![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 25 of 27. This is the beginning of the thread.
Posted by SandyWeb on July 3, 2007, at 15:07:08
My PTSD is raging out of control. On Thursday my doc is starting me on Valium because he wants me to have a longer-acting benzo. I'm on clonazepam now, but I need too high of a dose on it. I've also tried the other benzos.
Anyone have stories relating to Valium? It shocked me that he even offered it. I know that docs don't like to prescribe this one, for some reason. Thanks.
Sandy
Posted by Phillipa on July 3, 2007, at 17:46:16
In reply to Valium, posted by SandyWeb on July 3, 2007, at 15:07:08
Sandy true they don't like to prescribe it . I've been on it for 35years at 20mg total all taken at night. How high was the klonopin as I feel it's stronger at least it affects me more reguardless of the half-life. Someone once said to me a benzo is a benzo but it's not as I've been on them all. Write to me and fill me in Love Phillipa sorry about the raging anxiety is there a trigger? Geez hope you're not getting tolerant as I am. so I go around basically unmedicated.
Posted by Maria3667 on July 3, 2007, at 17:55:12
In reply to Valium, posted by SandyWeb on July 3, 2007, at 15:07:08
Hi Sandy,
As I've tried both, I think I can give a fair assessment. As a matter of fact, I found Klonopin to be stronger than Valium. The doc started me on 10 mgs of Valium, but this really didn't do a hoot for me except diarreah (talk about 'adverse events'!).
I also have PTSD due to sexual abuse as a child. Klonopin was quite effective at keeping the 'stress' at bay. I took 1.5 mgs for about a year.
> My PTSD is raging out of control. On Thursday my doc is starting me on Valium because he wants me to have a longer-acting benzo. I'm on clonazepam now, but I need too high of a dose on it. I've also tried the other benzos.
>
> Anyone have stories relating to Valium? It shocked me that he even offered it. I know that docs don't like to prescribe this one, for some reason. Thanks.
>
> Sandy
Posted by cactus on July 3, 2007, at 18:08:00
In reply to Valium, posted by SandyWeb on July 3, 2007, at 15:07:08
I don't understand why doctors are so anti valium in the US, it's probably the best benzo I have ever taken for anxiety. It worked so much better for me than clonazepam ever did. It's funny how it works, North America "generally" tends to prescribe clonazepam as a long acting benzo and the rest of the world "generally" prescribes valium if a long acting benzo is needed. Clonezepam is not on label for anxiety in Australia, you have to have epilepsy to get it unless you have an open minded pdoc like mine who let me give it a try and I didn't like it. I found it way too strong and it really messed with my head, making it hard to focus and left me feeling like my head was stuffed with cotton wool. It also gave me shocking headaches. Valium rocks for anxiety. It just brings you back down to earth and lets you function normally. Good luck I hope that was of some help.
Posted by saturn on July 3, 2007, at 20:52:42
In reply to Re: Valium » SandyWeb, posted by cactus on July 3, 2007, at 18:08:00
>>> I don't understand why doctors are so anti valium in the US,
I agree. Though I have very limited experience with benzos (valium, ativan and xanax), if I ever decide to opt for long-term treatment valium will definitely be my first choice. It's long half-life and active metabolites (not sure if other benzos have active metabolites) are major reasons why. Peace...Saturn.
Posted by SandyWeb on July 5, 2007, at 19:52:40
In reply to Re: Valium, posted by saturn on July 3, 2007, at 20:52:42
Thanks, everyone, for your responses. Yes, there are a few events in my life that each caused PTSD, and now I have a major stressor that is jumbling all the events together. Now it's 24/7 anxiety.
I was taking in total about 14 mg of clonazepam per day. Way too much. I've also tried the other benzos, but they didn't work nearly as well.
I started Valium today. I take 10 mg twice per day. I can even take a 2 mg clonazepam with it if I want. I go back to see the doctor in 30 days, and if the dose isn't working well enough for my stress, he will raise it more. He didn't want to do that right now because he didn't want to turn me "into a zombie." What the heck does that mean? If I increase the dose, am I going to become a couch-sitting tv watcher??
Anyways, I didn't feel anything from the 10 mg. He said it could take about 3-4 days to start feeling the effects, so just be patient and then I'll notice that my anxiety will begin to not be so overwhelming. Is that how it was with you all?
Thanks for your info!
Sandy
Posted by cactus on July 5, 2007, at 21:32:35
In reply to Re: Valium, posted by SandyWeb on July 5, 2007, at 19:52:40
I find valium less sedating than clonezapam but 14mg of clonezapam is a very large dose. The thing with valium is you don't notice it's physical effects as much as clonazepam. I find it just calms me down without zonking me out and lets me go about my daily business. Check out a Benzodiazepine Equivalence Chart to see how different the dosagage is. You might find with valium you can function without feeling a bit out of it, you have more control which you don't quite realise at first, just give it a few days and see if you need to up your dose.
