Potential hook effect in prolactin assay in patients with giant prolactinoma

Sirs, We herewith report an interesting case of recurrent Graves’ disease in whom the initiation of oestrogen therapy for climacteric symptoms may have led to the relapse of hyperthyroidism. In 1986, a 39-year-old woman was referred to us with hyperthyroidism. We confirmed Graves’ disease based on the presence of marked thyrotoxic symptoms, a moderately swollen, diffuse, non-tender goitre, a marked elevation of serum thyroid hormones and suppressed thyrotrophin (TSH), and a positive thyroid-stimulating antibody (TSAb). Treatment was started with 30 mg of methimazole per day. Within 2 months, we reduced the daily dosage of methimazole to 5 mg. TSAb levels gradually decreased, and disappeared within 6 months. A maintenance dose of methimazole (2 :5–5:0 mg/day) was continued for the following year. After the maintenance therapy was over, the triiodothyronine (T3) suppression test and TRH test were performed as indicators of remission. Since both tests were normal, the patient was judged to be in remission and the anti-thyroid treatment was discontinued. The patient remained well for the following 8 years. At the age of 49, she noticed an occasional occurrence of facial flushing and a diminished frequency of periods. She therefore sought medical attention at the gynaecology department of Mutsu Hospital. Her condition was diagnosed as climacteric disorder, and oral administration of 1:25 mg per day of conjugated oestrogen (of which primary component was oestrone) was started. This alleviated her climacteric symptoms, but within one month she had a relapse of thyrotoxic symptoms which were very similar in severity to what she had experienced when she had been diagnosed as suffering Graves’ disease 10 years before. She had overt clinical and biochemical hyperthyroidism associated with suppressed TSH secretion and markedly elevated TSAb titres. We therefore diagnosed the patient as in a relapse of Graves’ disease after 8 years’ remission, and resumed anti-thyroid therapy with methimazole. McKenzie and Zakarija (1995) have reported that of those patients with Graves’ disease who were destined to suffer relapse after anti-thyroid drug withdrawal, 75% have done so within 3 months and 90% within 2 years. Based on these clinical data, which are largely similar to what was reported by other investigators, it may be reasonable to consider our patient to belong to a minor subgroup of Graves’ recurrence, because she had remained in remission for as long as 8 years before relapsing. Therefore, we believe that the initiation of oestrogen therapy for climacteric symptoms which developed in our patient should not be disregarded in terms of its cause-andeffect relationship with Graves’ recurrence. It is well known that there exists a sexual dimorphism in immunological function, with mammalian females having more vigorous humoral and cell-mediated immune responses than males (Grossman, 1990). This is in keeping with considerable clinical evidence that autoimmune diseases are more prevalent in women than in men, and also that the clinical course of various autoimmune diseases in females occasionally alters with physiological changes in the hormonal profile (puberty, pregnancy, post-partum periods, etc). It has been shown in mice that oestrogen increases production of various autoantibodies, while testosterone seems to exert an opposing effect (Blank et al., 1990). Therefore, it is likely that in our patient the administration of oestrogen, a potent immunostimulatory steroid, restored the production of TSAb, which then led to the recurrence of Graves’ disease. Although we are not aware of any published case report similar to ours, oestrogens are commonly prescribed for climacteric disorders, oesteoporosis, and so on, which could develop in patients of perimenopausal age with remitted Graves’ disease. Thus, we may propose that a possible aggravation of Graves’ disease by oestrogen therapy should be borne in mind in the management of the patients with autoimmune thyroid disorders. Hajime Watanobe* and yHiroyasu Kawabe *Third Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036, Japan; and yDepartment of Medicine, Mutsu Hospital, Mutsu, Aomori 035, Japan