Cryopreservation, culture, and transplantation of human fetal mesencephalic tissue into monkeys.

Studies in animals suggest that fetal neural grafts might restore lost neurological function in Parkinson's disease. In monkeys, such grafts survive for many months and reverse signs of parkinsonism, without attendant graft rejection. The successful and reliable application of a similar transplantation procedure to human patients, however, will require neural tissue obtained from human fetal cadavers, with demonstrated cellular identity, viability, and biological safety. In this report, human fetal neural tissue was successfully grafted into the brains of monkeys. Neural tissue was collected from human fetal cadavers after 9 to 12 weeks of gestation and cryopreserved in liquid nitrogen. Viability after up to 2 months of storage was demonstrated by cell culture and by transplantation into monkeys. Cryopreservation and storage of human fetal neural tissue would allow formation of a tissue bank. The stored cells could then be specifically tested to assure their cellular identity, viability, and bacteriological and virological safety before clinical use. The capacity to collect and maintain viable human fetal neural tissue would also facilitate research efforts to understand the development and function of the human brain and provide opportunities to study neurological diseases.

Effects of hydroxycinnamic acids on blue color expression of cyanidin derivatives and their metal chelates.

Mechanisms to recreate many anthocyanin blue hues in nature are not fully understood, but interactions with metal ions and phenolic compounds are thought to play important roles. Bluing effects of hydroxycinnamic acids on cyanidin and chelates were investigated by addition of the acids to triglycosylated cyanidin (0-50×[anthocyanin]) and by comparison to hydroxycinnamic acid monoacylated and diacylated Cy fractions by spectrophotometry (380-700nm) and colorimetry in pH 5-8. With no metal ions, λmax and absorbance was greatest for cyanidin with diacylation>monoacylation>increasing [acids]. Hydroxycinnamic acids added to cyanidin solutions weakly impacted color characteristics (ΔE<5); while acylation (covalent acid attachment) resulted in ΔE 5-15. Triglycosylated cyanidin expressed blue color (pH 7-8), suggesting glycosylation pattern also plays a role. Al3+ chelation increased absorbance 2-42× and λmax≳40nm (pH 5-6) compared to added hydroxycinnamic acids. Metal chelation and aromatic diacylation resulted in the most blue hues.

Spectral and colorimetric characteristics of metal chelates of acylated cyanidin derivatives.

Colorants derived from nature are increasingly popular due to consumer demand. Anthocyanins are a class of naturally occurring pigments that produce red-purple-blue hues in nature, especially when interacting with metal ions and co-pigments. The role of various acylations of cyanidin (Cy) derivatives on color expression and stability of Al3+ and Fe3+ chelates in pH 6-7 were evaluated by spectrophotometry (380-700nm) and colorimetry (CIE-L∗a∗b∗) during dark, ambient storage (48h). Increased substitution generally increased λmax of Cy chelates: malonic acid monoacylationferulic-sinapic>sinapic-sinapic)>monoacylated (malonic≈sinapic>ferulic>p-coumaric).

Evaluating the role of metal ions in the bathochromic and hyperchromic responses of cyanidin derivatives in acidic and alkaline pH.

In many food products, colorants derived from natural sources are increasingly popular due to consumer demand. Anthocyanins are one class of versatile and abundant naturally occurring chromophores that produce different hues in nature, especially with metal ions and other copigments assisting. The effects of chelation of metal ions (Mg(2+), Al(3+), Cr(3+), Fe(3+), and Ga(3+)) in factorial excesses to anthocyanin concentration (0-500×) on the spectral characteristics (380-700nm) of cyanidin and acylated cyanidin derivatives were evaluated to better understand the color evolution of anthocyanin-metal chelates in pH 3-8. In all pH, anthocyanins exhibited bathochromic and hyperchromic shifts. Largest bathochromic shifts most often occurred in pH 6; while largest hyperchromic shifts occurred in pH 5. Divalent Mg(2+) showed no observable effect on anthocyanin color while trivalent metal ions caused bathochromic shifts and hue changes. Generally, bathochromic shifts on anthocyanins were greatest with more electron rich metal ions (Fe(3+)≈Ga(3+)>Al(3+)>Cr(3+)).

