Transcript

PLEASE NOTE: While an effort has been made to correct errors in this AI-generated transcript, some mistakes may have been missed. This transcript should be taken merely as supporting material to the podcast discussion and neither is as an authoritative last word on the subject matter.

MIC CAVAZZINI: Welcome to Pomegranate Case Report. I’m Mic Cavazzini for the Royal Australasian College of Physicians. In a second I will hand you over to Associate Professor Stephen Bacchi, who has recently returned from his academic sojourn to Boston. And he is straight back into the Trainee education with today’s fascinating case report. It was published as a letter in the Australian and New Zealand Journal of Psychiatry in April 2010 and you’ll find a link to it in the show notes if you want to follow along. But even the title gives away too many spoilers so I suggest you sit back and put your diagnostic reasoning skills to the test.

Remember, these Case Report podcasts have been developed by volunteers to help Trainees work through their long-case presentations. They’re supposed to be a helpful and easily digested resourced, not the authoritative last word on the clinical subject matter. So please don’t sue if you hear something that doesn’t sound quite right. Okay, over to Dr Bacchi and today’s all-Adelaide cast.

STEPHEN BACCHI:            Hi, I'm Stephen. I'm a neurologist at the Lyle McEwen Hospital. And today with us, we have Peak Mann Mah who is an endocrinologist at the Lyell McEwen Hospital. She is interested in diabetes and clinical trials. And Dr Malcolm Borg, who is an endocrine advanced trainee who is practicing at the Royal Adelaide Hospital alongside undertaking his PhD. Thank you for joining us.

PEAK MANN MAH: Hi, I'm Peak Mann Mah. Thank you for having me and it's my first time doing this so looking forward to learning.

MALCOLM BORG: Hi. Malcolm Borg. Thanks for having me along, Steve.

STEPHEN BACCHI:            Brilliant. So today, we have a 46-year-old male who has presented to the emergency department after barricading himself inside his neighbour's home. He had disorganised speech and was responding to internal stimuli with described persecutory and paranoid delusions.

And this is his first episode of psychosis. Now we have two endocrinologists with us, which may provide a clue as to where the case is going. But in the first instance, Malcolm, may for our medical student listeners, could you please provide a general overview of the types of medical workup that such a patient may benefit from? And how would it differ if they were older?

MALCOLM BORG:            Yeah, sure, Stephen. I guess we all have to be well-versed in the physician training world about an approach to psychosis. Often we're either called to provide medical safety and approval to go to the psychiatric ward for an ED, or it might be a presentation of a problem while on the ward or that we're dealing with from a medical sense. I I think most often the problem is either psychiatric or drug-induced.

The medical problems that cause it are of big concern because they may be the thing that threatens the person's life and the psychosis may be refractory if not treated. I guess the approach then needs to consider a number of differentials. And I think a lot of them are neurological in a sense, sort of brain tumours. And we've mentioned the elderly, we're more often considering a cognitive impairment, a dementia or a delirium, but stroke encephalitis, these are other neurological conditions we consider.

Then there's sort of a wide array of systemic pathologies that often need to be of the more severe kind to cause psychosis, which is a hint. Usually, I think more severe problems will be clinically apparent. These might be infections such as a neurosyphilis. These might be a severe hypo or hyperthyroidism or Cushing syndrome. Other sort of endocrine or metabolic might be hepatic encephalopathy, Wernicke's encephalopathy, and even paraneuroplastic issues such as from testicular cancer. So I think then in trying to pick these up, you still have your history because even if that patient can't provide it, there's the collateral history that might provide some insights. And your examination, I think, needs to include a neurological examination and really then honing in if you find any findings to consider that in your investigation. And I think a systemic examination that would look at things like temperature, cardiac, lungs, looking for as well. Sometimes maybe the changes in reflexes might be part of an endocrine or metabolic pathology such as thyroid disease.

That lends to the investigations which I think neuroimaging would be performed in most cases if there's a medical concern. Certainly, at the very least a CT brain but some of these pathologies may warrant an MRI if that is normal. And I think some common things to do that are appropriate are your cell counts looking for signs of infection. kidney, liver function, thyroid function, B12 and folate still can contribute to this problem. And I think syphilis is one not to forget, but I think that's just a starting place and if you have more concerns, you may do more tests such as HIV, a Cushing’s screen, ammonia levels, LPs, et cetera.

