Acromegaly Caused by Ectopic Growth Hormone Releasing Hormone Secretion: A Review

Abstract

IntroductionEctopic acromegaly is a rare condition caused most frequently by growth hormone releasing hormone (GHRH) secretion from neuroendocrine tumors. The diagnosis is often difficult to establish as its main symptoms do not differ from those of acromegaly of pituitary origin.ObjectivesTo determine most common clinical features and diagnostic challenges in ectopic acromegaly.Patients and MethodsA search for ectopic acromegaly cases available in literature was performed using PubMed, Cochrane, and MEDline database. In this article, 127 cases of ectopic acromegaly described after GHRH isolation in 1982 are comprehensively reviewed, along with a summary of current state of knowledge on its clinical features, diagnostic methods, and treatment modalities. The most important data were compiled and compared in the tables.ResultsNeuroendocrine tumors were confirmed in 119 out of 121 patients with histopathological evaluation, mostly of lung and pancreatic origin. Clinical manifestation comprise symptoms associated with pituitary hyperplasia, such as headache or visual field disturbances, as well as typical signs of acromegaly. Other endocrinopathies may also be present depending on the tumor type. Definitive diagnosis of ectopic acromegaly requires confirmation of GHRH secretion from a tumor using either histopathological methods or GHRH plasma concentration assessment. Hormonal evaluation was available for 84 patients (66%) and histopathological confirmation for 99 cases (78%). Complete tumor resection was the main treatment method for most patients as it is a treatment of choice due to its highest effectiveness. When not feasible, somatostatin receptor ligands (SRL) therapy is the preferred treatment option. Prognosis is relatively favorable for neuroendocrine GHRH-secreting tumors with high survival rate.ConclusionAlthough ectopic acromegaly remains a rare disease, one should be aware of it as a possible differential diagnosis in patients presenting with additional symptoms or those not responding to classic treatment of acromegaly.

Ectopic acromegaly due to bronchial neuroendocrine tumors: the first description in Russia of three clinical cases

“…Только в двух случаях ГРРГ-продуцирующие опухоли имели не нейроэндокринную природу (диффузная крупная В-клеточная лимфома [ 15 ] и аденокистозная карцинома легкого [ 16 ]). Среди интракраниальных источников эктопической продукции ГРРГ чаще встречаются смешанные ганглиоцитомы-аденомы гипофиза [ 14 ].…”

“…Клиническая картина эктопической акромегалии не отличается от таковой при типичной акромегалии, а заподозрить ее можно при отсутствии визуализации аденомы гипофиза по данным магнитно-резонансной томографии (МРТ) головного мозга или при выявлении диффузной гиперплазии гипофиза [ 17 ]. Сложность диагностики эктопической акромегалии заключается в поиске источника продукции ГРРГ, а основным методом лечения является удаление первичной опухоли [ 13 ][ 14 ]. В случае невозможности радикального удаления опухоли могут быть назначены аналоги соматостатина длительного действия, пэгвисомант, химиотерапия, иммунотерапия, лучевая терапия [ 13 ][ 14 ].…”

“…Сложность диагностики эктопической акромегалии заключается в поиске источника продукции ГРРГ, а основным методом лечения является удаление первичной опухоли [ 13 ][ 14 ]. В случае невозможности радикального удаления опухоли могут быть назначены аналоги соматостатина длительного действия, пэгвисомант, химиотерапия, иммунотерапия, лучевая терапия [ 13 ][ 14 ].…”

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

“…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].…”