Depression post thyroidectomy ... but euthyroid?

[clausewitz2]

So I am just wrapping up a surgery rotation that ended up being all thyroids, all the time, and I have now seen what I am about to describe in more than one patient in the clinic. Per the patients, they have a remote history of fairly mild depression that did not really respond to SSRIs but was self-limited. They developed thyroid cancers at some later date and naturally had total thyroidectomies. Immediately following these surgeries they become very severely depressed, reporting that their symptoms are much, much worse than they ever were in the past.

Now, if they were hypothyroid, this would be not even a little bit mysterious. The thing that is striking, however, is that their symptoms have persisted for months, and, most importantly, the endocrinologists following them very closely for cancer treatment swear up and down that their are totally euthyroid, they are dosed appropriately on T3/T4 replacement, and that all their lab values look great.

I know there are a number of C/L folks on this board, and I was wondering if this is a common picture. I was struck by the fact that if this is triggered by hypothyroidism, resolution of the hypothyroidism biochemically does not seem to have resolved the depressive symptoms. I know that often endocrine interventions are much more effective at treating cardiac/metabolic type symptoms than mood/cognitive symptoms, but I was still a little puzzled by this.

Have you all seen this before? Any thoughts about what might be going on?

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[nitemagi]

Sounds like a case series. Read up on subclinical hypothyroidism. Consider dosing up the T3/T4 so their TSH is in the lower range of normal, and see if they respond.

 

[clausewitz2]

A case series would be awesome, though I think pitching it to the endocrine surgeons may be a bit of a losing battle, as their interest extended to "you have a PCP? Good, talk to them about that."

 

[Salpingo]

So I am just wrapping up a surgery rotation that ended up being all thyroids, all the time, and I have now seen what I am about to describe in more than one patient in the clinic. Per the patients, they have a remote history of fairly mild depression that did not really respond to SSRIs but was self-limited. They developed thyroid cancers at some later date and naturally had total thyroidectomies. Immediately following these surgeries they become very severely depressed, reporting that their symptoms are much, much worse than they ever were in the past.

Now, if they were hypothyroid, this would be not even a little bit mysterious. The thing that is striking, however, is that their symptoms have persisted for months, and, most importantly, the endocrinologists following them very closely for cancer treatment swear up and down that their are totally euthyroid, they are dosed appropriately on T3/T4 replacement, and that all their lab values look great.

I know there are a number of C/L folks on this board, and I was wondering if this is a common picture. I was struck by the fact that if this is triggered by hypothyroidism, resolution of the hypothyroidism biochemically does not seem to have resolved the depressive symptoms. I know that often endocrine interventions are much more effective at treating cardiac/metabolic type symptoms than mood/cognitive symptoms, but I was still a little puzzled by this.

Have you all seen this before? Any thoughts about what might be going on?

How would you characterize their depression? Depleted energy, general apathy, irritability, anxiety? Were there any physical symptoms/signs (including weight gain, cold intolerance, constipation, but also headache, spasticity, parathesia). I remember the first thing we looked for after thyroidectomy wasn't signs of hypothyroidism but hypocalcemia. The hypoparathyroidism from the accidentally removed gland would manifest before the hypothyroidism. Presumably they're checking for calcium and correcting for albumin, but have they sent out for the 1,25 Vitamin D?

Of course, this could also be an adjustment disorder to having a major surgery and terrifying diagnosis. It'd be interesting to compare this group with patient who underwent similarly intense head and neck surgery (that didn't involve the thyroid)

 

[clausewitz2]

Depleted energy, irritability, difficulty concentrating, severe sleep disruption. This clinic does parathyroid autotransplantation, so they ended up with normal calciums and PTH. I am thinking that adjustment disorder may play some part in this, one of them mentioned being very uncomfortable/ashamed of playing the sick role. It may not help that the thyroid oncologist associated with our center is nationally known for being super aggressive in his treatments and had a tendency to overlook the fact that most thyroid cancers are quite indolent.

In the case of one patient who appeared from scans to be utterly cured of the cancer, how far out would you start leaning towards alternatives to adjustment disorder?

 

[Psychobabbling]

TSH, T3, T4 levels should be MUCH lower than regular "euthyroid" levels after a total thyroidectomy...