Recent advances in the management of adrenal incidentalomas.

Modern imaging techniques have made adrenal incidentaloma a relatively common diagnostic problem. When an incidental adrenal mass is found, the clinician must try to determine its etiology and functionality, and the likelihood of malignancy. This task is complicated further in patients with a history of extra-adrenal malignancy. In this article, we present a review of the literature and propose a diagnostic algorithm for management of adrenal incidentalomas.

Unilateral toxic multicystic goiter.

We treated a 43-year-old woman who had multiple thyroid cysts and coexistent toxic nodules localized to the left lobe. After surgical excision of this lobe, the patient's right lobe proceeded to function normally, displaying no evidence of nodules, cysts, or hyperfunction. Since toxic multinodular goiter is usually a diffuse process involving the whole gland, this case is unique and underlines the wide variability in the manifestation of this disorder.

Growth hormone-releasing factor immunoreactivity in the hypothalamus and cortex of the rat: in vivo and in vitro studies.

Utilizing a specific RIA for rat (r) GRF, hypothalamus and cerebral cortex from adult rat and long term dissociated fetal rat hypothalamic and cerebral cortical cell cultures were investigated for the presence of rGRF immunoreactivity (IR-GRF). After homogenization in an acidic medium, tissues and cultures were extracted on octadecylsilyl-silica columns, and IR-GRF and somatostatin (IR-SS) were measured by RIA. In extracts from the hypothalamus from the adult rat the content of IR-GRF was 3.02 +/- 0.16 ng ( +/- SE) per hypothalamus. IR-GRF was identical with synthetic rGRF on gel filtration chromatography and by parallel displacement of dilutions of extract in RIA. In extracts from cerebral cortex isolated from the adult rat, no IR-GRF was detected. In extracts from long term dissociated cell cultures from fetal hypothalami, 7.3 +/- 7 pg/10(6) cells of IR-GRF were present and were identical with synthetic rGRF by chromatographic and immunological criteria. In the extracts from cerebral cortical cell cultures cross-reacting material was present which on gel filtration chromatography revealed two peaks of immunoreactivity of higher mol wt than synthetic rGRF. There was nonparallelism on dilution of the extract. The ratio of IR-SS to IR-GRF by weight (IR-SS/IR-GRF) was calculated to compare the relative abundance of IR-GRF in cultured hypothalamic cells. In the hypothalamus isolated from the adult rat the ratio of IR-SS/IR-GRF by weight was 15.8 +/- 1.4 as compared to 48.9 +/- 10.3 in hypothalamic cultures. We conclude that IR-GRF indistinguishable from synthetic rGRF is present in long term dissociated hypothalamic cell cultures, but is relatively less abundant than in the hypothalamus of the adult rat when compared on the basis of IR-SS. No IR-GRF was detectable in cerebral cortex of the adult rat. At least one cross-reacting molecular species is detected in cerebral cortical cultures by the rGRF RIA, but exhibits nonparallelism and has a higher mol wt than synthetic rGRF. The increase of the ratio of IR-SS/IR-GRF in hypothalamic cell cultures in vitro compared to hypothalamus in vivo suggests that the culture conditions change differentially the expression of IR-SS and IR-GRF.

Somatostatin biosynthesis by cerebral cortical cells in monolayer culture.

