Double Pituitary Adenomas Research Articles

Cushing Disease in a Patient with Double Pituitary Adenomas Complicated with Diabetes Insipidus

Managing a patient with both pituitary hypersecretory and hyposecretory manifestations may be perplexing. We report a 14-year-old female who presented with weight gain, polyuria and polydipsia. Biochemical results were consistent with Cushing disease with central diabetes insipidus. Pituitary magnetic resonance imaging showed right adenoma with stalk thickening. The immunohistochemistry staining of both adenomas was positive for adrenocorticotropic hormone, thyroid stimulating hormone, growth hormone and luteinizing hormone. Postoperatively, the patient developed panhypopituitarism with persistent diabetes insipidus. The coexistence of double adenomas can pose diagnostic and management challenges and is a common cause of surgical failure. Intraoperative evaluation is important in the identification of double or multiple pituitary adenomas in a patient presenting with multiple secretory manifestations.

Double Metachronous Pituitary Microadenoma: Literature Review and Case Report

Pituitary adenomas, which are benign, slow-growing neoplasms, are commonly associated with hormonal overproduction. They rank as the third most prevalent intracranial tumor, following gliomas and meningiomas. Although double pituitary adenomas are infrequent, they manifest when two adenomas develop within a single pituitary gland. These dual adenomas exhibit typical immunohistochemical and histopathological features. They can be further classified into two distinct types: contiguous and clearly distinct. Neuroradiological imaging facilitates the identification of clearly distinct tumors. We present imaging findings from a rare case of a double pituitary microadenoma. Early diagnosis of this uncommon condition is crucial to prevent potential complications.

Consecutive resections of double pituitary adenoma for resolution of Cushing disease: illustrative case.

Double pituitary adenomas are rare presentations of two distinct adenohypophyseal lesions seen in <1% of surgical cases. Increased rates of recurrence or persistence are reported in the resection of Cushing microadenomas and are attributed to the small tumor size and localization difficulties. The authors report a case of surgical treatment failure of Cushing disease because of the presence of a secondary pituitary adenoma. A 32-year-old woman with a history of prolactin excess and pituitary lesion presented with oligomenorrhea, weight gain, facial fullness, and hirsutism. Urinary and nighttime salivary cortisol elevation were elevated. Magnetic resonance imaging confirmed a 4-mm3 pituitary lesion. Inferior petrosal sinus sampling was diagnostic for Cushing disease. Primary endoscopic endonasal transsphenoidal resection was performed to remove what was determined to be a lactotroph-secreting tumor on immunohistochemistry with persistent hypercortisolism. Repeat resection yielded a corticotroph-secreting tumor and postoperative hypoadrenalism followed by long-term normalization of the hypothalamic-pituitary-adrenal axis. This case demonstrates the importance of multidisciplinary management and postoperative hormonal follow-up in patients with Cushing disease. Improved strategies for localization of the active tumor in double pituitary adenomas are essential for primary surgical success and resolution of endocrinopathies.

Double Pituitary Adenomas in Patients With Cushing's Disease.

Background and objective Double and multiple pituitary adenomas (PAs) are discovered in 2.6-3.3% of patients with Cushing's disease and in approximately1% of autopsies. Undiagnosed and unremoved second PA may be the cause of unsuccessful surgical treatment of Cushing's disease. In this study, we aimed todescribe our experience with the detection and treatment of patients with double PAs. Methods All patients in our series underwent transsphenoidal surgery (TSS) with endoscopic and neuronavigation assistance. Before 2017, we completely relied on MRI findings while planning surgery. From 2017 onwards, a broad revision of the sella turcica was conducted during surgeries regardless of the MRI data. Results Overall, 81 patients were included in the study: 51 before 2017 and 30 in 2017 after. In the pre-2017 group of patients, three out of 51had double adenomas, and all of them were seen on MRI images. We encountered four more double PAs during the next period. Only two of them had been predicted by MRI. The remission rate was higher after 2017 and amounted to 90% (27 out of 30 patients). In contrast, before the implementation of total revision (pre-2017), our success rate was 82% (42 out of 51 cases). Both neoplasms in cases of double PAs yielded similar histological and immunohistochemical (IHC) features but were consistent with multiple PAs. Conclusions Although the improvement in our results in recent years cannot be clearly attributed to a targeted search for the second microadenoma, we still recommend performing a broad inspection of the sella turcica after the excision of the pituitary microadenoma regardless of preoperative MRI data.

