Radiation‐induced Hypopituitarism Is Dose‐dependent

Abstract

Radiation-induced hypopituitarism has been studied prospectively for up to 12 years in 251 adult patients treated for pituitary disease with external radiotherapy, ranging in dose from 20 Gy in eight fractions over 11 days to 45 Gy in 15 fractions over 21 days. Ten further patients were studied 2-4 years after whole-body irradiation for haematological malignancies using 12 Gy in six fractions over 3 days and seven patients were studied 3-11 years after whole-brain radiotherapy for a primary brain tumour (30 Gy, eight fractions, 11 days). Five years after treatment, patients who received 20 Gy had an incidence of TSH deficiency of 9% and in patients treated with 35-37 Gy, 40 Gy and 42-45 Gy, the incidence of TSH deficiency (22, 35 and 52% respectively) increased significantly (P less than 0.001) with increasing dose. A similar relationship was observed for both ACTH and gonadotrophin deficiencies when the 20 Gy group was compared to patients treated with 35-45 Gy (P less than 0.01 and P less than 0.05 respectively). Growth hormone deficiency was universal by 5 years over the dose range 35-45 Gy. In seven patients who were treated with 30 Gy in eight fractions over 11 days, deficiencies were observed at a similar frequency to the 40 Gy group (15 fractions, 21 days). No evidence of pituitary dysfunction was detected in the ten patients who received 12 Gy (six fractions, 3 days). Both total radiation dose and fractionation schedule may determine the incidence of pituitary hormone deficiencies. The dose below which deficiencies do not occur is probably irrelevant to therapeutic irradiation of pituitary and other intracranial neoplasms.

Gamma knife radiosurgery is a successful adjunctive treatment in Cushing’s disease

“…Various treatments for recurrence have been proposed, but each has specific risks: Nelson's syndrome after bilateral adrenalectomy (4) and hepatic cytolysis during medical treatment such as ketoconazole (5). Conventional radiotherapy leads to more than 80% of cure in most of the series published, but it tends to be less employed because of a number of adverse effects, including hypopituitarism, cranial nerve neuritis, visual-field defects, possible cognitive disturbances or increased cerebro-vascular disorders, radiation-induced gliomas, and delayed brain necrosis (6)(7)(8)(9)(10).…”

Diagnosis and Management of Acromegaly in 2014 (Update from 2012)

“…57,59,61 The main limitation for radiotherapy is the development of hypopituitarism, which may occur in up to 50 % of patients after 5 to 10 years. 62,63 Radiationinduced secondary tumors and radionecrosis have been reported in fewer than 2 % of patients undergoing conventional radiotherapy.…”

Endocrine Complications Following Radiotherapy and Chemotherapy for Nasopharyngeal Carcinoma

“…Low radiation doses of less than 40 Gy mostly affects the most vulnerable GH axis in isolation resulting in variable degrees of GH deficiency (Clayton & Shalet, 1991;Constine et al, 1993;Duffner et al, 1985;Littley et al, 1989a). Deficiencies of other anterior pituitary hormones start to occur when the total radiation dose delivered to the h-p axis exceeds 40 Gy, but much less frequently than GH deficiency.…”

“…This has been shown in animal models (Hochberg et al, 1983;Robinson et al, 2001) and reflected in clinical observations in irradiated patients. Epidemiological studies reveal that the growth hormone (GH) axis is the most radiosensitive followed by the gonadotrophin (FSH & LH), adrenocorticotrophic hormone (ACTH) and thyroid stimulating hormone (TSH) axes (Clayton & Shalet, 1991;Constine et al, 1993;Duffner et al, 1985;Lam et al, 1991;Littley et al, 1989a) (Figures 1& 2).…”

“…repair (duration of the radiation schedule) (Thames & Hendry, 1987;Littley et al, 1989a). Radiation schedules utilising the same total dose administered over a shorter duration (larger fraction size) inflict more damage to the h-p axis.…”