We examined the ability of isolated rat cerebral cortical cells to synthesize and secrete immunoreactive somatostatin (IRS). Dispersed telencephalic cells (10(7] from rat embryos contain approximately 24 pg IRS. The IRS content of 10(7) cultured cells increased steadily to a level of 2800 pg by 20 days in vitro. The IRS content in the medium followed a parallel production curve and was, in general, 10% of the cellular content. The nature of this IRS was characterized by gel filtration. Bio-Gel P-10 chromatography resolved four discrete IRS peaks. The first peak had an apparent molecular weight of 11,500. The second peak, which comigrated with synthetic Somatostatin-28, had a molecular weight of 7,000. The third peak had a molecular weight of 1,800, and the fourth peak, which comigrated with Somatostatin-14, had a molecular weight less than 1,800. Incubation with [3H]phenylalanine (Phe) revealed that 3H was incorporated into each peak. Isolation of 3H-labeled peak 4 was carried out by double affinity column purification. Sequential automated Edman degradation of this material revealed [3H] Phe in the positions that Phe occupies in Somatostatin-14. These studies document the ability of isolated rat cerebral cortical tissue to synthesize several forms of IRS, establishing them as endogenous cortical peptides.

Sodium- and calcium-dependent somatostatin release from dissociated cerebral cortical cells in culture.

The influence of membrane depolarization on somatostatin release from cerebral cortical neurons was examined. Fetal rat telencephalic cells, obtained by mechanoenzymatic dispersal, were maintained as organotypic monolayer cultures for 12 days before experimental studies. The immunoreactive somatostatin (IRS) released into the medium during a treatment epoch was compared to the amount released from the same cells during an immediately preceding control period. Potassium (60 mM) induced an increase in IRS secretion which was dependent on extracellular calcium concentration and could be prevented by the addition of the calcium channel blockers, cobalt or verapamil. Depolarization by veratridine, a sodium ionophore, also stimulated IRS release. The effect of veratridine was reversed by simultaneous exposure of the cells to either tetrodotoxin, a sodium channel blocker, or verapamil, a calcium channel blocker. These findings indicate that IRS release by cerebral cortical cells is stimulated by membrane depolarization and is dependent on both Na+ and Ca++ entry into the cells.

The effects of growth hormone, prolactin, corticotropin, and thyrotropin on the production and secretion of somatostatin by hypothalamic cells in vitro.

The influence of GH and several other pituitary hormones on the secretion and intracellular content of immunoreactive somatostatin (IRS) in cultured hypothalamic cells was examined. Hypothalamic cells prepared from 17-day-old rat embryos and maintained as reaggregate monolayers for 12 days in vitro were used. Short term release of IRS from these cultures was found to be stable and relatively constant. IRS release was enhanced by 60 mM K+ in a calcium-dependent fashion and by dopamine at concentrations as low as 1 nM. GH (1 microM) increased medium IRS content above baseline 12, 24, and 48 h after the incubation was begun, but had no effect after only 4 h. Hypothalamic cell content of IRS was increased by a 24-h incubation in 0.3 and 1.0 microM GH, but not by 0.1 microM GH. TSH (1 microM) induced an increase in IRS release comparable to 1 microM GH. However, intracellular IRS content was decreased after exposure to TSH. Cosyntropin, an ACTH analog, inhibited both IRS release and cell content, whereas PRL had no effect on either medium or cellular IRS content. Our results demonstrate that developing somatostatinergic neurons in the hypothalamus have the capacity to respond to pituitary hormones, indicating that short-loop feedback pathways may exist in perinatal hypothalamic cells.

The effects of estradiol on the growth patterns of estrogen receptor-positive hypothalamic cell lines.

