Severe hypoglycemia associated with an illegal sexual enhancement product adulterated with glibenclamide: MR imaging findings.

PURPOSE: To describe the magnetic resonance (MR) imaging findings associated with severe hypoglycemia after consumption of an illegal sexual enhancement product (Power 1 Walnut) adulterated with glibenclamide, an oral hypoglycemic agent used to treat diabetes mellitus. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective study. Records in eight male patients with severe hypoglycemia of unknown cause, without prior treatment for diabetes, and with positive blood toxicology results for glibenclamide were reviewed. MR imaging included diffusion-weighted imaging and, in some patients, MR angiography, dynamic contrast material-enhanced perfusion MR imaging, and MR spectroscopy. RESULTS: In seven patients, there were hyperintense abnormalities on diffusion-weighted and T2-weighted images in the hippocampus and cerebral cortex, sparing the subcortical white matter and cerebellum. Three patients had abnormalities of the splenium of the corpus callosum, and one had widespread involvement, including the caudate nucleus, basal ganglia, and internal capsule bilaterally. In three patients, unilateral cortical involvement, which did not conform to the typical cerebral arterial territories, was noted. In one patient, perfusion MR imaging showed slightly increased relative cerebral blood volume, and MR spectroscopy revealed no evidence of abnormal lactate in the affected cerebral cortex. CONCLUSION: Diffusion-weighted MR imaging findings in patients with severe hypoglycemia showed typical lesions in the hippocampus and cerebral cortex, but the caudate nucleus and basal ganglia were involved in only the most severely affected patient. The splenium of the corpus callosum and internal capsule were also abnormal in three patients, and unilateral cortical lesions could be distinguished from acute ischemic stroke by the pattern of involvement and MR angiographic, perfusion, and spectroscopic findings.

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.

The utility of peripheral thyrotropin mRNA in the diagnosis of follicular neoplasms and surveillance of thyroid cancers.

BACKGROUND: Thyroid cells in peripheral circulation express uniquely thyrotropin receptor (TSHR) mRNA, and their detection may aid thyroid cancer management. METHODS: Since 2002, 258 patients had prospective TSHR mRNA measurement by quantitative RT-PCR from peripheral blood before and/or after thyroidectomy. Thyroid cancer detection was assessed from known clinical diagnostic criteria and mRNA for patients with follicular neoplasms (n = 64) and long-term cancer follow-up (n = 13). RESULTS: Adding TSHR mRNA to fine-needle aspiration biopsy (FNAB) maintained high sensitivity (90%) but improved specificity (73%) for thyroid cancer diagnosis. When FNAB specimens indicated follicular neoplasm, a decision algorithm combining TSHR mRNA and abnormal thyroid ultrasound features correctly diagnosed all cancer patients (100% sensitivity) and would have spared operation for benign disease in 38%. Elevated TSHR mRNA on postoperative day 1 predicted persistent/recurrent cancer. During long-term thyroid cancer surveillance, TSHR mRNA had a 91% concordance with radioactive iodine whole body scan (WBS)-detectable disease, agreed with thyroglobulin (Tg) levels in 64% of patents, missed disease in 5%, but was more sensitive to detecting disease than Tg levels in 31% of patients, including all patients with Tg antibodies. CONCLUSIONS: Detecting circulating thyroid cancer cells is useful for initial thyroid cancer diagnosis and postoperatively predicts recurrent cancer. This novel test promises to enhance thyroid cancer patient care by management algorithms that combine histologic, genomic, and clinical criteria.

Circulating thyroid cancer markers.

PURPOSE OF REVIEW: To describe the progress in the field of circulating markers of thyroid cancer. RECENT FINDINGS: Thyroid cancer cells in the circulation can be detected by measuring the mRNA of thyroid-specific genes. Among these, thyroglobulin, and more recently thyroid-stimulating hormone receptor mRNAs' provide high diagnostic sensitivity and specificity for thyroid cancer detection. These markers can be used in synergy with current diagnostic modalities, i.e. fine-needle aspiration and ultrasound, for preoperative diagnosis and serum thyroglobulin measurement for monitoring. SUMMARY: For the detection of recurrent/residual thyroid cancer, serum thyroglobulin remains the sole circulating marker, but lacks sensitivity and is unreliable in the presence of antithyroglobulin antibodies. The measurement of thyroid-specific mRNA in blood may provide sensitive/specific markers, but significant variability exists among various studies for thyroglobulin mRNA in particular, questioning the validity of this marker. Recent studies have demonstrated the high sensitivity and specificity of thyroid-stimulating hormone receptor mRNA in detecting recurrent/residual disease even in the presence of thyroglobulin antibodies. Fine-needle aspiration biopsy is currently the sole method for evaluating thyroid nodules. Indeterminate fine-needle aspiration cytology is found in approximately 15-30% of specimens. Thyroid-stimulating hormone receptor mRNA measurement in patients with indeterminate fine-needle aspiration may enhance cancer detection and save unnecessary surgeries.

Acute ataxia, Graves' disease, and stiff person syndrome.

Stiff person syndrome (SPS) has been associated with autoimmune diseases, such as Type 1 diabetes mellitus and autoimmune thyroid disease (Hashimoto's thyroiditis), among others. The association of SPS with hyperthyroidism is extremely rare. We describe a patient with uncontrolled Graves' disease and undiagnosed SPS, who presented initially with acute ataxia simulating a cerebrovascular accident. Initiation of immunosuppressive therapy dramatically improved the patient's Graves' disease within 2 weeks but the neurological symptoms were not alleviated after a follow-up period of 3 years.