Nonsecreting Pituitary Macroadenoma Research Articles

Prolactin at moderately increased levels confers a neuroprotective effect in non-secreting pituitary macroadenomas.

Prolactin, a hormone synthesized by the anterior pituitary gland demonstrates promise as a neuroprotective agent, however, its role in humans and in vivo during injury is not fully understood. To investigate whether elevated levels of prolactin attenuate injury to the retinal nerve fiber layer (RNFL) following compression of the optic chiasm in patients with a prolactin secreting pituitary macroadenoma (i.e., prolactinoma). A retrospective cross-sectional study of all pituitary macroadenoma patients treated at a single institution between 2009 and 2019. Primary outcome measures included RNFL thickness, mean deviation, and prolactin levels for both prolactin-secreting and non-secreting pituitary macroadenoma patients. Sixty-six patients met inclusion criteria for this study (14 prolactin-secreting and 52 non-secreting macroadenoma patients). Of 52 non-secreting macroadenoma patients, 12 had moderate elevation of prolactin secondary to stalk effect. Patients with moderate elevation in prolactin demonstrated increased RNFL thickness compared to patients with normal prolactin levels (p < 0.01). Additionally, a significant positive relation between increasing levels of prolactin and RNFL thickness was identified in patients with moderate prolactin elevation (R = 0.51, p-value = 0.035). No significant difference was identified between prolactinoma patients and those with normal prolactin levels. Moderately increased serum prolactin is associated with increased RNFL thickness when compared to controls. These associations are lost when serum prolactin is < 30 ng/ml or elevated in prolactinomas. This suggests a neuroprotective effect of prolactin at moderately increased levels in preserving retinal function during optic chiasm compression.

Shrinkage of a pituitary metastasis of melanoma induced by pembrolizumab: a case report

BackgroundPituitary metastases are rare, often deriving from lung or breast cancer owing to the upper vena cava proximity. Pituitary metastases can manifest with signs and symptoms of pituitary tumors, consequent to mass effect (headache, visual impairment) and/or hormonal alterations (hyperprolactinemia, hypopituitarism, and diabetes insipidus). Immune checkpoint inhibitors burst immunity against tumors, significantly increasing patients’ survival, but their autoimmune side effects frequently involve the skin, the gastrointestinal tract, and the endocrine glands (pituitary, thyroid, pancreas).Case presentationA 77-year-old Caucasian man had undergone trans-nasal sphenoidal surgery for a nonsecreting pituitary macroadenoma in 2001, without remnant or endocrine deficits. In 2016, he was operated for a shoulder melanoma. In February 2018, imaging evaluation demonstrated metastases in lung, liver, and femur. Therefore, treatment with pembrolizumab (anti-programmed death 1) was scheduled in May 2018, but, before starting this therapy, a brain computed tomography performed for a sudden loss of consciousness detected a sellar mass of 17 × 12 mm, which extended to the pituitary stalk and compressed the optic chiasma. Focused magnetic resonance imaging confirmed the size and characteristics of the lesion, while emergency evaluation of the hormonal profile demonstrated an impairment of adrenal and thyroid function. The pituitary lesion demonstrated a remarkable shrinkage (8 × 6 mm), which was confirmed by subsequent imaging evaluations.ConclusionsThis is the first case reporting on effectiveness of immune checkpoint inhibitors in a patient with pituitary metastasis from a melanoma.

Underappreciation of the “Hook Effect” leading to Mismanagement of a Patient, a Tale of Preventable Disaster