Metachronous Double Pituitary Adenomas: Presentation of A Case and Literature Analysis

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Double adenomas of the pituitary reveal distinct lineage markers, copy number alterations, and epigenetic profiles

PurposePituitary adenoma (PA) constitutes the third most common intracranial neoplasm. The mostly benign endocrine lesions express no hormone (null cell PA) or the pituitary hormone(s) of the cell lineage of origin. In 0.5–1.5% of surgical specimens and in up to 10% of autopsy cases, two or three seemingly separate PA may coincide. These multiple adenomas may express different hormones, but whether or not expression of lineage-restricted transcription factors and molecular features are distinct within multiple lesions remains unknown.MethodsSearching the data bank of the German Pituitary Tumor Registry 12 double pituitary adenomas with diverse lineage were identified among 3654 adenomas and 6 hypophyseal carcinomas diagnosed between 2012 and 2020. The double adenomas were investigated immunohistochemically for expression of hormones and lineage markers. In addition, chromosomal gains and losses as well as global DNA methylation profiles were assessed, whenever sufficient material was available (n = 8 PA).ResultsIn accordance with the literature, combinations of GH/prolactin/TSH–FSH/LH adenoma (4/12), GH/prolactin/TSH–ACTH adenoma (3/12), and ACTH–FSH/LH adenoma (3/12) were observed. Further, two out of 12 cases showed a combination of a GH/prolactin/TSH adenoma with a null-cell adenoma. Different expression pattern of hormones were confirmed by different expression of transcription factors in 11/12 patients. Finally, multiple lesions that were molecularly analysed in 4 patients displayed distinct copy number changes and global methylation pattern.ConclusionOur data confirm and extend the knowledge on multiple PA and suggest that such lesions may origin from distinct cell types.

An asynchronous double growth hormone secreting pituitary adenoma ofa different proliferative potential – a case report

An asynchronous double growth hormone secreting pituitary adenoma ofa different proliferative potential – a case report

SAT-265 An Asynchronous Double Growth Hormone Secreting Pituitary Adenoma as a Cause of Rapid Tumor Regrowth After Initially Successful Surgery

Background. Double pituitary adenomas are a rare entity, which requires clinical attention and a careful follow-up. Case report. A 37-year-old man presented with left-sided painful gynecomastia. He denied typical symptoms of excessive growth hormone (GH) secretion and did not show any acromegalic features. Due to low testosterone and LH levels with mild hyperprolactinaemia, the patient was referred to pituitary MR, which revealed an 11x13 mm right-sided sellar tumor. An increased IGF-1 was noted subsequently (1482 ng/mL; N 109-284 ng/mL), together with the lack of GH suppression in OGTT. Transphenoidal resection of pituitary tumor performed in 2012 led to biochemical (IGF-1 260 ng/mL, GH 0.08 ng/mL) and radiological remission of the disease. A histopathology report revealed a densely granulated somatotropic pituitary adenoma with mild nuclear atypia, expressing somatostatin receptors [sstr2A (+), sstr5 (+/-)]. Due to gradually increasing IGF-1 levels (with low, although rising, GH values ranging from 0.07 to 0.92 ng/mL) in subsequent years, OGTT was repeated in 2015, showing appropriate GH suppression. In 2016, however, acromegaly recurrence was confirmed both biochemically (increasingly high IGF-1 - 664 ng/mL - and unsuppressed post-OGTT growth hormone) and in MR imaging. The patient was reoperated in June 2017. The second histopathology reported an oncocytic somatotropic acidophil stem cell pituitary adenoma with Ki-67 >3% and mitotic figures. Subsequent anterior pituitary lobe insufficiency (adrenal, thyroid and gonadal axis) was found and adequately treated. Complete tumor removal was confirmed by MR performed three months after repeated surgery, as well as a low GH level (0.97 ng/mL), although accompanied by borderline IGF-1 values (277 ng/mL). Eighteen months after surgery, the recurrence of acromegaly was again confirmed, with adenoma regrowth and increased GH (2.31 ng/mL) and IGF-1 (474 ng/mL) levels. Octreotide LAR was started (despite retina wrinkling which was observed when lanreotide was administered before the first surgery), which led to a normalization of GH (0.96 ng/mL) and IGF-1 levels (152 ng/mL), as well as partial pituitary tumor regression after six months therapy. Conclusion. In a case of GH-secreting pituitary adenoma recurrence after apparent successful surgery, a double pituitary tumor with more aggressive histology should be considered.

