This is a case of thalamic and pituitary metastasis from breast cancer with accompanying central DI and panhypopituitarism, from which two learning points can be derived. First, an invasive intervention, specifically stereotactic biopsy in this study, may induce pituitary dysfunction. Second, central DI is masked by comorbid ACTH insufficiency.
Numerous reports have indicated that metastasis to the pituitary gland is rare [1, 2, 4, 5]. Specifically, pituitary metastases accounted for 0.4–0.87% of intracranial metastases [6, 7]. While pituitary adenomas accounted for 84.6% of pituitary tumors, pituitary metastases occurred in 0.6% of cases . Literature reviews for pituitary metastases showed that primary symptoms are visual involvement (49–62%), panhypopituitarism (38%), and DI (28–38%) [1, 9]. However, the frequent absence of symptoms makes diagnosis difficult, which delays detection of early-stage disease . The primary malignant disease usually manifests first, followed by incidental detection of pituitary metastasis on imaging . In this study, the primary malignancy was the breast cancer, reportedly one of the most common primary cancers for pituitary metastases [1, 7].
In this case, thalamic metastasis, as opposed to pituitary metastasis or the primary malignancy, caused the primary manifestation and chief complaint (that is, skilled movement disorder). The pituitary metastasis was asymptomatic before the biopsy surgery. As postoperative DI has been observed in 10.2% of endoscopic transsphenoidal surgery , the thalamic metastasis, as opposed to the pituitary metastasis, was selected as a biopsy target to preserve pituitary function. Nonetheless, postoperative pituitary dysfunction was observed, as evidenced by the unexpected DI and panhypopituitarism. Due to the probability that asymptomatic pituitary metastases could become symptomatic after an invasive intervention, regular monitoring for signs of possible pituitary dysfunction is important.
Another factor that delayed diagnosis and treatment in this case was masked DI. Central DI results from deficient ADH synthesis or secretion, and its most common causes of central DI are benign or malignant neoplasms of the HPA . Patients with central DI commonly present with polyuria and polydipsia. They may also suffer from severe dehydration and hypernatremia in cases of insufficient fluid intake. The symptoms and laboratory studies related to DI are masked by concomitant ACTH deficiency. Several reasons underlying masked DI have been proposed. Adrenal insufficiency impairs renal free water clearance . It may also upregulate corticotropin-releasing hormone (CRH), which stimulates both ADH and ACTH . Finally, since cortisol induces ADH resistance of the V2 receptor, adrenal insufficiency may amplify the ADH effects .
In this study, upon initiation of glucocorticoid replacement therapy, DI symptoms, such as polyuria, appeared. Therefore, the normal plasma sodium levels and daily urinary output observed until glucocorticoid replacement were due to masked DI. Glucocorticoid replacement is effective for the diagnosis of masked DI because glucocorticoid replacement increases the sensitivity for diagnosis in cases of pituitary metastasis . The fatigue and lethargy experienced by the patient after the biopsy surgery might be related to panhypopituitarism because these symptoms are common complaints among patients with this condition . In pituitary metastases, even in asymptomatic cases, physicians should not overlook these nonspecific symptoms. Prolonged fatigue and lethargy in cases of pituitary metastases could be a potential warning sign of masked DI and should be monitored to avoid misdiagnosis and delayed treatment.
Another case report of pituitary metastasis discussed severe hyponatremia, which was induced by secondary adrenal insufficiency accompanied by DI . In this case, a decreasing trend in plasma sodium levels was observed. Our patient may have suffered from hyponatremia if glucocorticoid replacement therapy had not been administered.
Previous studies have reported that most pituitary metastases occur in the posterior lobe [1, 2]. This could be because direct perfusion from the inferior hypophyseal arteries into the posterior lobe might increase the likelihood of metastasis to the posterior lobe rather than the anterior lobe, which is indirectly perfused . Moreover, this may account for the reports that DI is more common in pituitary metastases compared with other pituitary pathologies . The key MRI findings related to DI are the absence of the normal T1 PPBS, as well as enhancement and thickening of the pituitary stalk . In our case, we observed similar MRI findings before DI was detected. In retrospect, this should have been recognized as a sign of DI and should have prompted more thorough assessments and earlier treatment.
There are no standardized treatment guidelines for the management of pituitary metastases . Although surgery for pituitary metastasis facilitates symptomatic relief for optic pathway compression, it does not impact survival [2, 7]. Conversely, survival was positively impacted by radiotherapy and chemotherapy . A previous study demonstrated that there was no significant difference in estimated survival between radiation methods, such as conventional multiple fractionated radiation, Gamma Knife, and Cyberknife . However, some studies have reported that stereotactic radiotherapy leads to improved survival compared with conventional radiotherapy , as well as improvements in DI and neurological symptoms [17, 18]. However, we chose to perform conventional multiple fractionated radiation because peritumoral edema of the right thalamus lesions progressed into the brainstem and the edema could have worsened after stereotactic radiotherapy . The patient also underwent breast radiation therapy in combination with administration of oral molecularly targeted and cyclin-dependent kinases 4/6 inhibitor therapy.
The mean survival period after detecting pituitary metastasis is 10–14 months [1, 7]. In cases managed with conventional multiple fractionated radiation , such as in this case, the mean survival period is 10 months. Overall survival was significantly longer in recent studies than in studies before 2010 . This may be due to advances in neuroimaging and oncological therapies, which facilitated more timely diagnoses and improved treatments. Therefore, for earlier diagnosis and efficient management in rare cases such as in this report, careful monitoring by a multidisciplinary team is required.
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