|
 |
  |
 |
 |
|
 |
|
 |
|
 |
|
 |
|
 |
|
 |
|
 |
|
 |
|
|
|||||||||||||||||||
- Thyroid -
1/25/02 re: Chronic urticaria associated with thyroid disease
I have a question regarding one of my patients and I would like to know your opinion.
The patient is a 26-year-old white female who came to my office last July with a history of hives and pruritus. She had been having these symptoms for several weeks with no other systemic complaints. She described the hives in crops and all over her body. No pattern or association with food was found. She was not taking any meds. and had no diseases or relevant past medical history. The physical exam was completely normal. She was diagnosed with acute urticaria and was started on cetirizine 10 mg QD with resolution of her symptoms. Because she was doing so well, she missed her follow-up appointment. She is a track athlete and she trains on an everyday basis. During the month of August she felt different and complained of diarrhea, increase heart rate and went to see a cardiologist. She had an EKG and echocardiogram that were completely normal. The cardiologist reassured her that her heart was fine and he suggested visiting an endocrinologist for a thyroid work up.
An endocrinologist who diagnosed hyperthyroidism saw her. The blood work showed the following results:
TSH < 0.05 mUI/ml (0.20-0.50)
FT3 19.36 pg/ml (2.60-5.40)
FT4 4.60 ng/ml (0.70-2.20)She was started on methimazol and propranolol with resolution of the symptoms. She had another blood test a few weeks latter with following results:
TSH <0.05mUI/ml (0.20-0.50)
FT4 1.19 ng/ml (0.70-2.20)During that time she continued taking the cetirizine with no more hives. She came to my office in November to find out how much longer she had to be taking the cetirizine. At that time she informed me of the thyroid problem.
I saw the results of the blood work and I ordered anti-thyroid antibodies with the following results:
nti-thyroglobuline 5.1 U/ml (<0.3 U/ml)
Anti-microsomal > 30.0 U/ml (<0.3 U/ml)We know that urticaria can be associated either with hypo or hyperthyroidism. This patient clearly has an autoimmune thyroid disease, probably a Hashimoto's thyroiditis. I will contact her endocrinologist soon and inform him about the findings. I would like to know what would be the best current treatment in this case.
You have described a very interesting and instructive case, which you have approached in a careful, thorough manner. As you likely know, a number of studies have shown the presence of increased levels of serum anti-thyroid (mainly anti microsomal/peroxidase) antibodies in 10-25% of individuals with chronic idiopathic urticaria (CIU). This prevalence is about 3 times the frequency in age-matched control without CIU. As expected, this situation was much more common in females. Only a minority of such antibody-positive individuals manifest evidence of clinical thyroid disease, - generally Hashimoto’s thyroiditis. It is still debated whether there is a pathogenic relationship between the concomitant thyroid abnormality and the CIU. One line of evidence found by some groups, but not others, is that treatment of the thyroid disease is followed by significant improvement in the CIU. Indeed, some groups, such as Shocket’s group in Denver, have reported improvement in the CIU of some individuals following treatment with L-thyroxin even when the patients were euthyroid to begin with. In another recent report, improvement in the CIU was noted when anti-thyroid agents were given when the patients were clinically hyperthyroid and L-thyroxin when the patients were hypothyroid or euthyroid (see enclosed abstract below). The situation with your patient appears relatively clear-cut, since your patient was hyperthyroid to begin with. I agree that Hashimot’s thyroiditis is the most likely cause. As you likely know, individuals with Hashimoto’s may be transiently hyperthyroid ("Hashitoxicosis") but eventually may become hypothyroid if and when sufficient thyroid tissue is destroyed. The persistently low TSH level after treatment was started suggests that suppression of TSH production is still going on. Therefore, it is important to have close follow-up by the endocrinologist that you mentioned with appropriate treatment of Hashimoto’s disease (some investigators report additional benefit from addition of transient corticosteroid therapy). Your patient is fortunate in that cetirizine controlled her urticaria even before treatment of the thyroid problem. I would suggest continuation of cetirizine until there is evidence that her thyroid disease is persistently controlled, then try tapering off the cetirizine. As an aside, I would remind your patient, as I have done to all of my patients receiving cetirizine, that cetirizine is a low sedating, not a non-sedating, antihistamine (particularly if a 20 mg dose is taken).
I have enclosed a review I wrote of a recent report in this area for the Current Literature section of this AADMC website. I have also enclosed the abstract referred to above.