STEPHEN BACCHI:            Brilliant, thanks Malcolm. So, on further history for this patient, he described cold intolerance and occasional dizziness. On physical examination, he had slowed movement, cold peripheries, sparse axillary and pubic hair, and soft testicles of a normal adult size. So Dr Mah, what are these physical examination findings suggesting to you? And which investigations would you be thinking about next?

PEAK MANN MAH:          I guess for this particular case it could have been from the investigations that's been found and then you go back to look more into this examination. But from this slow movement, cold intolerance, for me I'll be thinking is there underlying hypothyroidism. The sparse axillary and pubic hair possibly related to hypogonadism. And normal adult size testicles would mean that they've gone through puberty and if there were any developing hypopituitarism or hypogonadism, it would be in adult life rather than during puberty.

And an investigation as what Malcolm has discussed, things like thyroid function and if you were to consider doing the testosterone level you would also do sex hormone binding globulin, LHFSH and if there were indications that this is a secondary cause where that's central then you do the rest of the pituitary panel which includes cortisol, ACTH, prolactin.

STEPHEN BACCHI:            Perfect. So now we've got some test results. So, the TSH was low, the T4 was also low. A short synacthen test was performed with no change in cortisol. The ACTH was undetectable. Testosterone was undetectable. LH was low. FSH was also low. IGF1 was also low. And prolactin was normal while on risperidone. So, Malcolm, these results sound like panhypopituitarism to me. What are the causes of panhypopituitarism and how would you proceed from here?

MALCOLM BORG:            All good questions. I guess, you know, we've got an investigative panel that's really localizing to the sort of secondary issues from the pituitary or hypothalamus. And from a neuroimaging perspective, which is undoubtedly indicated when we're suspecting that area, we need an MRI to look at the sella and look at the pituitary. And that's going to rule out a lot of things or identify a lot of causes.

I think, large tumours of the pituitary space could certainly do this. If there was sort of an infiltrative pathology, rare but an important consideration. Things like GPA, the old Wegener’s, or haemochromatosis are differentials on the rarest side. Sometimes we find hypophysitis and that's probably now become one of the most common pathologies, whether we find it on imaging or not. It's something we often retrospectively think is likely and that's in the setting of someone receiving cancer immunotherapy. I think that along with a pituitary tumour and past surgery are now really some of the most common causes of panhypopituitarism.

I think the others of note would probably be a pituitary apoplexy where there's a bleed in the pituitary space and that can happen after giving birth. So that's a situation we might see a young person without a known pituitary problem present shortly after birth, presenting with a severe headache often, a thunderclap type and with manifestations of hypopituitarism.

And there are genetic causes, which as an adult physician, usually would be diagnosed before adulthood. I've spoken about an MRI, and I think really you go from there, it’s the MRI and the history that kind of identify the suspected sort of causes. And I think we'll get to the findings in this particular case. I guess we have all these manifestations, they're all pointing to secondary, I think the MRI is probably the key thing. And perhaps the only other point that I'll flag here is that I guess we often use the term panhypopituitarism, and that can refer to older hormones from the anterior pituitary or from the anterior posterior. The posterior importantly include AVP. And this I think wasn't present in this case, but if someone had AVP deficiency, which is the new term for diabetes insipidus, that would be a very important consideration and may cause hypernatremia and polyuria. But in this setting, really, I think the focus was on the anterior pituitary.

STEPHEN BACCHI:            Great, thanks. That's really helpful. And just for me, making sure I've got up to date with my endocrinology acronyms, AVPs, arginine, vasopressin. Is that right?

MALCOLM BORG: Right. Or the old ADH, antithyretic online.

STEPHEN BACCHI:            ADH has gone the way of the dinosaurs, has it?

PEAK MANN MAH: Not quite.

STEPHEN BACCHI:            Okay, and in this case they've proceeded exactly as you've suggested Malcolm, and they've done a brain MRI which has revealed an empty sella. There was no history suggestive of pituitary apoplexy. He was commenced on hydrocortisone, thyroxine and risperidone, and there was improvement in the psychosis. He subsequently stopped the hydrocortisone and thyroxine, while reportedly adherent to the risperidone, but had a relapse in his psychosis at this time.

And he then resumed all of the medications and was subsequently able to cease the risperidone without worsening. So, basically it sounds like the hydrocortisone and thyroxine were the medications that were fixing his psychosis. So Dr Mah, this is a really interesting aetiology for psychosis. What can you tell the listeners about hypopituitarism and its association with psychosis?

