Hepatocellular carcinoma metastasis to the brain mimicking primary pituitary tumor around the sella turcica

We report on two cases of hepatocellular carcinoma (HCC) with metastasis to the cavernous sinus and sphenoid sinus. Both cases presented with diplopia and retro-orbital headache and both underwent surgery for a primary pituitary gland tumor. After surgery, both cases were diagnosed with metastases from HCC. Case 1 was a 67-year-old male with a history of HCC who was referred to our hospital for pituitary tumor surgery. The tumor appeared to be in the sella turcica and to invade the sphenoid sinus and right cavernous sinus. Transnasal transsphenoidal surgery (TSS) was performed. The tumor was postoperatively diagnosed by histology to be a metastatic pituitary tumor from HCC. Radiotherapy was administered to the metastatic site. Case 2 was a 58-year-old male with a history of TSS for a pituitary tumor 16 years previously. He was referred to our hospital for TSS for a recurrent pituitary adenoma. TSS was performed twice in 3 months. During a preoperative general examination, HCC and chronic hepatitis B were revealed. TSS was performed initially, followed by arterial infusion chemotherapy. After TSS, the pituitary tumor was diagnosed by histology to be a metastasis from HCC. As with Case 1, radiotherapy was administered to the metastasis. Most tumors in the sella turcica are pituitary adenomas, although some cases of metastatic pituitary tumors and skull base metastases have been reported. Distant metastases generally have a poor prognosis; however, surgery to the metastatic site can effectively control symptoms caused by the metastatic tumor.     

Long-term survival with ACTH-secreting carcinoma of the pituitary: a case report and review of the literature

A 48-yr-old woman was evaluated 21 yr after receiving treatment for an ACTH-secreting metastatic pituitary carcinoma. She had been diagnosed with Cushing's disease 35 yr earlier at the age of 14 yr and had undergone bilateral adrenalectomy. Six years later she developed Nelson's syndrome, which was treated with resection of a pituitary adenoma followed by radiotherapy to the sella turcica. Eight years later she was found to have craniospinal metastases with three remote intracerebral lesions. Two of these lesions were surgically resected and stained positive for ACTH by immunofluorescence. She subsequently received whole-brain radiotherapy and is doing well 21 yr later with no lesions seen on magnetic resonance imaging and no evidence of recurrent metastatic disease. We present this case in detail along with a literature review of ACTH-secreting pituitary carcinoma.     

Multifocal fibrosclerosis as a possible cause of panhypopituitarism with central diabetes insipidus

Multifocal fibrosclerosis denotes a combination of similar fibrous disorders occurring at different anatomical sites. We encountered a 53-year-old male patient with orbital pseudotumor, chronic paranasal sinusitis, fibrous nodules of the lungs, intracranial pachymeningitis, and panhypopituitarism with central diabetes insipidus (DI) as a possible manifestation of multifocal fibrosclerosis. It has been reported that intracranial pachymeningitis or orbital pseudotumor associated with multifocal fibrosclerosis could invade the sella turcica causing a variety of anterior and/or posterior pituitary dysfunctions. In our case, intracranial pachymeningitis apparently involved the pituitary stalk and gland. Isolated gonadotropin deficiency, in addition to central DI, preceded panhypopituitarism. Although panhypopituitarism with central DI due to multifocal fibrosclerosis is quite rare and only one case has ever been reported, this systemic fibrotic disorder can be a possible cause of panhypopituitarism with central DI.     

Supra- and extrasellar pituitary microadenoma as a cause of Cushing's disease.

There has been accumulating evidence that pituitary adenomas which cause Cushing's disease are located not only in sella turcica but also in various extrasellar and intracranial regions. We describe a case of Cushing's disease caused by a supra- and extrasellar ACTH-producing microadenoma, which originated in the anterior pituitary and extended upward without connecting to the stalk. The pituitary microadenoma was identified and removed by transsphenoidal microsurgery. After the surgery the patient experienced complete remission. This type of pituitary microadenoma is considered to be rare, but in order to accomplish successful surgical treatment, it is necessary to consider that pituitary adenomas which cause Cushing's disease may be located in such an unusual position.     