Posted by Phillipa on July 5, 2007, at 21:55:58
In reply to Re: Valium, posted by SandyWeb on July 5, 2007, at 19:52:40
Sandy I agree that's a lot of klonopin. I take a total of 20mg of valium a day and .5 of xanax when I go to bed. 35years ago first panic attack on 5mg of valim three times a day but also 450mg of Miltown and drank beer at night. It didn't take long for me to feel better. Can't remember how long. Now still basically the same doseage but I'm tolerant to benzos now so it pretty darn hard. I will not up the doses and sure glad I didn't when docs wanted me to years ago as look at the trouble I'd be in now. Oh the miltown was for a shorttime and I just stopped it to everyones amazement as I knew nothing about meds and that's a strong med . I doubt they use it anymore. Good luck to you. Love Phillipa
Posted by SandyWeb on July 7, 2007, at 11:49:18
In reply to Re: Valium » SandyWeb, posted by cactus on July 5, 2007, at 21:32:35
Hi Cactus,
I don't find either Valium or clonazepam to be sedating. The clonazepam was fine, except for all the stressors hitting all at once right now, I had to take a very high dose just to make it through the day. The doctor was concerned about that, so put me on a much longer-acting benzo (Valium). 20mg daily to start, but he expects to see me before the end of the month and we may need to increase the dose...or if sooner, he said I could call his secretary and he would take care of it for me.
He said it takes 3-4 days to feel the full effects of it, so just be patient. I don't know. I was almost having a panic attack today, and had to distract myself by writing emails and getting on Messenger. And then I took 2mg of clonazepam, and after awhile, I felt better but not happy with the results so far of the Valium.
I looked up a couple of equivalency charts, and I'm actually now taking LESS of a dose of benzo then I was with clonazepam. It appears that 10mg Valium equals 2mg clonazepam. So that means at 20mg Valium per day (for now), I'm only getting 4mg of clonazepam. That's ridiculous. The Valium may be longer lasting, but the dose is not strong enough. I guess that's why he said he "expected" to see me back before the end of the month. Not because it would be time for a refill, but because he knew the dose wouldn't hold me. Why would he ever think that a higher dose would turn me into a zombie?? Argh.
Anyways, thank you for everything. You've been very helpful. I wouldn't even have thought to look up an equivalency chart. I just would have thought that Valium didn't work for me for some reason. But now I know the dose is too low.
Have a wonderful weekend.
Sandy
Posted by SandyWeb on July 7, 2007, at 12:08:05
In reply to Re: Valium » SandyWeb, posted by Phillipa on July 5, 2007, at 21:55:58
Hi Phillipa,
The doctor has me on 20mg Valium now too, but it's not strong enough. What happens over time? Does it work better when you're on it longer? My minimum of clonazepam was 2mg three times per day, and this dose of Valium is even lower than that. I read that the maximum dose of Valium is 40mg, which works out to 8mg clonazepam. That's a possibility because I would take 2mg in the morning, 4mg at night, but it was the afternoon that depended on the total amount I'd actually take. He also said that if Valium doesn't work, they have other drugs. Like what?? I've tried the other benzos. I'm already on Effexor XR (which I like), and a beta blocker.
Anyways, once these stressors are not as bad, I won't be needing as high a dose....but right now I *do*. We'll see what happens.
Thanks for responding. Say "hi" to our mutual friend!!
Sandy
Posted by Phillipa on July 7, 2007, at 21:40:30
In reply to Re: Valium » Phillipa, posted by SandyWeb on July 7, 2007, at 12:08:05
Sandy I would like to lower the 20mg of valium but like you so many stressors right now like they can't get my thyroid back in line. I did cut out the lunesta and no difference still sleep the same. I'm seeing a PHD for anxiety. Was doing pretty well for me til the spider bite set off my autoimmune system made the thyroid crash so to speak. So working on that. My husband and decided tonight not to change any meds antidepressants til thyroid stable. Geez been working on that since last fall and something bad always happens. Right now I'm very tired during the day strange for me and it has to be throid related. Only variable to change. I couldn't take klonopin as it made me feel suicidal once and called pdoc backe to .5 of xanax and I was fine. Love Phillipa
Posted by cactus on July 8, 2007, at 0:41:28
In reply to Re: Valium » cactus, posted by SandyWeb on July 7, 2007, at 11:49:18
> Hi Cactus,
>
> I don't find either Valium or clonazepam to be sedating. The clonazepam was fine, except for all the stressors hitting all at once right now, I had to take a very high dose just to make it through the day. The doctor was concerned about that, so put me on a much longer-acting benzo (Valium). 20mg daily to start, but he expects to see me before the end of the month and we may need to increase the dose...or if sooner, he said I could call his secretary and he would take care of it for me.
>
> He said it takes 3-4 days to feel the full effects of it, so just be patient. I don't know. I was almost having a panic attack today, and had to distract myself by writing emails and getting on Messenger. And then I took 2mg of clonazepam, and after awhile, I felt better but not happy with the results so far of the Valium.
>
> I looked up a couple of equivalency charts, and I'm actually now taking LESS of a dose of benzo then I was with clonazepam. It appears that 10mg Valium equals 2mg clonazepam. So that means at 20mg Valium per day (for now), I'm only getting 4mg of clonazepam. That's ridiculous. The Valium may be longer lasting, but the dose is not strong enough. I guess that's why he said he "expected" to see me back before the end of the month. Not because it would be time for a refill, but because he knew the dose wouldn't hold me. Why would he ever think that a higher dose would turn me into a zombie?? Argh.
>
> Anyways, thank you for everything. You've been very helpful. I wouldn't even have thought to look up an equivalency chart. I just would have thought that Valium didn't work for me for some reason. But now I know the dose is too low.
>
> Have a wonderful weekend.
>
> Sandy
>
>
Yeah that was kind of my point, I thought it might not be a high enough dose of valium but I'm no doctor and didn't want to say you might need more. Good luck with the cross taper and give it time.I hope you have a great weekend too!!!
