This study evaluates the effect of radiosurgical LGK hypophysectomy on pain relief in patients with intractable cancer-related pain with multiple bone metastases. Our study confirms, that LGK hypophysectomy is an effective and safe treatment modality in this group of patients where the effect of analgesic treatment was insufficient.
The analgesic mechanism of radiosurgical hypophysectomy remains poorly understood.  Because of its effect on hormonally dependent bone metastases, the disruption of hormonal pathways was the first theory.[22, 23] This theory does not explain the immediate pain relief (hours) in many patients. Moreover, pain relief persists despite tumor growth and normal function of the pituitary gland, and patients with non-hormonal tumors also experienced pain relief. [10, 22, 24] Another theory considers an increased activity of pre-pro-opiomelanocortin (precursor to β-endorphin) as the reason for pain relief after hypophysectomy which was supported by a higher level of β-endorphin in cerebrospinal fluid and blood. Nevertheless, this elevation takes only 72 hours, and administration of naloxone after LGK hypophysectomy did not influence the analgesic effect of the procedure. Recent theory suggests that the hypothalamus and its afferent nociceptive pathways have a key role in pain relief. To better understand the pathophysiological changes after hypophysectomy more studies still have to be done.
Pain relief was achieved in all our analyzed patients (10 from 20) and persisted the whole life. We are by previous studies by Backlund et al., Hayashi et al., and Kwon et al. who evaluated the effect of LGK hypophysectomy in similar series of patients (8; 9 and 7 patients).[17, 26, 27] Moreover, in previous studies radiosurgical hypophysectomy was effective even in the treatment of non-hormonal cancer pain without bone metastases and non-malignant thalamic pain.[21, 24] The effect occurs from several hours to four weeks after the treatment which is much earlier than in other indications for LGK radiosurgery.[17, 26, 28, 29] Permanent duration of pain relief is the advantage over the other analgetic radiosurgical methods (e.g., cingulotomy and thalamotomy).
The maximal dose on the pituitary gland has been applied from 150 to 250Gy.[17, 26–28] In our study the maximal dose was on average 176Gy which is close to the lower limit of the range. This result confirms that the maximal dose of 150Gy is sufficient for pain relief and there is no need to elevate the maximal dose over this limit. The dose to the optic tract was 9,8Gy on average and no visual complication was reported. Other critical structures obtained much less dose than their tolerance.
Despite the relatively high administrated dose, we recorded only a few side effects of irradiation. Hormonal disbalance occurred in three patients. One patient developed the diabetes insipidus 3 months after the treatment with the success of substantial therapy. In two patients hypocortisolism was present with the need for substitutional therapy 5 and 12 months after hypophysectomy. One patient developed temporary abducens nerve palsy with full recovery after 5 months. The higher incidence of hormonal disbalance in the study of Backlund et all might be caused by a higher maximal dose which was 200-250Gy. In a study of Hayashi, no side effects occurred and in the study of Kwon, only one patient with pre-existing panhypopituitarism get worse.[26, 27] In these two studies the maximal dose was up to 200Gy. No other side effect was present.
In our study, the mean follow-up was 12,6 months and the longest follow-up was 26 months. In previous studies, the maximal follow-up was 12 months. Four of the ten patients in our study have lived more than 12 months after the hypophysectomy with permanent pain levels decreased from 50–100%. Two patients suffered from breast cancer and two from prostate cancer. This highlights that LGK hypophysectomy is well established in hormonally dependent bone metastases. Unfortunately, patients with lung, kidney, rectal and laryngeal cancer died due to primary disease before the first follow-up, or we did not receive any information from them after the treatment. That is the reason why we could not evaluate the effectiveness of this procedure for non-hormonally dependent tumors.
In conclusion, our study confirms radiosurgical hypophysectomy as an effective and safe palliative method for pain relief in patients with multiple bone metastases of hormone-dependent cancers who suffer from intractable medically refractory pain.