Long-term effect of 90Y pituitary implantation in acromegaly

Abstract

This report examines the long-term trends in GH levels and pituitary function in a group of 38 acromegalic patients who were selected insofar as we were able to follow them up for more than 10 years after a single dose of 90Y interstitial pituitary irradiation as the sole treatment. Mean serum GH had fallen from 106 to 24 mIU/l within 3\p=n-\6 months and then slowly declined to 4 mIU/l after 10 years. GH levels of \m=l e\5 mIU/l during a 50 g oral glucose tolerance test were obtained in 8% of patients at 3\p=n-\6months and in 18% at 1 year, the cumulative percentage increasing to 53% at 10, and 76% at 14 years. The percentage of patients requiring hormone replacement therapy rose from nil pre-implant to 16% by 3\p=n-\6 months, and then slowly increased to 39% by 14 years. Serial coned radiographs of the pituitary fossa were available for 32 patients. By 10 years, 16 showed thickening of the dorsum sellae and/or reduction of at least one diameter by 3 mm. Concerning symptoms, all 29 patients whose GH level fell to \ m=l e\ 5 mIU/l showed improvements, 22 becoming asymptomatic. Seven patients with lesser falls in GH levels (from a mean of 193 to a mean of 15 mIU/l) all improved, one becoming asymptomatic. Two showed no variation. These results show that 90Y pituitary implants have a cumulative effect over the years in inducing remission and hypopituitarism in acromegalic patients, the early decline in GH levels being swifter than from other forms of irradiation.A variety of means of treating acromegaly are available today, including surgical excision of the pituitary tumour, various forms of external or interstitial irradiation of the gland, and medical treatments. There is no clear agreement about the superiority of any particular procedure, all of them having relative merits and problems. One difficulty with making such an appraisal is the relative paucity of data for long-term trends.However, in the last few years, attention has been focussed on the long-term effects of treatment by external irradiation as evaluated by serum GH (Eastman et al. 1979;Kjellberg & Kliman 1979;Linfoot 1979;Dons et al. 1983; Feeket al. 1984).In the present study we analyse the effects of 90Y pituitary implants as the sole treatment in a group of 38 patients followed up by us for more than 10 years, in order to ascertain the time course of any decline of GH levels and any devel¬ opment of pituitary failure. We have also exam¬ ined the effect of the size and appearance of the sella turcica. This is the first time it has been possible to examine such long term effects. This analysis does not deal with the overall results nor with the early remission rate or complications as currently obtained with 90Y implants, which have already been reported (Joplin et al. 1978; Cassar étal. 1981). Patients Between 1.1. 1965 and 31.7. 1973 a total of 155 acrome¬ galie patients (79 women) were treated by implantation with 90Y in the Endocrine Unit at Hammersmith Hos¬ pital. During this period there were five operators. The planned irradiation dose at ...

The effectiveness of external beam radiotherapy for acromegaly is not affected by previous pituitary ablative treatments

“…Previous abla¬ tive treatments had been by surgery and yttrium-90, 4 subjects having been treated previously more than once, with combinations of yttium and surgery. Finally, two pa¬ tients, had previously received transphenoidal hypophysectomy and yttrium-90 (9), respectively, and also both underwent transphenoidal hypophysectomy (12 and 20 months, respectively) after radio therapy and are not in¬ cluded in Group 2. In each of the 18 pre-treated patients, the initial treatments were judged inadequate and hence their referral to us.…”

Differential radiosensitivity of hypothalamo-pituitary function in the young adult rat

“…The findings of studies in adults who received external radiation therapy for pituitary adenomas or nasopharyngeal carcinomas suggest that deficiency of either gonadotrophin or adrenocorticotrophic hormone (ACTH) occurs later than that of GH, and that thyroidstimulating hormone (TSH) is the least likely to be adversely affected (Littley et al 1989a, Lam et al 1991. In such patients, the relationship between dose and prevalence of pituitary hormone deficits is different from that seen in patients receiving direct intra-pituitary irradiation from yttrium-90 implants (Jadresic et al 1987), and is believed to reflect hypothalamic damage from external irradiation that reduces the output of hypophysiotrophic factors required to maintain a normal pituitary gland.…”

“…Among patients with pituitary adenomas treated with doses of 500 to 1500 Gy by the implantation of yttrium-90 directly into the pituitary gland, the combined incidence of TSH and ACTH deficiency was only 40% at 14 years (Jadresic et al 1987), whereas the incidence was more than 90% at 10 years among patients who received external irradiation at much lower doses, ranging from 37·5 to 42·5 Gy (Littley et al 1989b). The most likely explanation for this difference is that the fields for external irradiation included the hypothalamus, whereas this structure was relatively unaffected by yttrium-90 treatment.…”

Pathophysiology of radiation-induced growth hormone deficiency: Efficacy and safety of GH replacement

“…The hypothalamus is a highly radiosensitive structure and is thought to be the primary site of radiation damage, particularly with radiation doses of less than 50 Gy. For example, the frequency of ACTH and/or TSH deficiency after yttrium-90 implants delivering 500-1500 Gy to the pituitary only is much lower (40% after 14 years) [8] than that encountered after external irradiation (involving the hypothalamus) of pituitary tumors with doses ranging from 37.5 to 42.5 Gy (90% after 10 years) [9]. Furthermore, other abnormalities consistent with hypothalamic dysfunction are frequently observed after irradiation.…”