Long Term Management of Grave's Disease

[DrMetal]

[paging Endocrine]

What's your typical long term approach to manage Grave's Disease in the young? (say a 20-yo at initial diagnosis).

The literature seems to suggest that long term management with a thionamide (methimazole) is safe:
UpToDate

But said literature seems to only comment on 10-15 years of treatment. What if they're on it for life? (30-, 40-years, etc). Do we not worry more then about side effects, agranulocytosis (immunosuppression?), hepatotoxicity?

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[Drrrrrr. Celty]

Depends tbh.

If it's a 20 year old woman on bc who doesn't want kids for a long time then 2-5 years of methimazole therapy and see if the graves disease remits. If after that period antibodies are still high, cannot get off 5mg of methimazole we have a discussion about what they want long term.
If they want to get pregnant then it's not like I can't switch them to PTU peri conception or trying as well. But there is teratogenicity with methimazole in this population making it less savory. So often I will recommend they start birth control or prescribe it myself.

I think in truth it's a conversation you have with your patient. If it was me, I'd probably get a total thyroidectomy because levothyroxine dosing is predictable and it'll reduce my risk of TED.

I would never get radioactive iodine personally and I generally don't push it as much for my graves patients as methimazole and surgery.

 

[DrMetal]

I would never get radioactive iodine personally

Why so? Radiation concerns? Or is not as good of 'definitive' therapy as surgery?

 

[Drrrrrr. Celty]

Why so? Radiation concerns? Or is not as good of 'definitive' therapy as surgery?

It's gone out of favor. Sometimes up to a 3rd of people need redosing. There's a 2 week period radioactive isolation which many people cannot safely accommodate. And many people can record issues with salivary, lacrimal gland issues.

For me I'd prefer thyroidectomy with a high volume surgeon as I know multiple who do >100 a year.

 

[Crayola227]

I know one risk of total thyroidectomy is various nerve damage.

This can lead to issues with control of the lower lip. This sucks because of how it can affect eating, drinking, and speech.

I watched this happen in a surgery although the damage the patient sustained was minor and the symptoms after surgery were minor (some change in sensation but not much motor).

The other issue, a bigger deal, has to do with the recurrent laryngeal nerve. This can also lead to a total **** show as far and the larynx, speech, eating. I have a close relative who had this nerve damage from surgery (not thyroidectomy though).

Neurological Complications in Thyroid Surgery: A Surgical Point of View on Laryngeal Nerves

The cervical branches of the vagus nerve that are pertinent to endocrine surgery are the superior and the inferior laryngeal nerves: their anatomical course in the neck places them at risk during thyroid surgery. The external branch of the superior laryngeal ...

www.ncbi.nlm.nih.gov

(Not related but my cat had radioactive iodine for hyperthyroidism, which has become something of an epidemic amongst cats, theorized as owing to environmental exposures like the fire ******ants in carpeting/furniture). But the isolation of a cat is a lot easier. The advantage is avoiding surgery in the cat (doesn't always get all the tissue and leaves them hypothyroid) and basically any treatment that keeps you from having to medicate a cat twice a day tends to be easier too. The iodine can leave them hypothyroid but is not a sure thing to do so as surgery is. Methimazole for a cat is twice daily, levo is once daily.)

 

[Drrrrrr. Celty]

I know one risk of total thyroidectomy is various nerve damage.

This can lead to issues with control of the lower lip. This sucks because of how it can affect eating, drinking, and speech.

I watched this happen in a surgery although the damage the patient sustained was minor and the symptoms after surgery were minor (some change in sensation but not much motor).

The other issue, a bigger deal, has to do with the recurrent laryngeal nerve. This can also lead to a total **** show as far and the larynx, speech, eating. I have a close relative who had this nerve damage from surgery (not thyroidectomy though).

Neurological Complications in Thyroid Surgery: A Surgical Point of View on Laryngeal Nerves

The cervical branches of the vagus nerve that are pertinent to endocrine surgery are the superior and the inferior laryngeal nerves: their anatomical course in the neck places them at risk during thyroid surgery. The external branch of the superior laryngeal ...

www.ncbi.nlm.nih.gov

(Not related but my cat had radioactive iodine for hyperthyroidism, which has become something of an epidemic amongst cats, theorized as owing to environmental exposures like the fire ******ants in carpeting/furniture). But the isolation of a cat is a lot easier. The advantage is avoiding surgery in the cat (doesn't always get all the tissue and leaves them hypothyroid) and basically any treatment that keeps you from having to medicate a cat twice a day tends to be easier too. The iodine can leave them hypothyroid but is not a sure thing to do so as surgery is. Methimazole for a cat is twice daily, levo is once daily.)

