Kanji Kasagi

Familial Neonatal Transient Hypothyroidism Due to Maternal TSH-Binding Inhibitor Immunoglobulins

IN 1960, Sutherland et al.1 reported on children with familial nongoitrous cretinism born of a hypothyroid mother with Hashimotos disease. Subsequently, Goldsmith et al.2 studied this family in de...

Primary Myxedema with Thyrotrophin-Binding Inhibitor Immunoglobulins: Clinical and Laboratory Findings in 15 Patients

In a screening of 43 patients with primary myxedema, 9 patients were found to have IgG that inhibits the binding of 125I-thyrotrophin to its receptor (thyrotrophin-binding inhibitor immunoglobulins). Preparations of IgG from these patients did not stimulate thyroidal cyclic adenosine monophosphate generation and blocked thyroid stimulation by thyrotrophin in vitro. Clinical and laboratory features of 15 patients with this inhibitor, including 6 who were previously known, were compared with those of patients without the inhibitor. The patients with inhibitor, 2 men and 13 women, had onset of their hypothyroidism from age 2 to 49 years, and thyroid uptake in these patients was significantly lower than that in patients without inhibitor. Transient hypothyroidism was seen in all 5 infants born to 4 mothers having potent inhibitor immunoglobulins. These clinical findings indicate that thyrotrophin-receptor-blocking antibodies play a pathogenic role in a group of patients with primary myxedema.

Recruitment of T lymphocytes and induction of tumor necrosis factor in thyroid cancer by a local immunotherapy

SummaryTo elucidate the mechanism of action for intratumoral injection of immunopotentiators, infiltrating mononuclear cells and tumor necrosis factor (TNF) were assayed by immunostaining tissue samples of differentiated thyroid cancer resected with or without presurgical local application of OK-432, a streptococcal preparation. Frozen sections of resected specimens were stained with monoclonal antibodies using either a conventional or a modified immunoperoxidase method. The tumors injected with OK-432 showed increased T lymphocyte infiltration and HLA-DR expression on cancer cells as compared to the non-injected controls. Among these T cells, the CD4+ subset was more numerous than the CD8+ population. In four out of the seven cases constituting the injected group, numerous TNF-positive cells were seen in clusters or lines as well as scattered, while none of the seven cases in the control group was associated with a considerable amount of these cells. In their morphology and distribution pattern, these TNF-positive cells appeared to be of macrophage lineage. Thus local injection of OK-432 in thyroid cancer was shown to recruit T lymphocytes of predominantly the CD4+ subset and to induce in situ production of TNF, a known potent tumoricidal cytokine. The present data warrant further studies in this direction besides wider clinical intratumoral application of the reagent.

Metastatic thyroid cancer presenting as thyrotoxicosis: report of three cases.

Three patients with metastatic thyroid follicular carcinoma developed thyrotoxicosis. Two had mild T3 toxicosis without detectable TSH binding inhibitor immunoglobulins (TBII) or thyroid stimulating antibodies (TSAb). Considerable concentration of 131***I by tumours occurred, although serum TSH was undetectable. The third patient developed thyrotoxicosis several months after treatment with 131I had commenced and this was associated with concurrent increase in both TBII (90%; normal, less than 11%) and TSAb (2100%). We conclude that thyrotoxicosis in patients with metastatic thyroid carcinoma may result from a large bulk of tumour functioning either autonomously or after stimulation by TSH receptor antibodies.

Effect of Iodine Restriction on Thyroid Function in Patients with Primary Hypothyroidism

Dietary iodine intake in Japan varies from as little as 0.1 mg/day to as much as 20 mg/day. The present study was undertaken to assess the frequency of iodine-induced reversible hypothyroidism in patients diagnosed as having primary hypothyroidism, and to clarify the clinical backgrounds responsible for the spontaneous recovery of thyroid functions. Thirty-three consecutive hypothyroid patients (25 women and eight men) with a median age of 52 years (range, 21-77 years) without a history of destructive thyroiditis within 1 year were asked to refrain from taking any iodine-containing drugs and foods such as seaweed products for 1-2 months. The median serum thyrotropin (TSH) level, which was initially 21.9 mU/L (range, 5.4-285 mU/L), was reduced to 5.3 mU/L (range, 0.9-52.3 mU/L) after iodine restriction. Twenty-one patients (63.6%) showed a decrease in serum TSH by >50% and to <10 mU/L. Eleven patients (33.3%) became euthyroid with TSH levels within the normal range (0.3-3.9 mU/L). The ratios of TSH after iodine restriction to TSH before iodine restriction (aTSH/bTSH) did not correlate significantly with titers of anti-thyroid peroxidase antibody and anti-thyroglobulin antibody or echogenicity on ultrasonography, but correlated inversely with (99m)Tc uptake (r = 0.600, p < 0.001). Serum non-hormonal iodine levels, although not correlated significantly with aTSH/bTSH values, were significantly higher in the 21 patients with reversible hypothyroidism than in the remaining 12 patients. TSH binding inhibitor immunoglobulin was negative in all except one weakly positive case. In conclusion, (1) primary hypothyroidism was recovered following iodine restriction in more than half of the patients, and (2) the reversibility of hypothyroidism was not significantly associated with Hashimotos thyroiditis but with increased (99m)Tc uptake and elevated non-hormonal iodine levels.

Comparison of short inversion time inversion recovery (STIR) and fat-saturated (chemsat) techniques for background fat intensity suppression in cervical and thoracic MR imaging.

