Pituitary adenomas (PAs)/Pituitary Neuroendocrine Tumors (PitNETs) are a very heterogenous group of tumors in terms of clinical behavior, hormone secretion, and histo-morphological features [1], [2]. PitNETs can arise from any of the six types of hormone secreting cells and sustentacular folliculo-stellate cells, and can grow superiorly, laterally, or inferiorly to the sella turcica. Rarely, they originate from extra-sellar sites (ectopic lesions) [3].

The management of these tumors is challenging since, despite histological benignity, they often invade the adjacent structures, increasing the risk of clinical and surgical complication due to the mass effect, and, more rarely, metastasize. Moreover, they can relapse or persist even after surgery, therefore requiring a multimodal approach that includes medical (with variable response) and radiation therapy [1], [2].

The majority of somatotroph tumors or GH-secreting PAs/PitNETs are biochemically active and lead to gigantism and/or acromegaly; patients with mixed GH-prolactin-secreting forms often present with signs and symptoms of hyperprolactinemia as unique manifestation or in association with acromegaly/gigantism; silent forms have also been reported [4], [5]. Diagnosis is typically delayed for some years because of the non-specific and slowly progressive symptoms, as well as a relative lack of disease awareness among physicians and patients [6]. Patient with large and invasive tumors can present with ‘mass effect’ manifestations (i.e., headache, visual field abnormalities, hypopituitarism, hyperprolactinemia due to pituitary stalk deviation/compression, and pituitary apoplexy).

PitNETs are highly variable in terms of histological subtype, clinical behavior (i.e.age at diagnosis, phenotype, response to treatment), radiological features (i.e., tumor size and invasion), and secretory capacity (i.e., non-functioning vs. hyperfunctioning) [7*], [8], [9], [10]. GH-secreting tumors represent approximately 20% of all PitNETs [7]. Less than 5% of acromegaly cases result from ectopic GHRH and to a lesser extent, GH secretion by a neuroendocrine tumor, usually located in the bronchi, thymus or endocrine pancreas. Acromegaly and gigantism result from chronic hypersecretion of GH and Insulin-like growth factor 1 (IGF-1) [11], and are associated with prolactin (PRL) co-secretion in 30-50% of cases, with the typical signs and symptoms of hyperprolactinemia [3*], [7*]. Mean age at diagnosis is 45.2 years, with a slightly higher prevalence in women (54.5%) [12], [13], [14]. Men tend to be younger than women at diagnosis [3]. Gigantism occurs when the GH-secreting tumor develops during infancy, before epiphyseal closure [12], [13].