Ghrelin in human medullary thyroid carcinomas.

OBJECTIVE: Ghrelin is a novel gastrointestinal hormone involved in several metabolic functions. It has been identified previously in several normal and tumoral neuroendocrine tissues, including human medullary thyroid carcinomas (MTCs). The aim of the study was to evaluate ghrelin levels in patients with MTC and nontoxic goitre (NTG) with elevated calcitonin (CT) levels, as an additional marker of the disease.

PATIENTS AND DESIGN: The study included 22 patients with MTC (four before and 18 after thyroidectomy), 12 patients with NTG with basal CT levels exceeding 10 ng/l and 15 healthy subjects matched for age, sex and body mass index (BMI). After thyroidectomy, MTC patients were considered cured when basal and pentagastrin-stimulated CT levels were < 0.2 and < 10 ng/l, respectively. A pentagastrin-induced CT peak over 50 ng/l was considered as an abnormal response while 100 ng/l was the cut-off accepted for the diagnosis of C-cell hyperplasia or tumour. Circulating ghrelin and CT levels were evaluated at baseline in patients and controls and at -10, 0, 1, 2, 5 and 15 min after pentagastrin injection (0.5 microg/kg body weight) in 12 patients with MTC and nine with NTG. Four surgically removed MTCs were tested for ghrelin expression.

MEASUREMENTS: Total plasma ghrelin and CT levels were measured with a commercially available radioimmunoassay (RIA) and two-site chemiluminescence immunometric assays, respectively. In paraffin-embedded MTC samples ghrelin immunostaining was performed with a polyclonal antibody (1:1000) and the reaction visualized by an indirect immunoperoxidase system.

RESULTS: Plasma ghrelin levels found in cured or not cured MTC and in NTG patients were similar to those of BMI-matched healthy controls. No correlation between ghrelin and CT levels, thyroid disease or previous thyroidectomy was observed. The administration of pentagastrin caused a 17% increase in ghrelin levels (basal ghrelin vs. peak: 162 +/- 62 pmol/l vs. 189 +/- 58 pmol/l, P < 0.05) that was particularly evident (33% increase) in patients with an abnormal CT response to the test (CT > 50 ng/l). Immunohistochemistry showed positivity for ghrelin in a small proportion of CT positive cells from the four MTCs removed.

CONCLUSIONS: Patients with MTC, NTG and controls showed similar ghrelin levels, ruling out this parameter as a marker of MTC. The increase in ghrelin levels in patients with a positive CT response to pentagastrin, together with the immunopositivity for ghrelin in some MTC cells, suggests C cells as minor source of ghrelin production.