Pituitary enlargement in patients with intracranial hypotension syndrome

Patients and methods.

Eleven consecutive patients (seven women and four men), ranging in age from 20 to 56 years, were studied retrospectively. All were clinically diagnosed with intracranial hypotension syndrome. Seven patients had spontaneous intracranial hypotension, and the remaining four had intracranial hypotension secondary to lumbar puncture (three patients) or cervical spine surgery (one patient). Nine cases presented positional headache, which worsened shortly after assuming an upright position or with Valsalva maneuver, and improved or disappeared by lying flat. The remaining two cases presented continuous headache unaffected by positional changes, along with neck stiffness. Headache had a “bandlike” distribution in 10 cases; in one patient headache was occipital. Associated symptoms and signs were nausea and dizziness (n = 4), blurred vision and photophobia (n = 2), sixth cranial nerve palsy (n = 2), tinnitus (n = 1), and hearing loss (n = 1). Study of CSF revealed pressure less than 60 mm H₂O (n = 11), increased protein levels (n = 4), and slight pleocytosis (n = 3).

MRI exams were performed using 0.5 T GE vectra and 1.5 T GE Signa (St. Louis, MO) machines with spin echo (SE) sequences enhanced on T1 in the sagittal plane and double-eco axials. A total of 29 MRI studies were performed. They were evaluated by two neuroradiologists who knew the clinical state of the patients. Follow-up MRI studies allowed assessment of pituitary gland size.

The height and the morphology of the pituitary gland were analyzed on sagittal MRI images during and after the clinical picture. The pituitary gland is usually larger in women, with a mean height of 4.2 to 4.8 mm in women and 3.5 mm in men. We considered the gland enlarged when mean height of the gland was more than 1.5 times the aforementioned values.

Results.

The MRI follow-up ranged between 2 and 21 months, once the clinical picture reverted. All 11 patients studied showed diffuse pachymeningeal thickening with gadolinium enhancement, affecting convexity of brain and cerebellum, interhemispheric fissure, and tentorium. This finding was continuous, without patched areas, symmetric, and with a lineal shape. Enhancement and thickening was marked in seven patients and moderate in the rest. No case revealed leptomeningeal enhancement. Pachymeningeal enhancement only persisted in three patients, although less evident than in the initial study. Iter descent was observed in five patients, cerebellar tonsils descent in seven, and descent of both in four.

Three patients showed subdural small collections in the initial studies; two of the three were the patients who had continuous headache unaffected by positional changes, along with neck stiffness. No collection was surgically evacuated. Follow-up MRI showed disappearance of subdural collections in all three patients.

In every initial MRI, the pituitary gland was found to be enlarged with a convex superior margin. Pituitary heights reached a mean value of 9.03 mm (range 7.3 to 11 mm). Because this was a small series, the difference in size according to sex could not be properly assessed (mean value was 9.26 mm in women and 8.62 mm in men). Follow-up MRI studies revealed that the size of the gland invariably diminished in all patients, mean value 5.31 mm (range 3.8 to 7.2 mm) ( figures 1 and 2). In two patients, a small liquid collection was observed inside the gland. This collection disappeared on follow-up MRI studies at the time of clinical recovery (figure 2).

• Download figure
• Open in new tab
• Download powerpoint

Figure 1 (top). Contrast-enhanced T1-weighted sagittal MRI shows pituitary gland enlargement and pachymeningeal enhancement (left). In follow-up MRI (right) at the time of clinical recovery, normalization in size of the gland and disappearance of pachymeningeal enhancement were observed. Figure 2 (bottom)Contrast-enhanced T1-weighted sagittal MRI shows pituitary gland enlargement (left). Notice the fluid collection inside the gland. In follow-up MRI (right) at the time of clinical recovery, normalization of the gland and disappearance of the collection were observed.

Discussion.

Intracranial hypotension syndrome is a clinical entity characterized by headache that occurs or worsens usually less than 15 minutes after assumption of the upright position, and disappears or improves usually less than 30 minutes after resumption of the recumbent position. However, in some patients, as in two of ours, a persistent headache may be noted and the postural feature of the headache may become less prominent. The clinical picture is confirmed by demonstration of a low opening CSF pressure.1-3⇓⇓ MRI has become an invaluable diagnostic tool in this syndrome, with the cardinal features being diffuse pachymeningeal thickening with gadolinium enhancement, subdural collections of fluid, and downward displacement of the iter and cerebellar tonsils (resembling Chiari type I malformation).4

Pituitary gland enlargement has been previously described in women with spontaneous intracranial hypotension, with pituitary heights of between 8 and 11 mm.5 However, follow-up was performed in only one case. In this patient, her gland diminished from 11 mm to 5 mm. Our patients showed a similar range of enlargement (7.3 to 11 mm), and we proved a decrease in glandular height in every case, once the clinical picture reverted.

The pituitary gland is a densely vascularized organ surrounded by the cavernous sinus. The anterior lobe of pituitary gland receives its blood supply from the hypophyseal portal vessels, which form the second capillary bed. The posterior lobe is otherwisesupplied by the inferior hypophyseal arteries. Within the sinusoids, the blood comes into contact with the epithelial tissue and subsequently flows into general circulation through the sinuses that surround the body of the pituitary gland.6

Based on the Monro–Kellie doctrine, engorgement of the venous sinuses, meningeal veins, and pituitary vasculature is a volume compensatory phenomenon secondary to decreased CSF volume and pressure. We hypothesize that pituitary gland enlargement in intracranial hypotension syndrome is due to hyperemia of dural and epidural venous sinuses. This hyperemia would raise the pressure in the cavernous sinus, and secondarily would enlarge the hypophysis. Conversely, the liquid collection seen in two patients could be due to liquid extravasation inside the hypophysis, secondary to the aforementioned hyperemia. This data has not been previously reported.

Pituitary gland enlargement is therefore present in patients with intracranial hypotension syndrome. This finding is probably parallel to meningeal thickening, and both may share a common pathogenic mechanism. However, gland enlargement reverses earlier than meningeal thickening. This sign is simple to identify and quantify, but should not be mistaken with pre-existing anomalies of the pituitary. In this sense, pituitary enlargement associated with spontaneous CSF leaks may mimic pituitary adenoma.7 Also, clinicians should be aware that the pituitary may increase in size in girls at puberty.