Posted by SandyWeb on July 8, 2007, at 11:55:22
In reply to Re: Valium » SandyWeb, posted by cactus on July 8, 2007, at 0:41:28
I had a message from a PB member, and he showed me a chart that had 10mg Valium being equivalent to 0.5mg clonazepam. And I've also read in other places as the equivalency being 1 to 2 mg per 10mg Valium. Regardless of whether it's 0.5, 1, or 2mg.....it turns out that 20mg of Valium is definately not anywhere near what I've been taking. The only difference I've noticed in the past three days, though, is a nervous tummy and coming close to a panic attack once. I don't think I'm as nervous as I normally would be simply because my daughter is here visiting for the time being, so I'm not as anxious with her around. But once she leaves....
I hate the nervous tummy, though, and there's no reason for it. I'll just be reading a book or on the internet....like right now, my stomach is so nervous I think I'll be grabbing a 2mg clonazepam soon.
The doctor said he would start me out at 10mg Valium twice per day. Do not take it three times per day. Why not?? It still wouldn't be as high a dose as what I'm used to, and I don't want to start freaking out!! Would taking it 20mg at once be such a bad thing, or taking 10mg TID be so wrong? They're still so far below my usual. And without anti-anxiety in my system, I tend to get suicidal. Argh. I don't know why he's doing this to me.
Sandy
Posted by Zyprexa on July 8, 2007, at 13:11:47
In reply to Re: Valium » cactus, posted by SandyWeb on July 8, 2007, at 11:55:22
Sandy, I don't know, but i would bet that other drugs are Atipicals.
Phillipa, what I read is that a thiroid med like armour, which works on T3 and T4, is more likely to control thiroid better. The T3 is important, and synthroid is only T4. Many people can't metabolize T4 into T3 hormone. Just a thought.
Zyprexa
Posted by sdb on July 8, 2007, at 18:21:46
In reply to Re: Sandy and Phillipa, posted by Zyprexa on July 8, 2007, at 13:11:47
> Sandy, I don't know, but i would bet that other drugs are Atipicals.
>
> Phillipa, what I read is that a thiroid med like armour, which works on T3 and T4, is more likely to control thiroid better. The T3 is important, and synthroid is only T4. Many people can't metabolize T4 into T3 hormone. Just a thought.
>
> Zyprexayes, fT3 (free T3) and T4 is important and people may have more problems to metabolize T4 in T3 due to drug interactions sometimes.
warm regards
sdb
Posted by Phillipa on July 8, 2007, at 20:00:13
In reply to Re: Sandy and Phillipa, posted by sdb on July 8, 2007, at 18:21:46
Hi sdb endo just added 5mcg of cytomel. Do you like this combo? Love Phillipa
Posted by Paulbwell on July 8, 2007, at 20:37:01
In reply to Re: Valium » SandyWeb, posted by cactus on July 3, 2007, at 18:08:00
"Valium rocks for anxiety. It just brings you back down to earth and lets you function normally."
Yep-SOOOOO true.
Blame 60's,70's- housewife 'mothers little helper' media slag for Valiums reputation.
Posted by Phillipa on July 8, 2007, at 21:38:42
In reply to Re: Valium, posted by Paulbwell on July 8, 2007, at 20:37:01
Paul til you get tolerant like me then what? Love Phillipa
Posted by SandyWeb on July 9, 2007, at 14:32:20
In reply to Re: Valium » Paulbwell, posted by Phillipa on July 8, 2007, at 21:38:42
Valium does not work. I am out of clonazepam now, and only have the Valium left to rely upon. It does nothing. My stomach is nervous and I come very close to having panick attacks (just haven't yet). I'm starting to take more than prescribed simply because I can't live this way. I phoned my doctor, and he just so happens to be on vacation until Friday afternoon...which probably means I wouldn't be able to see him until next week. The memories are flooding me again, and the new stressors are not helping me cope with any of the memories. How many of these darn pills do I have to take to get some relief?? I don't want anxiety to get the better of me and make me start to freak out.
Sandy
Posted by Phillipa on July 9, 2007, at 19:07:52
In reply to Valium Is NOT Working, posted by SandyWeb on July 9, 2007, at 14:32:20
Sandy I would suspect you are in withdrawal from the high dose of klonopin. Can you get the covering doc to order you something like seroquel or zyprexa for a while? Too much of a benzo is not good. Love Phillipa
Posted by sdb on July 10, 2007, at 10:19:31
In reply to Re: Sandy and Phillipa » sdb, posted by Phillipa on July 8, 2007, at 20:00:13
> Hi sdb endo just added 5mcg of cytomel. Do you like this combo? Love Phillipa
This is difficult to say. If your thyreoiditis is subclinical maybe. If your chronic-lymphocyte thyreoiditis is clinical yes, depending of several parameters; tsh-level, thyroxin, cortisol etc. It is not clear if your neuropsychological status will be better. You have to take care of interactions, precautions etc. T3 has a shorter half-life than T4. If you're taking this in the morning it can eventually cause heart palpitations and sweating. The older you are the more careful you must be. A regular control of fT3/fT4/tsh is necessary. There are other treatments for this autoimmune disorder also.
love sdb
ps. busy now..:-(
Posted by sdb on July 14, 2007, at 20:47:28
In reply to Re: Sandy and Phillipa }} Phillipa, posted by sdb on July 10, 2007, at 10:19:31
> > Hi sdb endo just added 5mcg of cytomel. Do you like this combo? Love Phillipa
>
> This is difficult to say. If your thyreoiditis is subclinical maybe. If your chronic-lymphocyte thyreoiditis is clinical yes, depending of several parameters; tsh-level, thyroxin, cortisol etc. It is not clear if your neuropsychological status will be better. You have to take care of interactions, precautions etc. T3 has a shorter half-life than T4. If you're taking this in the morning it can eventually cause heart palpitations and sweating. The older you are the more careful you must be. A regular control of fT3/fT4/tsh is necessary. There are other treatments for this autoimmune disorder also.
