Title

Pituitary pseudo-adenoma from cerebrospinal fluid leak in Marfan syndrome

Authors

Niedzialkowska Ewelina, MD, Schanz Luke, DO, Kelekar Arati, MD

Introduction

Spontaneous intracranial hypotension (SIH) due to cerebrospinal fluid leaks are a rare clinical entity with an estimated annual incidence of 4-5 cases per 100,000, with a female predominance. Of those cases, 42% are caused by spinal meningeal diverticula, which have been associated with connective tissue disorders such as Marfan syndrome. Ectasia of the dura has been found to occur in up to 90% of Marfan patients. Typical symptoms of IH include postural headache, nausea, vomiting, tinnitus and dizziness. Pituitary enlargement has been reported on imaging findings and hypothesized to be caused by compensatory engorgement of the epidural venous plexus. With said enlargement having the potential to mimic a pituitary macroadenoma, increased awareness may avoid misdiagnosis and unnecessary procedures.

Case Presentation

We present a case of a 25 year old female with Marfan syndrome due to fibrillin gene mutation presenting with orthostatic headache, dizziness, tinnitus, fatigue, nausea and bitemporal hemianopsia that started 10 months prior without a precipitating event. The patient was initially assessed at an outside hospital and was diagnosed with a pituitary macroadenoma measuring 1.2cm x 0.9 cm and slightly remodeled optic chiasm. Brain MRI at that time also demonstrated tonsillar ectopia, dural venous sinus distention and mild pachymeningeal enhancement, concerning for IH. The patient was later transferred to our institution for further evaluation. A repeat brain MRI confirmed findings consistent with IH. Dedicated pituitary MRI showed similar enlargement of the adenohypophysis with normal neural hypophysis without signs of intraglandular nodule, further supporting the diagnosis. As the patient reported nausea, fatigue and orthostatic lightheadedness, an endocrinology evaluation was performed. Pituitary hormone levels including ACTH, FSH, LH, TSH, GH and prolactin were normal. MRI spine demonstrated thoracic and lumbar meningeal diverticula and significant dural sac ectasia at the L4-S2 level. Myelogram confirmed numerous lumbar spine diverticula with noted CSF leak at the right L5 and S1 nerve roots. The patient was recommended bed rest and received an epidural blood patch at the level of the leak with significant improvement in symptoms.

Discussion

Spontaneous intracranial hypotension is a rare clinical entity that has been associated with connective tissue disorders including Marfan syndrome. Dural weakness causing meningeal diverticula is believed to predispose patients to spontaneous CSF leaks. Imaging phenomena of IH include subdural fluid collections, diffuse pachymeningeal enhancement, brainstem descent with cerebellar tonsillar herniations as well as pituitary enlargement, which is believed to be secondary to compensatory venous engorgement and may be present in up to 57% of IH cases. The treatment of IH involves bed rest, high caffeine intake and epidural blood patches and has proven to reverse or diminish pituitary enlargement. Symptoms of IH can overlap with symptoms of adenohypophysis dysfunction and adrenal insufficiency including orthostatic dizziness and nausea. Hyperprolactinemia has also been detected in up to 24% patients with IH. As both imaging studies and symptoms may be mistaken for pituitary adenomas, with cases of transsphenoidal resection reported, it is crucial to recognize the clinical significance of this phenomenon in order to provide adequate therapy and avoid unnecessary procedures.

References

1. A classification system of spontaneous spinal CSF leaks. AU Schievink WI, Maya MM, Jean-Pierre S, Nuño M, Prasad RS, Moser FG SO Neurology. 2016;87(7):673. Epub 2016 Jul 20. 2. Fattori R, Nienaber CA, Descovich B, et al. Importance of dural ectasia in phenotypic assessment of Marfan's syndrome. Lancet 1999;354:910-913. 3. Pituitary enlargement in patients with intracranial hypotension syndrome J. Alvarez–Linera, J. Escribano, J. Benito–León, J. Porta–Etessam, A. Rovira Neurology Dec 2000, 55 (12) 1895-1897; DOI: 10.1212/WNL.55.12.1895 4. Forghani R, Farb RI. Diagnosis and temporal evolution of signs of intracranial hypotension on MRI of the brain. Neuroradiology. 2008 Dec;50(12):1025-34. doi: 10.1007/s00234-008-0445-z. Epub 2008 Sep 16. PMID: 18795275. 5. False pituitary tumor in CSF leaks B. Mokri, J.L. D. Atkinson Neurology Aug 2000, 55 (4) 573-575; DOI: 10.1212/WNL.55.4.573 6. Jennie Luna, Ila Khanna, Fiona J. Cook, Eric M. Marti, Regis G. Hoppenot, Sagging Brain Masquerading as a Pituitary Adenoma, The Journal of Clinical Endocrinology & Metabolism, Volume 99, Issue 9, 1 September 2014, Page 3043, https://doi.org/10.1210/jc.2014- 7. Michali-Stolarska M, Bladowska J, Stolarski M, Sasiadek MJ. Diagnostic Imaging and Clinical Features of Intracranial Hypotension - Review of Literature. Pol J Radiol. 2017 Dec 15;82:842-849. doi: 10.12659/PJR.904433. PMID: 29657653; PMCID: PMC5894032.