Islet cell-associated autoantibodies in Ethiopians with diabetes mellitus.

BACKGROUND & AIMS: Our understanding of the role of autoimmunity in the pathogenesis of diabetes in African populations is limited. This study aims to evaluate the prevalence of 4 different islet cell-associated antibodies in Ethiopian patients with diabetes and non-diabetic controls. METHODS: A total of 187 subjects from a diabetic clinic at an Ethiopian hospital were evaluated in a cross-sectional study. Fifty-five patients had type 1 diabetes mellitus (T1DM), 86 had type 2 diabetes mellitus (T2DM) and 46 were non-diabetic controls. Islet cell-associated antibodies were measured using 4 different assays for antibodies against islet cells (ICA), glutamic acid decarboxylase (GADA), insulin (IAA) and the protein tyrosine phosphatase-like IA-2 (IA-2A). RESULTS: Comparing the antibody positivity in subjects with T1DM versus T2DM, the results were as follows: 29% versus 3.5% for GADA; 21% versus 2.7% for ICA; 27% versus 16% for IAA. In the control group, the only positive result was for IAA at 2%. IA-2A was absent in all groups. The combi-assay for GADA and IA-2A detected all GADA-positive subjects. T2DM patients who were GADA positive had lower BMI, lower C-peptide levels and all of them were on insulin therapy. CONCLUSIONS: Compared to Caucasians, Ethiopians with T1DM have less prevalence of islet cell-associated antibodies, but the rates are higher than in T2DM. GADA is present in Ethiopians, whereas IA-2A seems to be absent. GADA positivity in T2DM correlates with clinical features of T1DM, indicating the existence in Ethiopia of the subgroup, latent autoimmune diabetes in adults.

Measurement of Serum Free Thyroxine Index May Provide Additional Case Detection Compared to Free Thyroxine in the Diagnosis of Central Hypothyroidism.

The diagnosis of central hypothyroidism is often suspected in patients with hypothalamic/pituitary pathology, in the setting of low, normal, or even slightly elevated serum TSH and low free thyroxine (FT4). We present four cases of central hypothyroidism (three had known pituitary pathology) in whom central hypothyroidism was diagnosed after the serum free thyroxine index (FTI) was found to be low. All had normal range serum TSH and free thyroxine levels. This report illustrates that the assessment of the serum FTI may be helpful in making the diagnosis of central hypothyroidism in the appropriate clinical setting and when free T4 is in the low-normal range, particularly in patients with multiple anterior pituitary hormone deficiencies and/or with symptoms suggestive of hypothyroidism.

Thyroid-stimulating hormone receptor messenger ribonucleic acid measurement in blood as a marker for circulating thyroid cancer cells and its role in the preoperative diagnosis of thyroid cancer.

CONTEXT: Thyroid cancer cells express TSH receptor (TSHR) mRNA, and its measurement in the circulation may be useful in the diagnosis/management of differentiated thyroid cancer (DTC). OBJECTIVE: Our objective was to assess the diagnostic value of circulating TSHR mRNA for preoperative detection of DTC in patients with thyroid nodules. PATIENTS: We measured TSHR mRNA levels by RT-PCR in 258 subjects: 51 healthy subjects and 207 patients (thyroid nodules, n = 180; recurrent thyroid cancer, n = 27) with fine-needle aspirations (FNA) and/or thyroid/neck surgery. Eighty-nine patients also had d-1 postoperative levels assessed. OUTCOME MEASURES: TSHR mRNA levels were compared with FNA cytology for cancer detection preoperatively and serum thyroglobulin and/or whole-body 131I scans postoperatively. RESULTS: Based on cytology/pathology, 88 patients had DTC and 119 had benign thyroid disease. The TSHR mRNA levels in cancer patients were significantly higher than in benign disease (P < 0.0001). At a cutoff value of 1.02 ng/microg total RNA, the TSHR mRNA correctly classified 78.7% of patients preoperatively (sensitivity = 72.0%; specificity = 82.5%). Of 131 patients with FNA and surgery, 51 were FNA positive (all cancer), 17 were FNA negative (15 benign, two cancer), and 63 were indeterminate. TSHR mRNA correctly diagnosed DTC in 16 of 24 (67%) and benign disease in 29 of 39 (74%) patients with indeterminate FNA (combined sensitivity = 90%; specificity = 80%). Combining TSHR mRNA and ultrasound features for follicular lesions correctly classified all follicular cancers and could have spared surgery in 31% of these patients with benign disease. TSHR mRNA has a short life in circulation, and normalized levels on postoperative d 1 correlated with disease-free status, whereas elevated levels predicted residual/metastatic disease. CONCLUSIONS: TSHR mRNA measured with FNA enhances the preoperative detection of cancer in patients with thyroid nodules, reducing unnecessary surgeries, and immediate postoperative levels can predict residual/metastatic disease.

Thyrotropin receptor/thyroglobulin messenger ribonucleic acid in peripheral blood and fine-needle aspiration cytology: diagnostic synergy for detecting thyroid cancer.