>
> love sdb
>
> ps. busy now..:-(monoclonal antibodies will developed but unfortunately these are tricky treatments and these are tricky and costly to produce.
the article isn't only of grave's disease.
-------------------------------------------------
http://eje-online.org/cgi/content/full/154/5/623statins
--------
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=15994744&dopt=Abstractcombined t3/t4 treatment is in discussion.
there is a time released version coming.
-----------------------------------------------
New River Pharmaceuticals Announces Filing of Investigational New Drug Application for NRP409RADFORD, Va., June 30 /PRNewswire/ -- New River Pharmaceuticals Inc. announced today that an investigational new drug application (IND) has been submitted to the U.S. Food and Drug Administration for NRP409.
On June 29, New River submitted an IND on NRP409, the company's Carrierwave(TM) triiodothyronine (T3) hormone, as a treatment for patients with primary hypothyroidism. The company hopes that by reducing the variability of the hormone's availability, while reducing the safety risk associated with other T3 based therapies, NRP409 will mark the first significant improvement in thyroid hormone replacement therapy in approximately half a century.
New River expects to begin enrollment in clinical studies of NRP409 by 3Q06. The company anticipates that NRP409 should warrant a relatively abbreviated development pathway and hopes to file a new drug application (NDA) by the end of 2007. While the U.S. market for thyroid HRTs is significant, with roughly 3 billion doses per year, the field of endocrinology is concentrated enough that the company expects to be able to commercialize and market NRP409 without a partner.
New River also announced that it is evaluating whether to exercise its option to co-promote NRP104 in accordance with a collaboration agreement with Shire plc (LSE: SHP; Nasdaq: SHPGY; TSX: SHQ). NRP104 is currently under review with the FDA as a potential treatment for pediatric attention deficit/hyperactivity disorder. Should New River decide to exercise this option, it expects to field approximately 100 sales representatives in the first half of 2007.
About New River
New River Pharmaceuticals Inc. is a specialty pharmaceutical company developing novel pharmaceuticals that are generational improvements of widely prescribed drugs in large and growing markets.
For further information on New River, please visit the company's website at http://www.nrpharma.com/.
"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
This press release contains certain forward-looking information that is intended to be covered by the safe harbor for "forward-looking statements" provided by the Private Securities Litigation Reform Act of 1995. Forward- looking statements are statements that are not historical facts. Words such as "expect(s)," "feel(s)," "believe(s)," "will," "may," "anticipate(s)" and similar expressions are intended to identify forward-looking statements. These statements include, but are not limited to, financial projections and estimates and their underlying assumptions; statements regarding plans, objectives and expectations with respect to future operations, products and services; and statements regarding future performance. Such statements are subject to certain risks and uncertainties, many of which are difficult to predict and generally beyond the control of New River Pharmaceuticals, that could cause actual results to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include: those discussed and identified in the New River Pharmaceuticals Inc. annual report on Form 10-K, filed with the SEC on March 15, 2006; the timing, progress and likelihood of success of our product research and development programs; the timing and status of our preclinical and clinical development of potential drugs; the likelihood of success of our drug products in clinical trials and the regulatory approval process; our drug products' efficacy, abuse and tamper resistance, resistance to intravenous abuse, onset and duration of drug action, ability to provide protection from overdose, ability to improve patients' symptoms, incidence of adverse events, ability to reduce opioid tolerance, ability to reduce therapeutic variability, and ability to reduce the risks associated with certain therapies; the ability to develop, manufacture, launch and market our drug products; our projections for future revenues, profitability and ability to achieve certain sales targets; our estimates regarding our capital requirements and our needs for additional financing; the likelihood of obtaining favorable scheduling and labeling of our drug products; the likelihood of regulatory approval under the Federal Food, Drug, and Cosmetic Act without having to conduct long and costly trials to generate all of the data which are often required in connection with a traditional new chemical entity; our ability to develop safer and improved versions of widely prescribed drugs using our Carrierwave (TM) technology; and our ability to obtain favorable patent claims. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof. New River Pharmaceuticals does not undertake any obligation to republish revised forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. Readers are also urged to carefully review and consider the various disclosures in New River Pharmaceuticals' annual report on Form 10-K, filed with the SEC on March 15, 2006, as well as other public filings with the SEC.
Contacts: The Ruth Group John Quirk (investors) 646-536-7029 [email protected] Zack Kubow (media) 646-536-7020 [email protected]
love sdb
Posted by Phillipa on July 14, 2007, at 22:10:16
In reply to Re: treatments hashimoto etc. }} Phillipa, posted by sdb on July 14, 2007, at 20:47:28
Thanks sdb I copied and pasted it and filed it. Love Jan so much work for me.
Posted by sdb on July 15, 2007, at 0:05:43
In reply to Re: treatments hashimoto etc. }} Phillipa » sdb, posted by Phillipa on July 14, 2007, at 22:10:16
> Thanks sdb I copied and pasted it and filed it. Love Jan so much work for me.
No problem, here is more information from harrison's. If you're interested in treatment then look this chapture.
love sdb, busy...