Abstract Introduction: When evaluating pituitary adenomas, one needs to be cognizant of the “hook effect” - an assay artifact leading to under-reporting of extremely high prolactin levels. We report a case of a patient with a macroprolactinoma with an initial reported prolactin level of less than 1.0 ng/dl. Such an extreme case of the “hook effect” in a prolactinoma has not been reported yet. Case Presentation: A 53-year-old male with a medical history of type II DM initially presented in 2017 with blurred vision. Vital signs and labs, including pituitary hormone levels, were all within normal range. Prolactin level was reported as less than 1.0 ng/dl (normal 2-18 ng/dl). MRI brain showed a large pituitary mass and he was diagnosed with a non-secreting pituitary macroadenoma with mass effect. The patient subsequently underwent transsphenoidal resection of the pituitary adenoma. Prolactin level was noted to be elevated at 1608 ng/dl after the procedure. Unfortunately, the patient was lost to follow up. Two years later, the patient presented again with persistent headaches and worsening vision. MRI brain revealed a large suprasellar mass, measuring at 4.9 x 4 x 3 cm, with extension into the third ventricle and left cavernous sinus, indicating a recurrence of the pituitary adenoma. Prolactin levels measured were elevated 12,030 ng/dl. At this time, the patient was started on cabergoline with significant improvement in symptoms and reduction in prolactin levels to 1792 ng/dl within 4 weeks after initiation of therapy. He is currently still in remission with weekly cabergoline therapy. Conclusion: The most used prolactin assay typically reports the presence of detectable heterotrimeric immune complex formations made up of prolactin antigens sandwiched between ‘capture antibodies‘ at one end and ‘reported antibodies’ at the other end of the prolactin antigen. In prolactinomas, prolactin levels are usually present in relative excess to the two assay antibodies. This leads to the oversaturation of antibody sites with most of prolactin being complexed to only a single antibody instead of two antibodies, thus impairing adequate immune complex formation. Only a few remaining prolactin antigen are “sandwiched” to form the heterotrimeric complex and are therefore reported as “detectable.” As a result, true prolactin levels are substantially underreported, potentially leading to incorrect diagnosis, treatment delay, exposure to surgical risk and complications and increased economic burden to the patient and the healthcare system. The best method to avoid the “hook effect” and to correctly interpret prolactin values would be to obtain prolactin levels in appropriately diluted serum specimens (10-100-fold dilution of the sample). This will lead to appropriate immune complex formations and increase the sensitivity and specificity of the prolactin assay.

SAT-468 Conversion of a Non-Secreting to a Growth Hormone-Secreting Pituitary Adenoma: A Case of Rapid Development of Acromegaly

Introduction: Acromegaly is known to have a slow and insidious course. As a result, the diagnosis is made very late, and at the time of diagnosis most patients have macroadenomas. The average interval from onset of symptoms of acromegaly and diagnosis is approximately 12 years. In addition, conversion of a non-functioning to a functioning pituitary adenoma is very rare. We report a case of a documented non-secreting pituitary macroadenoma turning into a growth hormone secreting one resulting in symptomatic acromegaly in less than 4 years. Clinical Case: A 28 year old African American female presented for evaluation of headaches in 2014. Her past medical history is significant for headaches and childhood epilepsy since age 9. During her workup she was found to have a 1.2 cm pituitary macroadenoma on MRI. Her review of systems showed no evidence of vision changes, galactorrhea, hand enlargement, weakness, changes in body weight or skin pigmentation. Her exam was unremarkable, in particular she did not have any acromegaloid or cushingoid features. Her pituitary hormone work-up was unremarkable, showing no evidence of hormone excess or deficiency. Her IGF-1 was found to be 251 ng/dL (Normal: 78-270). She was evaluated by neurosurgery at that time, who recommended conservative approach with serial follow-up imaging. About 3 years and 8 months later, she was admitted to the hospital for her worsening symptoms of headaches, which were noted approximately 3 times weekly. On further questioning, examination and comparison with old pictures, she was noted to have coarsening of her facial features as well as increase in her ring size. Laboratory tests showed elevated IGF-1 levels on 2 separate occasions at 570 and 551 ng/dL. On repeat imaging, the pituitary macroadenoma was noted to be increased in size to 1.8 cm with increasing suprasellar extension and abutting the anterior aspect of the optic chiasm. She underwent endoscopic excision of pituitary adenoma and reconstruction of sellar floor. The pathology came back positive for human growth hormone staining. IGF-1 level decreased to 244 ng/mL in less than 4 months after surgery. Conclusion: Conversion of non-secreting pituitary adenoma to a growth hormone secreting one can happen over a relatively short time span, resulting in symptomatic acromegaly. We had a unique opportunity to observe this since the patient had previous imaging and biochemical work-up which we could use for comparison. This is contrary to the classic description of acromegaly where the clinical picture develops very slowly over many years or even decades.

Beyond Gross Total and Subtotal: Does Volumetric Resection Matter in Nonfunctioning Pituitary Macroadenomas?

