Plurihormonal Pituitary Adenoma Research Articles

P-47 Rare case of acromegaly due to plurihormonal pituitary adenoma and ACTH-independent Cushing syndrome

Abstract Introduction The concurrence of acromegaly and Cushing syndrome is infrequent. Pituitary adenomas are responsible for acromegaly and for Cushing syndrome in about 95% and 80% of cases respectively. Except adrenal adenoma, the other causes of Cushing syndrome remain rare. We here describe a case of a Tunisian patient with acromegaly due to plurihormonal pituitary adenoma and ACTH-independent Cushing syndrome with bilateral macronodules. Clinical Case A 35-year-old male patient was diagnosed with acromegaly by acrofacial dysmorphia. He had a family history of type 2 diabetes mellitus and hypertension but no endocrine diseases. He has diabetes mellitus for 15 years, hypertension and obstructive sleep apnea. Physical examination showed multiple blue nevi in the trunk. IGF-1 was elevated (1680ng/mL) and GH levels were not suppressed after an oral glucose load (nadir 78ng/mL). He had hypogonadotropic hypogonadism with normal prolactin (9,66ng/mL). Basal cortisol, FT4 and TSH levels were in the normal ranges. Pituitary MRI showed pituitary macroadenoma of 25×20.7 mm, invading both cavernous sinuses and compression of optic chiasma. He underwent transsphenoidal resection with histology confirming a prolactin, GH and LH co-secretory pituitary adenoma. He received postoperatively somatostatin analogue and cabergoline, in addition to external radiotherapy. Ultrasonography found infracentimetric EU-TIRADS 2 left nodule and multiple colloid cysts of the thyroid, testicles microlithiasis and no cardiac myxomas. Nine years after the diagnosis of acromegaly, bilateral adrenal adenomas (left:14 mm, right: 9 mm) were incidentally discovered by CT-scan done for abdominal pain. Low dose dexamethasone suppression test was carried out showing no suppression of cortisol and the low ACTH level confirmed ACTH-independent Cushing syndrome. Conclusion In our patient, at least two endocrine syndromes deserve to be mentioned. The first syndrome is Multiple Endocrine Neoplasia Type 1 but calcium and PTH levels were normal and there was no sign for neuroendocrine tumors. The second one is Carney's complex since our patient has acromegaly and multiple blue nevi which are two major criteria confirming the diagnosis. Cushing syndrome in Carney's complex is related to primary pigmented nodular adrenal disease characterized by micronodular hyperplasia. However, bilateral macronodules could be found in up to 30% of cases.

Pathogenesis, clinical features, and treatment of plurihormonal pituitary adenoma.

Plurihormonal pituitary adenoma (PPA) is a type of pituitary tumor capable of producing two or more hormones and usually presents as an aggressive, large adenoma. As yet, its pathogenesis remains unclear. This is the first study to systematically summarize the underlying pathogenesis of PPA. The pathogenesis is related to plurihormonal primordial stem cells, co-transcription factors, hormone co-expression, differential gene expression, and cell transdifferentiation. We conducted a literature review of PPA and analyzed its clinical characteristics. We found that the average age of patients with PPA was approximately 40 years, and most showed only one clinical symptom. The most common manifestation was acromegaly. Currently, PPA is treated with surgical resection. However, recent studies suggest that immunotherapy may be a potentially effective treatment.

FRI319 Diagnostic And Management Challenges In A Patient With A Giant Pituitary Lactosomatotroph Adenoma

Abstract Disclosure: C.R. Peixe: None. D. López-Presa: None. M. Bugalho: None. P. Marques: None. Introduction: Giant prolactinomas are rare, accounting for only 2–3% of all prolactinomas. Although benign, several challenges may emerge at diagnosis and during their management. Case: A 38-yr man was incidentally diagnosed with a large skull base tumor on CT-scan undertaken due to head trauma. MRI showed a 55x33mm skull base mass, involving the clivus and sellar/parasellar regions, with bilateral cavernous sinus invasion. A chordoma was suspected leading to a transnasal biopsy, which revealed a PIT1+-plurihormonal pituitary adenoma. His serum prolactin levels were then assessed, which were markedly elevated at 50,414ng/mL (NR:4-15), with concomitant raised IGF-1 at 323ng/mL (NR:101-221). He was then referred to our Endocrine department. Retrospectively, there was a 3-yr history of erectile dysfunction, decreased libido, and infertility, although his testosterone levels were within reference range (307ng/dL; NR:240-830), and sperm analysis parameters were normal. He commenced on low dose cabergoline (0.5mg/week) and two months later clinical improvement was noted, accompanied by a marked reduction of prolactin (830ng/mL) and tumor shrinkage. He remains on cabergoline for ten months, and his latest prolactin and IGF-1 levels were, respectively, 496 and 224ng/mL. In the light of patient’s normal spermogram and restored sexual function, the couple has been referred to the Fertility clinic. Conclusions: The differential diagnosis of large skull base tumors, particularly those affecting sellar/clival regions, must always include prolactinoma, hence serum prolactin should be measured keeping in mind the possible occurrence of hook effect. Most giant prolactinomas respond to dopamine agonists, which should be considered as a first-line therapy, with marked reductions in both prolactin and tumor size often seen within the first weeks of treatment. GH-cosecretion may also ameliorate/normalize with dopamine agonists. In prolactinoma patients, infertility may or may not be directly related with hyperprolactinemia, hence a careful assessment is required, and its management may imply assisted reproductive techniques. Presentation: Friday, June 16, 2023

