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Lymphocytic hypophysitis in males
Case Reports / Journal of Clinical Neuroscience 20 (2013) 743–745
743
Lymphocytic hypophysitis in males Akshay Hindocha a, B. Roy Chaudhary a, Tara Kearney b, Piyali Pal c, Kanna Gnanalingham a,⇑ a
Department of Neurosurgery, Greater Manchester Neurosciences Centre, Salford Royal Foundation Trust (SRFT), Salford Royal Hospital, Stott Lane, Salford, Manchester M6 8HD, UK Department of Endocrinology, Salford Royal Hospital, Manchester, UK c Department of Neuropathology, Salford Royal Hospital, Manchester, UK b
a r t i c l e
i n f o
Article history: Received 13 December 2011 Accepted 14 April 2012
Keywords: Lymphocytic hypophysitis Males Transsphenoidal surgery
a b s t r a c t Lymphocytic hypophysitis (LH) is a rare inflammatory disorder of the pituitary gland that typically affects women in the peripartum period. We describe two male patients (ages 43 years and 36 years), who presented with headaches, visual disturbance and hypopituitarism. MRI revealed a heterogeneous pituitary lesion that extended into the suprasellar region and with a thickened pituitary stalk. In both patients a histopathological diagnosis of LH was made after endoscopic transsphenoidal surgery. LH in males, although rare, should be considered as a differential diagnosis in those with hypopituitarism and a heterogeneous pituitary fossa mass, extending into pituitary stalk. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
2.2. Patient 2
Lymphocytic hypophysitis (LH) is a chronic inflammatory disease of the pituitary gland thought to be autoimmune mediated.1 The lesion usually affects the adenohypophysis and involvement of the posterior pituitary or stalk is less common. LH predominates in females, particularly in relation to pregnancy or the early postpartum period.2,3 We describe the management of two male patients with LH, with unusual features on MRI and whose diagnosis was eventually made on histopathological grounds.
This 36-year-old Caucasian male presented with a 3-year history of headaches, lethargy, weight loss and more recent diplopia. There was a partial 6th nerve palsy on the right with diplopia, but visual fields were normal. Biochemically he had anterior hypopituitarism and he responded well to replacement with hydrocortisone, thyroxine, testosterone, and growth hormone. His prolactin was low (58 mU/L; range 86–324 mU/L) and there was no evidence of diabetes insipidus. MRI revealed a pituitary lesion that extended up into the suprasellar region (Fig. 2). To ascertain a definitive histological diagnosis, the lesion was debulked via a transsphenoidal endoscopic approach. At surgery the sphenoid sinus mucosa was found to be thickened and fibrotic. Likewise the pituitary fossa floor and the underlying dura were thickened. Piecemeal resection of a fibrotic pituitary lesion was undertaken. Post-operatively, the patient remained well at 1-year follow-up, with reduced headaches, resolution of his diplopia and no change in endocrine profile.
2. Case report 2.1. Patient 1 A 43-year-old Caucasian male presented with a 3-month history of a progressive bifrontal headaches, visual blurring, lethargy and polyuria. Clinical examination confirmed moderate bitemporal visual field deficits. MRI of the brain revealed a heterogeneous pituitary lesion that extended into the suprasellar region (Fig. 1). Endocrine assessment revealed pan-hypopituitarism, with low serum cortisol, gonadotrophs, testosterone, thyroid hormone (T4), thyroid-stimulating hormone, a slightly raised prolactin concentration (479 mU/L; range 29–452 mU/L), in keeping with a ‘‘stalk effect’’ and diabetes insipidus (DI) biochemically. Other investigations included serum angiotensin-converting enzyme, which was slightly elevated at 73 UL (range 11–55 UL), but serum alpha fetal protein, beta human chorionic gonadotropin, serum electrophoresis, autoantibody screen (anti-neutrophil cytoplasmic antibody and antinuclear antibody) and chest radiographs were all normal. His symptoms improved after replacement with thyroxine, hydrocortisone, desmopressin nasal spray and testosterone. At surgery (via an endoscopic transsphenoidal approach), a firm lesion with a thickened capsule attached to the dura was encountered. A piecemeal subtotal excision and decompression was undertaken. At 2.5-years follow-up, the patient remained well with improved headaches and normal vision. The endocrine deficiencies remained unaltered post-operatively.