Double pituitary adenomas in a large surgical series

PurposeTo explore the incidence of double pituitary adenomas in a tertiary center for pituitary surgery and asses their clinical, imaging and histopathological features.MethodsThe medical records of the patients operated on for pituitary tumors at the Department of Neurosurgery of Military Institute of Medicine in Warsaw, Poland between the years 2003 and 2018 were retrospectively analyzed. Among the 3270 treated patients, the diagnosis of double pituitary adenoma was established in 22 patients. Clinical, laboratory, detailed histopathological and diagnostics imaging data were collected and analyzed.ResultsThere were 21 cases of synchronous and one case of asynchronous double pituitary adenoma. The main clinical finding was acromegaly (12/22) followed by Cushing’s disease (3/22). The diagnosis of synchronous double pituitary adenoma was suspected in the preoperative MRI in 11 patients. In the remaining patients the diagnosis of contiguous double pituitary adenoma was confirmed in the histopathological examination. There was no predilection for gender and the mean observation time was 74.2 months. In one case of Cushing’s disease the occurrence of double pituitary adenoma led to the initial failure of achieving hormonal remission. One patient presented with double pituitary adenomas as a manifestation of Carney complex.ConclusionsDouble pituitary adenoma is a rare entity that can pose a significant challenge especially in the setting of Cushing’s disease. Careful inspection of preoperative MRI and diagnostic work-up before transsphenoidal surgery and thorough histopathological microscopic examinations with immunohistochemical staining for all pituitary hormones is essential for establishing the diagnosis of double pituitary adenoma.

Abstract #831 The Intriguing Case of Double Pituitary Adenoma in a Patient Receiving Prednisone

Abstract #831 The Intriguing Case of Double Pituitary Adenoma in a Patient Receiving Prednisone

Double Pituitary Adenomas Are Most Commonly Associated with GH- and ACTH-Secreting Tumors: Systematic Review of the Literature

Double adenomas in the pituitary gland are a rare occurrence. The ability to cure a hormone-producing adenoma with surgery is dependent on the ability to identify and completely remove the correct adenoma. The relative frequency of each subtype of hormone-secreting adenomas confirmed with magnetic resonance image (MRI), surgery and immunohistochemistry is not defined. Following PRISMA guidelines, we performed a systematic review of PubMed Central, Google Scholar, Scopus Database, Cochrane database and Science Research, using the key-words: “double pituitary adenomas”, “multiple pituitary adenomas” and only papers where multiple or truly separate double pituitary adenomas were identified pre-surgically by MRI and/or confirmed by pathology/immunohistochemistry staining were included. We reviewed papers from 1975 to 2016 and found 17 cases with two pituitary adenomas and 1 with three pituitary adenomas. The ages ranged from 22 to 67 years old, and there were twelve females and five males. Immunohistochemical staining showed that the most common double pituitary adenomas were growth hormone (GH)- followed by adrenocorticotropic (ACTH)-secreting. Double pituitary adenomas are rare but most commonly found with GH- or ACTH-producing tumors. It is critical to remove all identified possible adenomas to achieve biochemical cure and clinicians should have heightened sensitivity in patients with acromegaly or Cushing’s Disease.

Double pituitary adenomas associated with persistent trigeminal artery: a rare case report and the review of literature

Multiple pituitary adenomas are rare. We present a quite unique case of double pituitary adenomas associated with persistent trigeminal artery (PTA) treated by endoscopic surgery. To the best of our knowledge, this is the first report in the literature. A 64-year-old woman was referred to our hospital for suspicion of acromegaly. Preoperative magnetic resonance imaging revealed two separate intrasellar masses with intrasellar vascular structure. Right cerebral angiography showed medial-type PTA. The patient underwent endoscopic transsphenoidal surgery and both tumors were resected completely. Postoperative immunohistopathologic examination revealed two histologic types of adenoma: the first tumor was positive for growth hormone (GH), while the second was considered nonfunctioning. Postoperatively, the patient's serum levels of GH and insulin-like growth factor-1 returned to normal. We observed an extremely rare case of double pituitary adenomas associated with PTA. Preoperative neuroimaging and modern endoscopic surgery are valuable to confirm diagnosis of double pituitary adenomas and identify anatomical localization of PTA.