AUTOIMMUNE HYPOTHYROIDISM
Classification
Autoimmune hypothyroidism may be associated with a goiter (Hashimoto's, or goitrous thyroiditis) or, at the later stages of the disease, minimal residual thyroid tissue (atrophic thyroiditis). Because the autoimmune process gradually reduces thyroid function, there is a phase of compensation when normal thyroid hormone levels are maintained by a rise in TSH. Though some patients may have minor symptoms, this state is called subclinical hypothyroidism or mild hypothyroidism. Later, free T4 levels fall and TSH levels rise further; symptoms become more readily apparent at this stage (usually TSH > 10 mU/L), which is referred to as clinical hypothyroidism or overt hypothyroidism.
Prevalence
The mean annual incidence rate of autoimmune hypothyroidism is up to 4 per 1000 women and 1 per 1000 men. It is more common in certain populations, such as the Japanese, probably because of genetic factors and chronic exposure to a high-iodine diet. The mean age at diagnosis is 60 years, and the prevalence of overt hypothyroidism increases with age. Subclinical hypothyroidism is found in 6 to 8% of women (10% over the age of 60) and 3% of men. The annual risk of developing clinical hypothyroidism is about 4% when subclinical hypothyroidism is associated with positive TPO antibodies.
Pathogenesis
In Hashimoto's thyroiditis, there is a marked lymphocytic infiltration of the thyroid with germinal center formation, atrophy of the thyroid follicles accompanied by oxyphil metaplasia, absence of colloid, and mild to moderate fibrosis. In atrophic thyroiditis, the fibrosis is much more extensive, lymphocyte infiltration is less pronounced, and thyroid follicles are almost completely absent. Atrophic thyroiditis likely represents the end stage of Hashimoto's thyroiditis rather than a distinct disorder.
As with most autoimmune disorders, susceptibility to autoimmune hypothyroidism is determined by a combination of genetic and environmental factors, and the risk of either autoimmune hypothyroidism or Graves' disease is increased among siblings. HLA-DR polymorphisms are the best documented genetic risk factors for autoimmune hypothyroidism, especially HLA-DR3, -DR4, and -DR5 in Caucasians. A weak association also exists between polymorphisms in CTLA-4, a T cell–regulating gene, and autoimmune hypothyroidism. Both of these genetic associations are shared by other autoimmune diseases, which may explain the relationship between autoimmune hypothyroidism and other autoimmune diseases, especially type 1 diabetes mellitus, Addison disease, pernicious anemia, and vitiligo (Chap. 330). HLA-DR and CTLA-4 polymorphisms account for approximately half of the genetic susceptibility to autoimmune hypothyroidism. The other contributory loci remain to be identified. A gene on chromosome 21 may be responsible for the association between autoimmune hypothyroidism and Down syndrome. The female preponderance of thyroid autoimmunity is most likely due to the effects of sex steroids on the immune response, but an X chromosome–related genetic factor is also possible, which may account for the high frequency of autoimmune hypothyroidism in Turner syndrome. Environmental susceptibility factors are also poorly defined at present. A high iodine intake may increase the risk of autoimmune hypothyroidism by immunologic effects or direct thyroid toxicity. There is no convincing evidence for a role of infection, except for the congenital rubella syndrome, in which there is a high frequency of autoimmune hypothyroidism. Viral thyroiditis does not induce subsequent autoimmune thyroid disease.
The thyroid lymphocytic infiltrate in autoimmune hypothyroidism is composed of activated CD4+ and CD8+ T cells, as well as B cells. Thyroid cell destruction is believed to be primarily mediated by the CD8+ cytotoxic T cells, which destroy their targets by either perforin-induced cell necrosis or granzyme B–induced apoptosis. In addition, local T cell production of cytokines, such as tumor necrosis factor (TNF), IL-1, and interferon (IFN) γ, may render thyroid cells more susceptible to apoptosis mediated by death receptors, such as Fas, which are activated by their respective ligands on T cells. These cytokines also impair thyroid cell function directly, and induce the expression of other proinflammatory molecules by the thyroid cells themselves, such as cytokines, HLA class I and class II molecules, adhesion molecules, CD40, and nitric oxide. Administration of high concentrations of cytokines for therapeutic purposes (especially IFN-α) is associated with increased autoimmune thyroid disease, possibly through mechanisms similar to those in sporadic disease.
Antibodies to Tg and TPO are clinically useful markers of thyroid autoimmunity, but any pathogenic effect is restricted to a secondary role in amplifying an ongoing autoimmune response. TPO antibodies fix complement, and complement membrane attack complexes are present in the thyroid in autoimmune hypothyroidism. However, transplacental passage of Tg or TPO antibodies has no effect on the fetal thyroid, which suggests that T cell–mediated injury is required to initiate autoimmune damage to the thyroid. Up to 20% of patients with autoimmune hypothyroidism have antibodies against the TSH-R, which, in contrast to TSI, do not stimulate the receptor but prevent the binding of TSH. These TSH-R-blocking antibodies therefore cause hypothyroidism and, especially in Asian patients, thyroid atrophy. Their transplacental passage may induce transient neonatal hypothyroidism. Rarely, patients have a mixture of TSI- and TSH-R-blocking antibodies, and thyroid function can oscillate between hyperthyroidism and hypothyroidism as one or the other antibody becomes dominant. Predicting the course of disease in such individuals is difficult, and they require close monitoring of thyroid function. Bioassays can be used to document that TSH-R-blocking antibodies reduce the cyclic AMP–inducing effect of TSH on cultured TSH-R-expressing cells, but these assays are difficult to perform. Assays that measure the binding of antibodies to the receptor by competition with radiolabeled TSH [TSH-binding inhibiting immunoglobulins (TBII)] do not distinguish between TSI- and TSH-R-blocking antibodies, but a positive result in a patient with spontaneous hypothyroidism is strong evidence for the presence of blocking antibodies. The use of these assays does not generally alter clinical management, although they may be useful to confirm the cause of transient neonatal hypothyroidism.
