Journal of Neuro-Ophthalmology:
Intracranial hypertension (IH) has been associated with hypocortisolism caused by either primary adrenocortical insufficiency or corticosteroid withdrawal.
Method: The authors describe a case of IH in association with Sheehan syndrome (SS) in a postpartum 29-year-old woman.
Results: The clinical manifestations of IH resolved with corticosteroid replacement.
Conclusions: This case supports a causal role of hypocortisolism in IH. The authors are unaware of previous reports of hypocortisolism caused by SS leading to IH.
Departments of Neurology (KKM, KC, NFM) and Neuroradiology (NAS), Kings College Hospital, United Kingdom; Department of Neurology (RB, NFM), Kent and Canterbury Hospital, United Kingdom; and Department of Ophthalmology (PR-E), Kings College London, United Kingdom.
Address correspondence to Nicholas F. Moran, MRCP, MSc, Department of Neurology, Kings College Hospital, Denmark Hill, London SE5 9RS, United Kingdom; E-mail: firstname.lastname@example.org
The authors report no conflicts of interest.
Sheehan syndrome (SS) refers to postpartum hypopituitarism caused by pituitary necrosis usually following peri-partum hemorrhage with hypovolemic shock (1,2). Our patient with SS initially presented with fatigue and agalactia. The presence of an intercurrent infection and administration of thyroxine exacerbated her corticosteroid insufficiency. Intracranial hypertension (IH) manifested as bilateral optic disc swelling with reduced visual acuity, bilateral sixth nerve palsies, and impaired consciousness.
A slim, 29-year-old Tamil-speaking woman presented 7 weeks postpartum with a 2-day history of left periorbital swelling, fever, nausea, and vomiting. She had consulted with her primary care doctor a week earlier complaining of fatigue, occipital headache, blurred vision, and insufficient lactation. She was found to be hypothyroid: thyroid-stimulating hormone (TSH) of 2.2 mIU/L, free T4 (fT4) of 6.0 pmol/L (normal values: TSH = 0.4–5.0 mIU/L; fT4 = 9–19 pmol/L), and thyroxine was prescribed. Her pregnancy had been complicated by hyperemesis gravidarum and prolonged labor associated with excessive hemorrhage and hypotension, prompting an emergency Caesarean section.
She was alert and coherent with a mild fever (37.8°C) and hypotension (92/65 mm Hg). There was left periorbital edema and ciliary injection. Positive clinical findings included: visual acuity of 20/40, right eye, and 20/200, left eye, bilateral optic disc edema, and left sixth nerve palsy. Pupillary reactions and facial sensation were normal, and there was no meningism. General medical examination was normal.
Initial empiric treatment consisted of intravenous benzylpenicillin and flucloxacillin and subcutaneous enoxaparin to treat presumed periorbital cellulitis and possibly cavernous sinus thrombosis. Noncontrast computed tomography (CT) of the brain, undertaken within hours of admission, revealed no evidence of intracranial hemorrhage or cerebral venous sinus thrombosis, and enoxaparin was reduced to a venous thromboembolic prophylactic dose. Admission blood results revealed erythrocyte sedimentation rate of 48 mm/h and C-reactive protein of 30 mg/L (normal: <5 mg/L), with normal renal and liver function. Complete blood count demonstrated normocytic, normochromic anemia, hemoglobin of 10.0 g/dL (normal: 11–15 g/dL), with normal white cell and platelet counts. Repeat thyroid function on 25 μg of levothyroxine revealed TSH of 0.5 mIU/L and fT4 of 13 pmol/L.
After 48 hours, the patient was switched to intravenous ceftriaxone and clindamycin because of inadequate resolution of periorbital edema and fever. Despite subsequent improvement in these signs, the patient's condition deteriorated over the next 5 days.
She became inattentive, disorientated, and somnolent with intractable nausea, requiring continuous parenteral antiemetics. Her score on the Glasgow Coma Scale fluctuated between 11 and 14, and she developed a right sixth nerve palsy.
The patient was transferred to a tertiary neurosciences center for further management. Upon arrival, she was hypoglycemic, hypotensive, and tachycardic but afebrile. Venous blood gas was consistent with nonlactic metabolic acidosis with pH of 7.32, lactate 0.9 mmol/L (normal: 0.6–2.0 mmol/L), bicarbonate 18.5 mmol/L (normal: 20–32 mmol/L), and base excess −6.9 mmol. On examination, the patient had bilateral sixth nerve palsies and bilateral optic disc edema. Her level of consciousness precluded an assessment of visual acuity, visual fields, or color vision. Acetazolamide (500 mg twice a day) was begun in addition to intravenous saline.