PEAK MANN MAH:          Right, well this is not a common thing that we see. We see many people with hypothyroidism, hypercortisolism and hypopituitarism and I think this association encountered with this case was also something fairly new for me and I've seen case reports related to that. So, we think it might be, you know, it's not quite clear but I think it's related to the hormone imbalance of hypothyroidism, hypercortisolism. And I think not just in this case, but like the different types of endocrine causes that Malcolm has mentioned, hypercortisolism, Cushing's disease, thyrotoxicosis, that can be associated with psychosis. Not common, but it can be.

STEPHEN BACCHI:            Great, thank you. So, this is a really interesting case and I know it hasn't come up in this case, but it could come up in the future for this patient and it seems to come up so often in practice so, if you don't mind me asking, if this patient was on chronic steroids and they became unwell in the future, say with an infection, what should generalists do in terms of stress dosing steroids? And how's it right to their baseline dose? And what would a normal stress dose look like, Malcolm?

MALCOLM BORG:            Yeah, it's a really good question and this comes up all the time both for just general physician care and as well for consults to the endocrine team. I guess we first have to consider the dose the person is on and so most of the time we're talking about people who have adrenal insufficiency and are receiving typical replacement doses of steroid. That's the equivalent of 15 to 25 milligrams of hydrocortisone per day. That would be the standard, which is around five milligrams of prednisolone might be another way that would commonly be seen. With that dose, perhaps we could consider the easy way to consider stress dosing and that's often going two to three times that dose for three days.

I think outside of hospital, that's going to cover most problems. I often use a template that comes from the Endocrine Society of Australia in my action plan that I give patients. And that goes on to a bit more detail, which is perhaps easier when you've got an informed patient who uses these resources and it sort of stratifies giving double dose or triple dose depending on the degree or severity of that problem. Steroids are something where we don't have a level in a sense when we're monitoring what someone needs in terms of a treatment dose. It's a lot more clinical and by guess, in a sense. And so really, we have to guess a certain dose that's going to be required to start and those would be the common doses used.

Now, I did start with saying you have to consider that person's dose and that's because if they have a much higher dose, say they're on prednisolone 20 milligrams chronically, then they don't necessarily need a stress dose. And what I mean there is because they're already at four times the normal physiological dose. They don't need that dose doubled or triple during illness. They probably don't need that dose increased at all. The converse to that is someone in the middle. Let's say they have pred 10 milligrams per day. That is double the physiological dose. And in most circumstances that doesn't need stress dosing.

However, if they're really, really sick in hospital, they may still need a stress dose because that illness may be pushing them to higher extremes. I think the other part of stress dosing that comes up is what to do around surgery or severe illness. And I preface and say that I think the endocrinologist or endocrine department should be involved in making a plan for these patients generally. I guess we often are giving a high IV dose at the start. So, it's sort of 25 or 50 milligrams. There are doses of 100 milligrams given, and that's typically the sort of adrenal crisis dose. And I guess then we often tailor that down and give smaller IV doses or back to the oral, depending on the degree of stress expected from the surgery and how well or unwell that person is.

STEPHEN BACCHI:            Great, thanks Malcolm. And just my understanding, you were talking about the prednisolone doses earlier, but when you're talking about intravenous doses, say 25, 50, 100, that's hydrocortisone, is that right?

MALCOLM BORG:            Indeed, good clarification, I guess. We don't have an IV of pred and we tend to give those acute IV sort of stress doses with hydrocortisone.

STEPHEN BACCHI:            And Dr Mah, one other question just for my edification. So the short synacthen test is one that comes up in multiple choice questions for trainees now and again. But I think that it's one that's probably significantly less frequently performed in hospital. Could you talk us through just some of the logistics around performing that test and what some of the common pitfalls might be that you see it done not quite as well as they could be?

PEAK MANN MAH:          Okay, so synacthen is synthetic ACTH and what we'll do is a baseline cortisol level and ACTH and the injection of the 250 micrograms of synacthen, synthetic ACTH will be given intravenously and I think in some protocols it's given intramuscularly but you we've been using it intravenously and then a blood sample for cortisol is taken at 30 minutes and then 60 minutes.

And the rationale is when the adrenal gland is stimulated by the synthetic ACTH, if there's a rise in current laboratory cutoff of above 450 nanomol per litre, means that the adrenal gland has sufficient reserve and it's working fine. The ACTH is used to determine if, let's say there's a flat response on suboptimal response, the ACTH will help guide whether it's a primary adrenal gland insufficiency or whether it's a secondary pituitary issue.

