Analgesic effect of long-acting somatostatin receptor agonist pasireotide in a patient with acromegaly and intractable headaches

Abstract

A 22-year-old woman presented with worsening vision loss and headaches. A diagnosis of acromegaly was confirmed after detection of an invasive pituitary macroadenoma and biochemical testing. Despite two attempts of surgical debulking of the tumour and administration of long-acting octreotide and cabergoline, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were uncontrolled. The patient experienced persistent headaches despite surgery, gamma knife radiation and ventriculoperitoneal shunt placement; she was then enrolled in the ACCESS trial (ClinicalTrials.gov identifier, NCT01995734). Pasireotide (Signifor; Signifor LAR) was initiated, which led to reduced GH and IGF-1 levels and resolution of her intractable headaches. This highlights the use of monthly pasireotide in resolving headaches and improved biochemical control in a patient with acromegaly. We postulate that the headaches improved due to an analgesic and/or anti-inflammatory effect mediated by somatostatin receptors targeted by pasireotide. This may represent an additional benefit of pasireotide and requires further investigation.

Impairment in insulin secretion without changes in insulin resistance explains hyperglycemia in patients with acromegaly treated with pasireotide LAR

“…The therapeutic indication for the initiation of pasireotide was resistance to first-generation SRLs in 25 out of 33 patients (76%) or side effects of pegvisomant in 4 out of 33 patients (12%). In 4 out of 33 patients (12%), pasireotide was started because of severe headache, which has been previously pointed out in a case report (23). Two patients (6%) were biochemically controlled with their IGF-I serum levels within their age-and sex-specific reference range before the initiation of pasireotide and were switched to pasireotide because of side effects of the ongoing treatment or severe headache.…”

A study of acromegaly-associated headache with somatostatin analgesia

“…In all cases, headache was localised ipsilateral to the residual tissue, suggesting that a combination of structural and biochemical features are linked to headache (Donangelo et al 2004;Marina et al 2015;Lovato and Kapsner 2018). The cavernous sinus has significant neurovascular structures for head pain, including the trigeminal ganglion and internal carotid artery, which are likely to cause symptoms when irritated either chemically or physically or both.…”

“…Considering the role of the somatostatin receptors within the tumour, we found one patient from the current study who had an improved biochemical and analgesic response to pasireotide over octreotide and lanreotide. Pasireotide analgesic effect in acromegaly related headaches (not responding to another long-acting SSA) has been previously observed, suggesting that additional somatostatin receptor affinity may lead to increased analgesic action (Marina et al 2015;Lovato and Kapsner 2018). Unfortunately, pasireotide was not available at the time of study for all patients.…”

“…Rapid timing of action (headache relief) after subcutaneous administration of octreotide (comparable to intravenous administration) suggests a direct somatostatin receptor mediated (Sicuteri et al 1984b;Caleri et al 1987;Williams et al 1987;Popovic et al 1988;Sicolo et al 1990;Musolino et al 1990;Pascual et al 1991;Schmidt et al 1993;May et al 1994;Levy et al 2003;Donangelo et al 2004;Matharu et al 2004;Marina et al 2015;Lovato and Kapsner 2018). Both effect on vasculature and on neuron activation could be considered here.…”

MANAGEMENT OF ENDOCRINE DISEASE: Individualised management of acromegaly

“…In the PAOLA study, 15% of the patients experienced a tumour volume reduction more than 25% (46). Further, pasireotide seems to be efficient in the treatment of patients with intractable headache and could be considered as a treatment option in such cases (48).…”