Oh my. Now another American desiccated thyroid (NDT) brand recall?
Earlier this year, Acella’s NP thyroid was found to be superpotent (over 110% on the T3 content), and they issued a voluntary recall.
Now, as of August 25, 2020, Nature-Throid and/or WP-Thyroid are sub-potent, so their manufacturer RLC Labs is issuing a voluntary recall.
QUOTE:
“RLC Labs, Inc. is dedicated to the health and safety of our hypothyroid community.
As our number one priority, we want to ensure that you are aware of our decision to issue a recall of all unexpired lots of Nature-Throid® (Thyroid USP Tablets) and WP Thyroid® (Thyroid USP Tablets) that are currently in commercial distribution.
This recall has been initiated because testing found that certain lots of these products may be sub-potent (i.e. contain less than 90% of the labeled amount of liothyronine or levothryroxine).
We have voluntarily decided to recall all unexpired lots in the marketplace to ensure that patients only receive product that meets our high quality standards.
As of this release, we have not been notified of any adverse reactions from patients related to this recall of Nature-Throid® and/or WP Thyroid®.
We are currently working in tandem with the FDA to ensure the quality and safety of our products.”
See the original on the RLC website.
In case they update the notice, a copy is also publicly archived on Archive.org here.
Tell us how much.
They say that their batches were found to be less potent than the FDA permitted variance, <90% on T4 and/or T3, but they won’t say exactly.
UPDATE SEP 6, 2020: “The products are being recalled because testing of samples from six (6) lots by the U.S. Food and Drug Administration found the samples to be sub potent. The product may have as low as 87% of the labeled amount of Liothyronine (T3) or Levothyroxine(T4).” (FDA notice ) We still do not know whether it is the T3 or the T4 and which hormone (s) it was in the Nature Throid and the WPThyroid.
In the Acella NP thyroid recall, we were told exactly how much and which hormone was superpotent, so this recall of RLC labs’ Nature-Throid/WP-throid is rather more vague.
Not only that, it is unclear whether Nature-Throid and WP-thyroid are identical in the degree and type of subpotency. Maybe T4 was exactly 87% potency on both brands’ T4, or both brands’ T3, who knows:
- Reference: 100% potency T4 (38 mcg per 65 mg tablet), 100% potency T3 (9 mcg per 60 mg tablet) according to prescriber’s information.
- Option 1: Subpotent 87% in T4, meanwhile any shifts can happen within the allowed 90-110% potency in T3 and they don’t have to tell anyone.
- Option 2: Subpotent 87% in T3, Anywhere within allowed 90-110% potency in T4
- Option 3: Subpotent 87% in both T3 and T4.
We cannot assume that potency went down from 90% to 87% between lots, when the variability the FDA permits without any recall or notice is 90-110% of the stated potency.
- The best case scenario was that you were taking a lower-potency batch at 90%, and you had your doses adjusted and were fine. Then you went from 90 to 87% potency on one of the hormones. That’s only a 3.4% loss in potency.
- In the worst case scenario, you could have been dosed on higher-potency batch at 110% and found your optimal level. And then suddenly whooosh! You’re down at dosing 87% — Therefore, the maximum difference is 26% — you’re losing a quarter of your daily dose of T4 or T3! You’d notice. You’d have to increase your dose!
It makes a difference whether it’s the T3 or the T4 that is subpotent, because each of us converts T4 hormone at different rates. Some of us are poor converters and rely on the T3 content to boost our FT3 levels so we have more active hormone to bind with our receptors.
I’d get my replacement ASAP if I were taking it.
Shrug-worthy underdose?
2020/09/10: This was my first reaction when seeing the original notice, prior to the FDA risk statement being published: Interestingly, RLC Labs first notice didn’t load their recall notice with cautions about horrors in pregnancy outcomes (as Acella’s notice did). However, an underdose from sub-potency to both or the T4 content is far more a risk to pregnancy than an overdose due to superpotency of T3 alone. So, in the US regulatory context, a thyroid medication’s T3 superpotency hits the panic button, while a T3 and/or T4 subpotency that could lead to underdose? Underdose? Shrug. Meh. Let them eat more donuts and coffee. Oh wait. But coffee can reduce absorption of T4 hormone from the gut (Benvega et al, 2008).
But now we have more info about risk, not just a shrug!! …
The FDA risk statement: No longer a shrug.
