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A 29-Year-Old Nurse With Fatigue, Anxiety, and Depression

Leavitt, Jacqueline A. MD; Chen, John J. MD, PhD; Salomao, Diva R. MD; Rhee, John H. MD

Section Editor(s): Miller, Neil R. MD; Rucker, Janet MD

doi: 10.1097/WNO.0000000000000311
Clinical-Pathological Case Study

Departments of Ophthalmology (JAL, JJC) and Pathology (DRS), Mayo Clinic, Rochester, Minnesota; and Department Radiology (JHR), Providence Saint John's Health Center, Santa Monica, California.

Address correspondence to Jacqueline A. Leavitt, MD, Department of Ophthalmology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; E-mail: leavitt.jacqueline@mayo.edu

Supported in part by an unrestricted grant to the Department of Ophthalmology from Research to Prevent Blindness, Inc, New York, NY.

The remaining authors report no conflicts of interest.

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Drs. Leavitt and Chen:

A 29-year-old nurse reported an inability to clearly see her computer for the past 2 months. She denied eye pain, diplopia, numbness, tingling, or weakness, and the visual blurring did not change in bright vs dim illumination. She had an occipital headache that had been present for 2 months and was relieved with over-the-counter medications. She also complained of shortness of breath, unexplained weight loss, and extreme fatigue, and also sleeping 10 hours per night and taking naps over her lunch break at work. An evaluation by her primary care physician revealed a normal chest x-ray, an electrocardiogram that showed only sinus bradycardia, and anemia (hemoglobin 9.6 g/dL, normal: 12.0–15.5 g/dL; hematocrit 28.7, normal: 34.9–44.5). She was at 9-month postpartum and toward the end of her pregnancy, she had been evaluated for polydipsia (drinking up to 9 L/d) and nocturia (6–7 times per night). Water deprivation testing during pregnancy was not possible, but a serum sodium concentration of 133 nL values mg/L made the diagnosis of diabetes insipidus unlikely. Her symptoms improved after delivery, and the polyuria and polydipsia were attributed to pregnancy. During the postpartum period, the patient also developed fairly severe anxiety and depression that was being treated with sertraline and clonazepam.

On examination, vision acuity was 20/30 bilaterally. The patient correctly identified 11/13 Ishihara plates, right eye and 13/13 plates, left eye. There was no relative afferent pupillary defect. Visual fields were full to confrontation. Slit-lamp biomicroscopy and dilated fundus examination revealed no abnormalities. Although the results of kinetic perimetry were suggestive of a homonymous field defect (Fig. 1), her responses were variable and inconsistent. Optical coherence tomography demonstrated a normal average retinal nerve fiber layer thickness in both eyes.

FIG. 1

FIG. 1

It was suspected that the patient had the syndrome of fatigue, anxiety, and depression (FAD). Nevertheless, magnetic resonance imaging (MRI) of the brain was obtained.

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Dr. Rhee:

There is a well-defined suprasellar lesion (Fig. 2A) with involvement of the hypothalamus, infundibulum, and optic chiasm. The pituitary gland is uninvolved by the lesion; however, the normal expected T1 hyperintensity of the neurohypophysis is absent. Sagittal (Fig. 2B) and coronal (Fig. 2C) contrast-enhanced T1 images show diffuse enhancement of the mass. The suprasellar component of the mass is in direct contact with the floor of the third ventricle. Axial T2 image (Fig. 2D) demonstrates vasogenic edema surrounding the mass and involving both optic tracts, medial temporal lobes, and ventral aspect of the midbrain.

FIG. 2

FIG. 2

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Drs. Leavitt and Chen:

Laboratory studies showed an elevated erythrocyte sedimentation rate of 70 mm/h and a mildly elevated angiotensin-converting enzyme of 62 μg/L (normal 8–53 μg/L). An endocrinologic evaluation revealed evidence of hypopituitarism (AM cortisol 5.9 nmol/L [normal 7–25 mol/L], free thyroxine 0.7 μg/dL [normal 0.8–1.8 μg/L], ACTH 8.3 pg/mL [normal 10–60 pg/mL], luteinizing hormone and follicle stimulating hormone low but in setting of birth control pills, and prolactin 120 ng/mL [normal 3–27 ng/mL]). The patient was prescribed hydrocortisone and levothyroxine, resulting in an increase in her energy. Nevertheless, although she had previously been a marathon runner, she could no longer perform this activity because of right lower back pain and right lower extremity weakness. Accordingly, MRI of the pelvis was performed.

