Sellar germinoma mimicking IgG4-related hypophysitis: a case report

Background The differential diagnosis of IgG4-related hypophysitis and other inflammatory diseases or tumors involving sellar region is challenging even after sellar biopsy. Sellar germinoma is usually infiltrated by lymphocytes or plasma cells, and may be confused with hypophysitis. Case presentation A 36-year-old man with diabetes insipidus, elevated serum IgG4 level (336 mg/dl), and sellar mass was suspected to have IgG4-related hypophysitis, and no other lesion of IgG4-related disease was detected. After treated by prednisone and mycophenolate mofetil, the serum IgG4 decreased to 214 mg/dl. However, after withdrawal of the drugs, the IgG4 level increased to 308 mg/dl. Endocrine assessments revealed panhypopituitarism, and the sellar mass enlarged. Transsphenoidal sellar exploration and biopsy was conducted. Pathological examination showed that the lesion was germinoma with lymphocytes and plasma cells infiltration, and IgG4-staining was positive (70/HPF, IgG4/IgG ratio = 10%). The patient was then treated by cisplatin and etoposide. After four cycles of chemotherapy, the serum IgG4 was 201 mg/dl, and the sellar mass was invisible. Conclusion Sellar germinoma can mimic the clinical characteristics of IgG4-related hypophysitis. Poor response to glucocorticoids can be used as an exclusion criterion in the clinical diagnosis of IgG4-related hypophysitis.

Pituitary Apoplexy Complicated by Cerebral Infarction: A Case Report

Cerebral infarction is a rare complication of pituitary apoplexy, which can result in significant morbidity if not treated on time. Pituitary apoplexy mostly occurs in pre-existing adenoma, which can remain undiagnosed until symptoms arise. Here, we present a case of a 26-year-old man with undiagnosed acromegaly who presented with left retro-orbital pain, diminished vision of the left eye, and right hemiparesis. Neuroimaging revealed large hemorrhagic sellar mass and ischemic infarction in the left middle cerebral artery territory. Emergency transcranial tumor excision was done, which resulted in significant neurological recovery.

Pituitary microadenoma with hypopituitarism presenting as hyponatremia

The incidence of pituitary adenoma has been increasing these days. Majority of the cases are incidental findings on imaging; and these patients may be asymptomatic without any laboratory abnormalities. However, a non-functional sellar mass can initially present with hypopituitarism. The patient being described is an elderly female who presented with severe hyponatraemia. She has history of recurrent admissions for hyponatraemia in the past. Her biochemical evaluation revealed hypopituitarism and magnetic resonance imaging of brain showed pituitary microadenoma. Hyponatraemia as a presenting feature of hypopituitarism due to pituitary microadenoma is an uncommon scenario.

A case report of lymphocytic hypophysitis

Background: Lymphocytic hypophysitis (LH) is a rare condition that mostly affects women of the reproductive age. Because it is infrequently encountered, it is not often considered as a differential diagnosis of sellar masses. The diagnosis is made clinically with the aid of magnetic resonance imaging (MRI) and should be considered if the patient has endocrine derangements in addition to a sellar mass. Case Description: A 37-year-old female presents with a complaint of headaches and CT imaging showed a sellar mass. She was also being investigated simultaneously by the endocrine department and was diagnosed with panhypopituitarism. She proceeded to surgery for a presumed pituitary adenoma but histopathology returned as LH. Conclusion: It is important to have a wide differential diagnosis when managing pituitary masses. Clinical correlation with atypical MRI findings is useful to determine the diagnosis of LH.