Most studies have found a 10-20% prevalence of anti-thyroid antibodies in the sera of patients with chronic idiopathic urticaria (CIU), significantly higher than in age and gender-matched normal controls. In some of such CIU patients with anti-thyroid antibodies there has been evidence of thyroid dysfunction. Zauli et al of the Univ. of Bologna in Italy have found a 23% prevalence of anti-thyroid antibodies in the sera of those with CIU but also 33% in sera of individuals with chronic urticaria of "known" etiology. In both groups, the frequency of anti-thyroid antibodies was higher in females. Evidence of thyroid dysfunction was found in about 40% of those in both groups with anti-thyroid antibodies. The authors concluded that the prevalence of thyroid auto-immunity is increased in chronic urticaria, whether the etiology of such urticaria is known or not.Thyroid autoimmunity in chronic urticaria
Summary
Reference
Allergy Asthma Proc 2001;22:93-5Editor’s Comments
The pathogenic significance of the increased frequency of anti-thyroid antibodies in the sera of CIU patients is still being debated. Some, but not other, investigators have reported that treatment of such individuals with L-thyroxin is followed by an impressive decrease in the urticaria, whether the individual was hypothyroid or euthyroid to begin with. The findings described above suggest that anti-thyroid autoimmunity is increased in chronic urticaria, even if the etiology of such urticaria is defined. This conclusion depends on the validity of the diagnosed cause of the chronic urticaria in such cases. It was unclear from this report whether withdrawal of the suspected causal factor consistently lead to remission of the urticaria and whether re-introduction of such factor cause a recurrence of the urticaria in their cases of "urticaria of known etiology". I mention this because we have all seen cases where a cause of chronic urticaria was strongly suspected by history but not confirmed by withdrawal/reintroduction studies.
J Investig Allergol Clin Immunol 2000;10:342-5
Successful treatment of chronic idiopathic urticaria associated with thyroid autoimmunity.
Gaig P, Garcia-Ortega P, Enrique E, Richart C.
Department of Internal Medicine, Hospital Universitari de Tarragona Joan XXIII, Universitat Rovira i Virgili, Tarragona, Spain."The prevalence of thyroid autoimmunity is high in patients with chronic idiopathic urticaria (CIU), but in few selected patients the possible clinical benefit of levothyroxine sodium or antithyroid drugs has been studied. The objective of the present study was to confirm the prevalence of antithyroid antibodies in patients with CIU and to investigate the clinical response to levothyroxine sodium or methimazole. Antithyroglobulin and antiperoxidase antibodies were measured in 170 consecutive patients with CIU. Twenty-five (14.7%) had an antithyroglobulin or antiperoxidase antibody levels > 180 lU/ml and all but three were women. Twenty patients with CIU and thyroid autoimmunity were treated with levothyroxine sodium if hypothyroidism or normal thyroid function were present (18 patients) and with methimazole if hyperthyroidism was detected (two patients). Clinical response was evaluated by a clinical score. Autologous serum skin test before treatment was performed in 18 patients with thyroid autoantibodies. Urticaria resolved rapidly in two patients with Graves' disease. The clinical response of urticaria to levothyroxine sodium treatment was good in 15 patients and partial in two, whereas only one patient showed no improvement in clinical score (p < 0.0005). No changes in the antithyroglobulin or antiperoxidase levels were detected. Five patients reported adverse effects. The autologous serum skin test was positive in 10 patients and negative in eight. After successful treatment the test was repeated in six patients, proving negative in four and significantly diminished in two. We concluded that patients with CIU and thyroid autoimmunity benefit from treatment with levothyroxine sodium or antithyroid drugs. Antithyroid antibodies and positive autologous serum skin test in these patients could be markers of autoimmune disease with several target organs."
11/26/01 re: Synthroid therapy and asthma I have been an RN for thirty years and my current position of PI Coordinator requires that I interact on many levels with both physicians and patients. There has been discussion regarding whether there is any correlation between synthroid and asthma. One of our patients was started on synthroid about nine months ago and within a short period of time developed SOB and tachycardia; at first on an intermittent basis and now on an ongoing basis but with varying degrees of severity which respond only mildly to treatment with steroid inhalers. Slight wheezing has been present on two or three occasions. The patient's physician does not believe that the synthroid and asthma symptoms are related but the patient disagrees. I have researched and read all the information I can find with no conclusion findings. Can you please shed any light on this matter or refer me to other literature/resources? I would first need to know several things before being able to be of help in responding to your question. 1) Is there objective evidence that asthma was present (e.g.- spirometry measurement) when the patient became short of breath after taking Synthroid? It is not unusual for individuals who have drug-induced hyperthyroidism to feel short of breath when they exhibit tachycardia and other signs of hypermetabolism, You mentioned that wheezing was reported by the patient, - but was this verified by a careful physical exam by an experienced observer, preferably with spirometry at the time? Some patients may misidentify a sensation of breathlessness as wheezing
2) If asthma was indeed present at the time, did the patient have a history of asthmatic symptoms prior to taking Syntrhroid? There have been a number of case reports over the years describing aggravation of underlying asthma by the hyperthyroid state (see enclosed abstracts below). It is conceivable that Synthroid-induced hyperthyroidism (suggested by the presence of tachycardia) may have aggravated an underlying asthma.