Pituitary adenoma consecrating GH and ACTH: A rare case report

Plurihormonal Pituitary adenoma is defined as an adenoma that expresses more than one hormone on immunohistochemistry. The most common combination in these adenomas includes growth hormone (GH) and prolactin (PRL). We describe an interesting case of plurihormonal pituitary adenoma with double hormonal staining for adrenocorticotrophic hormone (ACTH) and GH in a patient who presented with acromegaly and subtle signs of Cushing disease due to a large pituitary macroadenoma

Case Report A Rare Case of Plurihormonal Pituitary Adenoma Associating Cushing's Disease and Silent Prolactinoma

Plurihormonal pituitary adenomas are rare conditions that secrete two or more pituitary hormones. The association of prolactin with other hormones is described but associated with ACTH is uncommon. We report a rare case of mixed adenoma associating Cushing’s disease and silent prolactin adenoma in 21 years old male patient. This case highlights an unusual plurihormonal pituitary adenoma case with a rare association between ACTH and prolactin. It pathogeny is less clearly define.

Clinicopathological Characteristics of Plurihormonal Pituitary Adenoma.

BackgroundAs the pathogenesis of plurihormonal pituitary adenoma (PPA) is unclear and the diagnostic criteria are inconsistent, clinicians still find it challenging to diagnose. To analyze the relationship between clinical and pathological characteristics in PPA.MethodsThe clinical data of patients with 70 PPAs admitted during 2008–2010 and 2019–2020 were collected and analyzed. In particular, hormone examination using cell culture supernatant was performed to confirm PPA cases from 2019 to 2020.ResultsPPA accounted for 13% of all pituitary cases recorded in the same period. There were 30 men and 40 women. Fifty-three percent of patients had one endocrine manifestation, and 1% presented with two endocrine symptoms. However, none of the patients had three endocrine manifestations. The level of one and two types of hormones was elevated in 52 (74.3%) and 5 (7.1%) patients, respectively and that of three types of hormones was increased only in one patient. Immunohistochemical staining for PRL + TSH or FSH/LH was most commonly performed (n = 17), followed by that for PRL + GH + ACTH and PRL + GH + TSH or FSH/LH (n = 14) and PRL + ACTH (n = 10). The primary culture results in vitro were consistent with the pathological findings in five (41.7%) patients. Moreover, 4 of 12 patients diagnosed with PPA during 2019–2020 tested positive for SOX2.ConclusionThe pathogenesis of PPA remains elusive due to the lack of specific clinical symptoms and endocrine changes. Examination of hormones on tumor culture supernatant is helpful for its diagnosis.

Plurihormonal pituitary macroadenoma:\xa0 a case report

BackgroundPlurihormonal pituitary adenomas are a unique type of pituitary adenomas that secrete two or more pituitary hormones normally associated with separate cell types that have different immunocytochemical and ultrastructural features. Although they represent 10–15% of all pituitary tumors, only a small fraction of plurihormonal pituitary adenomas clinically secrete multiple hormones. The most common hormone combinations secreted by plurihormonal pituitary adenomas are growth hormone, prolactin, and one or more glycoprotein hormones. The most common hormonal symptom is acromegaly (50%). The aim of this case report is to bring awareness about this rare type of pituitary adenomas and to describe the unique presentation of our patient, even though plurihormonal pituitary adenomas are known mostly as a clinically silent tumors.Case presentationHerein, we describe an unusual case of plurihormonal pituitary adenoma with triple-positive staining for adrenocorticotropic hormone, growth hormone, and prolactin. The patient is a 65-year-old Egyptian woman who presented with mass effect symptoms of the pituitary tumor, which primarily manifested as severe headache and visual field defects. She also presented with some cushingoid features, and further analysis confirmed Cushing’s disease; slightly high prolactin and normal growth hormone levels were observed. She underwent transsphenoidal surgery and has been in remission thus far. Only a few cases have been reported in the literature, but none has exhibited silent acromegaly or mass effect symptoms as the initial presentation.ConclusionThis case highlights an unusual plurihormonal pituitary adenoma case with a rare combination of secreted hormones; mass effect symptoms were dominant, as were uncommon visual field defects. Our case further proves that immunohistochemical analyses of all pituitary hormones are needed to ensure correct diagnosis and to alert clinicians to the need for more rigorous follow-up due to the higher morbidity of these patients. Our case report approval number Federal Wide Assurance NIH, USA is FWA00018774 IRB registration number with OHRP/NIH is IRB00010471.