Clinical Manifestations
The main clinical features of hypothyroidism are summarized in Table 320-5. The onset is usually insidious, and the patient may become aware of symptoms only when euthyroidism is restored. Patients with Hashimoto's thyroiditis may present because of goiter rather than symptoms of hypothyroidism. The goiter may not be large but is usually irregular and firm in consistency. It is often possible to palpate a pyramidal lobe, normally a vestigial remnant of the thyroglossal duct. Rarely, uncomplicated Hashimoto's thyroiditis is associated with pain.
Patients with atrophic thyroiditis, or the late stage of Hashimoto's thyroiditis, present with symptoms and signs of hypothyroidism. The skin is dry, and there is decreased sweating, thinning of the epidermis, and hyperkeratosis of the stratum corneum. Increased dermal glycosaminoglycan content traps water, giving rise to skin thickening without pitting (myxedema). Typical features include a puffy face with edematous eyelids and nonpitting pretibial edema (Fig. 320-4). There is pallor, often with a yellow tinge to the skin due to carotene accumulation. Nail growth is retarded, and hair is dry, brittle, difficult to manage, and falls out easily. In addition to diffuse alopecia, there is thinning of the outer third of the eyebrows, although this is not a specific sign of hypothyroidism.
Other common features include constipation and weight gain (despite a poor appetite). In contrast to popular perception, the weight gain is usually modest and due mainly to fluid retention in the myxedematous tissues. Libido is decreased in both sexes, and there may be oligomenorrhea or amenorrhea in long-standing disease, but menorrhagia is also common. Fertility is reduced and the incidence of miscarriage is increased. Prolactin levels are often modestly increased (Chap. 318) and may contribute to alterations in libido and fertility and cause galactorrhea.
Myocardial contractility and pulse rate are reduced, leading to a
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reduced stroke volume and bradycardia. Increased peripheral resistance may be accompanied by hypertension, particularly diastolic. Blood flow is diverted from the skin, producing the cool extremities. Pericardial effusions occur in up to 30% of patients but rarely compromise cardiac function. Though alterations in myosin heavy chain isoform expression have been documented, cardiomyopathy is unusual. Fluid may also accumulate in other serous cavities and in the middle ear, giving rise to conductive deafness. Pulmonary function is generally normal, but dyspnea may be caused by pleural effusion, impaired respiratory muscle function, diminished ventilatory drive, or sleep apnea.View Figure FIGURE 320-4 Facial appearance in hypothyroidism. Note puffy eyes and thickened, pale skin.
Carpal tunnel and other entrapment syndromes are common, as is impairment of muscle function with stiffness, cramps, and pain. On examination, there may be slow relaxation of tendon reflexes and pseudomyotonia. Memory and concentration are impaired. Rare neurologic problems include reversible cerebellar ataxia, dementia, psychosis, and myxedema coma. Hashimoto's encephalopathy is a rare and distinctive syndrome associated with myoclonus and slow-wave activity on electroencephalography, which can progress to confusion, coma, and death. It is steroid-responsive and may occur in the presence of autoimmune thyroiditis, without hypothyroidism. The hoarse voice and occasionally clumsy speech of hypothyroidism reflect fluid accumulation in the vocal cords and tongue.
The features described above are the consequence of thyroid hormone deficiency. However, autoimmune hypothyroidism may be associated with signs or symptoms of other autoimmune diseases, particularly vitiligo, pernicious anemia, Addison disease, alopecia areata, and type 1 diabetes mellitus. Less common associations include celiac disease, dermatitis herpetiformis, chronic active hepatitis, rheumatoid arthritis, systemic lupus erythematosus (SLE), and Sjögren's syndrome. Thyroid-associated ophthalmopathy, which usually occurs in Graves' disease (see below), occurs in about 5% of patients with autoimmune hypothyroidism.
Autoimmune hypothyroidism is uncommon in children and usually presents with slow growth and delayed facial maturation. The appearance of permanent teeth is also delayed. Myopathy, with muscle swelling, is more common in children than in adults. In most cases, puberty is delayed, but precocious puberty sometimes occurs. There may be intellectual impairment if the onset is before 3 years and the hormone deficiency is severe.
Laboratory Evaluation
A summary of the investigations used to determine the existence and cause of hypothyroidism is provided in Fig. 320-5. A normal TSH level excludes primary (but not secondary) hypothyroidism. If the TSH is elevated, an unbound T4 level is needed to confirm the presence of clinical hypothyroidism, but T4 is inferior to TSH when used as a screening test, as it will not detect subclinical or mild hypothyroidism. Circulating unbound T3 levels are normal in about 25% of patients, reflecting adaptive responses to hypothyroidism. T3 measurements are therefore not indicated.View Figure FIGURE 320-5 Evaluation of hypothyroidism. TPOAb+, thyroid peroxidase antibodies present; TPOAb-, thyroid peroxidase antibodies not present. TSH, thyroid-stimulating hormone.
