Double pituitary adenomas: report of two cases and systematic review of the literature.

Objective: Double pituitary adenomas (DPA) are a rare clinical condition, and our knowledge of them is limited. Missing the second lesion leading to incomplete biochemical remission after surgery is an important challenge in DPA management. This study aims to analyze independent prognostic factors in DPA patients and summarize clinical experiences to prevent surgical failure. Methods: Two cases of DPA patients with Cushing's disease diagnosed and surgically treated at Peking Union Medical College Hospital are reported. A literature review was performed on the online database Pubmed, and 57 DPA patients from 22 retrieved articles were included. Demographic characteristics, endocrine manifestations, diagnostic methods, tumor size, and immunohistochemical features of 59 patients were analyzed. Binary logistic regression models were used to identify independent prognostic factors affecting postoperative biochemical remission. Results: Among 59 DPA patients, the mean ± SD age was 43.64 ± 14.42 years, with 61.02% being female (n = 36). The most common endocrine manifestations were Cushing's syndrome (23/59, 38.98%) and acromegaly (20/59, 33.90%). The most prevalent immunohistochemical types were ACTH-immunopositive (31/118, 26.27%) and GH-immunopositive (31/118, 26.27%) tumors. Microadenomas (<1cm) were the most frequent in terms of tumor size (62/92, 67.39%). The detection rate for double lesions on 3.0T MRI was 50.00% (14/28), which significantly higher than 1.5T MRI (P = 0.034). Univariate analysis revealed that female, Cushing's syndrome and only single lesion detected by surgical exploration were associated with significantly worse prognosis (P<0.05). Multivariate analysis identified double lesion detected by surgical exploration (OR = 0.08, P = 0.003) and contiguous type tumor (OR = 0.06, P = 0.017) as independent protective factors for DPA patients. Conclusions: The double lesion detected by surgical exploration is independently associated with a better prognosis for DPA patients. Comprehensive intraoperative exploration are crucial measures to avoid missing causative lesions.

Two Cases of Double Pituitary Adenomas in a Surgical Series Over 16 Years in a Single Centre.

BACKGROUND: Double pituitary adenomas (DA) are two morphologically and immunohystochemically different tumours in the same gland. They are rare, generally small adenomas and divided in: separated, when clearly recognizable before or during surgery, and contiguous, when diagnosed only in the following histopathological examination. Acromegaly and Cushing's disease are the main prevalent clinical presentation. OBJECTIVE: We described two cases of DA in a surgical series over 16 years in a single center. METHODS: In September 2018, we diagnosed a DA in a man with acromegaly (case 1). In order to assess the presence of other cases of DA, we performed a retrospective analysis of the endonasal endoscopically operated sellar adenomas from January 2004 to December 2019. RESULTS: 468 pituitary adenomas were found. A DA with a Pit-1 positive macroadenoma (GH-TSH- PRL positive) and an ACTH microadenoma clinically silent in an acromegalic woman was retrospectively found (case 2). CONCLUSION: Our analysis confirms that DA are rare (0.4% of the pituitary adenomas) and often associated with acromegaly. Their pre-operatively diagnosis is difficult but clinician's awareness of DA can improve the diagnosis. The use of pituitary transcription factors could be useful in detecting DA.

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.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

Multiple Pituitary Adenomas: A Systematic Review.

PubMed, Scopus, and Web of Science Core Collection databases were systematically searched for studies reporting synchronous double or multiple pituitary adenomas (MPA), a rare clinical condition, with a vague pathogenesis. Multiple adenomas of the pituitary gland are referred to as morphologically and/or immunocytochemically distinct tumors that are frequently small-sized and hormonally non-functional, to account for the low detection rate. There is no general agreement on how to classify MPA, various criteria, such as tumor contiguity, immunoreactivity, and clonality analysis are being used. Among the component tumors, prolactin (PRL)-immunopositive adenomas are highly prevalent, albeit mute in the majority of cases. The most frequent clinical presentation of MPA is Cushing's syndrome, given the fact that in more than 50% of reported cases at least one lesion stains for adrenocorticotrophic hormone (ACTH). Plurihormonal hyperactivity may be diagnosed in a patient with MPA when more than one tumor is clinically active (e.g., ACTH and PRL) or in cases with at least one composite tumor (e.g., GH and PRL), to complicate the clinical scenario. Specific challenges associated with MPA include high surgical failure rates, enforcing second-look surgery in certain cases, and difficult preoperative neuroradiological imaging evaluation, with an overall sensitivity of only 25% for magnetic resonance imaging to detect distinct multiple tumors. Alternatively, minor pituitary imaging abnormalities may raise suspicion, as these are not uncommon. Postoperative immunohistochemistry is mandatory and in conjunction to electron microscopy scanning and testing for transcription factors (i.e., Pit-1, T-pit, and SF-1) accurately define and classify the distinct cytodifferentiation of MPA.

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.

A Case of Acromegaly Caused by Double Pituitary Adenomas / 대한내분비학회지

Acromegaly is a clinical syndrome, which is caused by an excess of growth hormone (GH), most commonly secreted from a pituitary solitary adenoma. However, our patient had bilateral GH-secreting pituitary tumors, the incidence of which has been reported in only 1.3 to 1.69% of all acromegalic patients. A 59-year-old female, with no family history of pituitary adenomas, demonstrated an increased level of serum insulin-like growth factor-1 (IGF-1), and GH not suppressed after 75 g oral glucose loading. On a preoperative MRI, only one pituitary tumor, measuring 1.1 x 0.7 cm, could be observed using sellar MRI. After surgical resection of the tumor, her headache and myalgia were sustained, and the IGF-1 level was still in a high titer. Therefore, a follow-up sellar MRI was taken, and a 0.6 x 0.7 cm sized newly growing pituitary tumor was found on the other side. With a retrospective review of radiological examinations, the patient was found to have bilateral tumors. The 0.3 cm sized tumor on the left was too small to be detected on the preoperative MRI. As the patient preferred medical treatment after surgery, she was treated with sandostatin analogues. Acromegaly with bilateral GH-secreting pituitary tumors, is a very rare disease, with no previous case having been reported in Korea. Herein, we report the case with a review of the literature.