Although it appears that the perinatal development of sexual phenotype in the rodent brain is determined by exposure to estradiol, generated locally via aromatization of androgen, the mechanisms underlying this process are not fully understood. We have, therefore, developed an in vitro model of hormone action based upon examining the effects of sex steroids on SV-40-transformed fetal rat hypothalamic cell lines. Using serum-free growth factor-deficient conditions the effects of 17 alpha- and 17 beta-estradiol, testosterone, dihydrotestosterone (DHT), and tamoxifen on survival of two estrogen-binding rat hypothalamic cell lines were examined. In one cell line, RCF-8, both 17 beta-estradiol and testosterone increased survival at picomolar concentrations. This effect was blocked by tamoxifen, but could not be reproduced by the nonaromatizable androgen DHT or the inactive isomer 17 alpha-estradiol. In the other cell line, RCA-6, addition of 17 beta-estradiol led to inhibition of cellular proliferation, which was reversed by the addition of tamoxifen. In an estrogen receptor-negative hypothalamic cell line, RCF-12, estradiol had no net effect on the growth pattern. In summary, the estrogen-binding capacity and the responsiveness to physiological concentrations of estradiol and testosterone, but not DHT, make the RCF-8 cell line a potential in vitro model of hypothalamic sexual differentiation. The use of estrogen-sensitive hypothalamic cell lines provides a unique opportunity for studying the cellular mechanisms underlying this process.

Clinical review 61: Effects of growth hormone on human bone biology.

GH has considerable importance in the normal development and growth of bone. An additional role in the maintenance of the adult skeleton is suggested by the alterations in bone mineral density observed in states of deficient or excess GH secretion and in the bone formation response to GH replacement in GHD patients. Deficiency in the secretion of GH is also observed, with increasing and striking frequency after middle-age despite the lack of any defined pituitary disease or injury. Although a causal relationship between hyposomatotropism and osteopenia in normal elderly patients is hypothetical, intriguing therapeutic questions are raised. Preliminary trials of hGH in osteoporosis have not resulted in increases in BMD, but such studies suffer from methodological limitations, chief of which is the failure to account for the GH/IGF-I status of their subjects. Osteopenic patients with the lowest IGF-I levels may need to be assessed independently. The utility of hGH may be in preventing the senile component of osteoporosis, which appears to result mainly from defective bone formation. Such studies will require appropriate patient selection, longer treatment periods, and more sensitive measures of bone density. Combination and/or coherence therapy with other agents, particularly those that attenuate bone resorption, may also prove useful.

Regional distribution of human growth hormone-releasing hormone in the human hypothalamus by radioimmunoassay.

The regional distribution of human GH-releasing hormone (hGHRH) in the hypothalamus was determined by RIA using a standardized microdissection technique. The antiserum used in the RIA is highly specific for human GHRH-44, and cross-reactivity to hGHRH-40 is minimal (less than 0.06%). The concentration and content of immunoreactive hGHRH-44 (IR-GHRH) were measured in extracts of 12 nuclei and areas microdissected from hypothalami from 5 autopsy subjects. Extracts of proximal and distal pituitary stalk were similarly analyzed for IR-GHRH. The highest concentration of IR-GHRH in the hypothalamus was in the infundibular nucleus, with lesser concentrations in the periventricular area and paraventricular and supraoptic nuclei. All other regions had measurable concentrations, except the mammillary nuclei. There was 56.1 +/- 12.4 (+/- SD) ng (11.1 +/- 1.2 pmol) IR-GHRH in the human hypothalamus and pituitary stalk, with 62% in the pituitary stalk. IR-GHRH in tissue extracts produced the same dose-response curve as did hGHRH in the RIA and coeluted with synthetic hGHRH-44 on gel filtration. Our results indicate the following. 1) The regional distribution of IR-GHRH in the human hypothalamus differs from the regional distributions of other neuropeptides. 2) The infundibular nucleus contains the greatest IR-GHRH regional concentration, in accord with immunohistochemical studies. 3) Appreciable concentrations of IR-GHRH are found in regions not previously identified by immunohistochemical techniques. 4) The IR-GHRH molar content in the hypothalamus-pituitary stalk is lower than that reported for other hypothalamic releasing hormones.

Serum vascular endothelial growth factor levels are elevated in metastatic differentiated thyroid cancer but not increased by short-term TSH stimulation.

