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Insights into non-classic and emerging causes of hypopituitarism

  • Review Article
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From Nature Reviews Endocrinology

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Abstract

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.

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.

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Fig. 1: Pituitary and non-pituitary tumours.
Fig. 2: Genetic combined pituitary hormone deficiency.
Fig. 3: Primary empty sella.
Fig. 4: Autoimmune lymphocytic hypophysitis.

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Acknowledgements

The authors thank E. Agosti for technical advice and assistance with preparation of the manuscript.

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  1. These authors contributed equally: Flavia Prodam, Marina Caputo.

Authors and Affiliations

  1. Endocrinology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy

    Flavia Prodam, Marina Caputo, Chiara Mele, Paolo Marzullo & Gianluca Aimaretti

  2. Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy

    Flavia Prodam & Marina Caputo

  3. Division of General Medicine, I.R.C.C.S. Istituto Auxologico Italiano, Ospedale San Giuseppe, Verbania, Italy

    Paolo Marzullo

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All authors wrote the article and made substantial contributions to discussion of content. F.P., M.C., C.M. and P.M researched data for the article. F.P., M.C. and G.A. reviewed and/or edited the article before submission.

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Supplementary information

Glossary

Pituitary stalk interruption syndrome

A congenital disorder with the triad of an absent or thin pituitary stalk, an ectopic or absent posterior pituitary and/or absent or hypoplastic anterior pituitary.

Empty sella

A herniation of the subarachnoid space within the sella, which is often associated with a variable degree of flattening of the pituitary gland.

Sella turcica

The superior depression of the sphenoid bone, where the pituitary gland is located.

Aneurysmal subarachnoid haemorrhage

(SAH). Bleeding into the subarachnoid space caused by a ruptured cerebral aneurysm.

Autoimmune polyendocrine syndrome type 2

A syndrome characterized by functional impairment of multiple endocrine glands due to loss of immune tolerance, with at least two of the following three endocrinopathies: type 1 diabetes mellitus, autoimmune thyroiditis and Addison disease.

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Prodam, F., Caputo, M., Mele, C. et al. Insights into non-classic and emerging causes of hypopituitarism. Nat Rev Endocrinol 17, 114–129 (2021). https://doi.org/10.1038/s41574-020-00437-2

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