A woman with visual loss, amenorrhoea and polyuria: the first reported case of nodular lymphocyte-predominant Hodgkin lymphoma presenting with hypopituitarism

Summary A 34-year-old woman presented 18 months post-partum with blurred vision, polyuria, amenorrhoea, headache and general malaise. Comprehensive clinical examination showed left superior temporal visual loss only. Initial investigations revealed panhypopituitarism and MRI demonstrated a sellar mass involving the infundibulum and hypothalamus. Lymphocytic hypophysitis was suspected and high dose glucocorticoids were commenced along with desmopressin and thyroxine. However, her vision rapidly deteriorated. At surgical biopsy, an irresectable grey amorphous mass involving the optic chiasm was identified. Histopathology was initially reported as granulomatous hypophysitis. Despite the ongoing treatment with glucocorticoids, her vision worsened to light detection only. Histopathological review revised the diagnosis to partially treated lymphoma. A PET scan demonstrated avid uptake in the pituitary gland in addition to splenic involvement, lymphadenopathy above and below the diaphragm, and a bone lesion. Excisional node biopsy of an impalpable infraclavicular lymph node confirmed nodular lymphocyte-predominant Hodgkin lymphoma. Hyper-CVAD chemotherapy was commenced, along with rituximab; fluid-balance management during chemotherapy (with its requisite large fluid volumes) was extremely complex given her diabetes insipidus. The patient is now in clinical remission. Panhypopituitarism persists; however, her vision has recovered sufficiently for reading large print and driving. To the best of our knowledge, this is the first reported case of Hodgkin lymphoma presenting initially as hypopituitarism. Learning points Lymphoma involving the pituitary is exceedingly rare and, to the best of our knowledge, this is the first reported case of nodular lymphocyte-predominant Hodgkin lymphoma presenting as hypopituitarism. There are myriad causes of a sellar mass and this case highlights the importance of reconsidering the diagnosis when patients fail to respond as expected to appropriate therapeutic intervention. This case highlights the difficulties associated with managing panhypopituitary patients receiving chemotherapy, particularly when this involves large volumes of i.v. hydration fluid.

A Case of Silent Corticotroph Adenoma

Background: Silent Corticotroph Adenomas (SCAs) are tumors with no biochemical or clinical features consistent with hypercortisolism but have positive immunostaining for ACTH. They account for approximately 1.1-6% of all pituitary adenomas and 5.5% of nonfunctioning adenomas. Clinical Case: A 49-year-old woman presented to clinic with a 6-month history of headache, vision changes, fatigue, hair thinning, brittle nails, lightheadedness, polydipsia, easy bruising, increased appetite, and weight gain of 178 pounds in 2 years. Labs obtained: morning cortisol 10 mcg/dl(7-25 mcg/dl), ACTH 59 pg/ml(7.2-63 pg/ml), IGF-1 96 ng/ml(52-328 ng/ml), LH 0.2 mIU/ml(1.9-12.5 mIU/ml), FSH 0.8 mIU/ml(2.5-10.2mIU/ml), alpha subunit <0.1 ng/ml(52-328 ng/ml), TSH 0.991 uIU/ml(0.358-3.74 uIU/ml), free T4 1.12 ng/dl(0.76-1.46 ng/dl), salivary cortisol 66 ng/dl(<100 ng/dl), 24-hour urine cortisol 10 mcg/24hr(3.5-45 mcg/24hr) and prolactin 64.3 ng/ml(2.8-29.2 ng/ml). No hook effect noted with serial dilution. MRI brain showed a 22 x 29 x 26 mm sellar mass extending into the suprasellar cistern displacing and compressing the optic nerves and chiasm superiorly with partial invasion into the right cavernous sinus. She had an endoscopic resection of the sellar mass. She developed diabetes insipidus post-operatively and required desmopressin transiently. In the immediate post-operative period, morning cortisol and ACTH were 16.9 ug/dl(6.2-19.4 ug/dL) 24.8 pg/ml(7.2-63.3 pg/ml) respectively. She was sent home without steroids. Pathology showed a staining pattern consistent with pituitary adenoma with positive staining for ACTH. One month after her surgery she was admitted with symptoms of orthostatic hypotension. Cortisol at 5pm was 3 ug/dl(2.3-11.9 ug/dl), ACTH 31.7 pg/ml(7.2-63.3pg/ml). She had a cosyntropin stimulation test done with peak cortisol of 19.3 ug/dl at 60 minutes. Due to her symptoms, she was started on oral hydrocortisone (HC) for secondary adrenal insufficiency (AI), but was eventually tapered off the steroids. Six months after her surgery, she developed worsening headaches. Repeat MRI obtained showed significant growth of the residual adenoma on the right side of the sella, invading the cavernous sinus. Morning cortisol level of 5.3 mcg/dl(4.3-22.4 mcg/dl) and ACTH level was 11 pg/ml(6-50 pg/ml). She had a repeat endoscopic resection of the pituitary tumor. Her post-surgery cortisol at 2 PM was 3 mcg/dl at which time patient reported symptoms of AI. She was discharged on HC. Pathology again showed a staining pattern consistent with pituitary adenoma with positive staining for ACTH. MIB-1 proliferative index was 5.6%. P53 immunostaining showed a moderate density of moderately intense nuclei in the adenoma. Conclusion: This case illustrates aggressive nature of SCAs with higher risk of recurrence compared to other non-functioning adenomas and therefore requires close follow up.

