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Cluster headache and macroprolactinoma: Case report of a rare, but potential important causality
Journal of Clinical Neuroscience xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case report
Cluster headache and macroprolactinoma: Case report of a rare, but potential important causality Lukas Andereggen a, Marie-Luise Mono b, Frauke Kellner-Weldon c, Emanuel Christ d,⇑ a
Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland c Department of Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland d Department of Endocrinology, Universtiy Hospital Basel, University of Basel, Basel, Switzerland b
a r t i c l e
i n f o
Article history: Received 2 November 2016 Accepted 25 January 2017 Available online xxxx Keywords: Cluster headache Prolactinoma Dopamine agonists
a b s t r a c t While headache is not an uncommon symptom in patients suffering from pituitary adenomas, cluster headache (CH) has rarely been reported in such cases. Headache associated with hyperprolactinemia has been reported to be responsive to dopamine agonists (DA agonists) in many patients. We report on a patient with refractory CH secondary to a macroprolactinoma who showed immediate and permanent clinical and radiologic recovery following medical treatment with DA agonists. Measurement of prolactin levels in addition to cranial magnetic resonance imaging might be considered in patients with refractory CH, until the significance of this potential causality becomes clearer. Ó 2017 Elsevier Ltd. All rights reserved.
1. Introduction While headache is not an uncommon symptom in patients suffering from pituitary adenomas, cluster headache (CH) has rarely reported in them [1]. Headache associated with hyperprolactinemia has been reported to be responsive to dopamine agonists (DA-agonists) in many patients. Nevertheless, the pathophysiology of secondary CH associated with pituitary disorders is not well established. Besides structural factors, other mechanisms on a biochemical- neuroendocrine basis with activity of the tumor might be equally important determinants of headache [2].
2. Case report A 46-year-old farmer had suffered from nonspecific holocephalic cephalalgia for several years. Due to aggravation of his symptoms, with the pain newly located in the periorbital area on the right side, he presented at his general practitioner’s office. The headache was accompanied by restlessness and autonomic symptoms like lacrimation and conjunctival injection. The attacks lasted for about 3–4 h. Treatment with mefenamic acid was initiated, which showed promising results at first. Eventually, however, his headache symptoms showed a strictly nocturnal pattern, and ⇑ Corresponding author at: Department of Endocrinology, University of Basel, 4031 Basel, Switzerland. Fax: +41 61 265 51 00. E-mail address: [email protected] (E. Christ).
he was referred for neurological evaluation. The patient reported that he had approximately 3–5 headache attacks a month. The headaches, which lasted for 3–5 h, recurred nightly between 01:00 and 03:00, and on rare occasions very early in the morning. The pain was located strictly in the right periorbital region, characterized as a sharp, throbbing pain with an intensity of 8/10 rated on a visual analog scale from 0 to 10. The headache was accompanied by restlessness and infrequent lacrimation in the right eye. No other dysautonomic features, agitation, nausea, photophobia, or phonophobia were noted and the patient did not report rhinorrhea, nasal obstruction, or reddening of the eye. The patient’s past medical history was unremarkable. His family history revealed that his mother possibly suffered from migraine. He was an active smoker but denied drinking alcohol regularly and had no allergies. Neurological examination was otherwise normal. Given fulfillment of the criteria set out by the International Headache Society including the unilateral location of headaches, attacks <15 times per month with associated lacrimation and restlessness, although infrequent, CH rather than hypnic headache was postulated and zolmitriptan nasal spray was prescribed. The CH was initially completely responsive to zolmitriptan, but eventually became refractory. Due to the refractory, strictly nocturnal recurrences of CH symptoms in contrast to the initial presentation, cranial magnetic resonance imaging (MRI) was performed to look for secondary etiologies. The MRI revealed a macroadenoma with infiltration of the cavernous sinus affecting the right ophthalmic and maxillary nerve and no involvement or elevation of the optic chiasm
http://dx.doi.org/10.1016/j.jocn.2017.01.028 0967-5868/Ó 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Andereggen L et al. Cluster headache and macroprolactinoma: Case report of a rare, but potential important causality. J Clin Neurosci (2017), http://dx.doi.org/10.1016/j.jocn.2017.01.028
2
Case report / Journal of Clinical Neuroscience xxx (2017) xxx–xxx
Fig. 1. (A) Coronal MRI showing the voluminous extension of the macroadenoma with infiltration of the cavernous sinus on the right side encompassing the carotid artery, affecting the right ophthalmic and maxillary nerve, and showing slight elevation of the optic chiasm. (B) Following treatment with DA-agonist, there is marked tumor melting with delineation of the pituitary stalk and normal pituitary gland.