RT-PCR for thyroglobulin (Tg) and TSH receptor (TSHR) mRNA has been used to detect circulating thyroid cancer cells. Little is known, however, regarding the preoperative sensitivity of this test to detect cancer. Seventy-two patients with thyroid disease (36 with malignancy and 36 with benign disease) were evaluated preoperatively. TSHR and Tg mRNA transcripts were detected by RT-PCR assays, previously determined to be specific for cancer cells. There was 100% concordance between TSHR and Tg mRNA RT-PCR results. Of 36 cancer patients, 11 had recurrent disease, and all were positive by RT-PCR. Among 25 patients with no prior thyroid surgery, 18 tested positive preoperatively (sensitivity 72%). Seven of 36 patients with benign disease tested positive (specificity 80%). The overall preoperative diagnostic accuracy was 77%. Preoperative fine-needle aspiration (FNA) biopsy was performed on 46 of 61 patients with no prior thyroid surgery. FNA was diagnostic in 28 (61%) patients. Preoperative cytology was adequate but not diagnostic in 18 (39%) patients. RT-PCR correctly classified 14 of these 18 patients with indeterminate FNA, and the test detected three of four cancer patients as positive (75% sensitive) and 11 of 14 patients (78% specific) with benign disease as negative. The combined diagnostic performance characteristics for RT-PCR and FNA cytology were sensitivity = 95%, specificity = 83%, and diagnostic accuracy = 89%, with positive and negative predictive values of 84 and 95%, respectively. Our results suggest that the molecular detection of circulating thyroid cancer cells by RT-PCR for TSHR/Tg mRNA complements FNA cytology in the preoperative differentiation of benign from malignant thyroid disease and their combined use may save unnecessary surgeries.

Detection of thyrotropin-receptor messenger ribonucleic acid (mRNA) and thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease: sensitive and specific markers for thyroid cancer.

Because thyroid cancer cells express functional TSH receptors (TSHR), TSHR-mRNA in peripheral blood might serve as a tissue-/cancer-specific marker. We measured circulating TSHR-mRNA by RT-PCR in 51 normal controls, 27 patients with benign thyroid disease, 67 patients with treated differentiated thyroid cancer (DTC), and eight patients with newly diagnosed DTC, preoperatively. Results were compared with thyroglobulin (Tg) mRNA and serum Tg levels. TSHR-mRNA signals were not detected in normal controls and in 24 of 27 (89%) patients with benign thyroid disease. All 19 patients with treated DTC with evidence of distant or local disease tested positive for TSHR-mRNA (sensitivity 100%). Among patients with no evidence of disease, TSHR-mRNA was detected in 1 in 48 (specificity 98%). Six of the eight newly diagnosed DTC patients tested preoperatively were positive for TSHR-mRNA. The concordance between TSHR-mRNA and Tg-mRNA and between TSHR-mRNA and serum Tg was 95%. Fourteen patients with DTC (21%) had Tg antibodies, three with local disease (all positive for TSHR-mRNA), and 11 with no evidence of disease (all negative for TSHR-mRNA). Our results indicate that TSHR-mRNA and/or Tg-mRNA in peripheral blood are both equally sensitive and specific markers for monitoring thyroid cancer patients. Their principal value resides in the Tg antibody-positive patients in whom a positive or a negative mRNA value might have indicated or obviated the need for a whole-body scan. Furthermore, the high specificity combined with their ability to predict thyroid cancer preoperatively suggests a potential role in detecting thyroid cancer in patients with thyroid nodules.

Raloxifene causing malabsorption of levothyroxine.

To our knowledge, raloxifene hydrochloride, a selective estrogen receptor modulator, has never been reported to interfere with absorption of levothyroxine. We describe a 79-year-old woman with chronic, treated primary hypothyroidism, presenting with increasing levothyroxine requirement while taking raloxifene at the same time as levothyroxine. For two 6- to 8-week periods, we separated the ingestion of raloxifene and levothyroxine by about 12 hours. In addition, we tested the absorption of 1.0 mg of levothyroxine sodium with and without the coadministration of 60 mg of raloxifene hydrochloride on 2 separate occasions by collecting serial blood samples for 6 hours. Hypothyroidism occurred in a reproducible fashion whenever levothyroxine and raloxifene were administered together and improved whenever they were taken separately. Combined administration of levothyroxine and raloxifene resulted in lower levels of serum thyroxine compared with administration of levothyroxine alone. By a yet unknown mechanism, raloxifene caused malabsorption of levothyroxine in our patient when coadministered.

Propylthiouracil-induced chemical hypothyroidism with high-dose tamoxifen prolongs survival in recurrent high grade glioma: a phase I/II study.

BACKGROUND: High-dose tamoxifen has had disappointing results as a palliative therapy in recurrent glioma. Insulin-like growth factor 1 (IGF-1) is a thyroid hormone modulated naturally occurring antagonist of tamoxifen-induced cytotoxicity. Thyroid function was suppressed to reduce IGF-1 levels in glioma patients and high-dose tamoxifen administered. MATERIALS AND METHODS: Propylthiouracil was used to induce chemical hypothyroidism in 22 patients with recurrent glioma. Tamoxifen was started within one month and given in escalating doses from 40 mg twice a day up to 80 mg 3 times a day. No significant toxicity developed. RESULTS: Eleven out of 22 patients became hypothyroid. No patients experienced symptoms of clinical hypothyroidism. Median survival was significantly longer in the hypothyroid group (10.1 months versus 3.1 months); p = 0.03. There was a significant decrease in blood levels of IGF-1 (p = 0.02). in hypothyroid patients. CONCLUSION: Patients treated for recurrent high-grade gliomas with high-dose tamoxifen had significantly longer survival when chemical hypothyroidism was induced with propylthiouracil.