No study has volumetrically examined resection degree and recurrence in pituitary macroadenoma (PMA). We analyzed the impact of volumetric tumor resection on prediction of tumor recurrence and retreatment in a cohort of patients with nonfunctioning PMA ≥2 cm. Records were reviewed from 1998-2008 for patients with null cell or nonsecreting PMA ≥2 cm. Inclusioncriteria were surgically resected PMA and ≥4 years' follow-up or recurrence before 4 years. Seventy-eight patients were found. PMA tissue volume preoperatively and postoperatively was quantified by a board-certified neuroradiologist. Extent of resection (EOR) was calculated. The primary end point was tumor recurrence with a secondary end point of treated tumor recurrence. Median age was 58 (20-85). Forty-one (53%) had no tumor recurrence at a median of 113 (48-203) months. Thirty-seven (47%) patients had tumor recurrence with a median time of 55 (9-176) months. On univariate analysis, increasing age, decreasing preoperative and postoperative volumes, and increasing EOR were statistically significant for decreasing the risk of recurrence or treated recurrence. On multivariate analysis, only age and EOR remained significant. Receiver operating characteristic showed EOR <86% was associated with PMA regrowth. Kaplan-Meier analysis demonstrated a statistically significant difference for recurrence comparing groups by EOR ≥86% or <85%. We found younger age and increasing EOR are significant predictors of tumor regrowth and retreatment. These results indicate EOR assessment may have a role in large PMA. Further study with volumetric analysis is needed in a larger cohort of patients.

Intrasellar dermoid cyst mimicking pituitary apoplexy: A case report and review of the literature

Intrasellar dermoid cysts are extremely unusual lesions, with only four cases reported to date, and have not been previously reported in association with sudden-onset symptoms. Here, we present the case of an intrasellar dermoid cyst with sudden-onset symptoms mimicking pituitary apoplexy in an elderly woman. A 69year-old woman presented with sudden onset of headache, dizziness, and decreased visual acuity. Magnetic resonance imaging of the sellar region showed an intrasellar lesion, which showed mixed hyper- and hypointense signal on T1-weighted and T2-weighted images and enhanced peripherally. Endocrine workup showed pituitary hormones within normal levels. According to these findings, the initial diagnosis of nonsecreting pituitary macroadenoma apoplexy was made. Intraoperatively, a large amount of whitish-yellow purulent material was found in the mass and the lesion was partially removed, owing to tight adhesion between remanent mass and surrounding neurovascular structures. Pathology showed a dermoid cyst with abundant neutrophil infiltrations.

Very late presentation of a disorder of sex development

Disorders of sex development generally present in the neonatal period with ambiguity of external genitalia. We report a very old male patient presenting at 75years because of panhypopituitarism and a large nonsecreting pituitary macroadenoma secondary to long-standing primary hypogonadism due to 46,XX sex reversal disorder now first diagnosed. Sex development disorders may go unrecognised for the entire life span, despite infertility and long-standing primary gonadic failure may lead to uncommon complications.

Granular cell tumor (GCT) mimicking a nonsecreting anterior pituitary adenoma

A 33-year-old male with right eye amaurosis and panhypopituitarism previously submitted to surgery and radiotherapy was admitted with a presumptive recurrence of a nonsecreting pituitary macroadenoma (the first diagnosis, in another service). Magnetic Resonance Imaging (MRI) confirmed an expansive solid isointense lesion in the posterior region of the sella with suprasellar component (). After a new surgery, histological revealed granular cell tumor (GCT) (). […] Granular cell tumor (GCT) mimicking a nonsecreting anterior pituitary adenoma

Clinical nonsecreting pituitary macroadenoma managed by cabergoline: anybody, anytime?

Clinical nonsecreting pituitary macroadenoma managed by cabergoline: anybody, anytime?

Necrotizing infundibulo-hypophysitis: an entity too rare to be true?

We report a young woman with sudden and severe retroorbital headache, neck pain, and a large sellar mass extending to the suprasellar cistern. A presumptive diagnosis of non-secreting pituitary macroadenoma undergoing apoplexy was made and transphenoidal surgery performed. Histopathology revealed mononuclear infiltration and marked non-hemorrhagic necrosis of the anterior pituitary consistent with a diagnosis of necrotizing infundibulo-hypophysitis. The possible pathogenesis of this rare variant of hypophysitis is discussed.