Diagnosis of Sinonasal Ectopic Pituitary Adenomas

Abstract Ectopic pituitary adenomas (EPAs) are uncommon sinonasal neoplasms that present a diagnostic challenge in practice. We present a case of a patient presenting with progressive headache. Workup revealed an enhancing mass on magnetic resonance imaging at the anterior clivus with extension into the sphenoid sinus. Resection of the tumor was performed, and microscopic examination showed a neuroendocrine tumor composed of monomorphic cells arranged in nests. The tumor expressed synaptophysin, chromogranin, growth hormone, prolactin, thyroid-stimulating hormone, follicle-stimulating hormone, α-subunit of the glycoproteins, and transcription factors steroidogenic factor 1 and Pit-1, diagnosed as a plurihormonal pituitary adenoma. Given the radiologic and surgical impression of an intact and uninvolved pituitary gland, the lesion was identified as a pituitary adenoma arising in ectopic adenohypophyseal tissue. This case demonstrates the multitude of possible tissue types involved in tumor histogenesis in the sinonasal cavity. We highlight the radiographic, intraoperative, cytologic, and histologic features of sinonasal pituitary adenoma to emphasize the role of an expanded differential, including central nervous system lesions, for neoplasms in this anatomic region.

Abstract #763568: A Rare Plurihormonal Pituitary Adenoma: A Case Report and Review of the Literature

Abstract #763568: A Rare Plurihormonal Pituitary Adenoma: A Case Report and Review of the Literature

Abstract #807046: Cyclical Plurihormonal Pituitary Adenoma: The Ups and Downs

Abstract #807046: Cyclical Plurihormonal Pituitary Adenoma: The Ups and Downs

SAT-LB081 Growth Hormone and Prolactin Secreting Plurihormonal Pituitary Adenomas, Experience of a National Health Institute in Mexico

Introduction Pituitary adenomas represent approximately 15% of all intracranial neoplasms. Those with the ability to produce more than one hormone are called plurihormonal pituitary adenomas. They are divided into monomorphic, single cell type may produces two or more hormones, and plurimorphic, different cell types may produce multiple hormones. Materials and methods We performed a retrospective review of all patients diagnosed with hyperprolactinemia and acromegaly secondary to pituitary adenoma during the period 2004-2018. Then, we identified 10 patients with high serum levels of PRL and IGF-1. Six of these patients were excluded due to hyperprolactinemia secondary to pituitary stalk compression. We collected clinical, biochemical and medical imaging information. We compared the clinical and biochemical characteristics before and after treatment. Results We identified 4 female patients with GH/PRL-secreting plurihormonal pituitary adenoma. The average age at diagnosis was 25 years-old (20-32). We documented high serum levels of IGF-1 with average of 818 ng/mL (474-1340 ng/ml) and PRL with average of 185.62 ng/mL (120.95 to 280.13 ng/ml). On admission, a pituitary Magnetic Resonance Imaging (MRI) revealed macroadenoma, with mean diameter 23.5 mm (18-32 mm). All patients were prescribed cabergoline in average dose of 0.75 mg (0.5-1 mg) per week. Half of the patients had their IGF-1 ng/mL plasma level normalized. PRL ng/ml plasma levels were decreased in all patients. In their last pituitary MRI, the size of the macroadenoma decreased in all patients (8.1mm), with a mean diameter of 15.4 mm. Conclusion We consider that the primary management of the plurihormonal pituitary adenomas is the use of dopamine receptor agonists; in case there is not a clinical or biochemical control of the disease, we suggest to evaluate using additional therapy. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SAT-487 Unusual Case of Plurihormonal Pituitary Macroadenoma