Formation of a direct arterial blood supply to the anterior pituitary gland following complete or partial interruption of the hypophyseal portal vessels

If regions of the anterior pituitary gland received systemic blood via a direct arterial blood supply these regions would escape hypothalamic regulation and thus be a sequela in endocrine disorders. Since, in the untreated rat, all of the blood supply to the anterior pituitary gland is via the hypophyseal portal vessels, we hypothesized that partial interruption of the portal vessels could provoke the establishment of a direct arterial blood supply (arteriogenesis). We utilized the injection of polystyrene microspheres (15 or 9 micron diameter) into the left ventricle of the heart to test this hypothesis. Microspheres are trapped in the first capillary plexus they reach since they are too large to traverse the capillaries. No microspheres reached the anterior pituitary gland of control rats, a finding consistent with the fact that the anterior pituitary gland receives all of its blood supply via the hypophyseal portal blood vessels. Microspheres were observed in the primary portal capillary plexus in the infundibulum (median eminence), infundibular stalk (pituitary stalk), and infundibular process (pars nervosa), the first capillary plexus which they reached. A lesion of the medial basal hypothalamus (MBH) which destroyed the long portal vessels did not result in arteriogenesis since few, if any, microspheres were observed in the anterior pituitary gland. We confirmed, using vascular casts, that these lesions resulted in the long-term destruction of the primary portal capillaries in the infundibulum and of the long portal vessels. In MBH-lesioned animals it appears that all of the blood supply of the anterior pituitary gland is via short portal vessels arising from the infundibular stem and process.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diabetes insipidus and breast cancer.

Diabetes insipidus, resulting from metastatic involvement of the neurohypophysial system, is a rare complication of breast cancer. This review examined the clinical features, metastatic pattern, and radiological and postmortem findings of 39 breast cancer patients with this complication. All patients had polyuria and polydipsia, and all had evidence of advanced metastatic breast cancer. A high incidence of meningeal carcinoma carcinomatosis and/or sellar metastases was observed. In view of the anatomical proximity of the posterior pituitary to the dura mater and the sella turcica, our findings suggest that metastases to the neurohypophysis can occur not only as a result of hematogenous dissemination of malignant cells, but also from direct tumor extension and/or invasion from adjacent structures. Although satisfactory symptomatic relief can be obtained with vasopressin tannate, complete resolution of the diabetic insipidus syndrome was evident only in those patients who had achieved control of the underlying breast disease.     

Acromegaly and somatotroph hyperplasia with adenomatous transformation due to pituitary metastasis of a growth hormone-releasing hormone-secreting pulmonary endocrine carcinoma

CONTEXT: GHRH excess from extracranial endocrine tumors is known to cause somatotroph hyperplasia and acromegaly. Hypothalamic gangliocytomas producing GHRH are also known to be associated with pituitary adenomas causing acromegaly. OBJECTIVES: The objective of this study was to describe a case of acromegaly due to a pulmonary GHRH-secreting endocrine carcinoma with metastasis to the pituitary gland and to look at the peculiar histological features of this case. SUBJECT: The patient was a 44-yr-old woman who was diagnosed with a biopsy-proven metastatic pulmonary endocrine tumor during pregnancy. After delivery, she underwent radiation and chemotherapy for pulmonary and skeletal metastases. Her disease was clinically stable for 7 yr until she developed bitemporal hemianopia. She had symptoms and signs of acromegaly. METHODS: Imaging, biochemical, and histological studies were performed. RESULTS: Magnetic resonance imaging (MRI) of the brain confirmed the presence of a 2.6-cm lesion within the sella turcica extending above the sella and compressing the optic chiasm. Endocrine studies showed elevated serum levels of GH, prolactin, alpha-subunit of glycoprotein hormones, IGF-I, chromogranin A, and GHRH. The patient underwent uneventful transsphenoidal resection of the sellar tumor. Postoperatively, she noted an improvement in symptoms of acromegaly. Histological examination confirmed metastatic endocrine carcinoma to the pituitary, and immunohistochemistry localized GHRH to the tumor cells. The adjacent pituitary exhibited somatotroph hyperplasia with abundant reactivity for GH and alpha-subunit. In addition, there was focal neoplastic transformation to a sparsely granulated somatotroph phenotype with fibrous bodies. CONCLUSION: This is the first report of a GHRH-producing endocrine tumor metastasizing to the pituitary and causing local hyperstimulation with somatotroph hyperplasia and adenomatous transformation.     