Double pituitary adenomas are most commonly associated with GH- and ACTH-secreting tumors: systematic review of the literature.

Double adenomas in the pituitary gland are a rare occurrence. The ability to cure a hormone-producing adenoma with surgery is dependent on the ability to identify and completely remove the correct adenoma. The relative frequency of each subtype of hormone-secreting adenomas confirmed with magnetic resonance image (MRI), surgery and immunohistochemistry is not defined. Following PRISMA guidelines, we performed a systematic review of PubMed Central, Google Scholar, Scopus Database, Cochrane database and Science Research, using the key-words: "double pituitary adenomas", "multiple pituitary adenomas" and only papers where multiple or truly separate double pituitary adenomas were identified pre-surgically by MRI and/or confirmed by pathology/immunohistochemistry staining were included. We reviewed papers from 1975 to 2016 and found 17 cases with two pituitary adenomas and 1 with three pituitary adenomas. The ages ranged from 22 to 67 years old, and there were twelve females and five males. Immunohistochemical staining showed that the most common double pituitary adenomas were growth hormone (GH)- followed by adrenocorticotropic (ACTH)-secreting. Double pituitary adenomas are rare but most commonly found with GH- or ACTH-producing tumors. It is critical to remove all identified possible adenomas to achieve biochemical cure and clinicians should have heightened sensitivity in patients with acromegaly or Cushing's Disease.

Adrenocorticotropic hormone secreting monohormonal double pituitary microadenomas causing Cushing's disease

Double pituitary adenomas are rare, and they account only 1%–4% of all pituitary adenomas. Single or multiple adrenocorticotropic hormone (ACTH) producing adenomas are rare; even small adenomas can produce potent endocrinological effects. So far only two case reports mentioning monohormonal ACTH-secreting double adenoma have been reported. Higher resolution magnetic resonance imaging and postcontrast thin T1 spoiled gradient acquisitions can improve detection of these tumors. Surgery should be done with caution, sella should be explored meticulously to assure complete resection of all tumors as many studies have earlier documented high recurrence rates with ACTH adenomas.

Isolated double adrenocorticotropic hormone-secreting pituitary adenomas: A case report and review of the literature.

Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas.

Double separate versus contiguous pituitary adenomas: MRI features and endocrinological follow up.

Double pituitary adenomas are defined as two adenomas within a gland. These have distinct light microscopic and immunohistochemical features and may be clearly-separate or contiguous. Most reports have focused on the various hormonal combinations in double tumors rather than on any potential increased risk for residual mass or endocrinopathy. Departmental files were searched to identify all double adenomas from 1/1/2000 to 3/1/2016, with review of magnetic resonance imaging (MRI) to determine if the dual nature of the lesions could be discerned retrospectively after histologic diagnosis of double adenoma. All cases were immunostained for standard anterior pituitary hormones. Eight cases were identified: 2 follicle-stimulating hormone (FSH)/alpha subunit (ASU)+prolactinoma (PRL); 1 PRL+corticotroph (ACTH); 1 hormone-negative+PRL; 1 ACTH+ASU/growth hormone (GH)/PRL; 1 GH/PR+PRL; 1 FSH/ASU,+ACTH; 1 GH+luteinizing hormone (LH). One patient had clearly-separate lesions identified preoperatively and required two surgical procedures for gross total resection. A second patient had 2 lesions recognized at surgery and afterwards on retrospective neuroimaging. The remaining 6 patients had double adenomas discovered at the time of histologic examination that were not resolvable at surgery or on retrospective neuroimaging. Four patients, 2 with clearly-separate and 2 with contiguous double adenomas, had persistent MRI abnormalities, and one had continued endocrine abnormalities. Double contiguous pituitary adenomas are difficult to anticipate preoperatively or to resolve intraoperatively. Although double contiguous adenomas are much more common than double separate lesions, both have a risk for subtotal resection and, thus, residual mass and/or endocrinopathy may ensue.

