention by the kidney.
Notes:
Idiopathic isolated central adrenal insufficiency (IIAD) is a rare condition where the pituitary gland fails to produce enough ACTH , leading to secondary adrenal insufficiency, which is characterized by low cortisol levels. Isolated means that only ACTH production is affected, while other pituitary hormones are typically normal.
Postural orthostatic hypotension is when your blood pressure drops when you go from lying down to sitting up, or from sitting to standing.
POMC deficiency is a rare genetic disorder that affects the production of hormones that regulate appetite, metabolism, and pigmentation.
© 2025, J D Faccinetti. All rights reserved.
My 39 year old son is astral insufficient and pan- hypopituitary due to 3 craniopharyngiomas. He is morbidly obese by no fault of his own. I admit I don’t understand a lot of medic terms and just thought I would ask if any of this research would pertain to him? He is followed regularly by his endocrinologist who is wonderful
Might this also be associated with my most recent additional diagnosis:
Dx: Vaovagal syncope
A (2006) study found that there is a significant finding of this with people with Acromegaly, such that data showed:
Acro patients: * lower LFc/HFc
& Lfo/Hfo (p0.001
Hfo* higher (p0.001)
My “idiopathic” panhypopituitarism began after being bitten by a tick inside the city limits of Portland, Oregon. Subsequent to the tick bite, I developed Lyme disease. It took four years to be clinically diagnosed with borreliosis, so I am in the late stage or tertiary form, of Lyme. The test for Lyme disease is unreliable, but please do not rule this out when considering causation for idiopathic panhypopituitarism.
Thank you Dr. Blevins! This is a great start. I finally have something on line to refer my doctors to!
By the way, Did you mean for the acronym to be IICAI, rather than IIAD?
I had a prolactinom, but when a dexametason text was done the result came as 19 and 23. (Cortisol prior to the test was198) But the endo said it was nothing because I was already gaining some weight and being swallow.
Long story but I got the HC and Florinef and 2 years later I won up to 30 Kg. I’ve been under steroids since 2014 but the pituitary issues since ever. I’m 52.
Two years ago Insel Spital Bern offer me a HRT treatment but because it learning to balance my unbalanced hormones was enough, I declined.
Would you recommend it?
Thanks again, Dr. Blevins. There are a few more things I’d like to say about ICAI, for the benefit of your readers:
1) I was very underweight for most of my life, until I started steroid treatment. Patients may present as skinny before diagnosis and treatment.
2) According to Dr. Sinn at Stanford’s Autonomic Disorders Clinic, I have Orthostatic Hypotension, not Postural Orthostatic Tachycardia Syndrome (POTS). They might feel similar to the patient, but a Tilt Table test will differentiate.
3) ICAI co-morbid with OH makes increasing altitude/elevation dangerous for us. I nearly died on two separate flights before figuring this out. The first time the plane was nearly forced to land in the wrong country because my blood pressure was 60/40, and I was med-evaced from the plane to the ER where they worked on me for 12 hours before my blood pressure came up to something safe enough to release me. The second time, I was med-evaced from the plane to the ER where they had to reboot my heart with adenosine, and I was hospitalized for 2 days. The combination of ICAI and OH is much worse than either of them alone. They get into a feedback loop that snowballs. ICAI patients who have anything like OH or POTS symptoms, should only fly with a stress dose before take off and a rescue injection of solu-cortef in their carry-on bag, just in case. The higher the plane flies, the greater the risk, even in a pressurized cabin. Dr Sinn told me that OH patients are known to have problems flying and he explained why, but that triggers a life threatening domino effect if you have ICAI too.
4) I’ve only ever talked to 2 other ICAI patients online. All three of us had Cardiac Arrhythmia issues. I’ve had an ablation and I still have SVT, VT, and PACs for short intervals here and there. No one is asking us these questions in AI studies or in clinics. We patients figured this associated incidence because we spoke to each other, briefly. How much more would we discover if we were all invited to the same online conference and allowed to ask each-other, “Does this happen to you?”
In conclusion, ICAI patients need to be studied as a separate cohort, not lumped into studies with CAI and Addison’s. We have very different presentations (which is why in some countries we are only diagnosed post-mortem) and different problems.