Risk Section added Sept. 10, 2020
Let’s digest what the FDA announcement says about risks in this recall:
Risk Statement: Patients being treated for hypothyroidism (underactive thyroid), who receive sub potent Nature-Throid® or WP Thyroid®, may experience signs and symptoms of hypothyroidism (underactive thyroid) which may include, fatigue, increased sensitivity to cold, constipation, dry skin, puffy face, hair loss, slow heart rate, depression, swelling of the thyroid gland and/or unexplained weight gain or difficulty losing weight.
There is reasonable risk of serious injury in newborn infants or pregnant women with hypothyroidism including early miscarriage, fetal hyperthyroidism, and/or impairments to fetal neural and skeletal development.
In elderly patients and patients with underlying cardiac disease toxic cardiac manifestations of hyperthyroidism may occur, such as cardiac pain, palpitations or cardiac arrhythmia.
RLC Labs, Inc. has not received any reports of adverse events related to this recall.
On the symptoms of hypothyroidism, we can be thankful for their inclusion of such a detailed list. It is rare to see people care about listing the symptoms of hair loss and weight gain, two things that can be incredibly damaging to our identity and our social lives.
I’m not sure why they mentioned “fetal hyperthyroidism” and “cardiac manifestations of hyperthyroidism” near the end, because this is a potency DEcrease not an INcrease. It looks like filler text someone plunked in without thinking clearly!
Other risks not mentioned?
Symptoms, maternal risks, and cardiovascular risks. These are stereotypical top 3 things to mention. They have to be covered.
But the simple fact is that if they listed all the risks to all the organs and tissues affected by thyroid hormone levels, they would have a list as long as your leg.
There is no disease or disorder in the body that is immune to the effects of a severe reduction in thyroid hormone receptor signalling. Thyroid hormone is just that essential to everything functioning well.
If you have another autoimmune disease, skin disorder or kidney or liver dysfunction, your symptoms and overall health could get worse when you are hypothyroid.
But woe unto the people who are just coming out of surgery, or fighting for their lives in hospital intensive care, or struggling in the final stages of cancer or a neurological disease. You can’t risk being hypothyroid without adequate T3 supply for recovery if you’re in Nonthyroidal Illness.
Click to read more about risk to thyroid patients being hypothyroid during nonthyroidal illness
What is Nonthyroidal illness syndrome (NTIS)? It is a metabolic derangement that happens in all sorts of acute and chronic illnesses and after surgeries and accidents. Your deiodinase type 3 (D3) dumps your thyroid hormones and depletes T3 to lower your metabolic rate very quickly (See GRAPHIC and discussion: T3 Depletion). But sometimes D3 dumps T3 way too far, and T3 stays low for too long. If your TSH was normal to start with, it stays normal during the acute phase (early phase) like an apathetic observer, because the body isn’t ready yet for a T3 refill.
The body will need a T3 refill from a TSH-driven healthy thyroid (or from a hormone pill) to turn it around just at the right time, to aid your recovery of health. If you can’t get your T3 refill at that crucial turning point (whenever that is…), the risk of morbidity and mortality escalates.
Why “woe unto the people…”? Because people on a thyroid hormone leash — people who depend on pills for their thyroid hormone supply — are going to see a loss in T3 levels, too, just like others with healthy thyroids.
- The natural way to recover is by TSH stimulating a healthy thyroid, which then rapidly secretes more T3 to fill the T3 hole. TSH rises fast, and as TSH rises, the T3 portion of the T3:T4 ratio of thyroidal secretion escalates significantly to give a T3-refill to the body even while there’s still a hole in the T3 bucket. Eventually enough T3 and T4 are in circulation and you can recover.
- But you, the thyroid disabled person, will need enough T3 from your hormone pill (plus any residual thyroid tissue you may have) to dig yourself out of the hole and to recover health.
GOOD News: Be thankful you’re on a hormone pill that includes some T3, and do not let them switch you to LT4-Levothyroxine while you are in hospital (they can be sneaky if they are programmed to believe that LT4 is best for you!) Bring your supply of NDT. Tell a family member that if you ever go to hospital, they will need to bring your pills to the hospital.
Scientists and doctors are ignorant about our risk as thyroid patients because, as I’ve pointed out before, Thyroid patients are routinely excluded from low T3 syndrome (NTIS) research. It’s called nonthyroidal illness, and we have an illness that is thyroidal but we’re still at risk. But scientists can be easily tricked by language and definitions, so they routinely eliminate us from most research studies of NTIS. Out of ignorance and blind faith, doctors have been told that all we need is our daily T4 dose and we’re fine. No, you can’t say that with enough research. We have to use science and thyroid physiology to surmise what is risky, and not having a thyroid with adjustable TSH-driven T3 secretion rate is a risk because that’s key to recovery!
