Ectopic growth hormone-releasing hormone secretion by a metastatic bronchial carcinoid tumor: a case with a non hypophysial intracranial tumor that shrank during long acting octreotide treatment

Abstract

Ectopic acromegaly represents less than 1% of the reported cases of acromegaly. Although clinical improvement is common after treatment with somatostatin (SMS) analogs, the biochemical response and tumor size of the growth hormone-releasing hormone (GHRH)-producing tumor and its metastases are less predictable. Subject A 36-year-old male was referred because of a 3-year history of acromegaly related symptoms. He had undergone lung surgery in 1987 for a "benign" carcinoid tumor. Endocrine evaluation confirmed acromegaly Plasma IGF-1: 984 ng/ml (63-380), GH: 49.8 ng/ml (<5). MRI showed a large mass in the left cerebellopontine angle and diffuse pituitary hyperplasia. Pulmonary, liver and bone metastases were shown by chest and abdominal CT scans. Ectopic GHRH secretion was suspected. Methods Measurement of circulating GHRH levels by fluorescence immunoassay levels and immunohistochemical study of the primary lung tumor and metastatic tissue with anti-GHRH and anti-somatostatin receptor type 2 (sst2A) antibodies. Results Basal plasma GHRH: 4654 pg/ml (<100). Pathological study of liver and bone biopsy material and lung tissue removed 19 years earlier was consistent with an atypical carcinoid producing GHRH and exhibiting sst2A receptor expression. Treatment with octreotide LAR 20-40 mg q. month resulted in normalization of plasma IGF-1 levels. Circulating GHRH levels decreased dramatically. The size of the left prepontine cistern mass, with SMS receptors shown by a radiolabeled pentetreotide scan, decreased by 80% after 18 months of therapy. Total regression of pituitary enlargement was also observed. No changes were observed in lung and liver metastases. After 24 months of therapy the patient is asymptomatic and living a full and active life.

Acromegaly secondary to an incidentally discovered growth-hormone-releasing hormone secreting bronchial carcinoid tumour associated to a pituitary incidentaloma

“…Long-acting somatostatin analogues (octreotide or lanreotide) can represent a first-line therapy, since they may control the endocrine hypersecretion and tumour proliferation, but experience is still limited [1,2].…”

“…About 50 cases of ectopic GHRH-dependent acromegaly have been so far described in the literature [1][2][3].…”

Paraneoplastic endocrine syndromes

“…In a recent review, only 74 published cases were identified and except for a recent French series of 21 cases most were case reports . Tumours secreting GHRH are mainly NETs, usually welldifferentiated and of pancreatic or bronchial origin accounting for approximately 2/3 of cases (Fainstein et al 2007, Butler et al 2012, Lock et al 2014. The clinical presentation is variable with features similar to those caused from a somatotroph adenoma.…”

“…Hypothalamic tumours, including hamartomas, choristomas, gliomas and gangliocytomas, may also produce excessive GHRH resulting in acromegaly (Di Lorgi et al 2007). Ectopic secretion of GH has only been described in single cases (Melmed et al 2006, Fainstein et al 2007 and represents approximately 0.1% 24:6 of paraneoplastic acromegaly cases (Melmed et al 2006, Fainstein et al 2007). …”

Ectopic acromegaly due to growth hormone releasing hormone

“…In most cases in the literature, the preliminary diagnosis was pituitary acromegaly and diagnosis of ectopic acromegaly was confirmed either during the diagnostic work up or after unsuccessful pituitary surgery. There was a delay of 2 to 18 years between pituitary surgery and establishment of correct diagnosis [29, 45, 66]. Most patients had pituitary hyperplasia visible on imaging with some characteristics indistinguishable from pituitary adenomas, leading often to unnecessary transsphenoidal surgery (TSS) [14, 21, 22, 28, 29, 34, 39–41, 43, 44, 51, 53, 56, 62, 63, 66, 67, 69, 70, 74, 78, 79, 81, 94, 95].…”