Non-immunogenic Hyperthyroidism Research Articles

Separation of Autonomous Function from Cell Density in Non-Immunogenic Hyperthyroidism

SummaryRegional autonomous cell mass (Q: cell density ratio) and function (T: toxicity index) were compared by double isotope parametric thyroid scintigraphy (Als et al., Nucl. Med. 1995; 34) in 53 patients with non-immunogenic hyperthyroidism before and after radioiodine therapy (aRIT) and showed a break-down (medians) of Q: 4.3→1.0 (toxic adenomas: TA), 2→1.1 (multifocal functional autonomies: MFA) (p <0.0001) as of T: 96→1.7 (TA), 15→1.1 (MFA) (p <0.001). Five functional aRIT patterns resulted: euthyroidism (n = 37, 70%), at half with scarred/non-scarred autonomous areas (low/higher T, respectively), primary hypothyroidism (n = 4), residual hyperthyroidism (n = 7), secondary hyperthyroidism (n = 5). The last two groups with persistent subnormal TSH values were clearly separated by divergent T, thyroxine and triiodothyronine levels. A resulting T >1 may represent a clinically sub-critical mass of residual autonomous tissue. This new technique facilitates individual prethera-peutic evaluations and aRIT quality control.

Immunogenic and Non-Immunogenic Hyperthyroidism

SummaryAnnual occurrences of immunogenic (IH) and non-immunogenic hyperthyroidism (NIH) between Berne (1976, 1982, 1991) and Szczecin (1973, 1980, 1991) were compared. Out of 21,025 patients referred for thyroid examinations, 10.1% (average) were hyperthyroid. In Berne (former endemic goiter region) and Szczecin (without goiter endemicity) IH occurred in 41% and 68%, NIH in 59% and 32% of hyperthyroid patients, respectively. Within a stable incidence of NIH in Berne, toxic adenomas (TA) decreased from 41% (1976) to 17% (1991) (p <0.005). In Szczecin, where iodine deficiency is in an early stage, the TA frequency did not change significantly: from 24% (1973) to 28% (1991). Increases of TA or of multifocal functional autonomy apparently “mark” incipient or, respectively, decreasing deficiencies in nutritious iodine. Hyperthyroid patients in Berne compared to Szczecin were older, both with IH (54 versus 45 y) and NIH (65 versus 52 y). Age at diagnosis was stable in Berne but increasing (p <0.05) in Szczecin (from 43 to 52 y).

Separation of Autonomous Function from Cell Density in Non-Immunogenic Hyperthyroidism

SummaryA new quantitative subtraction method of thyroid scans is proposed which shows that regional function (F) by far exceeds regional cellularity or cell density (C) in potentially toxic thyroidal areas of non-immunogenic hyperthyroidism (NIH). Methods: A multistep processing of radioiodine and MIBI thyroid scans of patients with non-immunogenic hyperthyroidism led to normalized images of regional function excess and of perinodular enhancement. Two numeric factors were derived from regions of interest: Q (cell density ratio) comparing MIBI uptake in autonomous and suppressed areas and T (toxicity index): the maximal F/C contrast. Results: Q never exceeded 61; T, however, expanded toxicity levels over a range of 6-8735 with toxic adenomas (median = 165) and with hot areas of multifocal functional autonomy (median = 15). T was weakly correlated to serum TT3 (r = 0.41), but not to autonomous tissue mass, ultrasonographic or cytologic criteria. Conclusions: T is governed by inherent features of autonomous tissue and the response of the imbedded thyroid tissue to TSH stimulation. This standardized technique consolidates experiences from visual analysis; the huge T range mirrors the natural evolution from compensated autonomy towards hyperthyroid, decompensated stages.

