INSUFFICIENCY OF LEVOTHYROXINE THERAPY IN AUTOIMMUNE HYPOTHYROIDISM: EFFECT OF GLUCOCORTICOID ADMINISTRATION.

OBJECTIVE: The non-effectiveness of levothyroxine administration in hypothyroidism depends on many factors and mechanisms influencing its absorption in small intestins or bounding of circulating hormone with different active molecules. METHODS: Thyroid hormones, TSH, rT3, TGl, TPO-Ab, TG-Ab, were measured using commercially available assays. For anti-T4ab, radioiodine-labeled T4 was added to the patient's serum and the IgG fraction subsequently precipitated by addition of 15% polyethylene glycol. Background was determined by testing 100 control sera from individuals without autoimmune thyroid disease. RESULTS: A 42-year old woman (71.5 kg) with Hashimoto thyroiditis receiving levothyroxine (L-T4) 150 µg and liothyronine (L-T3) 37.5 µg was admitted to the hospital with clinical data of hypothyroidism, TSH-23.8 mU/L, FT4-6.18 pmol/L (n.range 9-19 pmol/L), TPO-Ab 696 IU/mL, TG-Ab 818 IU/mL, circulating T4- antibodies positive. She has a good adherence to medication, malabsorption or administration of other drugs were excluded. L-T4 absorption test revealed 44% increase of serum FT4 at 120 min after ingestion of 150 mcg L-T4 (2.1 mcg/kg). Methylprednisolone pulses of 500 mg i.v. administered in three consecutive days at equal doses of L-T4/L-T3 resulted in a rapid increase of FT4 to 14.5 pmol/L, fall of TSH to 0.18 mU/L and decrease of anti-T4 antibodies to referent range; TPO-Ab and TG-Ab also decreased significantly. Monotherapy by 150 mcg L-T4 was continued in the next three months. A recurrence of hypothyroidism with increase of circulating T4-Ab was observed 100 days later. New administrations of methylprednisolone two pulses of 500 mg revealed a similar normalization of thyroid hormones and anti-T4 antibodies. CONCLUSION: The data showed that T4-antibodies might be a cause of insufficient effects of levothyroxine therapy in autoimmune hypothyroidism. This could be overcome by glucocorticoid administration probably resulting in FT4 release from circulating immune complexes.

Prevalence of goitre in the southern mountainous regions of Bulgaria, 1986-1989.

Iodine supplementation programmes began in designated high risk mountainous districts in Bulgaria in 1958. The prevalence of goitre fell. But the programmes became less effective and by the mid 1980s there were strong indications that goitre was resurgent. Ten villages that had been surveyed in 1956 and 1974 were re-surveyed between 1986 and 1989. All persons available were examined (not just residents)--at home, workplace or school--by a trainee or specialist endocrinologist. Goitres were graded according to the WHO/ICCIDD system. 2,901 females and 1,885 males were examined. Diffuse, stage 1 enlargements were common in males and females under 35, with prevalences exceeding 20% in several age/sex groups. Nodular stage 1 and 2 enlargements became commoner at ages above 45, with prevalences exceeding 15% in females over 55. Overall prevalences were 28% in females and 14% in males. 6 cretins were identified. In recognised endemic areas of Bulgaria, epidemiological surveillance of IDD should be maintained. Detailed studies are required to determine why iodine supplementation became less effective after the mid 1970s and to develop and test new, cost-effective public health strategies appropriate to the changed socio-political circumstances.

[The effect of thyrostatic treatment on circulating thyrotropin-receptor antibodies in Basedow's disease]. / Vliianie na tireostatichnoto lechenie vurkhu tsirkulirashtite tireotropinretseptorni antitela pri bazedova bolest.

In 80 patients with Basedow's disease (20 nontreated and 60 under treatment with methimazole) were examined. The antibodies inhibiting the binding of TSH (TBII) by the radioreceptor method (Thyrotropin-Receptor-Anti-Körper Assay = TRAK), TRH-test, T3, T4, FT4, FT. TRAK-positive) values above 15 u/l) were 80% of the nontreated and 20% of the treated patients. In the course of 3 up to 6 months from the start of the treatment 60% of the examined patients were negative and at the end of the 18th month--92% were negative. A significant difference in the frequency of the recurrences was found between the TRAK-positive and the TRAK-negative patients. Between the TRAK, FT3, FT4, the size of the struma, the presence of ophthalmopathy [correction of ophthalmycthere] are positive relations. The following conclusions are made: 1. The determination of TBII and TRAK is not only of diagnostic but also of prognostic importance. 2. Methimazole exerts a specific immunosuppressive action and can lead to an immunologic remission in a comparatively short time.

