Chromogranin A and the α -subunit of glycoprotein hormones in medullary thyroid carcinoma and phaeochromocytoma

Abstract

Summary Using specific immunoradiometric assays, we evaluated the clinical usefulness of chromogranin A and the α-subunit of glycoprotein hormones in neuroendocrine tumours of neuroectodermic origin. The serum α-subunit of glycoprotein hormones was only slightly increased in 2 out of 44 medullary thyroid carcinoma or phaeochromocytoma patients with increased calcitonin or 24-hour urinary metanephrine levels. Serum chromogranin A was increased in 12 of 45 (27%) medullary thyroid carcinoma patients with an elevated calcitonin level and in 4 of 16 medullary thyroid carcinoma patients (25%) with an undetectable calcitonin level, in 5 of 7 phaeochromocytoma patients with increased urinary catecholamine and metabolite excretion, and in 2 of 3 patients with a non-functioning phaeochromocytoma. During follow-up, the course of chromogranin A was found to parallel that of tumour burden and/or 24-hour urinary metanephrine in 5 phaeochromocytoma patients. We conclude that chromogranin A measurement is not recommended for the diagnosis of medullary thyroid carcinoma patients. It may be useful in patients with functioning and non-functioning phaeochromocytomas as a follow-up marker. In neuroendocrine tumour patients with elevated calcitonin secretion, the serum α-subunit of glycoprotein hormone measurement may help differentiate medullary thyroid carcinoma or phaeochromocytoma patients from other endodermal-derived neuroendocrine tumour patients in whom it is frequently elevated. (MTC and phaeochromocytoma); (ii) CgA sensitivity in these tumours and its relationship with calcitonin and with 24-h urinary metanephrine measurements in MTC patients and in phaeochromocytoma patients respectively, using referenced assays and (iii) the potential interest of CgA in the follow-up of phaeochromocytoma patients. PATIENTS AND METHODS Patients61 patients with MTC, and 17 patients with phaeochromocytoma (13 eutopic, 4 ectopic) were studied consecutively. There were 37 females and 41 males, with a mean age at diagnosis of 40 ± 12 years (mean ± SEM, range: 2-78 years). Among MTC patients, 20 patients had a familial form of the disease (either multiple endocrine neoplasia (MEN) type 2A or MEN type 2B, or familial MTC), and 41 had a sporadic MTC. All patients with MTC had undergone a thyroidectomy, and 25 patients had been resubmitted to surgery for neck or mediastinum recurrences. 8 patients had also been treated with external beam radiotherapy, and 8 with chemotherapy (Schlumberger et al, 1995). At the time of the present study, 16 patients had an undetectable plasma calcitonin (CT) level. 45 patients had an elevated CT level and were considered as having persistent disease. These 45 patients underwent the following examinations: neck and liver ultrasound (US), computed tomography (CT scan) of the thorax and abdomen and a bone scintigraphy. Distant metastases were discovered in 16 patients.Among phaeochromocytoma patients, 5 had a familial form of the disease (either MEN 2A, Von Hippel-Lindau disease, or neurofibromatosis type 1), and 12 had...

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

“…The present review is focused on CgA, a hydrophilic glycoprotein abundantly expressed in large dense core vesicles of neuroendocrine cells, whose main biological role is to regulate calcium-mediated exocytosis (Borges et al 2010). Consistent with the definition of a common marker, elevated levels of circulating CgA have been associated with almost all types of NEN, including those arising from the gastroenteropancreatic tract and the bronchopulmonary area, which represent the majority, but also pheocromocytomas/paragangliomas, medullary thyroid carcinoma, Merkel cell carcinoma of the skin and (even if data are controversial) pituitary and parathyroid adenomas (Sobol et al 1986, Blind et al 1992, Kimura et al 1997, Nobels et al 1997, Guignat et al 2001, Tomassetti et al 2001b, Campana et al 2007, Zatelli et al 2007). Despite having a long recognized role for the histological definition of NEN (Solcia et al 2000), actual use of CgA as a circulating marker is far more tricky than expected (Modlin et al 2014c).…”

Medullary thyroid carcinoma

“…Atypical MTC should be differentiated from thyroid metastases from a foregut‐derived endocrine tumour that produces CT in 15% of cases, mainly when metastases are present; diagnosis relies on clinical presentation, histological features and serum marker levels (Leboulleux et al ., 1999; Guignat et al ., 2001).…”

Chromogranin A as a marker of neuroendocrine neoplasia: an Italian Multicenter Study

“…Elevated circulating CgA levels have been demonstrated in serum or plasma of patients with various NE tumors (NETs; Nobels et al 1997, Guignat et al 2001, Tomassetti et al 2001.…”