Introduction Plurihormonal Pituitary adenoma is defined as an adenoma that expresses more than one hormone on immunohistochemistry. The most common combination in these adenomas includes growth hormone (GH) and prolactin (PRL). Case Description: A 65-year-old woman known to have known to have type 2 diabetes, hypertension, and class-III obesity, presented with an intractable headache and blurring vision. She also had significant worsening of her diabetes control recently despite being on insulin. CT brain and later Magnetic resonance imaging (MRI) pituitary showed a large sellar mass which measured 2.9 cm x 1.5 cm, compressing the neurophysis and the optic chiasm. Her initial investigations showed elevated corticotrophin (ACTH) level 33.6 pmol/L (1.03 - 10.7), prolactin level was high at 66.3 ng/ml (5.18 - 26.53ng/ml) and the rest of anterior pituitary hormones and IGF-1 were normal apart from primary hypothyroidism. She didn’t particularly look cushingoid, apart from the rounded face and central obesity. Cushing’s disease was confirmed on a failure of cortisol to suppress to 1mg dexamethasone (serum cortisol 783 nmol/L) and high 24-hour urinary free Cortisol at 391 ug/24 (6-123. She underwent transsphenoidal surgery (TSS) for decompression of the optic chiasm which was successful to normalize the visual fields, however, a residual tumor was still present on follow up MRI after 3 months. Interestingly, immunohistochemistry showed staining for ACTH, GH, and prolactin, Ki67 was less than 2%. Follow up evaluation showed a normal response to 1 mg suppression test and normal 24-hour urinary free cortisol. Conclusions: We present a very interesting case of plurihormonal pituitary adenoma with triple immunohistochemical stating for ACTH, GH, and Prolactin, This triple immunostaining combination is very rare and only reported in the literature once. In contrast to the other case, our patient is diagnosed in a post-menopausal woman who didn't experience florid cushingoid symptoms and she never experienced any hormonal symptoms of acromegaly or hyperprolactinemia

How does pregnancy affect the patients with pituitary adenomas: a study on 113 pregnancies from Turkey.

Data regarding pregnancies in relation to pituitary tumors are limited. The effects of pregnancy on pituitary adenomas and the effects of adenoma itself (hormonal activity, mass effects and pituitary insufficiency) and/or treatment on the ongoing gestation and developing fetus were evaluated. The study was a retrospective study. A questionnaire involving questions regarding medical history before index gestation, history of related pregnancy, result of index gestation and postpartum follow-up of the patients was filled by the investigator in one of the eight Referral Endocrinology Centers from Turkey. One hundred and thirteen (83 prolactinoma, 21 acromegaly, 8 NFPA and 1 plurihormonal pituitary adenoma) pregnancies of 87 (60 prolactinoma, 19 acromegaly, 7 NFPA and 1 plurihormonal pituitary adenoma) patients were reviewed. The clinically important pregnancy-related tumor growth of pituitary adenomas was found to be low in previously treated adenomas. Prolactinomas were more likely to increase in size during pregnancy especially if effective prior treatment was lacking. The risk of hypopituitarism is also minimal due to pituitary adenomas during pregnancy. The results of pregnancies did not differ in patients who were on medical treatment or not for prolactinomas and acromegaly during gestation. Neural tube defect and microcephaly associated with maternal cabergoline use; Down syndrome and corpus callosum agenesis associated with maternal bromocriptine use; unilateral congenital cataract, craniosynostosis and microcephaly associated with maternal acromegaly were detected for the first time. Medical treatment can be safely done stopped in patients with prolactinoma and acromegaly when pregnancy is confirmed and reinstituted when necessary. Prospective studies may help to determine the effects of medical treatment during gestation on the mother and fetus.

Hypersecretion of ACTH and PRL from pituitary adenoma in MEN1, adequately managed by medical therapy.