⇑ Corresponding author. Tel.: +44 161 206 4340; fax: +44 161 206 4606. E-mail address: [email protected] (K. Gnanalingham).
2.3. Histopathology The histopathological appearance of the lesions from both patients were similar, notably a diffusely inflamed pituitary gland with widespread infiltration by inflammatory cells composed of polymorphs, lymphocytes, plasma cells, histiocytes and occasional eosinophils (Fig. 3). Immunohistochemical staining confirmed the presence of both B (CD20 positive) and T (CD3 positive) lymphocytic cells admixed with scattered infiltrates of macrophages (CD68 positive). Overall, these findings were consistent with a diagnosis of LH in both patients. 3. Discussion LH is rare, and is diagnosed in less than 1% of pituitary surgeries.1,2,4 There is a strong female association, with its risk increasing in pregnancy suggestive of an autoimmune link.1,2,4 Therefore, the present cases of histologically confirmed LH in males are unusual,1,3 and account for around 20% of the 379 cases of LH noted in a comprehensive review in 2005.4 LH typically presents with symptoms that reflect destruction and expansion of the pituitary gland. Progressive headaches (60%) and visual field defects (40%) are common symptoms.1,2,4
744
Case Reports / Journal of Clinical Neuroscience 20 (2013) 743–745
Fig. 1. MRI of Patient 1: (A) coronal T2-weighted, (B, D) sagittal T1-weighted and (C) axial T1-weighted MRI, with (C, D) gadolinium contrast showing a heterogeneously enhancing pituitary lesion with chiasmal compression and thickening of the pituitary stalk. The lesion was isointense on T1-weighted and partly hyperintense on T2weighted MRI, in keeping with necrotic or cystic contents. On T1-weighted MRI, there was no high signal in the region of the posterior pituitary. (D) There was peripheral enhancement of the lesion that extended up the thickened pituitary stalk.
Fig. 2. MRI of Patient 2 showing: (A) sagittal T1-weighted, (B) coronal T2-weighted and (C) axial T1-weighted MRI with gadolinium contrast showing a uniformly enhancing pituitary lesion, with no chiasmal compression and thickening of the pituitary stalk. (A) There is mucosal disease within the sphenoid sinus, with altered signal in the bone marrow of the clivus. The pituitary lesion was isointense on T1-weighted and T2-weighted MRI and there was no high signal on T1-weighted MRI in the region of the posterior pituitary. The optic chiasm was not compromised. (C) There was diffuse contrast enhancement that extended up to the pituitary stalk. On (B) T2-weighted MRI, there was a low signal area in the periphery of the lesion.
Case Reports / Journal of Clinical Neuroscience 20 (2013) 743–745
745
In LH, MRI can suggest the diagnosis, typically with uniform enlargement and enhancement of the pituitary gland that extends along a thickened pituitary stalk.1,5 However, in the present patients a number of unusual features were seen on the MR scans, which were not characteristic of LH. MR images in our first patient revealed a heterogeneous appearance and enhancement with contrast. The MRI scan of our second patient also showed a region of low signal at the periphery of the pituitary gland, which may represent the fibrotic changes resulting from the inflammatory process (Fig. 2b).1,5 The appearance of mucosal disease in the sphenoid sinus and the signal change within the clivus in Patient 2 are further unusual findings that have been reported also in association with pituitary apoplexy.1,5 On T1-weighted MRI, absence of the high signal of the normal posterior pituitary may suggest extension of the disease process into the neurohypophysis. But, as shown in our patients, this may not always be associated with the onset of clinical DI.4,5 Given the unusual presentation of both our patients, an inflammatory process was suspected and the eventual diagnosis of LH was made on histological grounds. The treatment for LH is controversial, and partly complicated by numerous reports of spontaneous shrinkage of the lesion over time, with improvement in endocrine function.1,2,4,5 Consequently some authors suggest that in patients clinically and radiologically suspected to have LH, an initial period of supportive treatment as well as a trial of high dose steroids may be advisable.1–5 However, in patients where the diagnosis is in doubt and/or there is visual impairment, surgical debulking should be considered. Although surgery leads to rapid relief of visual symptoms, the endocrinological deficits are unlikely to recover.1–5 In both patients in this report, the option of a steroid trial has been deferred for symptomatic recurrence.