Solid tumor formation requires the development of a blood supply adequate to meet the metabolic demands of the enlarging tumor mass that cannot be sustained by simple diffusion. One principal stimulant to endothelial cell growth and migration, vascular endothelial growth factor (VEGF), is synthesized and secreted by thyroid cancer cells. Furthermore, VEGF overexpression is associated with an aggressive thyroid cancer phenotype in both animal models and clinical-pathological studies. In other malignancies, elevated serum levels of VEGF often correlate with stage of disease and other poor prognostic clinical features. Therefore, we hypothesized that serum VEGF levels would be significantly higher in patients with persistent or recurrent thyroid cancer than in those cured of the disease. Because TSH stimulates both normal and neoplastic thyroid cells, we also proposed that serum VEGF would be further increased by TSH stimulation. Sixty-nine patients with either papillary or follicular thyroid cancer, status post total thyroidectomy, and prior radioactive iodine ablation, who had undergone routine recombinant human TSH (rhTSH, Thyrogen, Genzyme Transgenics Corp., Cambridge, MA) assisted whole-body radioactive iodine scanning, were included in this study. This cohort (mean age 53 +/- 16 yr, 51% female) included 21 patients with no evidence of disease and 48 patients with local or distant metastases. Stored serum samples obtained for standard Tg determinations before and 72 h following standard rhTSH stimulation were identified and assayed for VEGF 165 (R \[amp ]\ D Systems, Minneapolis, MN). Baseline serum VEGF levels obtained at a time of TSH suppression were significantly higher in patients with known metastatic disease than in those with no evidence of disease (416 +/- 62 pg/ml vs. 185 +/- 25 pg/ml, P = 0.001). Patients with distant metastases had baseline serum VEGF levels that did not differ significantly from patients with only cervical recurrences (455 +/- 90 pg/ml in distant metastases vs. 330 +/- 44 pg/ml for local cervical recurrences). Short-term TSH stimulation, although causing a significant rise in serum Tg, resulted in no significant increase in serum VEGF measured 72 h after rhTSH injection in either the patients with known metastatic disease (416 +/- 62 pg/ml baseline vs. 419 +/- 71 pg/ml after TSH stimulation) or in cured patients (185 +/- 25 pg/ml baseline vs. 191 +/- 33 pg/ml after TSH stimulation). Subgroup analysis revealed that patients with metastatic disease arising from well differentiated primary thyroid cancers had significantly higher serum VEGF levels than patients with metastatic disease arising from poorly differentiated thyroid cancer primaries (485 +/- 74 pg/ml vs. 167 +/- 32 pg/ml, P = 0.003 by ANOVA). Poorly differentiated metastatic thyroid cancers had serum VEGF levels indistinguishable from patients cured of disease (167 +/- 32 pg/ml vs. 186 +/- 25 pg/ml). In summary, serum VEGF is significantly elevated in patients with metastatic differentiated thyroid cancer but not in those with poorly differentiated thyroid cancer metastases. No measurable increase in serum VEGF levels can be detected 72 h after short-term TSH stimulation with rhTSH. We conclude that serum VEGF may serve as a clinical useful marker of residual differentiated thyroid cancer.

Syndrome of inappropriate antidiuresis in the absence of arginine vasopressin.

The syndrome of inappropriate antidiuresis (SIAD) is usually associated with inappropriately elevated plasma arginine vasopressin (AVP) concentrations. We describe herein a patient with a macroprolactinoma who had symptomatic hyponatremia due to SIAD. Although the patient had excessive thirst, severe plasma hypoosmolality, and hyperosmolar urine, no immunoassayable AVP could be detected. During long term treatment with bromocriptine, there was gradual shrinkage of the prolactinoma coincident with improvement in the ability to excrete a water load and normalization of the thirst threshold. At this point, plasma immunoactive AVP was measurable during a hypertonic saline infusion for the first time. By high pressure liquid chromatographic analysis, this immunoactive substance coeluted with AVP. These studies suggest that the SIAD in this patient was due to the production of an antidiuretic substance distinct from AVP in association with his prolactinoma.

Preparation by recombinant human thyrotropin or thyroid hormone withdrawal are comparable for the detection of residual differentiated thyroid carcinoma.