Cerebrospinal Fluid Leak After Medical Management of Prolactinoma

Introduction: Dopaminergic agonists such as cabergoline are commonly used to treat prolactinomas, and often lead to significant adenoma shrinkage. Rarely, macroprolactinomas may invade the sphenoid sinus and pose a therapeutic challenge, as treatment with dopamine agonists and subsequent tumor shrinkage can lead to a cerebrospinal fluid (CSF) leak. Clinical Case: A 32-year-old female with no prior medical history presented to the emergency room of an outside hospital for headaches and visual changes. MRI demonstrated a 4.3 x 4.0 x 3.0 cm sellar mass with extension into the right cavernous sinus and sphenoid sinus, and prolactin was elevated to 1,859 ng/ml (3.4 - 21.4). Cabergoline was initiated at a dose of 0.25 mg twice a week with a decrease in her prolactin to 646 ng/ml one month later. Six months after initiation of therapy she transferred her care to our institution and presented for a routine endocrinology visit. She complained of rhinorrhea worse when upright that had begun two weeks prior to this encounter. Urgent MRI of the sella revealed an interval decrease in the size of the sellar mass to 2.1 x 2.7 x 1.5 cm and a fluid collection extending from the sella turcica to the left sphenoid sinus consistent with a CSF leak, and labs showed a prolactin level of 169 ng/ml. Cabergoline was discontinued and the patient was admitted to the hospital for treatment with antibiotics and acetazolamide. She underwent lumbar drain placement while awaiting definitive surgical management, which was delayed due to the COVID-19 pandemic. While off cabergoline, the sellar mass increased in size and her prolactin rose to 1,449 ng/ml, with no effect on the optic chiasm and visual fields. Three months later, she underwent transsphenoidal debulking of the pituitary mass with repair of the sellar floor and removal of lumbar drain. Her postoperative course was uncomplicated and she resumed cabergoline 0.25 mg twice weekly. A prolactin measured two weeks postoperatively was 337 ng/ml. Tumor histopathology revealed a 1.3 x 0.4 x 0.3 cm pituitary adenoma. Immunohistochemistry stained positive for chromogranin A, synaptophysin, and prolactin only. An MRI of the sella and prolactin level will be repeated at her next endocrinology visit. Conclusions: CSF leak is a rare but serious complication from tumor shrinkage after medical management of large invasive prolactinomas, and patients with such tumors should be monitored closely for its development. CSF leaks can increase a patient’s risk for meningitis and subsequent morbidity and mortality. The management of patients with large prolactinomas with local invasion should involve a multidisciplinary approach for decision making, extensive patient education, and close follow up in order to identify and treat a CSF leak should it develop.

