A study of acromegaly-associated headache with somatostatin analgesia

in Endocrine-Related Cancer
Authors:
Sonia Kaniuka-Jakubowska Department of Endocrinology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland
Department of Endocrinology at the Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

Search for other papers by Sonia Kaniuka-Jakubowska in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0001-6894-8648
,
Miles J Levy Department of Endocrinology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK

Search for other papers by Miles J Levy in
Current site
Google Scholar
PubMed
Close
,
Aparna Pal Department of Endocrinology at the Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

Search for other papers by Aparna Pal in
Current site
Google Scholar
PubMed
Close
,
Dayakshi Abeyaratne Department of Endocrinology at the Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Diabetes and Endocrinology Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka

Search for other papers by Dayakshi Abeyaratne in
Current site
Google Scholar
PubMed
Close
,
William M Drake Department of Endocrinology, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK

Search for other papers by William M Drake in
Current site
Google Scholar
PubMed
Close
,
Nikolaos Kyriakakis Department of Endocrinology, Leeds Centre for Diabetes & Endocrinology, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK

Search for other papers by Nikolaos Kyriakakis in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0001-6414-5629
,
Robert D Murray Department of Endocrinology, Leeds Centre for Diabetes & Endocrinology, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK

Search for other papers by Robert D Murray in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0001-6730-6109
,
Steve M Orme Department of Endocrinology, Leeds Centre for Diabetes & Endocrinology, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK

Search for other papers by Steve M Orme in
Current site
Google Scholar
PubMed
Close
,
Shailesh Gohil Department of Endocrinology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK

Search for other papers by Shailesh Gohil in
Current site
Google Scholar
PubMed
Close
,
Antonia Brooke MacLeod Diabetes and Endocrinology Centre, Royal Devon and Exeter Hospital, Exeter, UK

Search for other papers by Antonia Brooke in
Current site
Google Scholar
PubMed
Close
,
Graham P Leese Department of Endocrinology, NHS Tayside, Dundee, UK

Search for other papers by Graham P Leese in
Current site
Google Scholar
PubMed
Close
,
Márta Korbonits Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, UK

Search for other papers by Márta Korbonits in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-4101-9432
, and
John AH Wass Department of Endocrinology at the Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

Search for other papers by John AH Wass in
Current site
Google Scholar
PubMed
Close

Correspondence should be addressed to S Kaniuka-Jakubowska or J A Wass: sonia.kaniuka@gumed.edu.pl or john.wass@nhs.net

*(S Kaniuka-Jakubowska and M J Levy contributed equally to this work)

Restricted access
Rent on DeepDyve

Sign up for journal news

The aim of this study is to characterise somatostatin analogue-responsive headache in acromegaly, hitherto not systematically documented in a significant cohort. Using the UK pituitary network, we have clinically characterised a cohort of 18 patients suffering from acromegaly-related headache with a clear response to somatostatin analogues. The majority of patients had chronic migraine (78%) as defined by the International Headache Society diagnostic criteria. Headache was present at the time of acromegaly presentation and clearly associated temporally with disease activity in all cases. Short-acting somatostatin analogues uniquely resolved pain within minutes and the mean duration of analgesia was 1–6 h. Patients on long-acting analogues required less short-acting injections (mean: 3.7 vs 10.4 injections per day, P = 0.005). 94% used somatostatin analogues to control ongoing headache pain. All patients presented with macroadenoma, most had incomplete resection (94%) and headache was ipsilateral to remnant tissue (94%). Although biochemical control was achieved in 78% of patients, headache remained in 71% of them. Patients selected for this study had ongoing headache post-treatment (mean duration: 16 years after diagnosis); only four patients reached headache remission 26 years (mean range: 14–33) after the diagnosis. Headache in acromegaly patients can be persistent, severe, unrelieved by surgery, long-lasting and uncoupled from biochemical control. We show here that long-acting analogues allow a decrease in the number of short-acting analogue injections for headache relief. Further studies are needed to understand the mechanisms, markers and tumour tissue characteristics of acromegaly-related headache. Until then, this publication serves to provide the clinical characteristics as a reference point for further study.