There needs to be a forum where doctors, first responders, and especially endocrinologists, are told that “Zebras” need to be recognized as the doctor’s/responder’s responsibility to learn to spot and treat. Most were educated that “If you hear hoof beats, look for a horse, not a zebra”. In other words, focus on the garden variety conditions that are more prevalent in the population, don’t get side tracked testing for rare diseases ,”zebras”. That attitude literally kills those of us who are zebras. Additionally, it traumatizes us in several ways:
1) We are gaslit (gaslighted?) by our doctors, even chairs of endocrinology departments at famous hospitals. We are often labeled as hypochondriacs, or mentally ill, by a doctors who:
a) are too lazy to study us and rare diseases, and dismiss all medical mysteries as psychological
b) have fragile egos threatened by a patient who presents with a puzzle they can’t solve, haven’t seen before, don’t know how to help, etc.
c) would have to admit that an earlier diagnosis was wrong, if they made it, or if a colleague they dare not offend made it.
d) think anyone would be legally liable/exposed to litigation.
e) are retaliatory when a patient is vindicated or when a patient documents / reports abuse by the doctor
f) hold implicit biases or outright bigotries against the patient’s gender or ethnicity etc
In my place of origin, I was one of only 4 patients diagnosed with ICAI in 40 years, and I had to go 10 thousand miles to UCSF to get the diagnosis put in writing, even after I’d started treatment for it. This is not because ICAI is THAT rare, it is because doctors refuse to diagnose it, or admit that it exists and presents differently than CAI.
2) Insurance companies deny “medical need” when we make claims, citing a doctor’s cynical or erroneous diagnosis of “anxiety”. This results in bankruptcy, homelessness, and the traumas that go with that, as well as remaining too sick to hold a job. Mental illness becomes a self fulfilling prophecy, as we end up with PTSD, created by doctors and med insurance companies.
3) We are treated by first responders and ER staff like despised junkies. When we try to tell them that their protocol for treating our adrenal crises is out of date, and tell them that NADF has published the new protocol, or hand that to them, they become extremely adversarial, passive aggressive, and deliberately, dangerously cruel. They not only won’t give us the bolus we need, they rob us of our own rescue injection kits, so that we won’t be able to access them, ourselves. The most dangerous places I’ve ever been were ERs when sadistic doctors or nurses were on shift, and in ambulances where first responders didn’t have authorization to give me a bolus or let me take my own. I’ve been told by some that they would knowingly choose to let me die rather than risk litigation or being fired. I’d have been safer begging a random untrained pedestrian for help on a sidewalk, because they’d have been covered by the “good Samaritan” law and would follow my written directions for the bolus injection (IM).
4) Our primary care physicians in the US are instructed to defer almost everything to specialists, and our specialists are told to defer most things to other specialists and to the primary care physician. Rare disease patients become hot potatoes. The buck has to stop somewhere.
5) Occam’s razor does not apply to us! Hickam’s dictum does: “A patient may have as many diseases as s/he damn well pleases.” In the case of ICAI and the steroid treatment for that, it seems to come with a cascade of other conditions–but not expected ones, because they don’t involve other pituitary hormones, like they would for CAI. That would be enough to short circuit most doctor’s brains, but our clinical presentation of ICAI is also different than that of CAI, and they sometimes dismiss the possibility of our AI at all, based on our ability to menstruate, our lack of giraffe like pigmentation, and G-d forbid, our metyrapone results. We suffer from blood sugar problems, like insulin resistance, and that creates false negatives in metyrapone tests (which are dangerous and outdated anyway). That didn’t stop the chair of the endocrinology department of a prestigious hospital from ordering it though, even though the study warning of false negatives had already been published. I have been told the most ignorant and nonsensical rationalizations by doctors who never studied ICAI, and can’t find anything recently published to read on the subject, because no one (other than Dr. Blevins) is writing about his/her experience treating it. Until he wrote this very article (above), you couldn’t google ICAI or IICAI.
6) Sympathetic allies in the medical community promise to help us meet with hospital medical directors, ER directors, ambulance company directors, paramedic training course classes, etc, in order to disseminate the new protocols (published by NADF and conveniently made into posters) for adrenal crises and to explain differences in presentation and treatment of different types of AI, but then they suddenly ghost us. There are administrative , insurance driven , and other financial conflicts of interest that silence even the well intended allies, and make them too scared to follow through or to even communicate. They seem to have been gagged by the institutions they work for.
In conclusion, the deck is very much stacked against the survival, let alone the well being, of ICAI patients. The other two survivors I was in contact with online had more than just our disease in common, all three of us have science back grounds, and all three of us stood up against multiple institutions and many doctors. That’s why we’re still alive when most of our cohort aren’t, and why we need to write testimonies where they can be found by people who want to improve the field.
ps I wrote that with proper spacing and paragraphs, but the formatting is lost when I submit it.