It's rare you'll have an experienced surgeon hit the recurrent laryngeal nerve in a non-thyroid cancer thyroidectomy.

In Thyroid Ca it's not uncommon for it to be touching, concrete like, and harder to distinguish. In Advanced thyroid cancers that are more metastatic you can literally have the thyroid gland surrounding the nerve completely and you basically have to trash it.

Graves disease by comparison, you treat with Methimazole and the gland shrinks to a normal size. Emergent thyroids or those on lugols may be more tricky. Lugols is kind of a debated topic for endo surgeons these days as many think it increases risk of injury.

 

[Crayola227]

It's rare you'll have an experienced surgeon hit the recurrent laryngeal nerve in a non-thyroid cancer thyroidectomy.

In Thyroid Ca it's not uncommon for it to be touching, concrete like, and harder to distinguish. In Advanced thyroid cancers that are more metastatic you can literally have the thyroid gland surrounding the nerve completely and you basically have to trash it.

Graves disease by comparison, you treat with Methimazole and the gland shrinks to a normal size. Emergent thyroids or those on lugols may be more tricky. Lugols is kind of a debated topic for endo surgeons these days as many think it increases risk of injury.

The point about experience is a good one. Although, the setting where I saw minor damage... the nerve was not near anything that complicated things. And the surgeon was one of the top ENTs in the country.... supervising a resident who had the bovie. Sooooo... just backs up what you are saying. It's always worth working out just who exactly is doing your surgery. It's a conundrum because how do we get more experienced surgeons if inexperienced ones don't do the surgery.

If you know, then you know. Meaning, it's often physicians or others who know about the "dangers" of resident surgeons, who will be the ones making requests regarding residents involved in care... many lay people don't really know about the "command" structure. So they end up being the "guinea pigs" doing their part to train residents. This is more palatable of a way of thinking about it than considering how income affects the care you can receive, if it comes down to what knowledge you have and what you ask for.

Personally, I generally like to consent to med students and residents doing things to my body, but I definitely think about/ask about experience level and consider what the procedural complications are. Of course, some institutions you have more or less input on training than others depending on policies.

The resident who did my c section left me with an asymmetrical scar 🤣 but I kept my uterus which I wanted to and I didn't bleed out. Also no one cut my baby's head. Win!

Yes I agree that given the stakes with the nerves in thyroidectomy an experienced surgeon is key.

 

[DrMetal]

For me I'd prefer thyroidectomy with a high volume surgeon as I know multiple who do >100 a year.

It's rare you'll have an experienced surgeon

Yeah, that's the problem, we don't have access to good Endocrine Surgery in the military. Our surgeons just don't get the case volume (unless they also moonlight out in town).

Riddle me this: why would successful treatment with methimazole (potentially) result in remission? Methimazole works by inhibiting thyroid hormone synthesis. Why should it have an affect on the TSH-Ab titer, does it? How often do you see remission?

 

[Drrrrrr. Celty]

Yeah, that's the problem, we don't have access to good Endocrine Surgery in the military. Our surgeons just don't get the case volume (unless they also moonlight out in town).

Riddle me this: why would successful treatment with methimazole (potentially) result in remission? Methimazole works by inhibiting thyroid hormone synthesis. Why should it have an affect on the TSH-Ab titer, does it? How often do you see remission?

Can you fly them to one?

The mechanism isn't fully known. Methimazole likely has pleomorphic immunological effects. And my guess is that with less inflammation, less blood flow, smaller gland, less thyroglobulin release and thyroid activity the T and B cells start to be less angry at the thyroid gland. The question of whether the remission stays in remission however is debated as a lot of patient do eventually get potential definitive therapy or return to small doses of methimazole.

Like for my >50 y/o pts they generally do quite fine on 2.5-5mg a day. And I really don't bat an eye and basically don't see them more than yearly. However for folks on 20-30mgs a day I move them towards definitive therapy.

 

[rokshana]

I know one risk of total thyroidectomy is various nerve damage.

This can lead to issues with control of the lower lip. This sucks because of how it can affect eating, drinking, and speech.

I watched this happen in a surgery although the damage the patient sustained was minor and the symptoms after surgery were minor (some change in sensation but not much motor).

The other issue, a bigger deal, has to do with the recurrent laryngeal nerve. This can also lead to a total **** show as far and the larynx, speech, eating. I have a close relative who had this nerve damage from surgery (not thyroidectomy though).