Fig. 3. Photomicrographs from (A) Patient 1 and (B) Patient 2 showing destruction of the pituitary gland acinar structure by an inflammatory infiltrate composed of lymphocytes, plasma cells, histiocytes and occasional eosinophils (hematoxylin and eosin, 40). (This figure is available in colour at www.sciencedirect.com.)
Most patients suffer varying degrees of anterior hypopituitarism. The presence of DI in the first case is unusual, reflecting involvement of the posterior pituitary gland. About 20% to 30% of patients suffer from DI in LH, and this seems to be slightly more prevalent in males with LH.1,4 doi:http://dx.doi.org/10.1016/j.jocn.2012.04.021
References 1. Bellastella A, Bizzarro A, Coronella C, et al. Lymphocytic hypophysitis: a rare or underestimated disease? Eur. J. Endocrinol. 2003;7:363–76. 2. Caturegli P, Lupi I, Landek-Salgado M, et al. Pituitary autoimmunity: 30 years later. Autoimmun Rev 2008;7:631–7. 3. Hamnvik OP, Laury AR, Laws ER, et al. Lymphocytic hypophysitis with diabetes insipidus in a young man. Nature Reviews Endocrinology. 2010;6:464–70. 4. Caturegli P, Newschaffer C, Olivi A, et al. Autoimmune hypophysitis. Endocr Rev 2005;26:599–614. 5. Gutenberg A, Larsen J, Lupi I, et al. A radiologic score to distinguish autoimmune hypophysitis from nonsecreting pituitary adenoma preoperatively. Am J Neuroradiol 2009;30:1766–72.
743
Lymphocytic hypophysitis in males Akshay Hindocha a, B. Roy Chaudhary a, Tara Kearney b, Piyali Pal c, Kanna Gnanalingham a,⇑ a
Department of Neurosurgery, Greater Manchester Neurosciences Centre, Salford Royal Foundation Trust (SRFT), Salford Royal Hospital, Stott Lane, Salford, Manchester M6 8HD, UK Department of Endocrinology, Salford Royal Hospital, Manchester, UK c Department of Neuropathology, Salford Royal Hospital, Manchester, UK b
a r t i c l e
i n f o
Article history: Received 13 December 2011 Accepted 14 April 2012
Keywords: Lymphocytic hypophysitis Males Transsphenoidal surgery
a b s t r a c t Lymphocytic hypophysitis (LH) is a rare inflammatory disorder of the pituitary gland that typically affects women in the peripartum period. We describe two male patients (ages 43 years and 36 years), who presented with headaches, visual disturbance and hypopituitarism. MRI revealed a heterogeneous pituitary lesion that extended into the suprasellar region and with a thickened pituitary stalk. In both patients a histopathological diagnosis of LH was made after endoscopic transsphenoidal surgery. LH in males, although rare, should be considered as a differential diagnosis in those with hypopituitarism and a heterogeneous pituitary fossa mass, extending into pituitary stalk. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
2.2. Patient 2
Lymphocytic hypophysitis (LH) is a chronic inflammatory disease of the pituitary gland thought to be autoimmune mediated.1 The lesion usually affects the adenohypophysis and involvement of the posterior pituitary or stalk is less common. LH predominates in females, particularly in relation to pregnancy or the early postpartum period.2,3 We describe the management of two male patients with LH, with unusual features on MRI and whose diagnosis was eventually made on histopathological grounds.