Post traumatic pituitary apoplexy with contiguous intra cerebral hematoma operated through endonasal route—a case report

Pituitary apoplexy is a clinical syndrome occurring as a consequence of fulminant expansion of pituitary tumor due to massive infarction, necrosis, and hemorrhage. Its association with head injury is rare and only few reports are available. Shear forces on stalk and arterial vasospasm have been proposed to be the possible reasons. The clinical picture is characterized by sudden onset headache, visual symptoms, multiple cranial nerves involvement, meningismus, altered mental status, and hormonal dysfunction. Transsphenoidal decompression is the standard treatment but suprasellar and widespread extension of hematoma may need intracranial approach. We are reporting a rare association of head injury with pituitary apoplexy, where endonasal surgery proved to be a simple useful approach to evacuate contiguous intra-cerebral hematoma with excision of apoplectic pituitary adenoma.     

Symptomatic pituitary metastases from renal cell carcinoma

Symptomatic metastases to the pituitary (MP) from renal cell carcinoma (RCC) are rare. In this largest case series reported, we describe the clinical features, treatment and outcome of 5 patients. Over a 6-year period (2000–2006), we treated 5 patients (3 males; mean age 61 years) with large sellar masses and RCC. Four patients had a history of RCC, while in one, RCC was diagnosed after surgery. RCC was diagnosed a median of 11 years prior to diagnosis of MP (range 0–27 years). Four patients had previously developed distant metastases. Clinical presentation included bitemporal hemianopia (3 patients), lethargy (3), headaches (2) and diabetes insipidus (DI) (2). Panhypopituitarism was present in 3 patients and the other two had deficiency of at least ACTH and gonadotropin axes. Elevated prolactin was seen in 3 patients. MRI showed an enhancing sellar mass with suprasellar extension and chiasmal compression in all; prominent vascular flow voids were seen in 2. Three patients underwent transsphenoidal surgery and radiation, while 2 underwent radiotherapy alone. Four patients are alive (follow up 6–46 months); 1 patient died due to systemic metastases at 12 months. Metastases to the pituitary from RCC cause more severe hypopituitarism and visual dysfunction compared to those from other primaries, whereas DI is less common. MRI shows contrast enhancement, stalk involvement, sclerosis and/or erosion of sella and presence of vascular flow voids. Combined treatment using decompressive surgery and stereotactic radiotherapy may result in better outcomes.     

Suprasellar Germinoma Masquerading As Lymphocytic Hypophysitis Associated With Central Diabetes Insipidus,Delayed Sexual Development,and Subsequent Hypopituitarism

We report the case of an 18-year-old woman with suprasellar germinoma masquerading as lymphocytic hypophysitis, which was associated with central diabetes insipidus, delayed sexual development, and hypopituitarism. Magnetic resonance imaging revealed an enlarged pituitary gland, thickened pituitary stalk, and a mass lesion in the inferior hypothalamus; these findings are typical of lymphocytic hypophysitis. Despite the administration of prednisolone therapy for 3 months, an enlarged irregular cystic mass lesion developed in the pituitary stalk and inferior hypothalamus. Open cranial surgery of the posterior pituitary revealed the presence of a germinoma. Therefore, chemotherapy and stereotactic radiation therapy were administered, resulting in complete remission of the germinoma. This case illustrates that the presence of an intrasellar mass lesion in association with pituitary stalk thickening can often cause difficulties in differential diagnosis. We believe that lymphocytic hypophysitis in pubertal children may be the first sign of a host reaction to an occult germinoma.     