Circulating soluble interleukin 2 receptor concentration is increased in both immunogenic and nonimmunogenic hyperthyroidism

High serum concentration of soluble interleukin-2 receptor (sIL-2R) is considered a reliable marker of T lymphocyte activation. It has been recently reported that sIL-2R levels are increased in untreated Graves' disease. This finding has been interpreted as the consequence of an active autoimmune state, but the relevance of the thyroid function per se was not investigated. In the present study we assayed sIL-2R by ELISA in 20 normal subjects and in a series of patients with immunogenic (Graves' disease, GD) or nonimmunogenic (toxic adenoma, TA) hyperthyroidism. Significant increased concentrations of sIL-2R were found in 46 patients with untreated hyperthyroid GD (mean +/- SD: 1,683 +/- 1016 U/ml, vs 461 +/- 186 U/ml in normal controls, p less than 0.0001) and in 21 with untreated TA (1,111 +/- 617 U/ml, p less than 0.0001 vs normals). Restoration of the euthyroid state by antithyroid drugs or 131I administration was associated with a normalization of sIL-2R (516 +/- 174 U/ml in 38 patients with GD and 365 +/- 90 U/ml in 12 with TA; p = NS vs normals and p less than 0.001 vs the untreated state for both groups). A highly significant positive correlation between serum sIL-2R and free triiodothyronine (FT3) (r = 0.724, p less than 0.0001) or free thyroxine (FT4) (r = 0.698, p less than 0.0001) concentrations was found in combined sera obtained from all untreated and treated patients, irrespectively of the autoimmune or nonautoimmune nature of the underlying hyperthyroid disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Ergebnisse der Radiojodtherapie der manifesten Hyperthyreose und der autonomen Struma mit Euthyreose

In 200 patients follow-up examinations were performed up to one year after radioiodine therapy (RITh) with individual dose calculation. The mean applied dose was significantly lower in patients with immunogenic hyperthyroidism (Graves’ disease) as compared to patients with non-immunogenic hyperthyroidism (disseminated/multifocal autonomy, HYDA). In Graves’ disease the rate of recurrent hyperthyroidism was significantly higher and that of posttreatment hypothyroidism lower. Considering the high recurrence rate in Graves’ disease a higher dose, e. g. 150 Gy, seems to be appropriate. In patients with HYDA who received antithyroid drugs during RITh, recurrence of hyperthyroidism appeared slightly more, and posttreatment hypothyroidism slightly less, frequent. The efficiency of RITh was not significantly reduced by additional treatment with antithyroid drugs. Posttreatment hypothyroidism in patients with euthyroid goiter and disseminated/multifocal autonomy (EUDA) occurred significantly more frequent if the basal TSH level was ≥0.5 µlE/ml before therapy. The goiter size was reduced independent of the basal TSH level. In this group protection by thyroxine could avoid posttreatment hypothyroidism without impairing the reduction of goiter. In HYDA patients after thyroid surgery recurrence appeared less, and in those with EUDA posttreatment hypothyroidism significantly more, frequent. A lower dose seems to be suitable in patients who underwent thyroid surgery before. In patients with focal autonomy after RITh no recurrence of hyperthyroidism was observed. In 9% a suppressed basal TSH level indicating persistent autonomy was seen. Posttreatment hypothyroidism in focal autonomy appeared only in patients without manifest hyperthyroidism before RITh and was significantly more frequent in this group as compared to the other groups of patients. In patients with focal autonomy who developed hypothyroidism the dose calculation was based on a significantly higher volume of the adenoma. In 3 cases cystic parts of the adenoma were not subtracted. This caused a higher radiation dose to the paranodular tissue, which might have been one reason for the high rate of posttreatment hypothyroidism in this group of patients.

Rezidivrisiko nach thyreostatischer Behandlung immunogener und nicht-immunogener Hyperthyreosen

Data of 196 patients treated for hyperthyroidism exclusively with antithyroid drugs were analyzed retrospectively concerning the relapse rate within a follow-up period of four years. Patients were subdivided for primary or recurrent disease, and for immunogenic or non-immunogenic hyperthyroidism, respectively. In immunogenic as well as in non-immunogeriic hyperthyroidism, the relapse rate was significantly lower for patients with primary disease (35% and 52%, respectively) compared to those with recurrent hyperthyroidism (82%, p <0.001 and 83%, p <0.001, respectively). In patients with primary disease, clinical, biochemical and scintigraphic parameters were tested with respect to their capability of predicting a relapse. For immunogenic hyperthyroidism the highest relapse rates were observed in young patients and in those with large goitres, whereas for non-immunogenic hyperthyroidism they were highest in old patients, in those with nodular goitres and in those without an increased urinary iodine excretion at the time of diagnosing hyperthyroidism.