This 36-year-old Caucasian male presented with a 3-year history of headaches, lethargy, weight loss and more recent diplopia. There was a partial 6th nerve palsy on the right with diplopia, but visual fields were normal. Biochemically he had anterior hypopituitarism and he responded well to replacement with hydrocortisone, thyroxine, testosterone, and growth hormone. His prolactin was low (58 mU/L; range 86–324 mU/L) and there was no evidence of diabetes insipidus. MRI revealed a pituitary lesion that extended up into the suprasellar region (Fig. 2). To ascertain a definitive histological diagnosis, the lesion was debulked via a transsphenoidal endoscopic approach. At surgery the sphenoid sinus mucosa was found to be thickened and fibrotic. Likewise the pituitary fossa floor and the underlying dura were thickened. Piecemeal resection of a fibrotic pituitary lesion was undertaken. Post-operatively, the patient remained well at 1-year follow-up, with reduced headaches, resolution of his diplopia and no change in endocrine profile.
2. Case report 2.1. Patient 1 A 43-year-old Caucasian male presented with a 3-month history of a progressive bifrontal headaches, visual blurring, lethargy and polyuria. Clinical examination confirmed moderate bitemporal visual field deficits. MRI of the brain revealed a heterogeneous pituitary lesion that extended into the suprasellar region (Fig. 1). Endocrine assessment revealed pan-hypopituitarism, with low serum cortisol, gonadotrophs, testosterone, thyroid hormone (T4), thyroid-stimulating hormone, a slightly raised prolactin concentration (479 mU/L; range 29–452 mU/L), in keeping with a ‘‘stalk effect’’ and diabetes insipidus (DI) biochemically. Other investigations included serum angiotensin-converting enzyme, which was slightly elevated at 73 UL (range 11–55 UL), but serum alpha fetal protein, beta human chorionic gonadotropin, serum electrophoresis, autoantibody screen (anti-neutrophil cytoplasmic antibody and antinuclear antibody) and chest radiographs were all normal. His symptoms improved after replacement with thyroxine, hydrocortisone, desmopressin nasal spray and testosterone. At surgery (via an endoscopic transsphenoidal approach), a firm lesion with a thickened capsule attached to the dura was encountered. A piecemeal subtotal excision and decompression was undertaken. At 2.5-years follow-up, the patient remained well with improved headaches and normal vision. The endocrine deficiencies remained unaltered post-operatively.
⇑ Corresponding author. Tel.: +44 161 206 4340; fax: +44 161 206 4606. E-mail address: [email protected] (K. Gnanalingham).
2.3. Histopathology The histopathological appearance of the lesions from both patients were similar, notably a diffusely inflamed pituitary gland with widespread infiltration by inflammatory cells composed of polymorphs, lymphocytes, plasma cells, histiocytes and occasional eosinophils (Fig. 3). Immunohistochemical staining confirmed the presence of both B (CD20 positive) and T (CD3 positive) lymphocytic cells admixed with scattered infiltrates of macrophages (CD68 positive). Overall, these findings were consistent with a diagnosis of LH in both patients. 3. Discussion LH is rare, and is diagnosed in less than 1% of pituitary surgeries.1,2,4 There is a strong female association, with its risk increasing in pregnancy suggestive of an autoimmune link.1,2,4 Therefore, the present cases of histologically confirmed LH in males are unusual,1,3 and account for around 20% of the 379 cases of LH noted in a comprehensive review in 2005.4 LH typically presents with symptoms that reflect destruction and expansion of the pituitary gland. Progressive headaches (60%) and visual field defects (40%) are common symptoms.1,2,4
744
Case Reports / Journal of Clinical Neuroscience 20 (2013) 743–745
Fig. 1. MRI of Patient 1: (A) coronal T2-weighted, (B, D) sagittal T1-weighted and (C) axial T1-weighted MRI, with (C, D) gadolinium contrast showing a heterogeneously enhancing pituitary lesion with chiasmal compression and thickening of the pituitary stalk. The lesion was isointense on T1-weighted and partly hyperintense on T2weighted MRI, in keeping with necrotic or cystic contents. On T1-weighted MRI, there was no high signal in the region of the posterior pituitary. (D) There was peripheral enhancement of the lesion that extended up the thickened pituitary stalk.
