The Dead-Sea thyrotoxicosis’ -- a side-effect of the Dead-Sea climatotherapy?

ARTICLE

Auteur(s) : Bruno MUELLER, Raphaël STADELMANN, Emanuel CHRIST, Peter DIEM

Recently, Schiffner et al. evaluated safety and efficacy of synchronous balneophototherapy using narrowband UVB and bathing in Dead sea salt solution for patients with atopic dermatitis [1]. The authors concluded, that synchronous balneophototherapy is efficient and safe. Most frequent side effects were: erythema in 7.3% and burning of skin in 3.6%. Further side effects were circulation disorders and claustrophobia in less than 1% of patients each. The latter symptoms can possibly be related to excessive thyroid hormone production. We report a patient with underlying, asymptomatic autoimmune thyroid disease who developed thyrotoxicosis in the course of a Dead Sea climatotherapy. 

A 26-yr-old nurse was referred to our division, because of moderate hyperthyroidism detected two weeks ago.

 The patient’s medical history revealed erythrodermic psoriasis known for 12 years and psoriatic arthritis known for 7 years. Psoriasis was successfully treated with methotrexate-monotherapy, 7.5mg weekly. On examination a diffuse goiter was palpable and there were minimal signs of endocrine ophthalmopathy. Serologic tests were positive for thyroperoxidase antibodies 1:1284 (reference range: < 1:100) and for thyrotropin receptor antibodies 58.1 U/l (reference range: 0-9). Based on these findings, Graves’ disease was diagnosed and treatment with carbimazole 30mg daily was initiated. Euthyroidism was achieved after 6 weeks’ treatment. Carbimazole dosage was tapered to maintance therapy with 5mg daily and treatment was continued for 12 months and then stopped in May 1998, followed by long-term remission. In March 1999 thyroid function tests were normal. 

In May 99 the patient went to the Dead-Sea for climatotherapy of her psoriasis. During the climatotherapy the patient complained of headache, insomnia, irritability, anxiety, difficulty concentrating, restlessness, increased heart rate and multiple joint edema, similar to the symptoms of the initial course of Graves’ disease. At this time laboratory testing was not available. Thyroid function tests after 3 weeks revealed subclinical hypothyroidism (thyrotropin 5.79 mU/L, reference range: 0.35-4.5 mU/L; free thyroxine 12.0 pmol/L, reference range: 9.5-25 pmol/L; free triiodothyronine 3.9 pmol/L, reference range: 3.5-6.5 pmol/l) with spontaneous normalisation after 4 weeks. The Dead-Sea is known to have a high content of iodione. Spontaneously resolving thyrotoxicosis followed by transient subclinical hypothyroidism is a typical clinical presentation of iodide-induced thyrotoxicosis (IIT) [2,3]. IIT can develop especially in predisposed patients with positive family history of thyroid disease, residence in areas with insufficient iodine intake and underlying autoimmune thyroiditis [4]. To our knowledge, this is the first report of a patient with iodine-induced ‘Dead-Sea thyrotoxicosis’. A relapsing hyperthyroidism due to Graves’ disease is unlikely in the view of transient hyperthyroidism, followed by hypothyroidism with spontaneous resolution. Since patients with dermatological pathologies may have increased iodine uptake due to their specific skin lesions evalution of thyroid function should be introduced in the workup of symptoms suggesting hyperthyroidism. In view of the large number of patients with psoriasis and atopic dermatitis seeking climatologic treatment in the Dead-Sea area this particular thyroid disease is worth keeping in mind. Patients with dermatitis may be at even higher risk for this unique side-effect because of enhanced transcutaneous uptake of minerals due to the specific skin lesions [5]. Thus, evaluation of thyroid function should be introduced in the first step of the diagnostic workup of side effects in such patients.

References

1. Schiffner R, Schiffner-Rohe J, Gerstenbauer M, Landthaler M, Hofstädter F, Stolz W. Dead-Sea treatment- principle for outpatient use in atopic dermatitis: safety and efficacy of synchronous balneophototherapy using narrowband UVB and bathing in Dead Sea salt solution. Eur J Dermatol 2002; 12: 543-8.

2. Fradkin JE, Wolff J. Iodide-induced thyrotoxicosis. Medicine 1983; 62: 1-20.

3. Roti E, Vagenakis AG. Effect of excess iodide: clinical aspects. In: Braverman LE, Utiger RD, eds. The Thyroid. Philadelphia, PA: JB Lippincott 1996; 316-27.

4. Harjai KJ & Licata AA. Effects of amiodarone on thyroid function. Ann Intern Med 1997; 126: 63-73.

5. Schaefer H, Zesch A, Stuttgen G. Penetration, permeation, and absorption of triamcinolone acetonide in normal and psoriatic skin. Arch Dermatol Res 1977; 258: 241-9.

Dear Sir,

Mueller et al. suggested in their letter to the editor a possible relationship between the development of thyrotoxicosis and treatment of atopic dermatitis at the Dead Sea as observed in a single patient. Furthermore, they interpret “circulation disorders and claustrophobia” - side effects observed in our study performed in out-patients in Bavaria, Germany - as possible signs for thyrotoxicosis. We do not agree with this interpretation. First - from our point of view and long-term experience with out-patient synchronous balneophototherapy using 10% Dead-Sea-salt-solution - “claustrophobia” seemed to be a psychological problem for a few patients caused by the design of the treatment system. The treatment system consists of a bath tub and a light console above. Starting treatment, the light console comes down and remains at about 50 centimeters above the patient for the complete treatment. Therefore, a feeling of “claustrophobia” might be possible. Second - patients are bathing in warm water (37 °Celsius) during treatment with UVB lamps above them also providing heat. We think that “circulation disorders” were more probable caused by the treatment situation which could really influence patient’s circulation by physical strain. Meanwhile, more than 8000 patients (including psoriasis patients) were treated with this out-patient treatment system during our study performed under GCP conditions, but no case of thyrotoxicosis or its clinical signs was documented as adverse event or even serious adverse event until now. Nevertheless, we cannot exclude a possible relation between thyrotoxicosis and treatment at the Dead-Sea as observed in this case report especially considering the concentrations of salt solutions: 10% Dead-Sea salt solution in our treatment system versus more than 20% at the real Dead Sea. However, two additional questions should be discussed by Mueller et al.: 1) Which concentration of iodid is necessary in a Dead-Sea salt solution and/or which extent of skin contact is necessary to force a thyrotoxicosis exclusively by skin penetration? 2) Can it be excluded that the patient had intensive gastrointestinal contact to seafood containing also iodid during her stay at the Dead Sea country?

References

Schiffner R, Schiffner-Rohe J, Gerstenhauer M, Landthaler M, Hofstädter F, Stolz W. Dead-sea-treatment-principle for outpatient use in atopic dermatitis: safety and efficacy of synchronous Balneophototherapy using narrowband UVB and bathing in Dead-Sea-salt solution. Eur J Dermatol 2002; 12: 543-8.