 

  • Collapse
  • Expand
  • Abe T, Matsumoto K, Kuwazawa J, Toyoda I & Sasaki K 1998 Headache associated with pituitary adenomas. Headache 38 782786. (https://doi.org/10.1046/j.1526-4610.1998.3810782.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Arafah BM, Prunty D, Ybarra J, Hlavin ML & Selman WR 2000 The dominant role of increased intrasellar pressure in the pathogenesis of hypopituitarism, hyperprolactinemia, and headaches in patients with pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 85 17891793. (https://doi.org/10.1210/jcem.85.5.6611)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Beltrutti DP, Moessinger S & Varrassi G 2000 The epidural and intrathecal administration of somatotrophin-release inhibiting factor: native and synthetic analogues. Current Review of Pain 4 8290. (https://doi.org/10.1007/S11916-000-0013-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Caleri D, Marabini S, Panconesi A & Pietrini U 1987 A pharmacological approach to the analgesizing mechanism of somatostatin in cluster headache. Ricerca in Clinica e in Laboratorio 17 155162. (https://doi.org/10.1007/BF02909410)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Candrina R & Galli G 1992 Intraventricular octreotide for cancer pain. Journal of Neurosurgery 76 336337. (https://doi.org/10.3171/JNS.1992.76.2.0336A)

  • Chapman V & Dickenson AH 1992 The effects of Sandostatin and somatostatin on nociceptive transmission in the dorsal horn of the rat spinal cord. Neuropeptides 23 147152. (https://doi.org/10.1016/0143-4179(9290115-D)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Conno De F, Saita L, Ripamonti C & Ventafridda V 1994 Subcutaneous octreotide in the treatment of pain in advanced cancer patients. Journal of Pain and Symptom Management 9 3438. (https://doi.org/10.1016/0885-3924(9490144-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Curtis SB, Hewitt J, Yakubovitz S, Anzarut A, Hsiang YN & Buchan AMJ 2000 Somatostatin receptor subtype expression and function in human vascular tissue. American Journal of Physiology. Heart and Circulatory Physiology 278 H1815H1822. (https://doi.org/10.1152/ajpheart.2000.278.6.H1815)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dahaba AA, Mueller G, Mattiassich G, Rumpold-Seitlinger G, Bornemann H, Rehak PH, Linck G, Mischinger HJ & Metzler H 2009 Effect of somatostatin analogue octreotide on pain relief after major abdominal surgery. European Journal of Pain 13 861864. (https://doi.org/10.1016/J.EJPAIN.2008.10.006)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dean A 2001 The palliative effects of octreotide in cancer patients. Chemotherapy 47(Supplement 2) 5461. (https://doi.org/10.1159/000049161)

