Friday, June 7, 2013

Transient Hypothyroidism in Cats Following Radioiodine


Transient hypothyroidism, with the development of subnormal thyroid hormone levels, is common after radioiodine therapy. However, such suppression in the circulating thyroid hormone concentrations is usually mild and generally does not require thyroid hormone replacement therapy.

Why Transient Hypothyroidism Develops after I-131 Treatment

Prior to treatment of a hyperthyroid cat, the high circulating levels of the thyroid hormones (T3 and T4) have a negative feedback effect on the pituitary gland to suppress thyroid stimulating hormone (TSH) release (1-4). Therefore, serum TSH concentrations in hyperthyroid cats fall to low or undetectable levels (Figure 1).

Fig. 1: In normal cat, normal levels of thyroid hormone (T4 and T3) are controlled by TSH, a hormone secreted by the pituitary gland. In hyperthyroid cats, their thyroid tumor(s) secrete too much T4 and T3, resulting in a decrease in pituitary TSH secretion. Without adequate amounts of circulating TSH, any remaining normal thyroid tissue stops working and will atrophy.
Since adequate amounts of circulating TSH are needed by normal thyroid tissue for both iodine uptake and thyroid hormone secretion, the decreased circulating TSH concentrations that accompany persistent hyperthyroidism lead to atrophy of the normal (nonadenomatous) thyroid tissue (Figures 1 & 2). In contrast, because the adenomatous thyroid nodules (thyroid tumors) are autonomous and do not require circulating TSH for iodine uptake or thyroid hormone secretion, these thyroid tumors continue to exhibit both growth and hyperfunction (Figure 2).

See the thyroid scans below (Figure 2), which illustrate how cats with a thyroid adenoma affecting only 1 of the 2 thyroid lobes will show complete suppression of the normal lobe and not take up any radioactivity (labeled Unilateral, left panel). In contrast, the cats in the middle and right panels have both thyroid lobes involved with tumor (5).

Fig. 2: Thyroid scans in 3 hyperthyroid cats. All had low serum TSH concentrations. In the cat with a unilateral thyroid adenoma (left panel), the normal thyroid lobe is not visible — it has stopped functioning properly and has atrophied as a result of the low circulating TSH concentrations.
Many cats treated with radioiodine go through a period of transient, mild hypothyroidism after the 131-I treatment has destroyed their thyroid tumor(s). When rechecked within the first month after radioiodine therapy, many hyperthyroid cats have low to low-normal serum T4 concentrations (Figure 3).

If not overdosed with radioiodine, almost all these cats have some remaining “normal” thyroid tissue surrounding the thyroid tumor tissue, which has been chronically suppressed by the hyperthyroid state. However, now that the hyperthyroidism has been cured, pituitary TSH secretion eventually recovers and serum TSH concentrations will rise, resulting in stimulation of any remaining normal, but previously dormant, thyroid tissue.

Fig. 3: In hyperthyroidism,  the high T4 and T3 levels suppress pituitary TSH secretion to very low levels. Once the thyroid tumor is irradiated and destroyed, the T4 and T3 levels will fall to normal or even low levels for 1-2 months. With time, however, the pituitary gland recovers and starts to secrete TSH once again (sometimes to higher-than-normal amounts for a time). This allows any remaining normal thyroid tissue to become active once again and secrete normal amounts of thyroid hormone.
Most cats with a sufficient volume of normal thyroid tissue regain the ability to produce adequate amounts of thyroid hormone to maintain euthyroidism within 3 months of radioiodine therapy. Rarely, cats require as long as 6 months of chronically increased endogenous TSH levels to recover lost thyroid function and regain the ability to maintain normal thyroid hormone levels.

Bottom Line
Since transient hypothyroidism is common and and most cats will recover normal thyroid function with time, L-T4 replacement is not generally indicated at the time of this early recheck period.

However, if evidence of new or worsening kidney disease is found, short-term or permanent L-T4 replacement may be indicated to help preserve any residual renal function and prevent irreversible renal injury. I'll be discussing more about hypothyroidism and kidney function in a upcoming post.

References:
  1. Baral R, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. Philadelphia: Elsevier Saunders, 2012;571-592.
  2. Mooney CT, Peterson ME. Feline hyperthyroidism In: Mooney CT, Peterson ME, eds. Manual of Canine and Feline Endocrinology Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;199-203.
  3. Peterson ME. Hyperthyroidism in cats In: Rand JS, Behrend E, Gunn-Moore D, et al., eds. Clinical Endocrinology of Companion Animals. Ames, Iowa Wiley-Blackwell, 2013;295-310.
  4. Peterson ME, Broome MR. Radioiodine for feline hyperthyroidism In: Bonagura JD,Twedt DC, eds. Kirk's Current Veterinary Therapy, Volume XV. Philadelphia: Saunders Elsevier, 2013;in press.
  5. Broome MR. Thyroid scintigraphy in hyperthyroidism. Clin Tech Small Anim Pract 2006;21:10-16. 

10 comments:

WBIJCS said...

Dr. Peterson, how many days post I131 injection does transient hypo-t (or permanent) typically set in?

Ty

Dr. Mark E. Peterson said...