Hypopituitarism in the elderly: two case-reports with heterogeneous presentation

Hypopituitarism (HYPO) is an under-investigated disease in older patients. Symptoms, which may be life-threatening, are aspecific and often attributed to aging and/or related morbidities. We describe here the cases of two elderly patients who were ultimately diagnosed as having HYPO, the clinical presentations and etiologies of which were different. In the first patient, an invasive non-secreting pituitary macroadenoma causing HYPO was detected on brain morphological evaluation for head trauma secondary to falling. Glucocorticoid replacement therapy was started. Thyroid function evaluation showed hyperthyroidism (due to a known toxic multinodular goiter), which was already on treatment with methimazole; ultimately, after withdrawal of the antithyroid drug, secondary hypothyroidism occurred. The patient underwent non-radical pituitary surgery. Cognitive function, gait impairment and falling, which had previously been attributed only to aging, improved markedly after cortisone acetate and L-thyroxine replacement therapy. The second patient was hospitalized one month after the onset of hypotension, edema and pain in the legs, and progressive psychomotor impairment, which ultimately resulted in an intermittent soporous state. She was diagnosed as having global anterior HYPO secondary to empty sella, which caused severe multifaceted clinical and biochemical abnormalities (hyponatremia, pancytopenia, rhabdomyolysis). After treatment with i.v. fluids and hydrocortisone, the patient's clinical condition and biochemical alterations improved, and normalized over time with oral cortisone acetate and Lthyroxine combination therapy. Several protean symptoms that impair the quality of life of elderly patients are usually ascribed to aging. Such symptoms should be investigated with regard to possible HYPO, treatment of which can result in significant clinical benefit.

Primary sellar melanocytic tumor: report of new case and literature review

Primary sellar melanocytic tumors are extremely rare, and they can mimic hormonally inactive pituitary macroadenoma both clinically and radiologically. The aim of this study was to describe a new case of primary sellar melanocytic tumor, and place it in the context of published literature. This is a case report. The case of a 61-year-old woman presenting with a 2-month history of fatigue and progressive bitemporal hemianopia is described. Endocrine investigation revealed anterior pituitary insufficiency and hyperprolactinemia without diabetes insipidus. Magnetic resonance imaging demonstrated a sellar tumor mass with suprasellar extension compressing the optic chiasm, and intense gadolinium enhancement. Transsphenoidal surgical excision of the pituitary tumor was undertaken. Histological examination showed a melanocytic tumor. An extensive search failed to find evidence of any other primary or secondary site. Due to the presence of significant tumor residue at 3-month follow-up, another surgical resection was done followed by post-operative stereotactic radiotherapy of the sellar region. Primary sellar melanocytic tumors are exceptional lesions presenting most often as a tumor syndrome and/or anterior pituitary insufficiency mimicking a non-secreting pituitary macroadenoma. The management of these tumors consists of surgical removal of the tumor. However, surgery is often incomplete and stereotactic fractionated radiotherapy is frequently indicated.

The Role of the Le Fort I Maxillotomy in the Management of Incompletely Resected Pituitary Macroadenomas

The options available for the treatment of a nonsecreting pituitary macroadenoma that has been incompletely resected include reoperation, fractionated radiation therapy, and radiosurgery. Reoperation in this setting may be hindered by the same obstacles that prevented a complete resection during the initial surgical procedure, and should prompt consideration of an alternate approach or exposure. Between January 1998 and December 2003, 10 consecutive patients were referred to the Department of Neurosurgery at the University of Texas Southwestern Medical Center for the evaluation of a nonsecreting pituitary macroadenoma that measured 3 cm or greater in diameter despite having undergone an attempt at a complete resection elsewhere. Each of these patients was reoperated using a Le Fort I maxillotomy to enhance the exposure provided by a traditional transsphenoidal approach. A total or near total (> 95%) resection was achieved in each case. One patient required reoperation for the repositioning of a fat graft to treat a cerebrospinal fluid fistula and one patient experienced a worsening of anterior pituitary function postoperatively. Five patients noted improved vision and no patient experienced further visual loss. Three patients have required subsequent treatment of small foci of recurrent or progressing tumor with stereotactic radiation therapy. No patient has received fractionated radiation therapy. The added exposure provided by a Le Fort I maxillotomy facilitates the resection of pituitary macroadenomas that have been incompletely resected by a traditional transnasal, trans-sphenoidal approach.

Thyrotropin suppression by thyroid hormone replacement is correlated with thyroxine level normalization in central hypothyroidism.