Once clinical or subclinical hypothyroidism is confirmed, the etiology is usually easily established by demonstrating the presence of TPO antibodies, which are present in 90 to 95% of patients with autoimmune hypothyroidism. TBII can be found in 10 to 20% of patients, but these determinations are not needed routinely. If there is any doubt about the cause of a goiter associated with hypothyroidism, FNA biopsy can be used to confirm the presence of autoimmune thyroiditis. Other abnormal laboratory findings in hypothyroidism may include increased creatine phosphokinase, elevated cholesterol and triglycerides, and anemia (usually normocytic or macrocytic). Except when accompanied by iron deficiency, the anemia and other abnormalities gradually resolve with thyroxine replacement.
Differential Diagnosis
An asymmetric goiter in Hashimoto's thyroiditis may be confused with a multinodular goiter or thyroid carcinoma, in which thyroid antibodies may also be present. Ultrasound can be used to show the presence of a solitary lesion or a multinodular goiter, rather than the heterogeneous thyroid enlargement typical of Hashimoto's thyroiditis. FNA biopsy is useful in the investigation of focal nodules. Other causes of hypothyroidism are discussed below but rarely cause diagnostic confusion (Table 320-4).
OTHER CAUSES OF HYPOTHYROIDISM
Iatrogenic hypothyroidism is a common cause of hypothyroidism and can often be detected by screening before symptoms develop. In the first 3 to 4 months after radioiodine treatment, transient hypothyroidism may occur due to reversible radiation damage rather than to cellular destruction. Low-dose thyroxine treatment can be withdrawn if recovery occurs. Because TSH levels are suppressed by hyperthyroidism, unbound T4 levels are a better measure of thyroid function than TSH in the months following radioiodine
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treatment. Mild hypothyroidism after subtotal thyroidectomy may also resolve after several months, as the gland remnant is stimulated by increased TSH levels.
Iodine deficiency is responsible for endemic goiter and cretinism but is an uncommon cause of adult hypothyroidism unless the iodine intake is very low or there are complicating factors, such as the consumption of thiocyanates in cassava or selenium deficiency. Though hypothyroidism due to iodine deficiency can be treated with thyroxine, public health measures to improve iodine intake should be advocated to eliminate this problem. Iodized salt or bread or a single bolus of oral or intramuscular iodized oil have all been used successfully.
Paradoxically, chronic iodine excess can also induce goiter and hypothyroidism. The intracellular events that account for this effect are unclear, but individuals with autoimmune thyroiditis are especially susceptible. Iodine excess is responsible for the hypothyroidism that occurs in up to 13% of patients treated with amiodarone (see below). Other drugs, particularly lithium, may also cause hypothyroidism. Transient hypothyroidism caused by thyroiditis is discussed below.
Secondary hypothyroidism is usually diagnosed in the context of other anterior pituitary hormone deficiencies; isolated TSH deficiency is very rare (Chap. 318). TSH levels may be low, normal, or even slightly increased in secondary hypothyroidism; the latter is due to secretion of immunoactive but bioinactive forms of TSH. The diagnosis is confirmed by detecting a low unbound T4 level. The goal of treatment is to maintain unbound T4 levels in the upper half of the reference range, as TSH levels cannot be used to monitor therapy.
TREATMENT
Clinical Hypothyroidism
If there is no residual thyroid function, the daily replacement dose of levothyroxine is usually 1.6 µg/kg body weight (typically 100 to 150 µg). In many patients, however, lower doses suffice until residual thyroid tissue is destroyed. In patients who develop hypothyroidism after the treatment of Graves' disease, there is often underlying autonomous function, necessitating lower replacement doses (typically 75 to 125 µg/d).
Adult patients under 60 without evidence of heart disease may be started on 50 to 100 µg levothyroxine (T4) daily. The dose is adjusted on the basis of TSH levels, with the goal of treatment being a normal TSH, ideally in the lower half of the reference range. TSH responses are gradual and should be measured about 2 months after instituting treatment or after any subsequent change in levothyroxine dosage. The clinical effects of levothyroxine replacement are often slow to appear. Patients may not experience full relief from symptoms until 3 to 6 months after normal TSH levels are restored. Adjustment of levothyroxine dosage is made in 12.5- or 25-µg increments if the TSH is high; decrements of the same magnitude should be made if the TSH is suppressed. Patients with a suppressed TSH of any cause, including T4 overtreatment, have an increased risk of atrial fibrillation and reduced bone density.
Although dessicated animal thyroid preparations (thyroid extract USP) are available, they are not recommended as potency and composition vary between batches. Interest in using levothyroxine combined with liothyronine (triiodothyronine, T3) has been revived, based on studies suggesting that patients feel better when taking the T4/T3 combination compared to T4 alone. However, a long-term benefit from this combination is not established. There is no place for liothyronine alone as long-term replacement, because the short half-life necessitates three or four daily doses and is associated with fluctuating T3 levels.
Once full replacement is achieved and TSH levels are stable, follow-up measurement of TSH is recommended at annual intervals and may be extended to every 2 to 3 years, if a normal TSH is maintained over several years. It is important to ensure ongoing compliance, however, as patients do not feel any difference after missing a few doses of levothyroxine, this sometimes leads to self-discontinuation.