Neurological Complications in Thyroid Surgery: A Surgical Point of View on Laryngeal Nerves

The cervical branches of the vagus nerve that are pertinent to endocrine surgery are the superior and the inferior laryngeal nerves: their anatomical course in the neck places them at risk during thyroid surgery. The external branch of the superior laryngeal ...

www.ncbi.nlm.nih.gov

(Not related but my cat had radioactive iodine for hyperthyroidism, which has become something of an epidemic amongst cats, theorized as owing to environmental exposures like the fire ******ants in carpeting/furniture). But the isolation of a cat is a lot easier. The advantage is avoiding surgery in the cat (doesn't always get all the tissue and leaves them hypothyroid) and basically any treatment that keeps you from having to medicate a cat twice a day tends to be easier too. The iodine can leave them hypothyroid but is not a sure thing to do so as surgery is. Methimazole for a cat is twice daily, levo is once daily.)

Which is why you should have thyroid surgery done by a high volume thyroid surgeon… the risks of complications are extremely low 1-3% in their hands .

 

[rokshana]

Yeah, that's the problem, we don't have access to good Endocrine Surgery in the military. Our surgeons just don't get the case volume (unless they also moonlight out in town).

Riddle me this: why would successful treatment with methimazole (potentially) result in remission? Methimazole works by inhibiting thyroid hormone synthesis. Why should it have an affect on the TSH-Ab titer, does it? How often do you see remission?

Because that the goal with mmi treatment… approx 40% of those exposed mmi for 2 yrs will go into lifelong remission… it is the definitive therapy. Some studies should that the % increases by another 20% of exposed to mmi for 5 yrs.
In the US, mmi isnt typically used as a long term medication ( in europe, they use it longer) and definitive therapy is recommended… either rai or surgery.
I’ve been lucky to have good high volume endocrine surgeons accessible to my pt, so I too generally lean towards surgery as definitive therapy. RAI hard to use in those with TED, active smokers, those looking to get pregnant, with young children, and takes a while before they become hypothyroid and treatment in flux… TT is pretty quick and most people stablize in 3-6 months and can get pregnant in 6 months ( typically recommended to wait a year after rai) and management easier on pregnancy.

 

[rokshana]

Why so? Radiation concerns? Or is not as good of 'definitive' therapy as surgery?

Personally, I’ve found RAI is not as good as surgery… while potentially dead thyroid, it still can be a source of antibodies, and pts with TED could still have active disease despite RAI.
And it’s Graves’ disease… named after Robert Graves .

 

[dozitgetchahi]

The point about experience is a good one. Although, the setting where I saw minor damage... the nerve was not near anything that complicated things. And the surgeon was one of the top ENTs in the country.... supervising a resident who had the bovie. Sooooo... just backs up what you are saying. It's always worth working out just who exactly is doing your surgery. It's a conundrum because how do we get more experienced surgeons if inexperienced ones don't do the surgery.

If you know, then you know. Meaning, it's often physicians or others who know about the "dangers" of resident surgeons, who will be the ones making requests regarding residents involved in care... many lay people don't really know about the "command" structure. So they end up being the "guinea pigs" doing their part to train residents. This is more palatable of a way of thinking about it than considering how income affects the care you can receive, if it comes down to what knowledge you have and what you ask for.

Personally, I generally like to consent to med students and residents doing things to my body, but I definitely think about/ask about experience level and consider what the procedural complications are. Of course, some institutions you have more or less input on training than others depending on policies.

The resident who did my c section left me with an asymmetrical scar 🤣 but I kept my uterus which I wanted to and I didn't bleed out. Also no one cut my baby's head. Win!

Yes I agree that given the stakes with the nerves in thyroidectomy an experienced surgeon is key.

One issue I’ve seen with requesting attending only care in academic centers is that the request may not actually be honored. There have been lawsuits about this.

 

[dgdg]

After IM residency at a tertiary care center, I was very good as a hospitalist. Of all the drug overdoses, sepsis, bleeding, etc, the most nerve wracking admissions I had were young women of poor socioeconomic status who were noncompliant with Methimazole. You had to assume the tachycardia induced cardiomyopathy was so severe, you did not dare give any beta blocker prior to obtaining an echo, or they would surely crash. I recall LVEF's in the range of 20%. It was an ICU stay with all the other standard treatments. After 48 hours, things started to settle down.

 

[rokshana]

After IM residency at a tertiary care center, I was very good as a hospitalist. Of all the drug overdoses, sepsis, bleeding, etc, the most nerve wracking admissions I had were young women of poor socioeconomic status who were noncompliant with Methimazole. You had to assume the tachycardia induced cardiomyopathy was so severe, you did not dare give any beta blocker prior to obtaining an echo, or they would surely crash. I recall LVEF's in the range of 20%. It was an ICU stay with all the other standard treatments. After 48 hours, things started to settle down.

which is why i have kept these pt input and had them get total thyroidectomy before discharge...levothyroxine is much easier to manage and the chances of them appearing in a severe hypothyroidism/myxedema is a lot lower.