Fig. 2. MRI of Patient 2 showing: (A) sagittal T1-weighted, (B) coronal T2-weighted and (C) axial T1-weighted MRI with gadolinium contrast showing a uniformly enhancing pituitary lesion, with no chiasmal compression and thickening of the pituitary stalk. (A) There is mucosal disease within the sphenoid sinus, with altered signal in the bone marrow of the clivus. The pituitary lesion was isointense on T1-weighted and T2-weighted MRI and there was no high signal on T1-weighted MRI in the region of the posterior pituitary. The optic chiasm was not compromised. (C) There was diffuse contrast enhancement that extended up to the pituitary stalk. On (B) T2-weighted MRI, there was a low signal area in the periphery of the lesion.
Case Reports / Journal of Clinical Neuroscience 20 (2013) 743–745
745
In LH, MRI can suggest the diagnosis, typically with uniform enlargement and enhancement of the pituitary gland that extends along a thickened pituitary stalk.1,5 However, in the present patients a number of unusual features were seen on the MR scans, which were not characteristic of LH. MR images in our first patient revealed a heterogeneous appearance and enhancement with contrast. The MRI scan of our second patient also showed a region of low signal at the periphery of the pituitary gland, which may represent the fibrotic changes resulting from the inflammatory process (Fig. 2b).1,5 The appearance of mucosal disease in the sphenoid sinus and the signal change within the clivus in Patient 2 are further unusual findings that have been reported also in association with pituitary apoplexy.1,5 On T1-weighted MRI, absence of the high signal of the normal posterior pituitary may suggest extension of the disease process into the neurohypophysis. But, as shown in our patients, this may not always be associated with the onset of clinical DI.4,5 Given the unusual presentation of both our patients, an inflammatory process was suspected and the eventual diagnosis of LH was made on histological grounds. The treatment for LH is controversial, and partly complicated by numerous reports of spontaneous shrinkage of the lesion over time, with improvement in endocrine function.1,2,4,5 Consequently some authors suggest that in patients clinically and radiologically suspected to have LH, an initial period of supportive treatment as well as a trial of high dose steroids may be advisable.1–5 However, in patients where the diagnosis is in doubt and/or there is visual impairment, surgical debulking should be considered. Although surgery leads to rapid relief of visual symptoms, the endocrinological deficits are unlikely to recover.1–5 In both patients in this report, the option of a steroid trial has been deferred for symptomatic recurrence.
Fig. 3. Photomicrographs from (A) Patient 1 and (B) Patient 2 showing destruction of the pituitary gland acinar structure by an inflammatory infiltrate composed of lymphocytes, plasma cells, histiocytes and occasional eosinophils (hematoxylin and eosin, 40). (This figure is available in colour at www.sciencedirect.com.)
Most patients suffer varying degrees of anterior hypopituitarism. The presence of DI in the first case is unusual, reflecting involvement of the posterior pituitary gland. About 20% to 30% of patients suffer from DI in LH, and this seems to be slightly more prevalent in males with LH.1,4 doi:http://dx.doi.org/10.1016/j.jocn.2012.04.021
References 1. Bellastella A, Bizzarro A, Coronella C, et al. Lymphocytic hypophysitis: a rare or underestimated disease? Eur. J. Endocrinol. 2003;7:363–76. 2. Caturegli P, Lupi I, Landek-Salgado M, et al. Pituitary autoimmunity: 30 years later. Autoimmun Rev 2008;7:631–7. 3. Hamnvik OP, Laury AR, Laws ER, et al. Lymphocytic hypophysitis with diabetes insipidus in a young man. Nature Reviews Endocrinology. 2010;6:464–70. 4. Caturegli P, Newschaffer C, Olivi A, et al. Autoimmune hypophysitis. Endocr Rev 2005;26:599–614. 5. Gutenberg A, Larsen J, Lupi I, et al. A radiologic score to distinguish autoimmune hypophysitis from nonsecreting pituitary adenoma preoperatively. Am J Neuroradiol 2009;30:1766–72.