STEPHEN BACCHI:            Excellent, thanks. And just for a point of, I contrast, Dr Mah, could you briefly explain, know, a dexamethasone suppression test is for a different issue, but just to compare and contrast that, describe where that one fits in in terms of an endocrinology service workup and how that one is done.

PEAK MANN MAH:          So, we endocrinologists are quite simple. Like if we want to find out whether it's there is enough, we do a stimulation test. So, in the setting of we want to know whether the adrenal gland is working, we would do this synthetic ACTH. So synacthen test is a stimulation test. The dexamethasone suppression test is when if you're thinking, is that too much or something? So, for example, in the use of dexamethasone suppression test is in Cushing syndrome, hypercortisolism, then you would give dexamethasone, which is an exogenous corticosteroid. And if your hypothalamic P23 adrenal gland system was working properly, you would expect that the adrenal gland will suppress and your cortisol level will be low. So, if it did not suppress properly, then you suspect that there is potentially either adrenal gland overproduction, such as an adrenal adenoma, or pituitary adenoma that's making too much of ACTH causing Cushing syndrome.

STEPHEN BACCHI:            Thank you, that's a really helpful comparison. So to wrap up the case for listeners, could you please outline a couple of key learning points or take home messages that you think would be relevant for trainees? Dr Mah would you like to go first with a couple of take home points?

PEAK MANN MAH:          Alright, so mine is actually more of a basic. I know that today we were discussing the cause that, know, as an endocrine cause related psychosis, but the workup is similar. So, the first thing is, is there an endocrine cause? And then the next thing is biochemical workup. And then you treat the acute problem. So, for example, in this case, hypochortisolism, hypothyroidism, you would replace the appropriate hormone and then find the cause of the problem. So, that's why we go on to do the MRI scan to see if there's any structural reasons. For example, a macroadenoma that could be causing compression of the normal pituitary gland resulting in hypopituitarism or pituitary apoplexy.

STEPHEN BACCHI: And Malcolm, what were your key take home points?

MALCOLM BORG:            I think I'll layer on two points. First is to think broadly when sort of medically evaluating someone with psychosis. There's pathologies from lots of different systems there that need to be considered. And I think the second is, I guess when you've got someone with suspected pituitary issues or sort of a suspected adrenal insufficiency and you come across panhypopituitarism—it's not every day for you, it is commonly endocrine sphere—I think you do think about consulting endocrine in that sphere. I think we should be involved.

And I think you think first about the most life-threatening sort of hormone deficiencies. And those would be the adrenal insufficiency. And if it's there, it would also be the AVP deficiency or ADH deficiency or diabetes insipidus, all of these, meaning the same phrases. They're the priorities, then probably the thyroid. And really the replacement of those other hormones is all less urgent after that.

STEPHEN BACCHI: Thanks again, Dr Mah and Malcolm. Great case and excellent discussion. So, for full details, listeners can refer to the article, which was titled Panhypopituitarism and psychosis in a male patient. It was published in the Journal of the Royal Australian New Zealand College of Psychiatrists in 2010, with the first author, Dr Jacob Alexander and second author, Dr Peak Man Mah, who has joined us today. Thanks again.

MIC CAVAZZINI:                That was Associate Professor Stephen Bacchi with another brilliant Pomegranate Case Report. I’m so grateful for his commitment to this. If you’ve got any suggestions for future episodes feel free send an email to podcast@racp.edu.au.

Please help us celebrate ten years of podcasting for the RACP by leaving a review at Spotify or Apple Podcasts or sharing the show with friends and colleagues. They just need to search for Pomegranate Health in any pod-catching app or there’s even an email alerts list you can subscribe to at the website racp.edu.au/podcast.

And don’t forget the College Learning Series. These lectures are written around the Basic Training Curriculum and there are more than a dozen on the endocrine disorders in both the Adult Medicine and Paediatric programs. To find them, just go to elearning.racp.edu.au and you’ll see the College Learning Series at top left.

Just next to it there’s another video library called Medflix with more advanced or diverse content. This contains another 18 videos in a series called Hormone School prepared for Advanced Trainees and Fellows of the RACP. Topics include thyroid cancer, primary aldosteronism, and osteoporosis.

Keep an eye on your College bulletins to find out how to sit in on such webinars as they are presented. There are other series of lectures called Brain School and Kidney School developed in collaboration with the speciality societies.

This podcast was recorded on the coastal lands of the Kaurna people in Adelaide and the Gadigal around Sydney Harbour. I pay respect to their elders past, present and in training. I’m Mic Cavazzini, thanks for listening.