A Case of Giant Prolactinoma Characterized by a Nasopharyngeal Extension and Diagnosed by Nasal Cavity Biopsy

Introduction: Giant prolactinomas represent 2-3% of all prolactinomas and less than 0.5% of all pituitary lesions. Uncommon extensions of giant pituitary adenomas to areas such as nasopharynx or paranasal sinuses are even rarer. There are about 50 cases described in the literature. Here, we report a giant prolactinoma case diagnosed by biopsy from the nasal cavity. Case: A 40-year-old male patient applied to the emergency room after falling on ice. Cranial CT revealed a giant sellar mass destroying the clivus and the sphenoid bone corpus. The patient has had frontotemporal headache for 5 years, and also loss of libido and erectile dysfunction. He had right superolateral visual field defect and right-sided ptosis. Pituitary MRI showed a T2-hyperintense sellar mass measuring 58x58x70 mm, with extension to the nasopharyngeal wall, right cavernous sinus, right petrous apex and ethmoid spaces at the base of the skull. A punch biopsy was taken from the vascular mass located in the right nasal cavity, in between the middle concha and the septum. Pathological examination revealed a neoplasm that showed strong diffuse immunostaining with PRL and CK8, and focal staining with GH. Ki-68 proliferation index was 2%. Serum PRL level was 11881 ng/mL, FSH: 1.5 mIU/mL, LH: 1.3 mIU/mL, testosterone: 35.7 ng/dL, GH: 0.5 ng/mL, IGF-1: 520 ng/mL, ACTH: 73 pg/mL, cortisol: 12 mcg/dL, TSH: 0.04 uIU/mL, fT4: 14.2 pmol/L, fT3: 4.9 pmol/L and electrolytes were normal. Five days later, a right pterygonal craniotomy was performed. The mass showed the same immunostaining characteristics as the earlier biopsy specimen, and also included fibrin, monotonous cells with ischemic necrosis and distorted architecture of the reticulin pattern. According to the post-operative MRI, the right cavernous and clival part of the mass was reduced in size. Cabergoline (0.5 mg/w), levothyroxine (100 mcg/d) and testosterone propionate (250 mg/m) were started. The patient received conventional radiotherapy in a total dose of 1250 Gy, because of the residual mass. Sixth months after radiotherapy, the nasopharyngeal part of the tumor was not visualized. Cabergoline was up-titrated to a maximum dose of 3 mg/w. Prolactin levels decreased to 136 and 22 ng/mL at the third and sixth months of the treatment, respectively. Superolateral right-sided visual field defect persisted. Five years after surgery, secondary hypocortisolism has emerged, and 5 mg/day prednisolone was added to the therapy. Eight years after diagnosis, MRI revealed significant reduction in the size of the heterogeneous residual mass lesion. Discussion: Giant macroadenomas extending to nasopharynx are mostly prolactinomas, but other functional or non-functional pituitary adenomas may also have the same presentation. These lesions tend to be surgically hard to excise due to uncommon localizations, as in our case, and radiotherapy may be needed to control the residual mass.

A Case of Unusual Initial Presentation of Panhypopituitarism From Metastatic Adenocarcinoma of Lungs

Introduction: Metastatic disease of the pituitary gland account for about 1 to 2 percent of the sellar masses with suprasellar extension. Approximately 7 percent of the patients are symptomatic with varying symptoms based on the location and extent of metastases. We present you a case in which patient presented with features of Panhypopituitarism starting with severe hypothyroidism in a previously undiagnosed lung cancer. The Patient also suffered with some serious complications such as diabetes insipidus, adrenal insufficiency and complete vision loss. Clinical Case: A 60 y/o male with a past medical history of Hypertension, Chronic Obstructive Pulmonary Disease, smoking 2 packs of cigarettes per day for 40 years, second-degree heart block requiring a pacemaker, Chronic kidney disease 3b presented to the emergency department with complaints of left ankle pain, swelling, and syncope. The Patient was admitted for further workup and Endocrinology was consulted for concerns of hypothyroidism with severe myxedema and adrenal insufficiency. CT head was done, which showed sellar and suprasellar mass lesion measuring 1.8 x 2.2 x 3.0 cm. Finding were confirmed on MRI. Pertinent labs were PTH 57.7 pg/ml, TSH 0.33 uIU/ml, Free T4 0.4 ng/dl, ACTH 8 pg/ml, Cortisol 2.5 ug/dl, FSH 0.5 MIU/ml, LH 0.1 MIU/ml, testosterone 4 ng/dl, Prolactin 17.7 ng/ml, Insulin-like GFBP-3: 2.1 mg/L. The Patient was started on high dose Hydrocortisone, IV Levothyroxine T4 and desmopressin for Diabetes Insipidus. The Patient complained of peripheral vision loss. Neurosurgery partially resected the sellar mass through the transsphenoidal approach. Histopathology came back with Metastatic adenocarcinoma. Further clinical course was complicated by complete vision loss from increase in the sellar mass size after 8 weeks. Patient received radiation therapy but unfortunately there was no significant improvement in the vision. Conclusion: This case highlights some serious complication from metastatic disease of Pituitary gland from lung cancer. There is a need for continued annual screening for dysfunction of the hypothalamic-pituitary axis to monitor therapy. This case also highlights the importance of widespread screening of smokers in accordance with the standard lungs cancer screening recommendations. This can potentially prevent some of the serious complications of metastatic lung disease. Reference: Ross, D. Cooper, D. Mulder, J. (2020, September) Central Hypothyroidism. https://www.uptodate.com/contents/central-hypothyroidismSnyder, P. Cooper, D. Martin, K. (2020, September) Causes, presentation, and evaluation of sellar masses. https://www.uptodate.com/contents/causes-presentation-and-evaluation-of-sellar-masses