[A combination of ectopic parathyroid adenoma and thalassemia with manifestations of extreme hyperparathyroidism]. / Suchetanie na ektopichen parashtitoviden adenom i talasemiia s proviavi na ekstremen khiperparatireoidizum.

A case is presented of a woman with primary hyperparathyroidism due to a parathyroid adenoma with deep mediastinal localization successfully treated surgically. The disease was manifested at the beginning with joint pains only, followed by extreme bone, renal and metabolic disorders endangering the life of the patient. The unusually severe sceleton decalcification is linked with the functional exhaustion of the calcitonin C producing cells. The changes in these cells in the resected thyroid tissue were discrepant with the hypercalciemia. A special feature of the case is the combination of parathyroid adenoma with a number of dysmorphic signs, with a persistent thymus and beta-thalassemia (heterozygotic form) with familial predisposition--thalassemia of the mother and malformations of the patient's child. On this basis the authors presume a genetic determination of the basic disease similar to other forms of primary hyperparathyroidism.

[Thyroid hormone level in the serum in untreated hypothyroidism and in substitution therapy]. / Uroven' tireoidnykh gormonov v syvorotke pri nelechenom gipotireoze i pri ego zamestitel'nom lechenii.

Forty-seven patients with clinically revealed hypothyrosis were examined. Of these, 31 subjects were untreated and 16 were in a compensatory stage of the disease after the substitution treatment. All the untreated patients had lowered serum concentration of total thyroxin (TT4) and free thyroxin (FT4I) indices, their mean arithmetical values being statistically different in the mild and moderate stages of the disease. The total triiodothyronine (T3) level was within normal in 10 of 31 patients. The reverse T3 concentration was normal in patients with the mild stage of the disease and three times lower in the moderate form. T3 concentration was moderately increased in 7 treated patients, whereas 2 of them had TT4 and FT4I indices below normal. T4 deficiency is likely to be the crucial factor in the clinical manifestations of all hypothyrosis forms. Dissimilar changes in the total and reverse T3 levels in some patients are seemed to be caused by the compensatory mechanism and cannot serve as the main diagnostic criterion.

[Thyrotropic hormone plasma level in thyrotoxicosis]. / Plazmeno nivo na tireotropniia khormon pri bolni s tireotoksikoza

Immunoreactive TTH plasma concentration was investigated twice a day (at 9 a.m. and 9 p.m.) in 30 patients with thyrotoxicosis, 10 out of them in acute stage and 20 in a state of remission after thymidazol treatment as well as in 17 healthy subjects. The authors established that in the acute state of thyrotoxicosis the latter is reduced to low normal or subnormal values (an average of 2.94 +/- 0.70 ng/ml) and after thyrostatic therapy leading to remission--is about the average norm (4.65 +/- 1.10 ng/ml) and does not differ much from that in healthy subjects (4.75 +/- 0.92 ng/ml). The negative correlation between the TIH levels and thyroid hormones (BOI, total thyroxin), typical for the healthy subjects, is found in the patients with acute thyrotoxicosis. No significant difference was established between the TTH values of the morning and evening hours in any of the groups. The physiological regulatory feedback mechanism in thyrotoxicosis is assumed not to be disturbed.

[131-I capture by the thyroid gland during and after stopping thyrostatic treatment in thyrotoxicosis]. / Kaptatsiiata na 131IJ ot shtitovidnata zhleza po vreme i sled spirane na tireostatichnoto lechenie pri tireotoksikoza

The accumulation of 131J in the thyroid gland was investigate in dynamics in 31 patients with thyrotoxicosis, treated with mercaptoimidazol (timidazol) for an average of 16 months. The patients were clinically euthyroid, with normal values of the basal metabolism, PBI, PBI131 AND TOTAL THYROXIN IN SERUM. The 131J captation, investigated in the course of a maintaining treatment without discontinuation of thyrostatics, show elevated percentages (55.4 per cent by the 6th hour, 61.3 per cent by the 24th hour), being within the norm only in eight patients. Its average values are significantly lower up to the 6th month post treatment discontinuation and closrm, with only 13 above the norm. Only three of them (10 per cent) developed recidivations till the end of the 9th month after e treatment. The authors concluded that thyrostatics, in maintaining doses, do not block thyroid gland 131J cumulation which in the majority of the cases persisted to be elevated a long time after the discontinuation. Its complete normalization in the later stages speak, most probably, for the development of a lasting remission of thyrotoxicosis.