Pituitary metastases (PMs) from various malignancies are relatively rare clinical conditions occurring in 1-3% of cancer patients, and accounting for only 1% of resected pituitary tumors (1). Breast and lung cancers are the most common type of cancers to metastasize to the pituitary gland. In one case series, metastases from breast cancer and lung cancer accounted for 33% and 36% of PMs, respectively (2). Prostate, renal, thyroid, and gastrointestinal cancers, and hematologic malignancies have also been reported to be associated with PM (3). The majority of PM is clinically silent with one series showing that 7% were symptomatic (4). In symptomatic patients, diabetes insipidus (DI) due to posterior lobe involvement is the most common clinical presentation, and headache, visual symptoms, and ophthalmoplegia can also occur (2). A hypofunction of the anterior lobe alone or both anterior and posterior lobe hypofunctions are relatively rare. We, herein, present the case of a 35-year-old woman suffering from breast cancer, who developed both DI and anterior hypopituitarism two years after the initial diagnosis of breast cancer.
A 35-year-old woman presented with a gradually decreasing level of consciousness starting one day before the admission. The patient reported generalized fatigue, nausea, polyuria, and polydipsia for the past two weeks. She was drinking about 5 liters of water with a daily urine output of 5.5 liter. She had been diagnosed with infiltrating ductal adenocarcinoma of the right breast (estrogen receptor and progesterone receptor positive), and had right mastectomy followed by chemotherapy (taxotere, epirubicin) and hormone therapy (tamoxifen) two years previously. One year after right mastectomy, she had left mastectomy and she was given chemotherapy (cisplatin, navelbine, trastuzumab, lapatinib, and letrozole), tamoxifen, and radiotherapy because of the relapsed breast cancer in the contralateral breast. She was taking only tamoxifen for the past three months. On physical examination, blood pressure was 100/60 mmHg, pulse 90/min. Her consciousness was reduced with no other remarkable finding on neurological examination. Laboratory test results revealed that she had hypernatremia and hyposthenuria (plasma sodium: 154 mmol/L, urine density: 1001) (Table 1). On admission, a magnetic resonance imaging (MRI) of the pituitary region (Figure 1) revealed heterogeneous appearance of the pituitary gland with heterogeneous contrast uptake, thickening of the pituitary infundibulum (8 mm) with enhancement after the injection of contrast agent, and a loss of the normal hyperintense signal of the posterior pituitary on T1-weighted images. Although fluid restriction test could not be performed due to cognitive impairment, central DI was diagnosed based on the clinical signs (polydipsia, polyuria), negative water balance, low urine density, high plasma osmolality in relation with a very low urine osmolality (315 mOsm/kg and 110 mOsm/kg, respectively), and MRI findings. After she was given desmopressin nasal spray (10 μg twice daily), the symptoms of nausea, polyuria, and polydipsia disappeared and hypernatremia resolved. As shown in Table 1, hormonal evaluation revealed anterior hypopituitarism and hyperprolactinemia. She was treated with L-thyroxine (100 μg/day) and prednisolone (7.5 mg/day in divided doses morning and afternoon). Soon after the onset of the treatment, she reported a gradual resolution of her fatigue. Imaging studies showed liver and vertebrae metastases with multiple involvement. She underwent Gamma Knife radiosurgery and chemotherapy. The patient needed ongoing medical treatment for DI and hypopituitarism after these treatments. Because of breast cancer progression, she died six months later.
Breast cancer is one of the most common cancers. Bones, liver, and lungs are the typical sites for metastasis in breast cancer patients whereas the pituitary gland is rarely affected (5). One study revealed that 0.9% of patients had PM five years after the diagnosis of the breast cancer (6). Therefore, our patient demonstrates a rare pattern of breast cancer metastasis.
PM resulting from breast cancer is more common in elderly patients with widespread disease (2), as in our patient with multiple liver and bone metastases. Hormone receptor status of the breast tumor does not seem to influence the risk of PM (2). The most important path for the development of PM is hematogenous spread. The posterior lobe is the most affected site due to rich blood supply through the hypophyseal arteries. In one autopsy series including 88 patients with PM, the posterior lob was involved in almost 70% of cases, anterior lob in 13%, both anterior and posterior lobes in 12%, and infundibulum in 5% (4). Therefore, the main clinical symptoms are polyuria, nocturia, and polydipsia due to DI in most cases. If the patients with DI have intact thirst mechanism and free access to oral fluids, they may not present with hypernatremia (7). In addition to DI, laboratory results of our patient demonstrated a central hypothyroidism, hypocortisolism, hypogonadism, and low IGF-1 levels, which was consistent with anterior pituitary insufficiency. Hyperprolactinemia seen in our case was most consistent with disconnection hyperprolactinemia due to stalk metastasis. Although the diagnosis of PM was not confirmed by biopsy in our case, MRI findings (inhomogeneous pituitary gland, thickening of the infundibulum, loss of normal hyperintense signal of the posterior pituitary) and the presence of advanced breast cancer were suggestive of PM (8,9).
The treatment modalities for PM are surgery, radiotherapy, and systemic treatment with endocrine therapy or chemotherapy (10,11). Surgery is usually palliative. A hormone substitution with desmopressin for DI and pituitary hormone replacement treatment for anterior pituitary insufficiency are usually needed, and these treatments improve quality of life substantially, as seen in our case. Radiotherapy and Gamma Knife radiosurgery are also good options for relief of symptoms (12,13). Chemotherapy combined with radiotherapy is preferred in patients with diffuse malignant disease. Our patient required ongoing treatment for DI and hypopituitarism after treatments with Gamma Knife radiosurgery and chemotherapy. Breast cancer patients with PM have poor prognosis with a median survival time of six months, as was in our case. Multiple metastases, short period between diagnosis of the primary and secondary tumor, older age at the time of diagnosis are worse prognostic factors (2,14).
Although the pituitary gland is a less common site for breast cancer metastasis, it should be considered in patients with metastatic disease who are diagnosed with DI and, in rare cases, anterior pituitary insufficiency. Although patients with PM have poor prognosis, early detection and pituitary hormone replacement therapy can provide improvement in the symptoms of patients.
Informed Consent: Consent form was filled out by all participants, Peer-review: Externally peer-reviewed.
Concept: Ayşe Arduç, Design: Ayşe Arduç, Data Collection or Processing: Ayşe Arduç, Berçem Ayçiçek Doğan, Mazhar Müslüm Tuna, Analysis or Interpretation: Ayşe Gül Alımlı, Dilek Berker, Serdar Güler, Writing: Ayşe Arduç, Ayşe Gül Alımlı, Conflict of Interest: The authors declare no conflicting interests, Financial Disclosure: The authors have nothing to disclose.
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