Lymphoma Metastasizing to the Pituitary: An Unusual Presentation of a Treatable Disease

Lymphoma involving the pituitary gland is particularly rare. We present two cases of patients with pituitary lymphoma, both of whom were symptomatic from pituitary dysfunction. The first patient demonstrated pituitary involvement on imaging, with mild biochemical diabetes insipidus but clear hypoadrenalism. Both adrenals were grossly enlarged on CT scanning and biopsy of one of the adrenal masses confirmed the diagnosis of diffuse large B cell lymphoma. The second patient presented with clinical diabetes insipidus but with no obvious abnormalities on pituitary imaging. CT scanning of abdomen and pelvis, however, revealed widespread lymphadenopathy. Lymph node biopsy revealed a T cell-rich B cell lymphoma. Review of the English-language literature of all published cases of pituitary lymphoma in the presence of generalised disease in immunocompetent patients revealed 13 cases. Most patients had large B cell non-Hodgkin's lymphoma. Involvement of the anterior lobe of the pituitary was more frequently seen than in patients developing pituitary metastases from solid tumour primaries. Patients with advanced lymphoma including the pituitary also appear to have a better prognosis than patients presenting with pituitary metastases. This is an important diagnosis to make as rapidly as possible to allow the early institution of effective therapy.     

以尿崩症为首发表现的肺癌伴垂体转移六例临床分析

目的通过对以尿崩症为首发表现的肺癌垂体转移患者的临床资料分析,总结其临床特点,提高对尿崩症和垂体转移性肿瘤的认识和诊治水平。方法回顾性分析6例肺癌伴有垂体转移患者的临床和随诊资料,分析和探讨肺癌垂体转移的临床特点、诊断和治疗。结果6例患者平均年龄57·5岁。除垂体转移以外,还有其他多个部位转移。转移病灶多累及垂体后叶和垂体柄,常以尿崩症为首发表现和就诊原因,鞍区MRI可以出现特征性改变。伴有不同程度的垂体前叶功能减退。结论肺癌是引起垂体转移肿瘤的常见原因之一,以转移到垂体后叶多见。对于中老年新出现的中枢性尿崩症,应该重视系统性疾病的影响,寻找可能的原发肿瘤。     

Intracranial dissemination of an ACTH secreting pituitary neoplasm--a case report and review of the literature.

A 52-year-old woman developed recurrent hypercortisolism 3 yr after successful surgical treatment of Cushing's disease. At postmortem, eosinophilic pituitary tissue showing positive ACTH immunohistochemical staining was present in the frontal lobe and cerebellum but there was no tumor in the sella. In the absence of a pituitary tumor, extrasellar ACTH producing tissue could arise from seeding of the cerebrospinal fluid with tumor cells at the time of operation or from an atypical pituitary carcinoma. In this report we review the mechanisms of intracranial dissemination of pituitary tissue and ACTH-secreting pituitary carcinomas, including parasellar invasion, meningeal seeding, and cerebrospinal and hematogenous spread.     

Extrapituitary parasellar microadenoma in Cushing's disease.

Negative sellar exploration (despite the results of endocrine evaluation indicating Cushing's disease), the high incidence of failure of total hypophysectomy, and remission of Cushing's syndrome after unsuccessful hypophysectomy and sellar irradiation suggest that the etiology of refractory Cushing's disease, in some patients, lies near the sella but not in the pituitary gland. We present 5 patients, out of 626 who received surgery for Cushing's disease, in whom an ACTH-secreting extrapituitary parasellar adenoma was identified: 2 after unsuccessful total hypophysectomy for the treatment of refractory Cushing's disease, 2 after unsuccessful hemihypophysectomy (the first, 2 yr before treatment at the NIH for Nelson's syndrome; and the second, with recurrent Cushing's disease 5 yr after negative transsphenoidal exploration), and 1 with a preoperative diagnosis of an intraclival microadenoma, which was cured by resection of the tumor. In all cases, an extrapituitary parasellar microadenoma was confirmed unequivocally as the cause of the disease, by negative pathology of the resected pituitary gland (patients 1, 2, 3, and 5), and/or the remission of the disease after selective resection of the extrasellar adenoma (patients 3, 4, and 5). Three of 5 patients had a partial empty sella. These patients support the thesis that ACTH-secreting tumors can arise exclusively from remnants of Rathke's pouch, rather than from the adenohypophysis (anterior lobe or pars tuberalis of the pituitary gland) and can be a cause of Cushing's disease. In the sixth presented case, an extrapituitary tumor was suspected at surgery after negative pituitary exploration, but serial sections of the hemihypophysectomy specimen revealed a microscopic focus of tumor at the margin of the resected gland. This case demonstrates the importance of negative pituitary histology to establish the presence of an extrapituitary parasellar tumor as an exclusive source of ACTH, and it supports the value of clinical outcome to establish the diagnosis with selective adenomectomy of an extrapituitary parasellar tumor. In patients with negative pituitary magnetic resonance imaging, especially in the presence of a partial empty sella, the diagnostic and surgical approach in Cushing's disease should consider the identification and resection of extrapituitary parasellar adenoma, which can avoid total hypophysectomy, as was possible in 3 of our 5 patients.     

