AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON TESTING FOR AUTONOMIC AND SOMATIC NERVE DYSFUNCTION.

This document represents the official position of the American Association of Clinical Endocrinologists and the American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.

Poor correlation of serum alpha-subunit concentration and magnetic resonance imaging following pituitary surgery in patients with nonfunctional pituitary macroadenomas.

OBJECTIVE: To review the clinical utility of measuring serum alpha-subunit as a marker for residual tumor in a group of patients with surgically resected nonfunctional pituitary adenomas. METHODS: In this retrospective cross-sectional chart review using the pituitary database at the Cleveland Clinic, we identified patients with nonfunctional pituitary macroadenomas over a 4-year period (2000-2004) and selected those patients who had an elevated alpha-subunit concentration measured before pituitary surgery. Presurgery and post-surgery measurements of alpha-subunit, luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone were documented. Findings from preoperative and postoperative pituitary magnetic resonance imaging (MRI) were reviewed. RESULTS: We identified 54 patients who were evaluated for nonfunctional pituitary macroadenomas during the study period. Of the 39 who underwent pituitary surgery, 34 had a serum alpha-subunit concentration measured before surgery. Eight of 34 patients had elevated preoperative alpha-subunit levels with a median value of 1.8 ng/mL (range, 1.0-3.4 ng/mL). Of the 8 patients, 7 had follow-up MRI a median of 12 months (range, 6-52 months) after surgery. One patient was lost to follow-up. Three of 7 patients had persistently elevated alpha-subunit levels postoperatively; in 2 of these 3, MRI did not identify residual tumor. Among the 4 patients with postoperative normalization of alpha-subunit, 2 patients had residual tumor on MRI. CONCLUSION: The discrepancy between alpha-subunit levels and postoperative MRI calls into question the value of routine alpha-subunit measurement as a tumor marker in patients with nonfunctional pituitary macroadenomas.

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.

Giant invasive pituitary prolactinoma with falsely low serum prolactin: the significance of 'hook effect'.

The authors report a case of a patient with giant, invasive skull base tumor extending to the parasellar area discovered incidentally during the work-up for decreased memory. The patient's neurological exam was otherwise unremarkable. Endocrine evaluation performed at a local hospital showed a moderate hyperprolactinemia 103 ng/ml (normal up to 20 ng/ml). Given the large size of the tumor, the elevated prolactin (PRL) was interpreted to be secondary to stalk effect and patient underwent debulking surgery through a transcranial approach. Immunostaining of the excised tumor tissue was strongly positive for prolactin. His prolactin was found to be 13,144 ng/ml in our lab after surgery confirming the diagnosis of invasive giant prolactinoma. The patient developed a complete right third, fourth and sixth nerve palsy postoperatively. He was started on Cabergoline with normalization of his prolactin level and more than 50% decrease in residual tumor size over 9 months periods. There has been no clinically significant improvement in his right eye ophthalmoplegia since surgery. This case highlights the importance of 'Hook Effect' resulting in falsely low prolactin level, which may have significant therapeutic implication.

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.

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.