  • Dimopoulou C, Athanasoulia AP, Hanisch E, Held S, Sprenger T, Toelle TR, Roemmler-Zehrer J, Schopohl J, Stalla GK & Sievers C 2014 Clinical characteristics of pain in patients with pituitary adenomas. European Journal of Endocrinology 171 581591. (https://doi.org/10.1530/EJE-14-0375)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Donangelo I, Rodacki M, Peixoto MC, Vaisman M, Caldas NR & Gadelha MR 2004 Dependency and analgesia related to treatment with subcutaneous octreotide in patients with growth hormone-secreting tumors. Endocrine Practice 10 107111. (https://doi.org/10.4158/EP.10.2.107)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Drummond PD & Anthony M 1985 Extracranial vascular responses to sublingual nitroglycerin and oxygen inhalation in cluster headache patients. Headache 25 7074. (https://doi.org/10.1111/j.1526-4610.1985.hed2502070.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gondim JA, de Almeida JP, de Albuquerque LA, Schops M, Gomes E & Ferraz T 2009 Headache associated with pituitary tumors. Journal of Headache and Pain 10 1520. (https://doi.org/10.1007/s10194-008-0084-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Howlett TA, Willis D, Walker G, Wass JAHH, Trainer PJ & UK Acromegaly Register Study Group 2013 Control of growth hormone and IGF1 in patients with acromegaly in the UK: responses to medical treatment with somatostatin analogues and dopamine agonists. Clinical Endocrinology (Oxford) 79 689–699. (https://doi.org/10.1111/cen.12207)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Johnson SA, Spiller PA & Faull CM 1997 Treatment of resistant pain in hypertrophic pulmonary osteoarthropathy with subcutaneous octreotide. Thorax 52 298–299. (https://doi.org/10.1136/THX.52.3.298)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jung SJ, Jo SH, Lee S, Oh E, Kim MS, Nam WD & Oh SB 2008 Effects of somatostatin on the responses of rostrally projecting spinal dorsal horn neurons to noxious stimuli in cats. Korean Journal of Physiology and Pharmacology 12 253258. (https://doi.org/10.4196/KJPP.2008.12.5.253)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kapicioǧlu S, Gökce E, Kapicioǧlu Z & Ovali E 1997 Treatment of migraine attacks with a long-acting somatostatin analogue (octreotide, SMS 201–995). Cephalalgia 17 2730. (https://doi.org/10.1046/J.1468-2982.1997.1701027.X)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Katai M, Sakurai A, Inaba H, Ikeo Y, Yamauchi K & Hashizume K 2005 Octreotide as a rapid and effective painkiller for metastatic carcinoid tumor. Endocrine Journal 52 277280. (https://doi.org/10.1507/ENDOCRJ.52.277)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH, Utz A, Wass JAH & Endocrine Society 2014 Acromegaly: an endocrine society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 99 39333951. (https://doi.org/10.1210/jc.2014-2700)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kreitschmann-Andermahr I, Siegel S, Weber Carneiro R, Maubach JM, Harbeck B & Brabant G 2013 Headache and pituitary disease: a systematic review. Clinical Endocrinology 79 760769. (https://doi.org/10.1111/cen.12314)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Levy MJ 2011 The association of pituitary tumors and headache. Current Neurology and Neuroscience Reports 11 164170. (https://doi.org/10.1007/s11910-010-0166-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Levy MJ, Bejon P, Barakat M, Goadsby PJ & Meeran K 2003 Acromegaly: a unique human headache model. Headache 43 794797. (https://doi.org/10.1046/j.1526-4610.2003.03139.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Levy MJ, Classey JD, Maneesri S, Meeran K, Powell M & Goadsby PJ 2004a The association between calcitonin gene-related peptide (CGRP), substance P and headache in pituitary tumours. Pituitary 7 6771. (https://doi.org/10.1007/s11102-005-5347-z)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Levy MJ, Jäger HR, Powell M, Matharu MS, Meeran K & Goadsby PJ 2004b Pituitary volume and headache: size is not everything. Archives of Neurology 61 721725. (https://doi.org/10.1001/archneur.61.5.721)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Levy MJ, Matharu MS, Bhola R, Meeran K & Goadsby PJ 2005a Octreotide is not effective in the acute treatment of migraine. Cephalalgia 25 4855. (https://doi.org/10.1111/j.1468-2982.2004.00807.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Levy MJ, Matharu MS, Meeran K, Powell M & Goadsby PJ 2005b The clinical characteristics of headache in patients with pituitary tumours. Brain 128 19211930. (https://doi.org/10.1093/brain/awh525)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lovato CM & & Kapsner PL 2018 Analgesic effect of long-acting somatostatin receptor agonist pasireotide in a patient with acromegaly and intractable headaches. BMJ Case Reports 2018 bcr-2017-219686. (https://doi.org/10.1136/bcr-2017-219686)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mampreso E, Maggioni F, Viaro F, Disco C & Zanchin G 2009 Efficacy of oxygen inhalation in sumatriptan refractory “high altitude” cluster headache attacks. Journal of Headache and Pain 10 465467. (https://doi.org/10.1007/s10194-009-0160-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Marina D, Burman P, Klose M, Casar-Borota O, Luque RM, Castaño JP & & Feldt-Rasmussen U 2015 Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues - observations in two patients with acromegaly and severe headache. Growth Hormone and IGF Research 25 262267. (https://doi.org/10.1016/j.ghir.2015.07.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Matharu MS, Levy MJ, Meeran K & Goadsby PJ 2004 Subcutaneous octreotide in cluster headache: randomized placebo-controlled double-blind crossover study. Annals of Neurology 56 488494. (https://doi.org/10.1002/ANA.20210)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • May A, Lederbogen S & Diener HC 1994 Octreotide dependency and headache: a case report. Cephalalgia 14 303304. (https://doi.org/10.1046/j.1468-2982.1994.1404303.x)