Clinical recurrences of differentiated thyroid carcinoma occur in 20% of patients after thyroid surgery. We performed a retrospective analysis of a cohort of patients undergoing routine follow-up testing to detect recurrent thyroid carcinoma over a 2-yr period. One group was prepared for testing by thyroid hormone withdrawal (THW), and the other group remained on thyroid hormone and received injections of recombinant human TSH (rhTSH) before diagnostic whole-body radioiodine scanning (DxWBS). We hypothesized that no differences in the ability to detect residual disease would exist between these 2 groups. Two hundred and eighty-nine patients were examined by both DxWBS and by measurement of the serum thyroglobulin (Tg) response to elevated TSH levels. THW was used for 161 patients, and rhTSH preparation was used for 128 patients. Based on all available testing results, we categorized patients as having metastatic disease, thyroid bed uptake only, or no evidence of disease. We examined the sensitivity, specificity, positive and negative predictive values of the DxWBS, and the stimulated Tg after preparation by THW or rhTSH. Patients with thyroid bed were not considered in accuracy testing. The sensitivity and specificity of the 2 tests were comparable between groups. No significant differences were present in the positive or negative predictive values between groups. The highest negative predictive value (97%) was in patients who had both a negative DxWBS and low stimulated Tg levels after rhTSH. In summary, we were unable to demonstrate a difference in the diagnostic accuracy of DxWBS and/or Tg between patients prepared by either THW or rhTSH. We conclude that preparing patients by rhTSH is diagnostically equivalent to preparing them by THW.

Prognostic value of [18F]fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer.

Poorly differentiated thyroid cancer lesions often lose the ability to concentrate radioactive [131I]iodine (RAI) and exhibit increased metabolic activity, as evidenced by enhanced glucose uptake. We incorporated [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning into the routine follow-up of a cohort of thyroid cancer patients undergoing annual evaluations. One hundred and twenty-five patients who had previous thyroidectomies were included. They had diagnostic RAI whole body scans, serum thyroglobulin measurements, and additional imaging studies as clinically indicated. During 41 months of follow-up, 14 patients died. Univariate analysis demonstrated that survival was reduced in those with age over 45 yr, distant metastases, PET positivity, high rates of FDG uptake, and high volume of the FDG-avid disease (>125 mL). Survival did not correlate with gender, RAI uptake, initial histology, or grade. Multivariate analysis demonstrated that the single strongest predictor of survival was the volume of FDG-avid disease. The 3-yr survival probability of patients with FDG volumes of 125 mL or less was 0.96 (95% confidence interval, 0.91, 1.0) compared with 0.18 (95% confidence interval, 0.04, 0.85) in patients with FDG volume greater than 125 mL. Only 1 death (of leukemia) occurred in the PET-negative group (n = 66). Of the 10 patients with distant metastases and negative PET scans, all were alive and well. Patients over 45 yr with distant metastases that concentrate FDG are at the highest risk. Once distant metastases are discovered in patients with differentiated thyroid carcinoma, FDG-PET can identify high and low risk subsets. Subjects with a FDG volume greater than 125 mL have significantly reduced short term survival.

[18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography localizes residual thyroid cancer in patients with negative diagnostic (131)I whole body scans and elevated serum thyroglobulin levels.