 

[DrMetal]

which is why i have kept these pt input and had them get total thyroidectomy before discharge...levothyroxine is much easier to manage and the chances of them appearing in a severe hypothyroidism/myxedema is a lot lower.

Do you make a firm recommendation for definitive therapy? In other words, do you recommend against long term methimazole? (let's just assume the compliant and reliable patient).

 

[Drrrrrr. Celty]

Do you make a firm recommendation for definitive therapy? In other words, do you recommend against long term methimazole? (let's just assume the compliant and reliable patient).

There's a certain type of patient: Bipolar or Psychotic or on polysubstance, in thyrotoxicosis with repeated hospitalizations. This patient almost every Endocrinologist would recommend an inpatient thyroidectomy ideally as it may help them be less psychotic as well.

 

[Drrrrrr. Celty]

After IM residency at a tertiary care center, I was very good as a hospitalist. Of all the drug overdoses, sepsis, bleeding, etc, the most nerve wracking admissions I had were young women of poor socioeconomic status who were noncompliant with Methimazole. You had to assume the tachycardia induced cardiomyopathy was so severe, you did not dare give any beta blocker prior to obtaining an echo, or they would surely crash. I recall LVEF's in the range of 20%. It was an ICU stay with all the other standard treatments. After 48 hours, things started to settle down.

Esmolol.

The problem is when that patient is also on Cocaine. Then you're left titrating Dilt and hoping for the best +/- getting them ready for pharesis.

 

[rokshana]

Do you make a firm recommendation for definitive therapy? In other words, do you recommend against long term methimazole? (let's just assume the compliant and reliable patient).

yes...but not all endocrinologist do...its actually quite a debated topic amongst endocrinologists...I actually moderated a presentation at ATA which was a debate on Long term Methimazole: Yay or Nay...and basically head two world renown experts that stand on the opposites of this discuss and debate the merits of both options...it was a very interesting discussion...I changed my practice a little in that i may go to 5 years of MMI, but i talk about definitive therapy on the first visit.

 

[Clean7795]

One issue I’ve seen with requesting attending only care in academic centers is that the request may not actually be honored. There have been lawsuits about this.

A lot of procedures require an assistant (resident/fellow) or the attendings are so used to having one that they cannot function without one. It's reasonable to see if it can be accommodated or for the attending to be doing the main portions of the case, but often some involvement cannot be avoided.

 

[DrMetal]

Because that the goal with mmi treatment… approx 40% of those exposed mmi for 2 yrs will go into lifelong remission… it is the definitive therapy. Some studies should that the % increases by another 20% of exposed to mmi for 5 yrs.
In the US, mmi isnt typically used as a long term medication ( in europe, they use it longer) and definitive therapy is recommended… either rai or surgery.
I’ve been lucky to have good high volume endocrine surgeons accessible to my pt, so I too generally lean towards surgery as definitive therapy. RAI hard to use in those with TED, active smokers, those looking to get pregnant, with young children, and takes a while before they become hypothyroid and treatment in flux… TT is pretty quick and most people stablize in 3-6 months and can get pregnant in 6 months ( typically recommended to wait a year after rai) and management easier on pregnancy.

With MMI, you expect free T4 to decrease quickly, right, can see an affect in weeks? What about the TSH, takes longer to recover? TSH stays undetectable for a while?

 

[rokshana]

With MMI, you expect free T4 to decrease quickly, right, can see an affect in weeks? What about the TSH, takes longer to recover? TSH stays undetectable for a while?

Mmi can take a few days to kick in, but you can see the changes in ft4 in the matter of days to weeks. I’ll recheck that every 1-2 days to monitor in a storm or severe thyrotoxicosis so o can start to drop the doses to a maintenance dose.
TSH does lag and it can take months to almost a year for TSH to become normal. If the TSH is supressed or low by ft4 has normalized, I’ll base treatment on the ft4 for a while.

 

[Drrrrrr. Celty]

With MMI, you expect free T4 to decrease quickly, right, can see an affect in weeks? What about the TSH, takes longer to recover? TSH stays undetectable for a while?

Graves patients in my opinion respond to Methimazole like a champ. If in 48 hours there's not a response you're really dealing with an outlier or doing really weak dosing.

With Amiodarone you're really screwed half the time because the patients are super sick, don't respond to medical therapy and are on storm dosing for weeks. These are my q1-2 week lab patients. Last thing I want is an LVAD patient to go into V tach because their FT4 is too high.