Laboratory blood tests revealed an undetectable cortisol level <30 nmol/L, growth hormone level <1.0 μg/L, and insulin growth factor 1 level <25 μg/L, with hypoglycemia and an undetectable prolactin level, establishing the diagnosis of hypopituitarism. Magnetic resonance imaging (MRI) of the brain showed a slightly enlarged pituitary gland with a central hypointense area with subtle enhancement and cerebellar tonsils 5 mm below the level of the foramen magnum (Fig. 1A). Although the brain parenchyma and cavernous sinuses appeared normal, the optic nerve sheaths were distended with flattening of the back of the globes (Fig. 1B). Magnetic resonance venography (MRV) showed reduced flow signal within the lateral portions of the transverse sinuses without evidence of venous sinus thrombosis (Fig. 2).
A lumbar puncture was not performed because of the risk of exacerbating cerebellar tonsillar herniation. The patient was begun on intravenous hydrocortisone (100 mg every 6 hours). Level of arousal improved, but she remained inattentive and disorientated. Three days later, both sixth nerve palsies had resolved and acetazolamide was stopped.
An intracranial pressure (ICP) bolt was inserted 1 week after admission. All readings for 48 hours were normal. Visual acuity was 20/30, right eye, and 20/40, left eye. The confusional state fully resolved over the next 2 weeks, and 4 months later, there was evidence of bilateral optic disc pallor with retinal pigment epithelial changes in the macula of each eye. There was no further improvement in visual acuity. Repeat brain MRI showed reduction in bulk of the pituitary gland and resolution of cerebellar tonsillar descent with less crowding of structures at the craniocervical junction (Fig. 3).
Although raised ICP was not confirmed directly, lumbar puncture being deemed unsafe and ICP monitoring being delayed until substantial clinical improvement had already occurred, it is very likely that our patient had SS complicated by IH. Cortisol deficiency seems to be the main etiological factor producing IH, given the dramatic response to steroid replacement therapy. In retrospect, agalactia and secondary hypothyroidism were early indicators of anterior pituitary failure.
An alternate diagnosis of cerebral venous sinus thrombosis was considered but not supported by findings on CT and MRV. It seemed highly unlikely that clinically significant venous sinus thrombosis would completely resolve within 1 week of using only low–molecular weight heparin. Microthrombosis of the venous sinus system as a complication of peripartum disseminated intravascular coagulation was also considered. Although this could not be excluded by neuroimaging, it would have been expected to produce symptoms immediately postpartum.
The reduction in visual acuity in our patient is unlikely to be explained entirely by raised ICP, as visual acuity is invariably preserved in acute papilledema unless it is very severe or there are additional factors such as compression or infiltration of the visual pathways (3). Visual acuity was recorded before we evaluated the patient, and it is possible that it was inaccurately measured or the patient was unable to fully cooperate because of impaired cognition.
SS was first described by Simmonds in 1913, and its prevalence in developed countries has been greatly reduced by improvements in obstetric care (4). Prolactin-mediated anterior pituitary hypertrophy during pregnancy seems to render the gland susceptible to ischemic necrosis in the presence of hypovolemic shock, and it is most frequently associated with hemorrhagic shock in the latter stages of labor (2,4,5). Disease severity is dependent on the degree of anterior pituitary dysfunction, and SS usually develops months to years after pregnancy (2). Acute presentations caused by circulatory collapse and hypoglycemia are less common (2,5–7). Agalactia is the most common symptom in the postpartum period, and MRI is useful in distinguishing SS from lymphocytic hypophysitis (4). The occurrence of hematologic abnormalities, ranging from normocytic anemia to pancytopenia, is well established in SS as is their reversal with hormone replacement (8,9). Typical T1 MRI features of SS include an enlarged pituitary gland with central hypointensity and peripheral enhancement with or without central heterogenous enhancement (10).
Steroid-responsive optic disc edema in association with adrenal insufficiency was first reported in 1952 (11). Subsequently, there have been other reports linking IH with adrenocortical insufficiency in children and adults (12–14). Steroid withdrawal, particularly in children, also is associated with IH (15,16). In our case, the rapid improvement in the clinical signs of raised ICP with cortisol and saline replacement, without the use of long-term acetazolamide or therapeutic lumbar puncture, indicates that cortisol deficiency was pivotal to the development and maintenance of raised ICP. Thyroxine administration, the co-occurrence of infection, and ongoing vomiting-related fluid loss contributed to the precipitation of an adrenocortical crisis.