3) For what reason was the Synthroid given? If there is no documented prior hypothyroidism (confirmed by an increased serum TSH level), then it is more likely that a drug-induced hypermetabolic state may be present, at least transiently.
: Rowe MS.
Thyroid hormones and asthma.
Ann Intern Med. 1991 Jan 1; 114(1): 97_________________________________________________________
J Endocrinol Invest 1994 Sep; 17(8): 675-7
Levothyroxine suppressive therapy: harmful and useless or harmless and useful?
Bartalena L, Pinchera A.
Istituto di Endocrinologia, Universita di Pisa, ItalJ Asthma 2000 Apr; 37(2): 125-30
Hyperthyroidism and asthma.
Luong KV, Nguyen LT.
Vietnamese American Medical Research Foundation, Westminster, California, USA."Two patients presented with new onset of thyrotoxicosis and they then developed episodic wheezing a few months afterward. The asthmatic attacks improved when the patients were rendered in an euthyroid state with treatment. The present paper discusses the relationship between two diseases, hyperthyroidism and asthma, and the underlying factors potentially contributing to their conditions. The present findings suggest that asthma may develop in a susceptible individual with hyperthyroidism and it is possible that the reactive oxygen species may be a contributory factor in exacerbating wheezing"
S Afr Med J 1990 Dec 15; 78(12): 750-2
Asthma and hyperthyroidism. A report of 4 cases.
White NW, Raine RI, Bateman ED.
Department of Medicine, University of Cape Town."For many years it has been known that thyrotoxicosis can worsen asthma, increasing both the frequency and severity of asthma attacks and increasing requirements for medication. Clinical recognition of this association may be difficult. Thyrotoxic asthmatics frequently experience side effects from medications, particularly beta-receptor agonists and theophyllines. Four case reports of asthmatics in whom thyrotoxicosis was diagnosed are presented. All 4 patients improved on returning to euthyroid status. The mechanism responsible for the harmful interaction is not known."
10/6/98 re: angioedema evaluation/management I have a 45-year-old white female with history of recurrent angioedema, mostly of hands and feet, but one episode of laryngeal edema. She had only one episode of slightly pruritic rash with edema. Work-up thus far included past history of positive hepatitis C test, but negative now with second generation test. Liver function test has always been normal. Recently, C4 was noted to be low, but C3 level was normal. Also positive antimicrosomal thyroid antibody level, with normal TSH and T4. Rheumatologist evaluated her prior to the low C4 and thyroid antibody test, and pronounced her without any rheumatologic diseases.
Do you any suggestions as to what to do next with the above information?
The information you provided suggested several areas worth exploring:
Angioedema, generally without pruritic urticaria, laryngeal edema, low serum C4 with normal C3 levels strongly suggests hereditary angioedema (HAE) or one of its acquired variants (type I or type II). I suggest you:
Check carefully for family history of angioedema without urticaria, acute death from respiratory obstruction (a real concern in HAE).
Obtain serum levels of C1 esterase inhibitor (C1INH). The usual lab test is an immunoassay. If normal, demand that a functional C1INH assay be done, since in 15% of HAE cases C1INH levels may be normal by immunoassay but the C1INH molecule is dysfunctional.
Obtain serum levels of C1 (1st complement component)
Normal in true HAE
Decreased in the 2 acquired variants - if tC1 is decreased, look for lymphoproliferative disease and/or refer to a clinical immunologist in your region who deals with such cases
If HAE is found, prophylactic treatment with attenuated androgen or (if available) C1INH concentrate (see my recent review of studies describing this treatment in the Current Literature section of this AADMC web site). The Acquired variants tend to be less responsive to these treatments
The presence of anti-thyroid microsomal antibodies is reportedly increased in chronic urticaria and could be related in your patient as well. Although the pathogenetic relationship of the skin and thyroid abnormalities is unclear, I would:
Get thyroid function panel to see if patient has thyroid hypofunction 2v to Hashimoto's thyroiditis.
Consider cautious use of thyroxin (Synthroid) therapy even if your patient is euthyroid. A group in the National Jewish Medical and Research Center has described marked improvement in some of those with chronic urticaria and anti-thyroid antibodies treated with Synthroid.
- Make sure the patients has not been taking ACE inhibitor drugs, particularly if the angioedema is mainly in the face, neck, upper chest. Laryngeal and pharyngeal edema occur frequently in such cases.