 

[clausewitz2]

I do not remember precise numbers off the top of my head, but the thryoid cancer folks were satisfied that the numbers were exactly where they wanted them post thyroidectomy and radioiodine ablation and that the current levels represented their ideal state going forward. Telling that there were not really any other hypothyroid sx in either.

As a result they were apparently unwilling to entertain the notion of any thyroid cause for these depressive sx, although both patients were convinced this was the problem, one of them going so far as to wishing they had never had the cancer removed.

 

[Armadillos]

TSH, T3, T4 levels should be MUCH lower than regular "euthyroid" levels after a total thyroidectomy...

I'm a little confused by this post.
Untreated, TSH would obviously be high and T3/T4 low post thyroidectomy. With thyroid replacement you would then expect normal thyroid hormone levels and normal TSH or extremely low TSH if your suppressing it as part of cancer treatment plan. I don't see how all 3 of those hormones should be low?

 

[Psychobabbling]

maybe its just the TSH that is supposed to be suppressed armadillos; i'm not an endocrinologist after all

 

[clausewitz2]

Glanced at some of my notes, TSH was indeed extremely suppressed in a kind of scorched-earth effort to wipe out every single potential scrap of micro-thyroid (told you this group was crazy-aggressive). T4 was being replaced back to the normal level. Interestingly, both of these patients had at one point been on T3 replacement instead, and reported that their depressive symptoms started emerging shortly after switching over to T4 therapy. Poking around further, there does actually seem to be scraps of a literature about this, or at least potential efficacy for combination T3/T4 therapy v. T4 monotherapy in alleviating hypothyroid-associated anxiety and depression. Not a huge amount of data, but some: http://eje-online.org/content/161/6/895.long

Now if only we could persuade the endocrinologists that this might be something to try, rather then concluding that this depression can't possibly be due to an endocrine issue, at which point their PCP will probably just start them on an SSRI, not unreasonably but one suspects also not very effectually.

 

[Salpingo]

Glanced at some of my notes, TSH was indeed extremely suppressed in a kind of scorched-earth effort to wipe out every single potential scrap of micro-thyroid (told you this group was crazy-aggressive). T4 was being replaced back to the normal level. Interestingly, both of these patients had at one point been on T3 replacement instead, and reported that their depressive symptoms started emerging shortly after switching over to T4 therapy. Poking around further, there does actually seem to be scraps of a literature about this, or at least potential efficacy for combination T3/T4 therapy v. T4 monotherapy in alleviating hypothyroid-associated anxiety and depression. Not a huge amount of data, but some: http://eje-online.org/content/161/6/895.long

Now if only we could persuade the endocrinologists that this might be something to try, rather then concluding that this depression can't possibly be due to an endocrine issue, at which point their PCP will probably just start them on an SSRI, not unreasonably but one suspects also not very effectually.

Its fairly standard to maintain a mildly exogenous hyperthyroid state to keep the TSH suppressed and slow down growth of micro-metastases (or whatever margins had to be maintained). Its possible you could have a paradoxical depression/anxiety due to hyperthyroidism. The fact that there's sleep disruption and irritability may indicate HYPERthyroidism. Generally this practice has only been established for intermediate or high-grade tumors, and groups are still figuring out the optimal TSH level to keep the patients at. There was a recent study showing that this is not an entirely benign practice, with significantly increased risk of osteoporosis without clear benefit over 6 years (http://online.liebertpub.com/doi/pdf/10.1089/thy.2014.0287)

The question of combination therapy has dated back to the 70's, and I don't think there's been any conclusive guidelines (but would defer to the endocrinologist). Like the article you cited mentioned, the presumption has been that the body naturally converts T4 to T3 at an established ratio. The problem is not all tissue has sufficient conversion capacity, and hypothetically the brain (or areas of the brain influencing mood) might not. In fact, the T4 could down-regulate the conversion of itself in the brain. Regardless, there are studies that show the combined therapy has more neuropsych benefits.
http://www.nejm.org/doi/full/10.1056/NEJM199902113400603#t=articleDiscussion

But take this all with a grain of salt. These endocrinologists do this for a living, and have hands-on experience with their patient. Be curious and interested, and hopefully they'll let you in on their thought process.

 

[clausewitz2]

I wish I could have been working with the endocrine folks on this, as I imagine I could have followed up with this. Sadly, I was with the endocrine surgeons in a different clinic, who made it very clear that they had zero interest in addressing this or following it up. Thanks for the cites and the insights, Salpingo!