Silent Pituitary Adenoma in Nasal Cavity

Introduction: Silent corticotroph adenomas (SCA) represent 3-6% of all pituitary adenomas. SCA are confirmed on post-surgical histological tumour staining and can either have no prior clinical or biochemical evidence of excess ACTH or alternatively only biochemical (not clinical) evidence of Cushing’s disease. SCA are potentially large and aggressive tumours with a greater tendency to post-surgical recurrence. We present a case of a giant SCA which pre-operatively didn’t exhibit any clinical signs of cortisol excess but showed signs of early recurrence on follow up imaging. Case: A 40-year-old man presented with frontal and maxillary sinus pain and nasal stuffiness. Nasal endoscopy revealed a mass in the nasal cavity and sphenoid sinus. Subsequent CT scan of his sinuses and MRI Pituitary reported a 4 x 3.5 x 2.5 cm sellar mass extending through the floor of sella into the sphenoid sinus and nasal cavity. Despite no clinical features of any pituitary hormone excess (including Cushing’s) or deficiency, his biochemical parameters were consistent with hypercortisolaemia. Post-low dose dexamethasone (2 mg over 48 hours) suppression cortisol was inadequate: 106 nmol/L (<50nmol/L). His corresponding serum dexamethasone level was 8.6 nmol/L (>3nmol/L), ACTH 46 ng/L (0-46 ng/L) and 24-hour urinary free cortisol levels were 502 and 260 nmol/24 hours (<165 nmol/24 hours)) on 2 separate occasions. The remainder of his pituitary profile was normal. He therefore underwent expanded endonasal endoscopic resection of tumour without significant complication. His post-operative cortisol was <50nmol/L (other pituitary hormone measurements normal) so hydrocortisone replacement therapy was commenced. A 3-month post-operative MRI pituitary scan revealed near total resection of the tumour with peripheral enhancement within the tumour resection site representing post-surgical changes. Histopathology showed sparsely granulated, diffuse cytokeratin immunostaining and immunopositivity for ACTH and T-pit consistent with a corticotroph PitNet of the sparsely granulated variety with low Ki 67 index. His six month post-operative scan showed recurrent sellar mass of 2.2 x 0.9 x 1.4 cm. Again there was an absence of clinical features of Cushing’s syndrome. After multidisciplinary discussion clinical, biochemical and radiological surveillance was continued with a view to further transsphenoidal surgery and/or radiotherapy depending on the progress of the tumour. Conclusion: Our patient solely had biochemical (not clinical) evidence of Cushing’s disease despite a large pituitary tumour in keeping with an SCA, which are aggressive, have high recurrence rate and shorter time to recurrence after surgery. Close and frequent post-operative clinical, biochemical and radiological surveillance is critical to detect and manage early recurrence that may require multimodal therapy.