Progressive dedifferentiation of thyroid cancer cells leads to a loss of iodine-concentrating ability, with resultant false negative, whole body radioactive iodine scans in approximately 20% of all differentiated metastatic thyroid cancer lesions. We tested the hypothesis that all metastatic thyroid cancer lesions that did not concentrate iodine, but did produce thyroglobulin (Tg), could be localized by [18F]2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET). We performed FDG-PET on 37 patients with differentiated thyroid cancer after surgery and radioiodine ablation who had negative diagnostic 131I whole body scans during routine follow-up. Serum Tg, Tg autoantibodies, neck ultrasounds, and other clinically indicated imaging procedures were performed to detect residual disease. In those with elevated Tg levels, FDG-PET localized occult disease in 71%, was false positive in one, and was false negative in five patients. The majority of false negative FDG-PET occurred in patients with minimal cervical adenopathy. Surgical resections, biopsies, 131 therapy, and differentiation therapy were performed based on the PET results. The FDG-PET result changed the clinical management in 19 of the 37 patients. In patients with elevated Tg levels, FDG-PET had a positive predictive value of 92%. In patients with low Tg levels, FDG-PET had a negative predictive value of 93%. No FDG-PET scans were positive in stage I patients; however, they were always positive in stage IV patients with elevated Tg levels. An elevated TSH level (i.e. hypothyroidism) did not increase the ability to detect lesions. FDG-PET is able to localize residual thyroid cancer lesions in patients who have negative diagnostic 131I whole body scans and elevated Tg levels, although it was not sensitive enough to detect minimal residual disease in cervical nodes.

Bromocriptine as primary therapy for prolactin-secreting macroadenomas: results of a prospective multicenter study.

To assess the effectiveness of bromocriptine in reducing the size of PRL-secreting macroadenomas with extrasellar extension, we conducted a prospective multicenter trial in patients without prior radiotherapy, applying a standard protocol of treatment and tumor size evaluation. Basal serum PRL levels [1441 +/- 417 (+/- SEM) ng/ml for women; 3451 +/- 1111 ng/ml for men] fell in all patients and to 11% or less of basal values in all patients but 1. Normal PRL levels were reached in 18 of the 27 patients. In 13 patients (46%), tumor size was reduced by greater than 50%, in 5 patients (18%) by about 50%, and in 9 patients (36%) by approximately 10-25%. The extent of tumor size reduction did not correlate with basal PRL, nadir PRL, percent fall in PRL, or whether PRL levels reached normal. However, a reduction in PRL levels always preceded any detectable change in tumor size. In 19 patients, reduction in tumor size was evident by 6 weeks, but in the other 8, such reduction was not noted until the 6 month evaluation. In the 4 patients in whom bromocriptine was discontinued at the end of 1 yr, tumor reexpansion occurred in 3. Visual fields improved in 9 of the 10 patients in whom they were abnormal. Because of the excellent results found in most of the patients in this series, we suggest that therapy with bromocriptine should be considered as initial management for patients with PRL-secreting macroadenomas.

A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma.

Recent studies have provided new information regarding the optimal surveillance protocols for low-risk patients with differentiated thyroid cancer (DTC). This article summarizes the main issues brought out in a consensus conference of thyroid cancer specialists who analyzed and discussed this new data. There is growing recognition of the value of serum thyroglobulin (Tg) as part of routine surveillance. An undetectable serum Tg measured during thyroid hormone suppression of TSH (THST) is often misleading. Eight studies show that 21% of 784 patients who had no clinical evidence of tumor with baseline serum Tg levels usually below 1 micro g/liter during THST had, in response to recombinant human TSH (rhTSH), a rise in serum Tg to more than 2 micro g/liter. When this happened, 36% of the patients were found to have metastases (36% at distant sites) that were identified in 91% by an rhTSH-stimulated Tg above 2 micro g/liter. Diagnostic whole body scanning, after either rhTSH or thyroid hormone withdrawal, identified only 19% of the cases of metastases. Ten studies comprising 1599 patients demonstrate that a TSH-stimulated Tg test using a Tg cutoff of 2 micro g/liter (either after thyroid hormone withdrawal or 72 h after rhTSH) is sufficiently sensitive to be used as the principal test in the follow-up management of low-risk patients with DTC and that the routine use of diagnostic whole body scanning in follow-up should be discouraged. On the basis of the foregoing, we propose a surveillance guideline using TSH-stimulated Tg levels for patients who have undergone total or near-total thyroidectomy and (131)I ablation for DTC and have no clinical evidence of residual tumor with a serum Tg below 1 micro g/liter during THST.