Pituitary MRI Features in Acromegaly Resulting From Ectopic GHRH Secretion From a Neuroendocrine Tumor: Analysis of 30 Cases

Abstract

Context Ectopic acromegaly is a consequence of rare neuroendocrine tumors (NET) that secrete growth hormone releasing hormone (GHRH). This abnormal GHRH secretion drives growth hormone (GH) and insulin-like growth factor 1 (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 its rarity, the imaging characteristics of the pituitary in ectopic acromegaly have not been analyzed in depth in 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 30 ectopic acromegaly patients due to 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 to 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.

Ockham’s Razor for a Retinal Lesion and Acromegaly and Breaking the Vicious Circle

“…Recent data suggest that patients with pituitary hyperplasia due to a GHRH-secreting tumor show a hypointense T2-weighted MRI signal, which can normalize when GHRH levels return to normal [ 40 ]. Our case, with a hypointense T2 signal both at diagnosis and more recently when the GHRH level is still 10× ULN, supports this observation.…”

European Neuroendocrine Tumor Society 2023 guidance paper for functioning pancreatic neuroendocrine tumour syndromes

“…However, in the absence of elevated PTH levels and bone metastases, Suspicion of acromegaly in a Pan-NET patient can be confirmed by screening serum insulin-like factor-1 (IGF-1) levels, which are 2.6-2.8 times the upper limit of normal in patients with ectopic GHRH secretion from a NET. 29 Moderate hyperprolactinaemia may also be present. Following the detection of elevated IGF-1 levels, GHRH levels should be assessed, after the addition of a protease inhibitor.…”

“…Suspicion of acromegaly in a Pan‐NET patient can be confirmed by screening serum insulin‐like factor‐1 (IGF‐1) levels, which are 2.6–2.8 times the upper limit of normal in patients with ectopic GHRH secretion from a NET 29 . Moderate hyperprolactinaemia may also be present.…”

“…Acromegaly due to ectopic GHRH secretion, similarly to acromegaly caused by a GH‐secreting pituitary tumour, responds favourably to SSA, 104,105 making them the first‐line choice [3, B]. In cases of continued IGF‐1 elevation, pegvisomant can be added to control the acromegaly effects [4, D].…”

“…When combined, two series have shown that PRRT led to improvement of VIPoma symptoms in nine out of 11 patients 92,103. Together, these limited retrospective data make chemotherapy, sunitinib and PRRT second-line options to be considered in patients with refractory advanced VIPoma, especially in cases of disease progression[4, D].Acromegaly due to ectopic GHRH secretion, similarly to acromegaly caused by a GH-secreting pituitary tumour, responds favourably to SSA,104,105 making them the first-line choice[3, B]. In cases of continued IGF-1 elevation, pegvisomant can be added to control the acromegaly effects[4, D].…”