Isolated thyrotropin deficiency secondary to primary empty sella in a patient with differentiated thyroid carcinoma: an indication for recombinant thyrotropin.

The primary empty sella syndrome is a common radiographic finding that is rarely associated with clinical pituitary dysfunction. Studies using dynamic endocrine testing, however, have shown altered pituitary reserve in some patients with the primary empty sella syndrome. We describe a patient with a primary empty sella and an isolated deficiency of thyrotropin reserve. This case is complicated by the presence of an aggressive metastatic papillary epithelial carcinoma of the thyroid. Standard treatment with radioactive iodine was unlikely to be effective in this patient due to the need for adequate thyrotropin (TSH) stimulation of the malignant tissue to optimize uptake of radioactive iodine by the tumor cells. Consequently, this patient was treated with human recombinant TSH before receiving radioactive iodine. The utility of this novel therapeutic agent and a review of hormonal abnormalities associated with the primary empty sella are also discussed.     

The sella turcica in Sheehan's syndrome: computerized tomographic study in 54 patients

A CT scan study of the sella turcica and its contents was conducted in patients with Sheehan's syndrome with a search for correlation between the radiological data and the degree of endocrine insufficiency on one hand, and the time course of the disease on the other. Fifty-four patients with Sheehan's syndrome were included: 32 with complete anterior hypopituitarism, 22 with at least one spared pituitary function. Subgroups of equal size were obtained with a cut-off of 9 years evolution. The CT scan appearance of the pituitary was never normal in Sheehan's syndrome. The sella turcica was totally empty in 39 patients. A pituitary remnant was visible in 15 patients, more frequently in those with incomplete hypopituitarism (p less than 0.005) and those with short evolution (p less than 0.025). The size of this pituitary residue never exceeded one third of the normal pituitary gland. The pituitary stalk was always visualized. On the other hand, the size of the fossa was significantly (p less than 0.001) smaller in the patients, as compared to a 12-female control group, matched for age and number of pregnancies. Among the patients there was no difference when considering the disease duration nor the degree of hypopituitarism. An empty or partially empty sella of normal or reduced size is a constant feature of Sheehan's syndrome. The presence of a pituitary remnant is inversely correlated to the duration and extension of the disease. Arachnoid herniation alone does not induce a dilatation of the fossa.     

Acromegaly with negative pituitary MRI and no evidence of ectopic source: the role of transphenoidal pituitary exploration?

Growth hormone (GH) producing adenomas of the pituitary gland are usually macroadenomas (>10 mm in size). Often these adenomas are locally invasive by the time of diagnosis. Acromegaly secondary to a very small pituitary microadenoma not visualized on pituitary magnetic resonance (MR) imaging is rare. We report a patient with acromegaly and an unremarkable pituitary MR imaging who had negative work up for ectopic growth hormone-releasing hormone (GHRH) or GH secreting tumors. Transsphenoidal pituitary exploration revealed a pituitary adenoma located on the left side of the sella against the medial wall of the cavernous sinus extending posteriorly along the floor of the sella all the way to the right side. The acromegaly was treated with resection of the pituitary adenoma and normalization of serum insulin-like growth factor 1 (IGF-1) and GH levels. In a patient with acromegaly and unremarkable pituitary MR imaging, with no evidence of ectopic GH and GHRH production, transsphenoidal pituitary exploration is a reasonable approach and may result in clinical improvement and biochemical cure in the hand of experienced surgeon. This approach may avoid long term medical treatment with its associated cost.     

