Supplementary Material for: A Rare Case of Concurrent Small Intestinal Neuroendocrine Neoplasms and Acromegaly: A Coincidence or a Clinical Association?

Introduction: Neuroendocrine neoplasms of the small intestine (SI-NENs), although rare, are the most prevalent primary neoplasms of this organ. Acromegaly is characterized by excessive secretion of growth hormone (GH), typically due to a pituitary neuroendocrine tumor (PitNET) but, in rare cases, it can result from ectopic secretion of growth hormone-releasing hormone (GHRH) by non-pituitary tumors, particularly neuroendocrine neoplasms (NENs) of the lung or pancreas. We reported a case of concurrent acromegaly and SI-NENs. Case Presentation: A 68-year-old male with a history of severe restrictive pulmonary syndrome secondary to thoracic kyphoscoliosis was referred for evaluation of iron-deficiency anemia and colorectal polyps. Video capsule endoscopy revealed an ulcerative-vegetative lesion in the distal ileum. CT enterography demonstrated multiple hypervascular lesions in the ileum, consistent with NENs. A 68Ga-DOTA-NOC PET/CT scan identified several foci of abnormal uptake, consistent with multiple intestinal NENs and suspected lymph node metastasis. Increased uptake was also observed in the pituitary gland. The patient was referred for endocrinology evaluation, where an acromegaloid phenotype was noted. Laboratory findings showed elevated levels of insulin-like growth factor 1 (IGF1) (454 ng/mL; reference range (RR) <225), growth hormone (GH) (66 µg/L; RR ≤3) and chromogranin A (625 ng/mL; RR≤ 102). Brain computed tomography (CT) scan suggested a PitNET (the patient could not tolerate MRI). No pathogenic variants were detected in the MEN1 and CDKN1B genes. Given the concurrent diagnoses of acromegaly and SI-NENs, the extent of the disease, the high surgical risk, and the patient's preference, long-acting octreotide therapy was initiated. Conclusion: The association between SI-NENs and acromegaly is rarely reported in the literature and remains unclear. Proposed mechanisms include the coexistence of independent tumors, the development of NENs in response to excessive IGF1 stimulation, and induction of acromegaly through ectopic GHRH secretion by NENs.