SummaryA 54-year-old man had gastrinoma, parathyroid hyperplasia and pituitary tumor. His family history indicated that he might have multiple endocrine neoplasia type 1 (MEN1). MEN1 gene analysis revealed a heterozygous germline mutation (Gly156Arg). Therefore, we diagnosed him with MEN1. Endocrinological tests revealed that his serum prolactin (PRL) and plasma adrenocorticotropic hormone (ACTH) levels were elevated to 1699 ng/mL and 125 pg/mL respectively. Immunohistochemical analysis of the resected pancreatic tumors revealed that the tumors did not express ACTH. Overnight 0.5 and 8 mg dexamethasone suppression tests indicated that his pituitary tumor was a PRL-ACTH-producing plurihormonal tumor. Before transsphenoidal surgery, cabergoline was initiated. Despite no decrease in the volume of the pituitary tumor, PRL and ACTH levels decreased to 37.8 ng/mL and 57.6 pg/mL respectively. Owing to the emergence of metastatic gastrinoma in the liver, octreotide was initiated. After that, PRL and ACTH levels further decreased to 5.1 ng/mL and 19.7 pg/mL respectively. He died from liver dysfunction, and an autopsy of the pituitary tumor was performed. In the autopsy study, histopathological and immunohistochemical (IHC) analysis showed that the tumor was single adenoma and the cells were positive for ACTH, growth hormone (GH), luteinizing hormone (LH) and PRL. RT-PCR analysis showed that the tumor expressed mRNA encoding all anterior pituitary hormones, pituitary transcription factor excluding estrogen receptor (ER) β, somatostatin receptor (SSTR) 2, SSTR5 and dopamine receptor D (D2R). PRL-ACTH-producing tumor is a very rare type of pituitary tumor, and treatment with cabergoline and octreotide may be useful for controlling hormone levels secreted from a plurihormonal pituitary adenoma, as seen in this case of MEN1.Learning points:Although plurihormonal pituitary adenomas were reported to be more frequent in patients with MEN1 than in those without, the combination of PRL and ACTH is rare.RT-PCR analysis showed that the pituitary tumor expressed various pituitary transcription factors and IHC analysis revealed that the tumor was positive for PRL, ACTH, GH and LH.Generally, the effectiveness of dopamine agonist and somatostatin analog in corticotroph adenomas is low; however, if the plurihormonal pituitary adenoma producing ACTH expresses SSTR2, SSTR5 and D2R, medical therapy for the pituitary adenoma may be effective.

Newly revealed diabetes mellitus as a manifestation of plurihormonal pituitary adenoma (GH/ACTH-producing). Case report

On the clinical example of acromegaly manifestation as a consequence of plurihormonal (GH/ACTH- producing) pituitary adenoma in young patient with hyperglycemia the questions about diagnosis of mixed pituitary adenomas and acromegaly treatment on the background of a subclinical Cushing syndrome and insulin resistance are considered.

Plurihormonal Pituitary Adenoma: Acromegaly Associated with Subclinical Cushing’s Disease

Plurihormonal Pituitary Adenoma: Acromegaly Associated with Subclinical Cushing’s Disease

Acromegaly due to a Macroinvasive Plurihormonal Pituitary Adenoma and a Rectal Carcinoid Tumor.

A macroinvasive pituitary adenoma with plurihormonality usually causes acromegaly and hyperprolactinemia, and also accompanies with neurologic symptoms such as visual disturbances. However, its concurrent presentation with a rectal carcinoid tumor is rarely observed. This study reports the history, biochemical, colonoscopic and immunohistochemical results of a 48-year-old female with acromegaly and hyperprolactinemia. Despite the large size and invasive nature of the pituitary adenoma to adjacent anatomical structures, she did not complain of any neurologic symptoms such as visual disturbance or headache. Immunohistochemical staining of the surgical specimen from the pituitary adenoma revealed that the tumor cells were positive for growth hormone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH). Staining for pituitary-specific transcription factor-1 (Pit-1) was shown to be strongly positive, which could have been possibly contributing to the plurihormonality of this adenoma. Colonoscopy found a rectal polyp that was identified to be a carcinoid tumor using immunohistochemical staining. A macroinvasive pituitary adenoma with concomitant rectal carcinoid tumor was secreting GH, PRL, and TSH, which were believed to be in association with over-expression of Pit-1. This is the first case report of double primary tumors comprising a plurihormonal pituitary macroadenoma and rectal carcinoid tumor.

A rare case of ACTH-LH plurihormonal pituitary adenoma: letter to the editor

A rare case of ACTH-LH plurihormonal pituitary adenoma: letter to the editor

Clinicopathologic Analysis of Pituitary Adenoma: A Single Institute Experience

Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent.

Plurihormonal pituitary adenoma with concomitant adrenocorticotropic hormone (ACTH) and growth hormone (GH) secretion: a report of two cases and review of the literature

Plurihormonal pituitary adenomas are tumours that show immunoreactivity for more than one hormone that cannot be explained by normal adenohypophysial cytodifferentiation. The most common combinations in these adenomas include growth hormone (GH), prolactin (PRL) and one or more glycoprotein hormone sub-units (β-TSH, β-FSH, β-LH and αSU). The authors report two cases of a plurihormonal pituitary adenoma expressing the rare combination of ACTH and GH. They both underwent successful transphenoidal hypophysectomy (TSH). Long-term post-operative follow-up revealed no evidence of tumour recurrence. Due to the multiple secretions and plurihormonal characteristics clinical diagnosis of composite pituitary adenomas can be difficult. The authors discuss the diagnosis and management of composite pituitary adenomas and review the literature regarding this rare phenomenon.