(Fig. 1A). Given the tumor expansion, the patient was referred for endocrinological evaluation. On direct questioning, the patient admitted to a loss of libido over the preceding 5 years. Laboratory analysis confirmed central hypogonadism, and prolactin levels were >7000 lg/ml (normal 6 20 lg/ml). The other pituitary hormonal axes (ACTH, TSH and GH) were clinically and biochemically unremarkable. The patient was started on a dopamine (DA) agonist (cabergoline 0.5 mg twice weekly). Due to prolonged symptoms of decreased libido, osteodensitometry was performed at the femur, tibia, spine, and neck, but showed no impairment of the bone mineral density. Upon initiation of DA-agonist treatment, the patient showed immediate and complete relief from CH. A follow-up examination 3 months later revealed decreased prolactin (>136 lg/ml). There was a marked decrease of the adenoma in the pituitary MRI 6 months after initiation of DA-agonist therapy (Fig. 1B). Five years later, the patient remained free from CH, the prolactin level was slightly elevated and no tumor recurrence was seen in the pituitary MRI. Hypogonadism resolved, the other pituitary axes remained intact, and therapy with cabergoline was maintained (0.5 mg twice weekly).
described above, other mechanisms on a biochemical- neuroendocrine basis with activity of the tumor might be equally important determinants of headache [2]. Given the immediate and permanent pain relief following DA agonist treatment, the normalization of prolactin levels and marked tumor shrinkage, an association between CH and neuroendocrine and local changes of the pituitary tumor may be hypothesized. Therefore, besides cranial MRI to rule out secondary etiologies in CH, a simple and inexpensive test to measure prolactin levels in refractory cases of CH might be considered, until the significance of this potential causality becomes clearer.
3. Discussion
Ethical standards and patient consent
While headache is not an uncommon symptom in patients with pituitary adenomas, with an incidence ranging between 33% and 72%, pituitary tumors have been associated mostly with migraine, or neuralgiform headache attacks [1,2]. The mechanisms for pituitary tumor-associated headaches have been classically attributed to the stretching of the dura or cavernous sinus invasion with irritation of trigeminal nerve fibers such as the ophthalmic and maxillary nerve. Nevertheless, the pathophysiology of secondary CH associated with pituitary disorders is not well established. CH is a form of primary neurovascular headache, and the hypothalamus is believed to play a pivotal role in the illness based on observations of neuroendocrine disturbances and circadian biological changes-as in our patient [3]. Presumably, the origin of pain is located in the suprachiasmatic nucleus of the hypothalamus, given that the attacks occur only during the night [4]. Not only the expansion of the macroadenoma into the cavernous sinus, but the local displacement of the hypothalamus might have contributed to the pain experienced by our patient. On the other hand, a link between the macroadenoma and CH might be reasonable given the spatial and temporal relationship between pain relief and DA agonist treatment. Thus, rather than structural factors as
This study fulfills the requirements of the Ethics Committee of Bern (Kantonale Ethikkommision, KEK, Bern, Switzerland), the Swiss Ethics Committee on research involving humans. The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Conflict of interests/disclosures No specific funding was received for this work. This work or part of this work has not been previously published and/or is not under consideration for publication anywhere else. The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Acknowledgements The assistance of Ms. Susan Kaplan in editing the manuscript is acknowledged. References [1] Yu B, Ji N, Ma Y, et al. Clinical characteristics and risk factors for headache associated with non-functioning pituitary adenomas. Cephalalgia 2016. [2] Levy MJ, Matharu MS, Meeran K, et al. The clinical characteristics of headache in patients with pituitary tumours. Brain 2005;128:1921–30. [3] May A. Cluster headache: pathogenesis, diagnosis, and management. Lancet 2005;366:843–55. [4] Tariq N, Estemalik E, Vij B, et al. Long-term outcomes and clinical characteristics of hypnic headache syndrome: 40 patients series from a tertiary referral center. Headache 2016;56:717–24.