Why is LT4 therapy bad for you in hospital? An early study on NTIS treatment showed that when they tried to “help” even healthy-thyroid people out of NTIS T3-depletion using T4 hormone alone, it backfired (Brent & Hershman, 1986). That’s because not only did the T4 dosing reduce the strength of their TSH elevation which meant loss of bonus T3 secretion, but also the body was in a mode of D3 enzyme upregulation, converting T4 quickly to RT3 at the same time as converting T3 to various T2s.
Maternal risks
We should be very thankful to them for noticing that risk to fetal life is real. To some people on the borderline of hypothyroidism, a small difference is enough to push them under.
The risk here is very present with REDUCED potency in the T4 portion of desiccated thyroid (NDT). Some women on NDT therapy are superconverters and have a very low FT4 level, hovering near the bottom end of reference, while their FT3 is much higher in range and compensates for the lower FT4.
Click to read more about pregnancy risks with a lower FT4
Pregnancy demands more thyroid hormones in circulation, in general, and FT4 / TT4 (total and free) is the hormone that naturally elevates (even above reference) in people who are pregnant with healthy thyroid glands. (But please do not try to elevate your FT4 above reference using NDT just to mimic their T4 levels! Because of your medication type, your FT3 would be super-high above your FT4 and you’d be overdosed! Just try to keep your FT4 in range bare minimum and half way up the range would be nice, trying to keep your FT3 from spiking too high above reference.)
The risk is that you may already be in your 1st trimester not knowing that you are pregnant, and the fetus really, really needs your maternal hormones in the first trimester. So if you are trying to get pregnant you cannot risk hypothyroidism.
The stablest hormone with the largest supply in blood is T4, and the placenta (which expresses a lot of D3 enzyme) does the labor of filtering the T4 down to levels that the fetus needs. The placenta converts a lot of your T4 to RT3 and only gives the fetus a trickle, and that’s what they need, just enough.
The older studies of fetal risk during pregnancy (1964 to 1970s by Dr. Evelyn Man and associates) focused on UNDERdosed people on desiccated thyroid (Proloid brand) versus women who were dosed with enough T4 supply (the T4 was measured by BEI, Butanol Extracted Iodine, before there was a reliable T4 hormone test. They did not have the technology to measure T3).
- The women who had enough T4 hormone in circulation while on NDT had perfectly healthy babies with normal mental development by 7 years old. The underdosed women’s children did not fare well.
I don’t have room here to give links to all 10 of these old articles on desiccated thyroid in pregnancy, and most are not fully online anyway. But here is Dr. Man’s most recent article on the topic, in 1991, after a rat study was done by Escobar-Morreale and team, which confirmed some of what Man’s team had found many years previously:
- Man, E. B., Brown, J. F., & Serunian, S. A. (1991). Maternal hypothyroxinemia: Psychoneurological deficits of progeny. Annals of Clinical & Laboratory Science, 21(4), 227–239. http://www.annclinlabsci.org/content/21/4/227
About heart rate / arrhythmias.
Yes, having hypothyroidism will overall slow the heart rate down (bradycardia). The risk with bradycardia can happen when your heart rate goes down naturally at night, especially if you already have sleep apnea. (Read about bradycardia in this US News & World Report article.)
But there are risks beyond slow heart rate in hypothyroidism that many doctors are not aware of:
- Hypothyroidism (especially low T3) can also cause intermittent spikes in heart rate.
- Low T3 can also cause heart rhythm problems like atrial fibrillation.
Click to read more about cardiovascular risks in hypothyroidism (underdose, poor T4-T3 conversion)
Fluctuating heart rate in hypothyroidism appears to happen because our adrenal hormones (catecholamines) try to compensate for loss of T3 activity in receptors, and they kick in to keep our heart rate going.
