Insights into non-classic and emerging causes of hypopituitarism

• Published in: Nature reviews. Endocrinology 2021-02, Vol.17 (2), p.114-129
• Main Authors: Prodam, Flavia, Caputo, Marina, Mele, Chiara, Marzullo, Paolo, Aimaretti, Gianluca
• Format: Article
• Language: English
• Subjects: 692/163/2743/2742/1738; 692/699/2743/2742/1738; Adenoma; Adenoma - complications; Adrenocorticotropic Hormone - deficiency; Adrenocorticotropic Hormone - genetics; Autoantibodies; Autoimmune diseases; Autoimmune Hypophysitis - complications; Brain Injuries, Traumatic - complications; Causes of; Children; Development and progression; Dwarfism, Pituitary - genetics; Empty Sella Syndrome - complications; Endocrine System Diseases - genetics; Endocrinology; Genetic aspects; Genetic Diseases, Inborn - genetics; Humans; Hypoglycemia - genetics; Hypogonadism - genetics; Hypophysitis - complications; Hypopituitarism; Hypopituitarism - chemically induced; Hypopituitarism - etiology; Hypopituitarism - genetics; Hypopituitarism - metabolism; Hypothalamus; Hypothyroidism - genetics; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Inflammatory diseases; Medicine; Medicine & Public Health; Oxytocin; Oxytocin - metabolism; Pituitary (posterior); Pituitary Apoplexy - complications; Pituitary hormones; Pituitary Neoplasms - complications; Quality of life; Radiation therapy; Review Article; Subarachnoid Hemorrhage - complications; Surgery; Traumatic brain injury; Tumors
• ISSN: 1759-5029; 1759-5037
• DOI: 10.1038/s41574-020-00437-2

Hypopituitarism is defined as one or more partial or complete pituitary hormone deficiencies, which are related to the anterior and/or posterior gland and can have an onset in childhood or adulthood. The most common aetiology is a sellar or suprasellar lesion, often an adenoma, which causes hypopituitarism due to tumour mass effects, or the effects of surgery and/or radiation therapy. However, other clinical conditions, such as traumatic brain injury, and autoimmune and inflammatory diseases, can result in hypopituitarism, and there are also genetic causes of hypopituitarism. Furthermore, the use of immune checkpoint inhibitors to treat cancer is increasing the risk of hypopituitarism, with a pattern of hormone defects that is different from the classic patterns and depends on mechanisms that are specific for each drug. Moreover, autoantibody production against the pituitary and hypothalamus has been demonstrated in studies investigating the development or worsening of some cases of hypopituitarism. Finally, evidence suggests that posterior pituitary damage can affect oxytocin secretion. The aim of this Review is to summarize current knowledge on non-classic and emerging causes of hypopituitarism, so as to help clinicians improve early identification, avoid life-threatening events and improve the clinical care and quality of life of patients at risk of hypopituitarism. This Review summarizes current knowledge on non-classic and less common causes of hypopituitarism, such as traumatic brain injury, genetic causes, use of immune checkpoint inhibitors, autoimmune diseases and inflammatory diseases. Furthermore, emerging evidence that posterior pituitary damage can affect oxytocin secretion is highlighted. Key points Growing evidence identifies new and complex phenotypes of hypopituitarism caused by different clinical conditions other than sellar and/or suprasellar lesions. Genetic causes, traumatic brain injury or aneurysmal subarachnoid haemorrhage, autoimmune and inflammatory diseases, and the use of immune checkpoint inhibitors as antineoplastic agents are all non-classic causes that can be associated with hypopituitarism. Data suggest that posterior pituitary damage can affect oxytocin secretion, potentially increasing depression, anxiety and alexithymia, thereby underlining the relationship between behaviour alterations, metabolism and regulation of food intake and pituitary function.