Malignant presacral ghrelinoma with long-standing hyperghrelinaemia

Abstract

Background. A 57-year old man with low-back pain was found to have a 3 × 3 × 3 cm presacral neuroendocrine tumour (NET) with widespread metastases, mainly to the skeleton. His neoplastic disease responded well to peptide receptor radionuclide therapy (PRRT) with the radiotagged somatostatin agonist 177Lu-DOTATATE. During almost 10 years he was fit for a normal life. He succumbed to an intraspinal dissemination.Procedures. A resection of the rectum, with a non-radical excision of the adjacent NET, was made. In addition to computerized tomography (CT), receptor positron emission tomography (PET) with 68Ga-labelled somatostatin analogues was used.Observations. The NET showed the growth pattern and immunoprofile of a G2 carcinoid. A majority cell population displayed immunoreactivity to ghrelin, exceptionally with co-immunoreactivity to motilin. Somatostatin receptor scintigraphy and 68Ga-DOTATATE PET-CT demonstrated uptake in the metastatic lesions. High serum concentrations of total (desacyl-)ghrelin were found with fluctuations reflecting the severity of the symptoms. In contrast, the concentrations of active (acyl-)ghrelin were consistently low, as were those of chromogranin A (CgA).Conclusions. Neoplastically transformed ghrelin cells can release large amounts of desacyl-ghrelin, evoking an array of non-specific clinical symptoms. Despite an early dissemination to the skeleton, a ghrelinoma can be compatible with longevity after adequate radiotherapy.

Multicenter Analysis of Presacral Neuroendocrine Neoplasms—Clinicopathological Characterization and Treatment Outcomes of a Rare Disease

“…In rectal NET, PRRT has shown efficacy in case series (82). PRRT is reported in nine cases with presacral NET, all with encouraging long-term stabilizations and remission (32,35,36,72). In accordance to this, PRRT was also one of the most effective treatments observed in our cohort, resulting in 43% responses (6/ 14) and 36% disease stabilizations (5/14).…”

Plasma acylated and plasma unacylated ghrelin: useful new biomarkers in patients with neuroendocrine tumors?

“…In the literature, only 11 NET patients with elevated total and/or acylated ghrelin levels have been described ( 23 , 24 , 25 , 26 , 27 ). Of these patients, only one patient had clinical symptoms of hypersecretion of vasoactive products by the NET.…”

“…NETs can also express ghrelin and its receptors ( 14 , 22 ). Although most NETs release ghrelin, hyperghrelinemia has been reported in only 11 patients with NETs ( 23 , 24 , 25 , 26 , 27 ).…”

The regulation of gastric ghrelin secretion

“…Furthermore, ghrelin induces lipid accumulation in the liver 38 . Regarding the role of ghrelin in the pathophysiology of obesity, available case reports have shown that individuals with ghrelinoma are overweight or obese, 39‐41 and although these neuroendocrine tumours are very rare, and available information is scarce, 39‐41 it is plausible the hyperghrelinaemia, observed in these patients, plays a role in the development of obesity. Furthermore, research has shown that ghrelin influences glucose homoeostasis by directly increasing glycaemia, 42 decreasing pancreatic insulin secretion 43 and plasma insulin levels, 44 as well as decreasing insulin sensitivity in humans 45 .…”