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Dr. Rhee:

MRI of the pelvis shows a well-circumscribed lesion in the right upper sacrum. The lesion is isointense with muscle on an axial T1 image (Fig. 3A) and hyperintense on an axial T2 fat-suppressed scan (Fig. 3B), with evidence of prominent surrounding edema within the adjacent bone marrow. A contrast-enhanced axial T1 MRI shows evidence of heterogeneous enhancement of the lesion (Fig. 3C).

FIG. 3

FIG. 3

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Drs. Leavitt and Chen:

Further evaluation included a normal bone marrow biopsy and computed tomographic scan of the chest. Positron emission tomography revealed only fluoro-deoxy-glucose uptake in the pelvic and intracranial lesions. The patient thus underwent a biopsy of the right sacral mass.

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Dr. Salomao:

Histopathologic evaluation of the sacral mass shows diffuse proliferation of cells with elongated nuclei with irregular nuclear membranes and a longitudinal groove. These cells have an eosinophilic cytoplasm and indistinct cell membranes. The morphologic features are consistent with Langerhans histiocytes that are positive for Langerin, S100, and CD1a immunostains (Fig. 4). These cells are intermixed with numerous neutrophils and eosinophils in a loosely arranged pattern. These findings are consistent with Langerhans cell histiocytosis (LCH).

FIG. 4

FIG. 4

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Drs. Leavitt and Chen:

The patient underwent cladribine chemotherapy, with an improvement in all of her symptoms. Visual acuity improved to 20/20 in each eye, with intact color vision. Automated perimetry revealed residual right inferior homonymous visual field defect (Fig. 5). Five months after beginning treatment, the patient underwent repeat brain MRI.

FIG. 5

FIG. 5

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Dr. Rhee:

There is marked reduction in the size of the suprasellar lesion, with minimal residual enhancement near the hypothalamus (Fig. 6).

FIG. 6

FIG. 6

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Final Diagnosis

Langerhans cell histiocytosis.

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Drs. Leavitt and Chen:

LCH is characterized by proliferation of CD1a+ dendritic cells. The term LCH encompasses a range of clinical presentations and includes diseases previously designated eosinophilic granuloma, Letterer–Siwe disease, and Hand–Schuller–Christian syndrome, which once were separated on the basis of organ involvement and disease (1–3 1–3 1–3). LCH can affect multiple sites including bone, lung, hypothalamus, pituitary gland, skin, lymph nodes, liver, and other organs. The disease predominantly affects children, whereas adult onset is seen in approximately 10% of patients.

Although any part of the central nervous system (CNS) can be affected, the hypothalamic-pituitary system is most frequently involved resulting in diabetes insipidus (4). Patients with CNS disease are more likely to have multisystem disease and skull lesions (5). Although visual compromise from LCH is common in patients with orbital lesions, there are few reports of intracranial involvement of the visual pathways (6).

Our patient presented with FAD, and her profound fatigue ultimately was found to be from infiltration of the hypothalamus by Langerhans histiocytosis. In addition, the polydipsia and polyuria that developed 1 year before presentation were likely a forme fruste of diabetes insidious, with which she was diagnosed months later. Our case emphasizes that, in addition to lesions such as craniopharyngiomas and germ cell tumors, the differential diagnosis of vision loss in a patient with hypothalamic/pituitary abnormalities and associated with an enhancing suprasellar mass should include LCH.

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REFERENCES

1. Histiocytosis syndromes in children. Writing Group of the Histiocyte Society. Lancet. 1987;1:208–209.
2. Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol. 1999;17:3835–3849.
3. Howarth DM, Gilchrist GS, Mullan BP, Wiseman GA, Edmonson JH, Schomberg PJ. Langerhans cell histiocytosis: diagnosis, natural history, management, and outcome. Cancer. 1999;85:2278–2290.
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5. Grois N, Flucher-Wolfram B, Heitger A, Mostbeck GH, Hofmann J, Gadner H. Diabetes insipidus in Langerhans cell histiocytosis: results from the DAL-HX 83 study. Med Pediatr Oncol. 1995;24:248–256.
6. Job OM, Schatz NJ, Glaser JS. Visual loss with Langerhans cell histiocytosis: multifocal central nervous system involvement. J Neuroophthalmol. 1999;19:49–53.
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