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Radiation-induced hypopituitarism after cancer therapy: who, how and when to test

Nature Clinical Practice Endocrinology & Metabolism volume 5, pages 88–99 (2009)Cite this article

Abstract

Subtle to frank abnormalities in hypothalamic–pituitary axis function are frequently seen in cancer survivors who have received prophylactic or therapeutic cranial irradiation. The growth hormone (GH) axis is the most vulnerable to radiation damage, and isolated GH deficiency can occur after doses as low as 18 Gy. Furthermore, the frequency of GH deficiency can reach 50–100% within 3–5 years of cranial irradiation with doses of 30–50 Gy. TSH and adrenocorticotropic hormone deficiency occur in 3–6% of patients after conventional irradiation (30–50 Gy). Abnormalities in gonadotropin secretion are dose-dependent: gonadotropin deficiency is seen only after doses of 30 Gy or more, whereas lower doses usually lead to precocious puberty. Hyperprolactinemia predominantly occurs in young women after intensive irradiation and is usually subclinical. The frequencies of gonadotropin, adrenocorticotropic hormone and TSH deficiencies substantially increase with intensive irradiation (greater than 60 Gy) and after conventional irradiation for pituitary tumors, with a cumulative incidence of 30–60% after 10 years. The irreversible and progressive nature of radiation-induced anterior-pituitary hormone deficiencies and their adverse effect on body image, growth, sexual function, skeletal health and quality of life makes it essential that cancer survivors are tested regularly to ensure appropriate diagnosis and timely hormone replacement therapy.

Key Points

  • Isolated growth hormone deficiency is the most commonly encountered neuroendocrine complication of cancer treatment and can occur after cranial irradiation doses as low as 10 Gy in children

  • Other anterior-pituitary hormone deficits and hyperprolactinemia are typically seen after high-dose irradiation and conventional irradiation of the hypothalamus and pituitary

  • Posterior pituitary function is not affected by radiation

  • Radiation-induced hypopituitarism is irreversible and progressive

  • Continued surveillance and management of hormone replacement therapy is required in both children and adults; an imperative concern is that patients are not lost in the transition from pediatric to adult clinics

  • The interval at which pituitary function tests are performed depends upon factors that relate to the radiation schedule and intensity, time since irradiation, patients' characteristics, and clinical needs

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Figure 1: The probability of hypothalamic–pituitary axis dysfunction after irradiation.
Figure 2: Radiation-induced growth hormone deficiency in children.

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Acknowledgements

Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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  1. Department of Diabetes and Endocrinology, Queen Elizabeth II Hospital, Howlands, Welwyn Garden City, Hertfordshire AL7 4HQ, UK ken.darzy@nhs.net

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  1. KH Darzy is a Consultant Physician in the Department of Diabetes and Endocrinology at the Queen Elizabeth II Hospital, Welwyn Garden City, Hertfordshire, UK.,

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Darzy, K. Radiation-induced hypopituitarism after cancer therapy: who, how and when to test. Nat Rev Endocrinol 5, 88–99 (2009). https://doi.org/10.1038/ncpendmet1051

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