Some authors have suggested that increased antidiuretic hormone levels contribute to the development of IH in hypocortisolism (13,14). However, documentation of posterior pituitary dysfunction with diabetes insipidus in SS would challenge this hypothesis (17). The putative pathophysiology of IH resulting from hypocortisolism remains unknown and is probably multifactoral (18–22).
In conclusion, our patient's SS led to hypocortisolism, which, in turn, contributed to IH. Corticosteroid replacement is essential in the treatment of this potentially life-threatening condition.
1. Kelestimur F. Sheehan's syndrome. Pituitary. 2003; 6:181–188.
2. Shivaprasad C. Sheehan's syndrome: newer advances. Indian J Endocrin Metab. 2011;15(suppl 3):S203–S207.
3. Corbett JJ, Savino PJ, Thompson HS, Kansu T, Schatz NJ, Orr LS, Hopson D. Visual loss in pseudotumor cerebri. Follow-up of 57 patients from five to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neurol. 1982;39:461–474.
4. Tessnow A, Wilson J. The changing face of Sheehan's syndrome. Am J Med Sci. 2010;340:402–406.
5. Molitch ME. Pituitary disorders during pregnancy. Endocrin Metab Clin N Am. 2006;35:99–116.
6. Gei-Guardia O, Soto-Herrera E, Gei-Brealey A, Chen-Ku CH. Sheehan's syndrome in Costa Rica: clinical experience on 60 cases. Endocr Pract. 2010;1:1–27.
7. Perlitz Y, Varkel J, Markovitz J, Ben Ami M, Matilsky M, Oettinger M. Acute adrenal insufficiency during pregnancy and puerperium: case report and literature review. Obstet Gynecol Surv. 1999;54:717–722.
8. Laway BA, Mir SA, Bashir MI, Bhat JR, Samoon J, Zargar AH. Prevalence of haematological abnormalities in patients with Sheehan's syndrome: response to replacement with glucocorticoids and thyroxine. Pituitary. 2011;14:39–43.
9. Laway BA, Bhat JR, Mir SA, Khan RS, Lone MI, Zargar AH. Sheehan's syndrome with pancytopaenia—complete recovery after hormone replacement. Ann Haematol. 2010;89:305–308.
10. Kaplun J, Fratila C, Ferenczi A, Yang WC, Lantos G, Fleckman AM, Schubart UK. Sequential pituitary MR imaging in Sheehan syndrome: report of 2 cases. Am J Neuroradiol. 2008;29:941–943.
11. Walsh FB. Papilledema associated with increased intracranial pressure in Addison's disease. AMA Arch Ophthalmol. 1952;47:8.
12. Legio MG, Cappa A, Molinari M, Corsello SM, Gainotti G. Pseudotumour cerebri as a presenting syndrome of Addisonian crisis. Ital J Neurol Sci. 1995;16:387–389.
13. Condulis N, Germain G, Charest N, Levy S, Carpenter TO. Pseudotumour cerebri: a presenting manifestation of Addison's disease. Clin Pediatr. 1997;36:711–713.
14. Sharma D, Mukherjee R, Moore P, Cuthbertson DJ. Addison's disease presenting with idiopathic intracranial hypertension in a 24-year-old woman: a case report. J Med Case Rep. 2010;4:60.
15. Neville BG, Wilson J. Benign intracranial hypertension following corticosteroid withdrawal in childhood. Br Med J. 1970;3:554–556.
16. Wall M. Idiopathic intracranial hypertension. Neurol Clin. 2010;28:593–617.
17. Atmaca H, Tanriverdi F, Gokce C, Unluhizarci K, Kelestimur F. Posterior pituitary function in Sheehan's syndrome. Eur J Endocrinol. 2007;156:563–567.
18. Lampl Y, Eshel Y, et al.. Serum leptin levels in women with idiopathic intracranial hypertension. J Neurol Neurosurg Psychiatry. 2002;72:642–643.
19. Dogulu CF, Kansu T, Leung MY, Baxendale V, Wu SM, Ozquc M, Chan WY, Rennert OM. Evidence for genetic susceptibility to thrombosis in idiopathic intracranial hypertension. Thromb Res. 2003;111:389–395.
20. Darvall KA, Sam RC. Obesity and thrombosis. Eur J Vasc Endovasc Surg. 2007;33:223–233.
21. Ooi L-Y, Walker BR, Bodkin PA, Whittle IR. Idiopathic intracranial hypertension: can studies of obesity provide the key to understanding the pathogenesis. Br J Neurosurg. 2008;22:187–194.
© 2013 by North American Neuro-Ophthalmology Society
22. Bruce BB, Biousse V, Newman NJ. Update on idiopathic intracranial hypertension. Am J Ophthalmol. 2011;152:163–169.