“Thyrotoxic patients have normal plasma norepinephrine (NE) levels, while hypothyroid patients have elevated plasma NE levels, perhaps to compensate for reduced adrenergic sensitivity […]
Epinephrine levels were not different in hyperthyroid or hypothyroid patients compared with normal […]
Catecholamines [such as norepinephrine, etc. secreted from the adrenals] increase T4 to T3 conversion, by stimulating activity of a specific deubiquitinase that acts on the D2 protein, upregulates D2 activity, and increases T3 levels in the nucleus. […](Mullur et al, 2014)
[For scientific readers: What is deubiquitinase? We need D2 to convert a lot of our T4 into T3. The “deubiquitinase” is an enzyme that takes a D2 enzyme that has been temporarily inactivated by being turned into ubiquitin, and turns it back into an active D2 enzyme once again. This means that even a higher-normal T4 level, which usually dulls the D2 enzyme by ubiquitination, will suddenly not suppress D2 as much, and you’ll convert T4 to T3 more efficiently within cells. (The D2 is expressed close to the nucleus in the cytosol of the cell, where it will usher the T3 hormones into the nucleus where they will bind with receptors and send signals.) ]
What is the effect of higher norepinephrine in hypothyhroidism? A tachycardia rush (high heart rate)!
“Norepinephrine, produced by the adrenal medulla, is a stress hormone that increases blood pressure, heart rate, and glucose from energy stores; in the kidneys, it will cause constriction of the smooth muscles, resulting in decreased or inhibited flow to the nephrons.”
(Biology LibreTexts, 41.5A Epinephrine and Norepinephrine)
How quickly does norepinephrine cause a heart rate spike? pretty fast.
Catecholamines
During stress or a need for increased cardiac output, the adrenal glands release a hormone called norepinephrine into the bloodstream at the same time that the sympathetic nervous system is also triggered to increase your heart rate. This hormone causes the heart to beat faster, and unlike the sympathetic nervous system that sends an instantaneous and short-lived signal, norepinephrine released into the bloodstream increases the heart rate for several minutes or more.
(Michigan Medicine, Electrical System of the Heart, 2019)
I experienced these erratic tachycardia flares myself when I was in my final 3 months on Synthroid as a poor converter. My FT3 was far below reference (2.9 in a ref range of 3.5 to 6.5), and I was in nonthyroidal illness with a high RT3 of 33 (8-25) and a FT4 at mid range or higher. That kind of biochemistry is high risk (see graph below).
I would be doing nothing, like sitting as a passenger in a car, not feeling stressed, when all of a sudden I’d have a painful squeeze in one of my arteries or areas of my chest. Then my HR would spike up to 115 and be erratically jumping around with odd jaggedy shapes on the heartbeat visualization line as I put my finger on the phone and did a heart rate test.
There is a stereotype out there that heart problems are only seen in hyperthyroidism, and that’s simply not true. Being hypothyroid is not good for people with cardiovascular risks.
There is an “U shaped” risk profile — meaning that the risk is high on both ends, low thyroid hormone and high thyroid hormone. However, it matters what hormone you are low in.
Atrial fibrillation risk in particular
Being low in T3 is the biggest risk, followed by high-normal Free T4.
If you are taking a desiccated thyroid pill, the good news is that you likely do not have a “low T3 high T4” profile like many poor converters on LT4 monotherapy.
Instead, you’d likely have the reverse, with higher FT3 than FT4. Your ratio of FT3:FT4 is far healthier for the heart as long as you are not overdosing yourself.
Strange rules about Narrow Therapeutic Index medications
So, back to the topic of potency variability.
Why are thyroid medications permitted to vary so much in potency that they can fall below 90%?
Narrow therapeutic index” (NTI) drugs like synthetic Levothyroxine (LT4) are held to a higher standard than most other drugs, at 95-105% of the labeled potency across its shelf life (FDA, 2009).
However, drugs containing Liothyronine LT3, which provide T3, the more active hormone we metabolize from T4, are not (yet) considered NTI drugs.
Just like all other non-NTI pharma, therefore, desiccated thyroid medications like RLC labs’ Nature Throid, WP-Throid, and even synthetic Cytomel (T3) can vary 20% from pill to pill, or batch to batch, as long as they stay within 90-110% of the stated dose.
It is completely illogical that the FDA says the less active hormone T4 has a narrower therapeutic index than T3. It’s because synthetic levothyroxine gets more attention.
Apparently the levothyroxine provided by desiccated thyroid preparations is not held to the narrower 95-105%.
Very strange. Very illogical. But that’s the way the policies are right now.
Relevant NDT recall posts:
See our extensive 2-part post that went into the background, history and regulatory context of the Acella recall and examined how much much their superpotency could have mattered to our health.
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