  • Mercado M, Espinosa de los Monteros AL, Sosa E, Cheng S, Mendoza V, Hernández I, Sandoval C, Guinto G & Molina M 2004 Clinical-biochemical correlations in acromegaly at diagnosis and the real prevalence of biochemically discordant disease. Hormone Research 62 293299. (https://doi.org/10.1159/000082032)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Miller MA, Levsky ME, Enslow W & Rosin A 2009 Randomized evaluation of octreotide vs prochlorperazine for ED treatment of migraine headache. American Journal of Emergency Medicine 27 160164. (https://doi.org/10.1016/J.AJEM.2008.01.015)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Musolino NR, Marino Júnior R & Bronstein MD 1990 Headache in acromegaly: dramatic improvement with the somatostatin analogue SMS 201–995. Clinical Journal of Pain 6 243245. (https://doi.org/10.1097/00002508-199009000-00013)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Olesen J 2018 Headache Classification Committee of the International Headache Society (IHS) the International Classification of Headache Disorders, 3rd ed. Cephalalgia 38 1211. (https://doi.org/10.1177/0333102417738202)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pascual J, Freijanes J, Berciano J & Pesquera C 1991 Analgesic effect of octreotide in headache associated with acromegaly is not mediated by opioid mechanisms. Case report. Pain 47 341344. (https://doi.org/10.1016/0304-3959(9190226-N)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Penn RD, Paice JA & Kroin JS 1992 Octreotide: a potent new non-opiate analgesic for intrathecal infusion. Pain 49 1319. (https://doi.org/10.1016/0304-3959(9290182-B)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pereira-Neto A, Borba AM, Mello PA, Naves LA, Araújo AS & Casulari LA 2010 Mean intrasellar pressure, visual field, headache intensity and quality of life of patients with pituitary adenoma. Arquivos de Neuro-Psiquiatria 68 350354. (https://doi.org/10.1590/S0004-282X2010000300004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Popovic V, Paunovic VR, Micic D, Nesovic M, Kendereski A, Djordjevic P, Manojlovic D & Micic J 1988 The analgesic effect and development of dependency to somatostatin analogue (octreoide) in headache associated with acromegaly. Hormone and Metabolic Research 20 250251. (https://doi.org/10.1055/s-2007-1010806)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schmidt K, Althoff PH, Harris AG, Prestele H, Schumm-Draeger PM & Usadel KH 1993 Analgesic effect of the somatostatin analogue octreotide in two acromegalic patients: a double-blind study with long-term follow-up. Pain 53 223227. (https://doi.org/10.1016/0304-3959(9390084-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shimada S, Shiosaka S, Takami K, Yamano M & Tohyama M 1985 Somatostatinergic neurons in the insular cortex project to the spinal cord: combined retrograde axonal transport and immunohistochemical study. Brain Research 326 197200. (https://doi.org/10.1016/0006-8993(8591404-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sicolo N, Martini C, Ferla S, Roggenkamp J, Vettor R, De Palo C & Federspil G 1990 Analgesic effect of Sandostatin (SMS 201–995) in acromegaly headache. Minerva Endocrinologica 15 3742.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sicuteri F, Geppetti P, Marabini S & Lembeck F 1984 Pain relief by somatostatin in attacks of cluster headache. Pain 18 359365. (https://doi.org/10.1016/0304-3959(8490048-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Stine SM, Yang HY & Costa E 1982 Evidence for ascending and descending intraspinal as well as primary sensory somatostatin projections in the rat spinal cord. Journal of Neurochemistry 38 11441150. (https://doi.org/10.1111/J.1471-4159.1982.TB05361.X)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sumatriptan Cluster Headache Study Group 1991 Treatment of acute cluster headache with sumatriptan. New England Journal of Medicine 325 322326. (https://doi.org/10.1056/NEJM199108013250505)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Taurà P, Planella V, Balust J, Beltran J, Anglada T, Carrero E & Burgués S 1994 Epidural somatostatin as an analgesic in upper abdominal surgery: a double-blind study. Pain 59 135140. (https://doi.org/10.1016/0304-3959(9490057-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Williams G, Ball JA, Lawson RA, Joplin GF, Bloom SR & Maskill MR 1987 Analgesic effect of somatostatin analogue (octreotide) in headache associated with pituitary tumours. British Medical Journal 295 247248. (https://doi.org/10.1136/bmj.295.6592.247)

    • PubMed
    • Search Google Scholar
    • Export Citation