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Acromegaly due to ectopic secretion of growth hormone-releasing hormone (GHRH) is a rare disorder. The signs and symptoms of ectopic acromegaly are indistinguishable from acromegaly due to a somatotroph adenoma. A 35-year-old female presented with secondary amenorrhea for 10 years, intermittent headache, and reduced vision in both eyes for 4 years, which worsened over 4 months before presentation. Additionally, she was diagnosed with uncontrolled diabetes mellitus. On examination, she had coarse facial features, a fleshy nose, and acral enlargement. She had diminished visual acuity (left>right) and bitemporal hemianopia on perimetry. Biochemical investigations revealed elevated IGF-1 [588 ng/ml, reference range (RR) 100-242], markedly elevated basal growth hormone (>80 ng/ml; RR, 0.12-9.88), and hyperprolactinemia in the tumoral range (832 ng/ml; RR, 5-25). MRI sella demonstrated a 22×30×34mm sellar-suprasellar mass with T2 hypointensity. Chest imaging revealed a 75×87×106mm left lung mass, which was found to be a well-differentiated neuroendocrine tumor (NET) on biopsy. Plasma GHRH levels were elevated [38,088 ng/l; RR, <250-300], and a diagnosis of ectopic acromegaly secondary to lung neuroendocrine tumor was considered. During workup, the patient developed in-hospital pituitary apoplexy, which improved with medical management. After a left pneumonectomy, her clinical features of acromegaly improved, her diabetes underwent remission, and there was a marked reduction in plasma GHRH and pituitary size. Histopathology was suggestive of a neuroendocrine tumor, with immunohistochemistry positive for GHRH and negative for prolactin. Her final diagnosis was ectopic acromegaly due to GHRH secreting a lung NET with pituitary somatotroph and lactotroph pituitary hyperplasia and apoplexy in the hyperplastic pituitary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gupta, Kasaliwal, Das, Sharma, Kaur, Vasiljevic, Raverot, Korbonits and Dutta.)

Context: Ectopic acromegaly is a consequence of rare neuroendocrine tumors (NETs) that secrete GHRH. This abnormal GHRH secretion drives GH and IGF-1 excess, with a clinical presentation similar to classical pituitary acromegaly. Identifying the underlying cause for the GH hypersecretion in the setting of ectopic GHRH excess is, however, essential for proper management both of acromegaly and the NET. Owing to the rarity of NETs, the imaging characteristics of the pituitary in ectopic acromegaly have not been analyzed in depth in a large series., Objective: Characterize pituitary magnetic resonance imaging (MRI) features at baseline and after NET treatment in patients with ectopic acromegaly., Design: Multicenter, international, retrospective., Setting: Tertiary referral pituitary centers., Patients: Thirty ectopic acromegaly patients having GHRH hypersecretion., Intervention: None., Main Outcome Measure: MRI characteristics of pituitary gland, particularly T2-weighted signal., Results: In 30 patients with ectopic GHRH-induced acromegaly, we found that most patients had hyperplastic pituitaries. Hyperplasia was usually moderate but was occasionally subtle, with only small volume increases compared with normal ranges for age and sex. T2-weighted signal was hypointense in most patients, especially in those with hyperplastic pituitaries. After treatment of the NET, pituitary size diminished and T2-weighted signal tended to normalize., Conclusions: This comprehensive study of pituitary MRI characteristics in ectopic acromegaly underlines the utility of performing T2-weighted sequences in the MRI evaluation of patients with acromegaly as an additional tool that can help to establish the correct diagnosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ectopic acromegaly is very rare and since the discovery of growth hormone-releasing hormone (GHRH), 30 years ago, only 74 cases have been reported in the literature. Except for a recent French series of 21 cases, most of them were case reports. The present review summarizes the current knowledge on clinical presentation, diagnosis and prognosis. Tumors secreting GHRH are neuroendocrine tumors, usually well differentiated and mainly from pancreatic or bronchial origin. They are usually large and easy to localize using TDM and somatostatin receptor scintigraphy. Clinical presentation is an acromegaly of variable intensity, whose features are similar to that of a somatotropic adenoma. Pituitary may be normal or enlarged at MRI which may be difficult to interpret especially in MEN1 patients where the association of a microprolactinoma to a pancreatic tumor secreting GHRH may be misleading. GHRH plasmatic measurement has an excellent specificity for the diagnosis, using a threshold of 250 to 300ng/L and is a good tool for follow-up of patients after treatment. These tumors have a good overall prognosis, even in metastatic forms which represent 50% of cases. Surgical approach is recommended and, when a complete tumoral resection is feasible, results, in most patients, in long-lasting remission. In such cases, GHRH concentration is normalized and its increase is an accurate indicator of recurrence. In uncured patients, somatostatin analogs control GH secretion but inhibit, only partially, GHRH secretion. MEN1 mutation should be systematically investigated in patients with a pancreatic tumor., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)