Please cite this article in press as: Andereggen L et al. Cluster headache and macroprolactinoma: Case report of a rare, but potential important causality. J Clin Neurosci (2017), http://dx.doi.org/10.1016/j.jocn.2017.01.028
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case report
Cluster headache and macroprolactinoma: Case report of a rare, but potential important causality Lukas Andereggen a, Marie-Luise Mono b, Frauke Kellner-Weldon c, Emanuel Christ d,⇑ a
Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland c Department of Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland d Department of Endocrinology, Universtiy Hospital Basel, University of Basel, Basel, Switzerland b
a r t i c l e
i n f o
Article history: Received 2 November 2016 Accepted 25 January 2017 Available online xxxx Keywords: Cluster headache Prolactinoma Dopamine agonists
a b s t r a c t While headache is not an uncommon symptom in patients suffering from pituitary adenomas, cluster headache (CH) has rarely been reported in such cases. Headache associated with hyperprolactinemia has been reported to be responsive to dopamine agonists (DA agonists) in many patients. We report on a patient with refractory CH secondary to a macroprolactinoma who showed immediate and permanent clinical and radiologic recovery following medical treatment with DA agonists. Measurement of prolactin levels in addition to cranial magnetic resonance imaging might be considered in patients with refractory CH, until the significance of this potential causality becomes clearer. Ó 2017 Elsevier Ltd. All rights reserved.
1. Introduction While headache is not an uncommon symptom in patients suffering from pituitary adenomas, cluster headache (CH) has rarely reported in them [1]. Headache associated with hyperprolactinemia has been reported to be responsive to dopamine agonists (DA-agonists) in many patients. Nevertheless, the pathophysiology of secondary CH associated with pituitary disorders is not well established. Besides structural factors, other mechanisms on a biochemical- neuroendocrine basis with activity of the tumor might be equally important determinants of headache [2].
2. Case report A 46-year-old farmer had suffered from nonspecific holocephalic cephalalgia for several years. Due to aggravation of his symptoms, with the pain newly located in the periorbital area on the right side, he presented at his general practitioner’s office. The headache was accompanied by restlessness and autonomic symptoms like lacrimation and conjunctival injection. The attacks lasted for about 3–4 h. Treatment with mefenamic acid was initiated, which showed promising results at first. Eventually, however, his headache symptoms showed a strictly nocturnal pattern, and ⇑ Corresponding author at: Department of Endocrinology, University of Basel, 4031 Basel, Switzerland. Fax: +41 61 265 51 00. E-mail address: [email protected] (E. Christ).
he was referred for neurological evaluation. The patient reported that he had approximately 3–5 headache attacks a month. The headaches, which lasted for 3–5 h, recurred nightly between 01:00 and 03:00, and on rare occasions very early in the morning. The pain was located strictly in the right periorbital region, characterized as a sharp, throbbing pain with an intensity of 8/10 rated on a visual analog scale from 0 to 10. The headache was accompanied by restlessness and infrequent lacrimation in the right eye. No other dysautonomic features, agitation, nausea, photophobia, or phonophobia were noted and the patient did not report rhinorrhea, nasal obstruction, or reddening of the eye. The patient’s past medical history was unremarkable. His family history revealed that his mother possibly suffered from migraine. He was an active smoker but denied drinking alcohol regularly and had no allergies. Neurological examination was otherwise normal. Given fulfillment of the criteria set out by the International Headache Society including the unilateral location of headaches, attacks <15 times per month with associated lacrimation and restlessness, although infrequent, CH rather than hypnic headache was postulated and zolmitriptan nasal spray was prescribed. The CH was initially completely responsive to zolmitriptan, but eventually became refractory. Due to the refractory, strictly nocturnal recurrences of CH symptoms in contrast to the initial presentation, cranial magnetic resonance imaging (MRI) was performed to look for secondary etiologies. The MRI revealed a macroadenoma with infiltration of the cavernous sinus affecting the right ophthalmic and maxillary nerve and no involvement or elevation of the optic chiasm
http://dx.doi.org/10.1016/j.jocn.2017.01.028 0967-5868/Ó 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Andereggen L et al. Cluster headache and macroprolactinoma: Case report of a rare, but potential important causality. J Clin Neurosci (2017), http://dx.doi.org/10.1016/j.jocn.2017.01.028
2
Case report / Journal of Clinical Neuroscience xxx (2017) xxx–xxx
Fig. 1. (A) Coronal MRI showing the voluminous extension of the macroadenoma with infiltration of the cavernous sinus on the right side encompassing the carotid artery, affecting the right ophthalmic and maxillary nerve, and showing slight elevation of the optic chiasm. (B) Following treatment with DA-agonist, there is marked tumor melting with delineation of the pituitary stalk and normal pituitary gland.