In patients of normal body weight who are taking ≥200 µg of levothyroxine per day, an elevated TSH level is often a sign of poor compliance. This is also the likely explanation for fluctuating TSH levels, despite a constant levothyroxine dosage. Such patients often have normal or high unbound T4 levels, despite an elevated TSH, because they remember to take medication for a few days before testing; this is sufficient to normalize T4, but not TSH, levels. It is important to consider variable compliance, as this pattern of thyroid function tests is otherwise suggestive of disorders associated with inappropriate TSH secretion (Table 320-3). Because T4 has a long half-life (7 days), patients who miss doses can be advised to take up to three doses of the skipped tablets at once. Other causes of increased levothyroxine requirements must be excluded, particularly malabsorption (e.g., celiac disease, small-bowel surgery), estrogen therapy, and drugs that interfere with T4 absorption or clearance such as cholestyramine, ferrous sulfate, calcium supplements, lovastatin, aluminum hydroxide, rifampicin, amiodarone, carbamazepine, and phenytoin.
Mild Hypothyroidism
By definition, subclinical or mild hypothyroidism refers to biochemical evidence of thyroid hormone deficiency in patients who have few or no apparent clinical features of hypothyroidism. There are no universally accepted guidelines for the treatment of mild hypothyroidism. As long as excessive treatment is avoided, there is little risk in correcting a slightly increased TSH, and some patients likely derive modest clinical benefit from treatment. Moreover, there is some risk that patients will progress to overt hypothyroidism, particularly when the TSH level is >6 mU/L and TPO antibodies are present. Treatment is administered by starting with a low dose of levothyroxine (25 to 50 µg/d) with the goal of normalizing TSH. If thyroxine is not given, thyroid function should be evaluated annually.
Special Treatment Considerations
Rarely, levothyroxine replacement is associated with pseudotumor cerebri in children. Presentation appears to be idiosyncratic and occurs months after treatment has begun. Women with a history or high risk of hypothyroidism should ensure that they are euthyroid prior to conception and during early pregnancy as maternal hypothyroidism may adversely affect fetal neural development. Thyroid function should be evaluated once pregnancy is confirmed and at the beginning of the second and third trimesters. The dose of levothyroxine may need to be increased by ≥50% during pregnancy and returned to previous levels after delivery. Elderly patients may require up to 20% less thyroxine than younger patients. In the elderly, especially patients with known coronary artery disease, the starting dose of levothyroxine is 12.5 to 25 µg/d with similar increments every 2 to 3 months until TSH is normalized. In some patients it may be impossible to achieve full replacement, despite optimal antianginal treatment. Emergency surgery is generally safe in patients with untreated hypothyroidism, although routine surgery in a hypothyroid patient should be deferred until euthyroidism is achieved.
Myxedema coma still has a high mortality rate, despite intensive treatment. Clinical manifestations include reduced level of consciousness, sometimes associated with seizures, as well as the other features of hypothyroidism (Table 320-5). Hypothermia can reach 23°C (74°F). There may be a history of treated hypothyroidism with poor compliance, or the patient may be previously undiagnosed. Myxedema coma almost always occurs in the elderly and is usually precipitated by factors that impair respiration, such as drugs (especially sedatives, anesthetics, antidepressants), pneumonia, congestive heart failure, myocardial infarction, gastrointestinal bleeding, or cerebrovascular accidents. Sepsis should also be suspected. Exposure to cold may also be a risk factor. Hypoventilation, leading to hypoxia and hypercapnia, plays a major role in pathogenesis; hypoglycemia and dilutional hyponatremia also contribute to the development of myxedema coma.
Levothyroxine can initially be administered as a single intravenous bolus of 500 µg, which serves as a loading dose. Although further levothyroxine is not strictly necessary for several days, it is usually continued at a dose of 50 to 100 µg/d. If suitable intravenous preparation is not available, the same initial dose of levothyroxine can be given by nasogastric tube (though absorption may be impaired in myxedema). An alternative is to give liothyronine (T3) intravenously or
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via nasogastric tube, in doses ranging from 10 to 25 µg every 8 to 12 h. This treatment has been advocated because T4 → T3 conversion is impaired in myxedema coma. However, excess liothyroxine has the potential to provoke arrhythmias. Another option is to combine levothyroxine (200 µg) and liothyronine (25 µg) as a single, initial intravenous bolus followed by daily treatment with levothyroxine (50 to 100 µg/d) and liothyronine (10 µg every 8 h).
Supportive therapy should be provided to correct any associated metabolic disturbances. External warming is indicated only if the temperature is <30°C, as it can result in cardiovascular collapse (Chap. 16). Space blankets should be used to prevent further heat loss. Parenteral hydrocortisone (50 mg every 6 h) should be administered, as there is impaired adrenal reserve in profound hypothyroidism. Any precipitating factors should be treated, including the early use of broad-spectrum antibiotics, pending the exclusion of infection. Ventilatory support with regular blood gas analysis is usually needed during the first 48 h. Hypertonic saline or intravenous glucose may be needed if there is hyponatremia or hypoglycemia; hypotonic intravenous fluids should be avoided because they may exacerbate water retention secondary to reduced renal perfusion and inappropriate vasopressin secretion. The metabolism of most medications is impaired, and sedatives should be avoided if possible or used in reduced doses. Medication blood levels should be monitored, when available, to guide dosage.
Posted by Phillipa on July 15, 2007, at 20:18:40
In reply to Re: treatments hashimoto etc. }} Phillipa, posted by sdb on July 15, 2007, at 0:05:43
sdb Didn't understand a lot of it but I do find myself extremely tired even a couple of hours after the cytomel. Do you feel that I should go back to synthroid only? It was my choice to take the T3. I have never been more tired in my life and this is only 5mcg of cytomel and down to 88mcg of synthroid a half on sunday. And for the stable nine years was on 125mcg of synthroid and took it with breakfast yougurt cereal, and a bananna and tea. Love Jan
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