Hypopituitarism and diabetes insipidus with localized hypertrophic pachymeningitis (Tolosa-Hunt syndrome) associated with Hashimoto thyroiditis

We report a 69-year-old woman with intracranial pachymeningitis showing hypopituitarism, diabetes insipidus, and Tolosa-Hunt syndrome associated with Hashimoto thyroiditis confirmed by autopsy. A large tumorous lesion of the hypothalamo-pituitary gland was revealed on magnetic resonance imaging, after the patient complained of gait and visual field disturbance. These symptoms subsided after thyroid hormone supplementation. Hypopituitarism and diabetes insipidus were diagnosed after cessation of the treatment by the patient herself. Multiple cranial nerve palsies and orbito-frontalgia appeared. Methylprednisolone pulse therapy improved the symptoms, but they recurred when the dose of glucocorticoid was decreased. The patient died of brain thrombosis. Autopsy revealed typical findings of Hashimoto thyroiditis and intracranial pachymeningitis involving the cranial base and pituitary gland. The high titer of rheumatoid factor and Hashimoto thyroiditis in this patient suggest an immunological role in the pathogenesis of pachymeningitis.     

Diabetes insipidus--diagnosis and management

Central diabetes insipidus (CDI) is the end result of a number of conditions that affect the hypothalamic-neurohypophyseal system. The known causes include germinoma/craniopharyngioma, Langerhans cell histiocytosis (LCH), local inflammatory, autoimmune or vascular diseases, trauma resulting from surgery or an accident, sarcoidosis, metastases and midline cerebral and cranial malformations. In rare cases, the underlying cause can be genetic defects in vasopressin synthesis that are inherited as autosomal dominant, autosomal recessive or X-linked recessive traits. The diagnosis of the underlying condition is challenging and raises several concerns for patients and parents as it requires long-term follow-up. Proper etiological diagnosis can be achieved via a series of steps that start with clinical observations and then progress to more sophisticated tools. Specifically, MRI identification of pituitary hyperintensity in the posterior part of the sella, now considered a clear marker of neurohypophyseal functional integrity, together with the careful analysis of pituitary stalk shape and size, have provided the most striking findings contributing to the diagnosis and understanding of some forms of 'idiopathic' CDI. MRI STIR (short-inversion-time inversion recovery sequencing) is a promising technology for the early identification of LCH-dependent CDI.     

Hypothalamitis: a diagnostic and therapeutic challenge

To report an unusual case of biopsy-proven autoimmune hypophysitis with predominant hypothalamic involvement associated with empty sella, panhypopituitarism, visual disturbances and antipituitary antibodies positivity. We present the history, physical findings, hormonal assay results, imaging, surgical findings and pathology at presentation, together with a 2-year follow-up. A literature review on the hypothalamic involvement of autoimmune hypophysitis with empty sella was performed. A 48-year-old woman presented with polyuria, polydipsia, asthenia, diarrhea and vomiting. The magnetic resonance imaging (MRI) revealed a clear suprasellar (hypothalamic) mass, while the pituitary gland appeared atrophic. Hormonal testing showed panhypopituitarism and hyperprolactinemia; visual field examination was normal. Pituitary serum antibodies were positive. Two months later an MRI documented a mild increase of the lesion. The patient underwent biopsy of the lesion via a transsphenoidal approach. Histological diagnosis was lymphocytic “hypothalamitis”. Despite 6 months of corticosteroid therapy, the patient developed bitemporal hemianopia and blurred vision, without radiological evidence of chiasm compression, suggesting autoimmune optic neuritis with uveitis. Immunosuppressive treatment with azathioprine was then instituted. Two months later, an MRI documented a striking reduction of the hypothalamic lesion and visual field examination showed a significant improvement. The lesion is stable at the 2-year follow-up. For the first time we demonstrated that “hypothalamitis” might be the possible evolution of an autoimmune hypophysitis, resulting in pituitary atrophy, secondary empty sella and panhypopituitarism. Although steroid treatment is advisable as a first line therapy, immunosuppressive therapy with azathioprine might be necessary to achieve disease control.