(Fig. 1A). Given the tumor expansion, the patient was referred for endocrinological evaluation. On direct questioning, the patient admitted to a loss of libido over the preceding 5 years. Laboratory analysis confirmed central hypogonadism, and prolactin levels were >7000 lg/ml (normal 6 20 lg/ml). The other pituitary hormonal axes (ACTH, TSH and GH) were clinically and biochemically unremarkable. The patient was started on a dopamine (DA) agonist (cabergoline 0.5 mg twice weekly). Due to prolonged symptoms of decreased libido, osteodensitometry was performed at the femur, tibia, spine, and neck, but showed no impairment of the bone mineral density. Upon initiation of DA-agonist treatment, the patient showed immediate and complete relief from CH. A follow-up examination 3 months later revealed decreased prolactin (>136 lg/ml). There was a marked decrease of the adenoma in the pituitary MRI 6 months after initiation of DA-agonist therapy (Fig. 1B). Five years later, the patient remained free from CH, the prolactin level was slightly elevated and no tumor recurrence was seen in the pituitary MRI. Hypogonadism resolved, the other pituitary axes remained intact, and therapy with cabergoline was maintained (0.5 mg twice weekly).
described above, other mechanisms on a biochemical- neuroendocrine basis with activity of the tumor might be equally important determinants of headache [2]. Given the immediate and permanent pain relief following DA agonist treatment, the normalization of prolactin levels and marked tumor shrinkage, an association between CH and neuroendocrine and local changes of the pituitary tumor may be hypothesized. Therefore, besides cranial MRI to rule out secondary etiologies in CH, a simple and inexpensive test to measure prolactin levels in refractory cases of CH might be considered, until the significance of this potential causality becomes clearer.
3. Discussion
Ethical standards and patient consent
While headache is not an uncommon symptom in patients with pituitary adenomas, with an incidence ranging between 33% and 72%, pituitary tumors have been associated mostly with migraine, or neuralgiform headache attacks [1,2]. The mechanisms for pituitary tumor-associated headaches have been classically attributed to the stretching of the dura or cavernous sinus invasion with irritation of trigeminal nerve fibers such as the ophthalmic and maxillary nerve. Nevertheless, the pathophysiology of secondary CH associated with pituitary disorders is not well established. CH is a form of primary neurovascular headache, and the hypothalamus is believed to play a pivotal role in the illness based on observations of neuroendocrine disturbances and circadian biological changes-as in our patient [3]. Presumably, the origin of pain is located in the suprachiasmatic nucleus of the hypothalamus, given that the attacks occur only during the night [4]. Not only the expansion of the macroadenoma into the cavernous sinus, but the local displacement of the hypothalamus might have contributed to the pain experienced by our patient. On the other hand, a link between the macroadenoma and CH might be reasonable given the spatial and temporal relationship between pain relief and DA agonist treatment. Thus, rather than structural factors as
This study fulfills the requirements of the Ethics Committee of Bern (Kantonale Ethikkommision, KEK, Bern, Switzerland), the Swiss Ethics Committee on research involving humans. The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Conflict of interests/disclosures No specific funding was received for this work. This work or part of this work has not been previously published and/or is not under consideration for publication anywhere else. The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Acknowledgements The assistance of Ms. Susan Kaplan in editing the manuscript is acknowledged. References [1] Yu B, Ji N, Ma Y, et al. Clinical characteristics and risk factors for headache associated with non-functioning pituitary adenomas. Cephalalgia 2016. [2] Levy MJ, Matharu MS, Meeran K, et al. The clinical characteristics of headache in patients with pituitary tumours. Brain 2005;128:1921–30. [3] May A. Cluster headache: pathogenesis, diagnosis, and management. Lancet 2005;366:843–55. [4] Tariq N, Estemalik E, Vij B, et al. Long-term outcomes and clinical characteristics of hypnic headache syndrome: 40 patients series from a tertiary referral center. Headache 2016;56:717–24.
Please cite this article in press as: Andereggen L et al. Cluster headache and macroprolactinoma: Case report of a rare, but potential important causality. J Clin Neurosci (2017), http://dx.doi.org/10.1016/j.jocn.2017.01.028