Recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal in the identification of metastasis in differentiated thyroid cancer with 131I planar whole-body imaging and 124I PET.

UNLABELLED: Various studies have compared the detection of functioning residual thyroid tissue after thyroidectomy using radioiodine whole-body (WB) imaging following preparation of patients with injections of recombinant human thyroid-stimulating hormone (rhTSH) and thyroid hormone withdrawal (THW). However, metastases may have radiopharmacokinetics different from normal thyroid tissue. The objective of this study was to evaluate these 2 methods of patient preparation for the detection of metastases from differentiated thyroid cancer (DTC) using (131)I WB imaging and (124)I PET. METHODS: A prospective study approved by the institutional review board was conducted at Washington Hospital Center from 2006 to 2010 recruiting patients who had DTC, were suspected of having metastasis from DTC (e.g., elevated thyroglobulin level without thyroglobulin antibodies, positive results on recent fine-needle aspiration, suspected enlarging mass, and abnormal findings suggesting metastasis on a diagnostic study) and were referred for (131)I WB dosimetry. All patients subsequently underwent both (131)I WB imaging and (124)I PET performed using the same preparation. All foci of uptake identified on these scans were categorized in a masked manner by consensus of 2 physicians in the following manner: 1, definite physiologic uptake or artifact; 2, most likely physiologic uptake or artifact; 3, indeterminate; 4, most likely locoregional metastases in the neck bed; 5, most likely distant metastases; or 6, definite distant metastases. Foci categorized as 4, 5, and 6 were considered positive for functioning metastases. RESULTS: Of 40 patients evaluated, 24 patients were prepared with rhTSH and 16 with THW. No statistical difference was noted between the 2 groups for any of the parameters evaluated, including serum thyroglobulin. The percentages of patients with positive foci detected on the rhTSH (131)I and THW (131)I WB scans were 4% (1/24) and 63% (10/16), respectively (P < 0.02). The number of foci detected on the rhTSH (131)I and THW (131)I WB scans were 2 and 58, respectively (P < 0.05). When (124)I PET was used for imaging, the percentages of patients with foci detected on the rhTSH and THW scans were 29% (7/24) and 63% (10/16), respectively (P < 0.03). The number of foci detected on the rhTSH and THW scans were 17 and 117, respectively (P < 0.03). CONCLUSION: Significantly more foci of metastases of DTC may be identified in patients prepared with THW than in patients prepared with rhTSH.

PERK eIF2alpha kinase regulates neonatal growth by controlling the expression of circulating insulin-like growth factor-I derived from the liver.

Humans afflicted with the Wolcott-Rallison syndrome and mice deficient for PERK (pancreatic endoplasmic reticulum eIF2alpha kinase) show severe postnatal growth retardation. In mice, growth retardation in Perk-/- mutants is manifested within the first few days of neonatal development. Growth parameters of Perk-/- mice, including comparison of body weight to length and organ weights, are consistent with proportional dwarfism. Tibia growth plates exhibited a reduction in proliferative and hypertrophic chondrocytes underlying the longitudinal growth retardation. Neonatal Perk-/- deficient mice show a 75% reduction in liver IGF-I mRNA and serum IGF-I within the first week, whereas the expression of IGF-I mRNA in most other tissues is normal. Injections of IGF-I partially reversed the growth retardation of the Perk-/- mice, whereas GH had no effect. Transgenic rescue of PERK activity in the insulin- secreting beta-cells of the Perk-/- mice reversed the juvenile but not the neonatal growth retardation. We provide evidence that circulating IGF-I is derived from neonatal liver but is independent of GH at this stage. We propose that PERK is required to regulate the expression of IGF-I in the liver during the neonatal period, when IGF-I expression is GH-independent, and that the lack of this regulation results in severe neonatal growth retardation.