We have retrospectively studied 41 patients with hypothalamic-pituitary disease and central hypothyroidism associated with hypopituitarism. Sixteen patients had nonsecreting pituitary macroadenoma, whereas different sellar and suprasellar pathologies affected all other patients. Pretreatment thyrotropin (TSH) level (mean +/- standard error of the mean [SEM]) was 2.04 +/- 0.25 mU/L (normal, 0.4-4), and gradually decreased to 0.51 +/- 0.19 mU/L (range, 0.009-3.38) by treatment with levothyroxine in a mean dose of 86 +/- 6 microg/d. TSH was suppressed by thyroid replacement to less than 0.5 mU/L in 80% of patients. Mean baseline free thyroxine (FT4) was 7.55 +/- 0.51 pmol/L (normal, 11.8-24.6) and gradually increased with thyroid hormone to 15.19 +/- 1.0 pmol/L, whereas total thyroxine (TT4) increased from 57.4 +/- 2.6 to 104.4 +/- 5.0 nmol/L (normal, 77-154). Mean pretreatment total triiodothyronine (TT3) was 1.44 +/- 0.09 nmol/L (normal, 1.1-2.7), and was not altered by treatment. Thyrotropin-releasing hormone (TRH) test was performed in 20 patients before thyroid replacement, and mean baseline and peak TSH levels were 1.33 +/- 0.3 and 7.14 +/- 1.62 mU/L, respectively. In 5 subjects TSH was stimulated to 6 mU/L or more, whereas in 5 others TSH was not affected. Based on linear regression of logarithm (Ln) TSH against FT4, a leftward shift of the TSH/FT4 ratio was demonstrated in patients with central hypothyroidism compared to 17 patients with primary hypothyroidism. Plotting measurements of TSH against FT4 for 6 individuals with central hypothyroidism showed different regression slope for each patient. Suppression of TSH by thyroid replacement to levels below 0.1 mU/L predicted euthyroidism in 92% of cases, compared to 34% when TSH was above 1 mU/L (p < 0.0001). In conclusion, in central hypothyroidism baseline TSH is usually within normal values, and is further suppressed by exogenous thyroid hormone as in primary hypothyroidism, but to lower levels. Thus, insufficient replacement may be reflected by inappropriately elevated TSH levels, and may lead to dosage increment.

Dorsum sellae meningioma mimicking pituitary macroadenoma: case report

BACKGROUND A dorsum sellae meningioma is a rare occurrence. It is difficult to evaluate dorsum sellae meningiomas preoperatively from the viewpoint of neuroimaging. We report a rare case of dorsum sellae meningioma mimicking pituitary macroadenoma in a 73-year-old woman. CASE PRESENTATION The patient presented with bitemporal hemianopsia and panhypopituitarism. Magnetic resonance imaging demonstrated a bright, homogeneously enhancing intra- and suprasellar mass and a hypointense region in this mass, which was interpreted as a dorsum sellae. Transsphenoidal extirpation was used because of a suspicion of nonsecreting pituitary macroadenoma. Histopathologically, the tumor was diagnosed as a meningioma. Superselective external carotid angiography before the second surgery revealed that the mass was supplied by the left accessory middle meningeal artery and appeared to originate from dorsum sellae. After preoperative embolization, the patient developed hyponatremia. The tumor was subtotally removed via a transcranial route, and the attachment to the dorsum sellae was coagulated extensively. She did well after a second surgical procedure. CONCLUSION These radiologic findings may be useful in differentiating dorsum sellae meningioma from pituitary macroadenoma.

Pituitary macroadenoma and diaphragma sellae meningioma: differential diagnosis on MRI.

Diaphragma sellae meningiomas are unusual tumours often not distinguished from pituitary macroadenomas. Preoperative differentiation is essential, because the trans-sphenoidal approach is used for surgical removal of adenomas, while meningiomas are approached via a craniotomy. We reviewed five patients in whom a diaphragma sellae meningioma was initially diagnosed as a nonsecreting pituitary macroadenoma. MRI criteria for differential diagnosis are discussed. The main findings considered are visibility of the pituitary gland, contrast enhancement, the centre of the lesion and sellar enlargement. These criteria, applied to a blind review, allow correct identification of the tumours.

P-5-623 - Predicting total extracapsular excision of a pituitary macroadenoma

BACKGROUNDA dorsum sellae meningioma is a rare occurrence. It is difficult to evaluate dorsum sellae meningiomas preoperatively from the viewpoint of neuroimaging. We report a rare case of dorsum sellae meningioma mimicking pituitary macroadenoma in a 73-year-old woman.CASE PRESENTATIONThe patient presented with bitemporal hemianopsia and panhypopituitarism. Magnetic resonance imaging demonstrated a bright, homogeneously enhancing intra- and suprasellar mass and a hypointense region in this mass, which was interpreted as a dorsum sellae. Transsphenoidal extirpation was used because of a suspicion of nonsecreting pituitary macroadenoma. Histopathologically, the tumor was diagnosed as a meningioma. Superselective external carotid angiography before the second surgery revealed that the mass was supplied by the left accessory middle meningeal artery and appeared to originate from dorsum sellae. After preoperative embolization, the patient developed hyponatremia. The tumor was subtotally removed via a transcranial route, and the attachment to the dorsum sellae was coagulated extensively. She did well after a second surgical procedure.CONCLUSIONThese radiologic findings may be useful in differentiating dorsum sellae meningioma from pituitary macroadenoma.