2011-08-30

Metastatic carcinoma of the pituitary gland

A 71 year old woman presented with a 3 week history of weight loss, nausea, vomiting and severe depression. Physical examination disclosed no abnormalities. Her past medical and family history was unremarkable. Standard laboratory tests including electrolytes were normal. In order to detect the reason for her symptoms extensive diagnostic procedures (CT-Scans, endoscopy of the lower and upper GI-tract) were done, but no pathologic changes were found. Some weeks later she was admitted to the psychosomatic unit because of worsening depression and a drug therapy with mirtazepine was initiated. Repeated laboratory tests showed elevated levels of sodium, calcium, creatinine and severe diabetes insipidus. Increased PRL level (170,5 µg/l) was found, accompanied with decreased levels for ACTH, TSH, LH, FSH and low levels for cortisol and T3/T4. An MRI-Scan (Figure 1) was performed. Substitution therapy with hydrocortisone, thyroxin and desmopressin was started, rapidly improving the clinical symptoms of the patient.

Cytological examination (high power field oil immersion 1000x) of the cerebrospinal fluid (CSF) revealed atypical cells, suspicious of malignancy (Figure 2). Cell count was 15/µl. Ophthalmological, ENT and gynaecological examination including mammography and breast ultrasound could not detect any malignant lesion. Infectious causes such as toxoplasmosis, brucellosis and syphilis were ruled out.

Within several weeks MRI-scan showed a progression with compression of the third ventricle and leptomenigeal enhancement. The patient developed bilateral hemianopsia. She underwent craniotomy, with tumour resection. Histology analysis revealed a carcinoma with expression of estrogen receptor 2 and Cytokeratin 7 (CK7) suspicious of breast cancer. Due to progressive leptomenigeal carcinomatosis the clinical condition of the patient deteriorated rapidly and she died.

We report an uncommon manifestation of metastatic disease presenting with psychiatric symptoms due to panhypopituitarism. Due to the lack of tumour growth, the MRI-scan was initially misinterpreted as hypophysitis. Hypophysitis was first descripted in 1962 by Goudie et al.1. Literature describes four subtypes of hyphophysitis: granulomatous hypophysitis, necrotising hypophysitis, xanthomathous hyphophysitis and the most common form called lymphohistiocytic hypophysitis (LH). LH is an autoimmune disorder often related with other endocrine disorders such as Hashimoto thyreoiditis. More than 80% of the cases are restricted to female gender, often following pregnancy2. Diagnosis is established by MR – imaging 3 – with a few characteristic features such as infundiblar thickening, pituitary enlargement and pituitary necrosis  – followed by histologic examination. Rare cases of secondary hypophysitis due to bacterial infections (meningitis, syphilis, tuberculosis) or systemic disease (Wegener`s granulomatosis, sarcoidosis, Langerhans-cell histiocytosis, Rosai-Dorfmann-disease) have also been reported4.

In the literature metastatic disease of the pituitary gland followed by menigeosis carcinomatosa is not rare, but in most of the cases reported in advanced cancer 5-10. Only a few authors report pituitary gland metastases in otherwise occult carcinoma11. The most common primary tumour sites are breast, lung or the gastrointestinal tract, in many cases the primary tumour remains undetected. Diabetes insipidus is the most common symptom followed by cranial nerve palsy and anterior pituitary insufficiency. Non-specific symptoms such as nausea and vomiting are also common, whereas hyperprolactinemia is reported to occur in less than 10% of the patients 10. To establish the correct diagnosis imaging studies are important, but often are not helpful in distinguishing cancer from benign processes. Biopsy is required in all cases before starting therapy. Prognosis remains poor and depends on the primary cancer.

In our case the key stone for establishing the correct diagnosis was the presence of malignant cells in the cerebrospinal fluid despite low absolute cell count and initial MRI findings not typical for malignancy. Careful examination of CSF in patients with unknown cause of pituitary pathology is therefore recommended.

Bommer M.1*, Etzrodt-Walter G.2*, Struve S.1, Pauls S.3, Eggermann J. 1, Bühler G.2, Boehm B.O.2

1Department of Internal Medicine III (Hematology/Oncology), 2 Department of Internal Medicine I (Gastroenterology/Endocrinology), 3 Department of Diagnostic and Interventional Radiology
University Hospital of Ulm, Germany

*Both authors contributed equally to this work

References

1. Goudie RB, Pinkerton PH. Anterior hypophysitis and Hashimoto’s disease in a young woman. J Pathol Bacteriol. 1962;83:584-585.

2. Beressi N, Beressi JP, Cohen R, Modigliani E. Lymphocytic hypophysitis. A review of 145 cases. Ann Med Interne (Paris). 1999;150:327-341.

3. Sato N, Sze G, Endo K. Hypophysitis: endocrinologic and dynamic MR findings. AJNR Am J Neuroradiol. 1998;19:439-444.

4. Sautner D, Saeger W, Ludecke DK. Tumors of the sellar region mimicking pituitary adenomas. Exp Clin Endocrinol. 1993;101:283-289.

5. Ersoy R, Topaloglu O, Aydin C, Dirikoc A, Cakir B. Pituitary metastasis of breast cancer confirmed by fluorine-18 fluorodeoxyglucose positron emission tomography: a case report. J Endocrinol Invest. 2007;30:532-533.

6. Sturm I, Kirschke S, Krahl D, Dorken B. Panhypopituitarism in a patient with breast cancer. Onkologie. 2004;27:480-482.

7. Van de Velde A, Wassenaar H, Strubbe A, Janssen P, Verhaert G. Metastatic breast cancer presenting with diabetes insipidus. JBR-BTR. 2000;83:68-70.

8. Azambuja E, Piccart MJ, Awada A. Long-term survival in pituitary metastasis from breast cancer. Breast. 2006;15:446-447.

9. Kurkjian C, Armor JF, Kamble R, Ozer H, Kharfan-Dabaja MA. Symptomatic metastases to the pituitary infundibulum resulting from primary breast cancer. Int J Clin Oncol. 2005;10:191-194.

10. Komninos J, Vlassopoulou V, Protopapa D, et al. Tumors metastatic to the pituitary gland: case report and literature review. J Clin Endocrinol Metab. 2004;89:574-580.

11. Lin CS, Lin SH, Chiang YH, Sheu LF, Chao TY. Diabetes insipidus revealing an isolated pituitary stalk metastasis of breast cancer. Eur J Neurol. 2007;14:e11-12.

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