Ergebnisse der Radiojod-Behandlung von Patienten mit immunogener und nicht-immunogener Hyperthyreose bei Anwendung unterschiedlicher Herddosen

The aim of this study was to check the efficacy of radioiodine (131I) therapy (RIT) in a large number of patients (n = 506) suffering from immunogenic or non-immunogenic hyperthyroidism (Graves’ disease, Plummer’s disease). Since there is no causal cure for immunogenic hyperthyroidism RIT provides, like all other modalities, only a moderate rate of success which is clearly dose-related. Applying 60 Gy, normal thyroid function can be achieved in only 54% of the cases. A dose of 150 Gy succeeds in 86% of the cases. The solitary decompensated autonomous adenoma (DAA) can be eliminated surgically as well as by RIT with a high degree of success (95%). Contrary to surgery, RIT does not have any noticeable early or late morbidity. The high rate of success of RIT in patients with DAA could be confirmed in two groups with different follow-up periods (16 and 65 months). As expected, the rate of hypothyroidism increased from 11 % in the early group to 23% in the late group. Multinodular autonomous adenomas can be eliminated successfully using RIT as well. The concept to apply a dose of 400 Gy to the total functional autonomous tissue as determined by ultrasound yields better results (95%) than 150 Gy to the whole thyroid gland as measured by ultrasound (88%). The rate of hypothyroidism as shown by these results (up to a maximum of 62% after RIT of Graves’ disease using 150 Gy) is the lesser evil compared to remaining or recurrent hyperthyroidism since these patients can be treated with thyroid hormones without problems.

Computed tomographic determination of thyroid iodine concentration in an endemic goiter area

We determined the CT density of the thyroid gland in 60 patients with normal thyroids and 176 patients with various thyroid disorders. The density was 75 +/- 6.2 H.U. in normal thyroids, which was markedly higher than in goiters (66 +/- 6.0 H.U.), while there was a considerable further decrease in patients with immunogenic hyperthyroidism, the density being 48.5 +/- 7.9 H.U. The thyroids of patients with nonimmunogenic hyperthyroidism differed from these by virtue of a significantly greater density, 79.8 +/- 12.5 H.U. The clinical importance of CT investigation of the thyroid is its ability to distinguish rapidly between immunogenic hyperthyroidism without ocular symptoms and the (mostly iodine induced) non-immunogenic form. There is a linear correlation between CT density and iodine concentration in the thyroid tissue; this was determined in surgical specimens from 17 patients. Iodine concentration in the thyroid, as well as the iodine content of the whole gland, can thus be calculated from the measured CT density at any time by estimating the volume of the gland with ultrasound and combining this value with the measured iodine concentration. The results correlate well with those found using the x-ray fluorescence method.

Immunological features of nonimmunogenic hyperthyroidism.

Blood lymphocyte subpopulations (Leu 4+ cells = pan-T cells, Leu 3a+ cells = helper/inducer cells, and Leu 2a+ cells = suppressor/cytotoxic cells), thyroid-stimulating immunoglobulins, microsomal antibodies and antibodies against thyroglobulin were determined in 10 patients with hyperthyroidism due to single autonomously functioning thyroid nodules (ATN), 11 patients with hyperthyroidism due to Graves' disease (GD) and in 20 normal subjects. Thyroidectomy was performed in 8 of the patients with ATN and in 6 of those with GD after 3 weeks of antithyroid drug treatment with methimazole. Lymphocytic infiltration of thyroid tissue, the amount of the various lymphocyte subsets (Leu 4+, Leu 3a+, and Leu 2a+ T cells as well as B+ B cells) in the thyroid gland, as well as the expression of the histocompatibility antigen HLA-DR on thyrocytes and intrathyroidal lymphocytes were examined. Blood Leu 4+ cells were reduced due to a lack of Leu 2a+ cells in patients with ATN and GD when compared to normal subjects. Thyroid-stimulating immunoglobulins were detected in all patients with ATN and GD, but in none of the normal subjects. Lymphocytic infiltration of thyroid tissue was present in patients with ATN and GD. The various lymphocyte subsets in the thyroid gland did not differ between the two patient groups. DR expression on thyrocytes was seen in 6 of the patients operated for ATN and in 5 of those who underwent surgery for GD. Infiltration with DR+-T lymphocytes was found in all thyroid glands investigated. Thus immunological findings usually classified as proof for the autoimmune origin of GD exist also in patients with ATN. An overlap in the pathogenetic background of both diseases seems possible.