Isolated double pituitary adenomas: A silent corticotroph adenoma and a microprolactinoma

We report a 27-year-old woman with amenorrhea and galactorrhea with mildly elevated serum prolactin levels. Her MRI demonstrated a cystic macroadenoma in the left aspect of the sella and a small microadenoma in the right aspect of the sella. Endoscopic transsphenoidal resection of the tumors revealed two histologically distinct tumors. The left tumor was consistent with a silent corticotroph macroadenoma and the right tumor was a prolactin producing microadenoma. Isolated double pituitary adenomas that are clearly separated by normal pituitary gland tissue are extremely rare. The incidence is approximately 0.37–2.6%. The coexistence of double adenomas can pose diagnostic and management challenges for the pituitary neuroendocrine team.

Double pituitary adenomas with distinct histological features: presentation of an interesting case

Introduction Double pituitary adenomas are rare. The incidence is approximately 1% of autopsy pituitaries and 0.4–2.6% of large surgical series. The growth hormone producing pituitary adenomas are classified as densely granulated type and sparsely granulated type. The latter shows a more aggressive clinical course. Case presentation A 27-year-old Bangladeshi male presented with acromegaly and a high serum IGF-1 (189 nmol/L with a normal range of 15–50 nmol/L). MRI showed a 9 mm hypo-enhancing nodule in his right pituitary consistent with a micro adenoma. During trans-sphenoidal surgery, no macroscopic lesion was found in the right side, however a well demarcated nodule was seen in the left pituitary (not identified on the imaging). This was resected and histologically confirmed as a growth hormone-producing adenoma of sparsely granulated type. Three monthly screening revealed a sustained high serum IGF-1 (142 nmol/L) leading to further investigation and a second operation to resect an encapsulated nodule in the right pituitary with no connection to the left. This lesion was proven to be another growth hormone-producing adenoma of densely granulated type. Discussion Double pituitary adenomas are rare. The distinction between different subtypes of growth hormone producing adenomas can impact on medical therapy and patients’ outcomes.

A somatotropin-producing pituitary adenoma with an isolated adrenocorticotropin-producing pituitary adenoma in a female patient with acromegaly, subclinical Cushing’s disease and a left adrenal tumor

A 67-year-old female with hypertension and impaired glucose tolerance was admitted to our hospital because of a typical acromegalic appearance, including large, thickened bulky hands and feet, and a large prominent forehead and tongue. She did not have a Cushingoid appearance, such as a moon-face, buffalo hump, purple striae or central obesity. The laboratory data revealed a serum GH level of 4.6 ng/mL and serum insulin-like growth factor-1 level of 811 ng/mL. The oral glucose tolerance test showed no suppression of the GH values. An endocrine examination showed a lack of circadian rhythmicity of ACTH and cortisol. Cortisol was not suppressed by a low dose of dexamethasone during the suppression test, but was suppressed by a high dose of dexamethasone. A radiological study revealed two isolated adenomas in the pituitary and a left adrenal tumor. These findings strongly suggested a diagnosis of acromegaly with subclinical Cushing's disease and a left adrenal incidentaloma. Transsphenoidal surgery was performed. Hematoxylin and eosin staining showed that the left and right pituitary adenomas were composed of basophilic and acidophilic cells, respectively. Immunohistochemical staining showed the left adenoma to be positive for ACTH and negative for GH. In contrast, the right adenoma was GH-positive and ACTH-negative. This is a rare case of independent double pituitary adenomas with distinct hormonal features. We also provide a review of the previously reported cases of double pituitary adenomas and discuss the etiology of these tumors.

Double, Synchronous Pituitary Adenomas Causing Acromegaly and Cushing’s Disease. A Case Report and Review of Literature

Double pituitary adenomas are very rare and present up to 1 % of pituitary adenomas in unselected autopsy series and up to 2 % in large surgical series. We report a case of a 47-year-old man presented slight clinical features of acromegaly with 2 years duration. Endocrine evaluation confirmed active acromegaly and revealed adrenocorticotropin hormone-dependent hypercortisolemia. Preoperative magnetic resonance imaging of the pituitary demonstrated clearly separated double microadenomas with different intensity. The patient underwent transsphenoidal surgery and both tumors were completely removed and were fixed separately. The histological and ultrastructural examination confirmed coincidence of the double, clearly separated pituitary adenomas in one gland. Postoperative function of the hypothalamo-hypophyseal axis was normalized. We conclude from this case and a literature review that double endocrinologically active pituitary adenomas leading to acromegaly and Cushing’s disease may occur. Additionally, a review of the literature regarding multiple pituitary adenomas has also been performed.