The time is quite variable, but generally the T4s fall to low-normal to low values by 2-3 weeks.

Dr. Mark E. Peterson said...

However, not all cats treated with radioiodine will develop low T4 values or transient hypothyroidism.

hearthefalconer said...

So given that I131 has been around approx. 30 years, what percentage of cats do develop hypothyroidism following I131 treatment?

Dr. Mark E. Peterson said...

It depends largely on the dose of I-131 given. With larger doses, this increases the rate of cure but also significantly increases the chances of hypothyroidism.

See this past blog post for more information:
http://animalendocrine.blogspot.com/2013/04/estimating-radioiodine-dose-to.html

Kim Fitzgerald said...

Dr Peterson,
Yesterday, my internist gave me a prescription for levothyroxine for my cat, who was treated with I-131 on 11/5/2012. She had preexisting kidney disease.
Mai Tai is a small Siamese, just under 5 lbs and 17 years old. She was diagnosed with stage 2/3 kidney disease (creatinine of 2.8) in July 2011, at age 14. She became hyperthyroid the following Spring. It was all very difficult from the diagnosis (only seen with Free T4) to the treatment with tapezole (she developed a low white blood cell count 90 days into treatment and had to be hospitalized).
After all of this, my internist and I agreed that I-131 would be the best solution. I asked a lot of questions, and had this done the best facility in IL. They did scintigraphy (which I recall revealed bilateral asymmetric noncancerous thyroid tumors) and administered 4.1 mCi in November 2012.
We routinely checked her thyroid in the months following. Her T4 was 1.2 in 2/17/13, 1.0 5/29/13, and 0.6 on 10/21/13. I became concerned after the last test, though she had no clinical signs and her kidney values were the same.
A month later, I brought Mai Tai in for an emergency visit for vomiting a lot, and another emergency a week later because I knew she had a UTI (she will cry and frequently visit the litterbox). Her creatinine had crept up to 3.1 and her calcium was also high. She got a month's worth of Baytril, and malignancy profiles revealed that her high calcium was likely idiopathic.
On 1/2/13, I brought her in to a new internist, and her creatinine was now 4.1. Her UTI seemed likely gone (via urine culture). Her calcium was about the same, and another profile revealed it was likely idiopathic. I had been reading up on cats who became hypothyroid after I-131, and decided to ask for the MSU thyroid +TSH panel.
Her TSH was tremendously high. Free T4 was low, and both Free and Total T4 were superlow. I like both of the internists I have had a lot, but I have to ask:
-Is this hypothyroidism likely transient?
-How often to you recommend rechecking thyroid levels now? Via both simple T4 and full thyroid panel?
-Is this damage to her kidneys possible at all reversible?
Thanks for any help!!

Dr. Mark E. Peterson said...

Transient hypothyroidism occurred immediately after treatment and lasts for 1-3 months. Your cat is permanently hypothyroidism and needs twice daily treatment with L-T4. I start with a dose of 0.075 mg (75 µg), given about an hour before the main meals or other medications (including phosphate binders). It's important to give the dose on an empty stomach because food inhibits the absorption of T4. If this isn't possible, putting the dose in a small amount of food, followed by the main main an hour later is ok.

I'd recheck a complete thyroid panel (at least a T4 and TSH) in a month. Also recheck the kidney values. We want the T4 to be above 2-2.5 µg/dl and the TSH to be normal. If that occurs, the creatinine generally falls but it will never normalize in your cat. Our hope would be to slow the progression of CKD but long term management of the renal disease will certainly be needed.

If not already done, you need to measure ionized calcium to confirm that the hypercalcemia is really a problem. Some cats with CKD will have a high total calcium, but the ionized calcium is normal - then we don't have to worry about it.

Deborah said...

Dr. Peterson: How do I find out if my cat was overdosed with I-131? It is two weeks post-treatment and he won't eat (anything) and is listless and sluggish. He has been this way since discharge and is not improving with time. Pre-treatment blood work was normal (including kidney functions). We hospitalized him for two days at one week post-treatment and, again, all blood work was normal. Thanks in advance for your response.

Dr. Mark E. Peterson said...

First of all, if your cat is hypothyroid, the serum T4 and T3 would be low. The TSH would also be high, but this might take a bit more time.

That said, hypothyroidism doesn't cause the signs that you describe. Most cats are relatively asymptomatic. The appetite might be decreased but total anorexia is not expected.

Have you tried an appetite stimulant (eg, mirtazapine)? If that doesn't work, then you need a further workup for other problems, such as x-rays or an abdominal ultrasound.

Deborah said...

Dr. Peterson: Thank you so much for your response. We have indeed tried Mirtazapine and it briefly stimulated the appetite for one sitting, although he didn’t consume much.  We also tried a benzodiazepine (Xanax) which again, briefly and mildly stimulated his appetite.  It seems odd to me that he would have suddenly and concomitantly developed another problem but we will most certainly take him in for a complete workup and abdominal ultrasound.  He had a chest X-ray as part of the I-131 screening process and it was normal, although it sounds as though other X-rays may be needed.  Any further thoughts on the matter would be much appreciated. Thanks again!