The purpose of this study was to compare short inversion time inversion recovery (STIR) fast spin‐echo (FSE), and fat‐saturated T2‐weighted FSE sequences in terms of uniformity of fat suppression and lesion conspicuity for magnetic resonance (MR) imaging of the neck and thorax. STIR FSE and fat‐saturated T2‐weighted FSE images were scored for uniformity of fat suppression (n = 40) and lesion conspicuity (n = 35). Five‐point rank score analyses were utilized by three experienced radiologists. The mean scores of STIR and fat‐saturated FSE techniques for uniformity of fat suppression were 4.3 and 2.3, respectively (P < 0.0001). The mean scores of STIR and fat‐saturated FSE techniques for lesion conspicuity were 4.2 and 3.5, respectively (P < 0.0001). Insufficient fat suppression was prominent in the mandible, supraclavicular region, anterior mediastinum, epipericardial fat, and subdiaphragmatic fat. In addition, fat‐saturated T2‐weighted FSE showed inadvertent water suppression in 25%. The STIR FSE technique was superior to the fat‐saturated FSE technique for cervical and thoracic MR imaging. J. Magn. Reson. Imaging 2000;11:56–60.

Lymphoproliferative disorders of the thyroid gland : radiological appearances

Images of lymphoproliferative disorders of the thyroid by ultrasonography (US), computed tomography (CT), 99Tcm and 67Ga scintigraphy were analysed in eight patients (two men and six women, aged 42-83 years). Seven patients were diagnosed as having primary lymphoma and one plasmacytoma. Ultrasound revealed a solid mass with homogeneous and very low echogenicity clearly distinguishable from residual thyroid tissue in five patients, diffuse hypoechoic goitre in one and multiple irregular hypoechoic nodules in both lobes in the patient with plasmacytoma (Case 8). Computed tomography demonstrated a focal low-density area in six cases of lymphoma and decreased density throughout the gland in the other two patients. 99Tcm scintigraphy showed hemilobar enlargement with decreased and uneven trapping, cold area or complete lobar defect in six patients with lymphoma and no trapping in the case of plasmacytoma. 67Ga scintigraphy demonstrated high accumulation in lymphoma and faint accumulation in the case of plasmacytoma. Radiological manifestations with a focal lesion were considered typical and diagnostic of primary thyroid lymphoma, while in one case with diffuse infiltration through the whole gland, the differential diagnosis from Hashimotos thyroiditis could not be made. In the final case, cells infiltrated diffusely to form islands with patchy distribution among well preserved follicles, correlating with the multiple hypoechoic areas observed by US.

Brain metastasis from differentiated thyroid cancer in patients treated with radioiodine for bone and lung lesions.

Brain metastasis of differentiated thyroid cancer (DTC) often is detected during treatment of other remote lesions. We examined the prevalence, risk factors and treatment outcome of this disease encountered during nuclear medicine practice. Of the 167 patients with metastasis to lung or bone treated 1–14 times with radioactive iodine (RAI), 9 (5.4%) also had lesions in the brain. Five were males and 4 females, aged 49–84, out of the original population of 49 males and 118 females aged 10–84 (mean 54.7) years. Three of them underwent removal of their brain tumors, 5 received conventional external beam irradiation, and 2 had stereotactic radiosurgery with supervoltage X-ray. None of the brain lesions showed significant uptake of RAI despite demonstrable accumulation in most extracerebral lesions. Seven patients died 4–23 (mean 9.4) months after the discovery of cerebral metastasis, brain damage being the primary or at least a contributing cause. The 8th and 9th patients remained relatively well for more than 42 and 3 months, respectively, without any evidence of intracranial recurrence. Our results confirmed that the brain is a major site of secondary metastasis from DTC. No statistically significant demographic risk factor was detected. Any suspicious neurological symptoms in the course of RAI treatment warrant cerebral computed tomography. As for therapy, from our initial experience, radiosurgery seemed promising as an effective and less invasive alternative to surgical removal.

Subclinical Graves' disease as a cause of subnormal TSH levels in euthyroid subjects.

In order to elucidate causes of subclinical thyrotoxicosis, we reviewed records of thyroid function tests obtained in our hospital between 1990 and 1992, showing normal thyroid hormones and subnormal TSH levels, and analyzed underlying clinical conditions of the patients. Of 186 patients with normal T4 and/or free T4 and normal T3 and/or free T3 but subnormal TSH (<0.1 mU/l) levels in serum, 150 were under treatment with antithyroid drugs for hyperthyroid Graves’ disease or with thyroid hormones for hypothyroidism. Twelve were in remission after treatment for Graves’ disease, and 4 had destructive thyroiditis. Of the remaining 20 patients, 4 had autonomously functioning thyroid nodule (AFTN), 9 had euthyroid ophthalmic Graves’ disease (EOG), and 7 had diffuse goiter without apparent ophthalmopathy (DG). When thyroid stimulating antibodies (TSAb) were measured in the last 3 groups of the patients, they were detected in none with AFTN but in all patients with EOG and DG. These 7 DG patients without ophthalmopathy had a clinical feature showing unstable thyroid functions, changeable to euthyroidism, overt hyperthyroidism and even hypothyroidism during follow-up. In conclusion, TSAb measurement is useful for detection of subclinical Graves’ disease in euthyroid subjects with subnormal TSH levels in serum.

Comparison of serum thyrotrophin concentrations determined by a third generation assay in patients with various types of overt and subclinical thyrotoxicosis.

Recent increases in the sensitivity of methods used to measure TSH, especially third generation assays, have enabled separation of partial from complete pituitary suppression in patients with thyrotoxicosis. We have investigated the use of a sensitive chemiluminescent enzymeimmunoassay in the differential diagnosis of thyrotoxicosis.