Long-term outcome of multimodal therapy for giant prolactinomas
Rocío Villar Taibo2016, Endocrine
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Abstract
Giant prolactinomas are rare tumors characterized by their large size, compressive symptoms, and extremely high prolactin secretion. The aim of this study is to describe our experience with a series of 16 giant prolactinomas cases in terms of clinical presentation, therapeutic decisions, and final outcomes. Retrospective analysis of adult patients diagnosed with giant prolactinomas at the endocrine departments of three university tertiary hospitals. We included 16 patients (43.7 % women); mean age at diagnosis: 42.1 ± 21 years. The most frequent presentation was compressive symptoms. The delay in diagnosis was higher in women (median of 150 months vs. 12 in men; p = 0.09). The mean maximum tumor diameter at diagnosis was 56.9 ± 15.5 mm, and mean prolactin levels were 10,995.9 ± 12,157.8 ng/mL. Dopamine agonists were the first-line treatment in 11 patients (mean maximum dose: 3.9 ± 3.2 mg/week). Surgery was the initial treatment in five patients and the second-line treatment in six. Radiotherapy was used in four cases. All patients but one, are still with dopamine agonists. After a mean follow-up of 9 years, prolactin normalized in 7/16 patients (43.7 %) and 13 patients (81 %) reached prolactin levels lower than twice the upper limit of normal. Mean prolactin level at last visit: 79.5 ± 143 ng/mL. Tumor volume was decreased by 93.8 ± 11.3 %, and final maximum tumor diameter was 18.4 ± 18.8 mm. Three patients are actually tumor free. Giant prolactinomas are characterized by a large tumor volume and extreme prolactin hypersecretion. Multimodal treatment is frequently required to obtain biochemical and tumor control.
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Giant Prolactinomas: Report of 6 Cases and Review of Literature
Introduction: Giant prolactinomas are rare tumors, representing only 2-3% of all prolactin (PRL)-secreting tumors. Endocrine symptoms are often present but overlooked for a long period of time. The management of giant prolactinomas remains a major challenge, despite dopamine agonists being the first line of treatment, owing to its efficacy to normalize prolactin levels and reduce tumor volume. Aim of the study: Describe clinical and radiological features, the treatment modalities and outcomes of 6 cases of giant prolactinomas and review of the literature. Methods: Retrospective data collection involving 6 patients diagnosed with giant prolactinoma in the Department of Endocrinology, Hedi Chaker Hospital, Sfax, Tunisia from January 2010 to December 2014. Results: All patients were men between the age of 19 and 65 years. The most common presenting features include headache and visual defects. Proptosis was reported in one patient. Tumor size ranged from 56 to 84 mm and pre-treatment PRL from 1470 to 642387 ng/mL. Endocrine evaluation performed at baseline showed secondary hypogonadism in all patients. Secondary hypothyroidism and adrenal insufficiency were found in one and four patients respectively. IGF-I level was within the normal range for age and gender for all patients. Dopamine agonists served as the primary therapy for all the patients in the present study. Trans-frontal pituitary surgery was performed in one patient with apoplexy and severe neuro-ophthalmic signs. Serum prolactin concentrations and tumor volume significantly decreased following treatment with dopamine agonists. Conclusion: Giant prolactinomas are uncommon and often raising both diagnostic and therapeutic challenges.
Giant prolactinomas: clinical management and long-term follow up
Journal of Neurosurgery, 2002
HE outcome and treatment of prolactinomas have improved dramatically within the past three decades. Transsphenoidal microsurgical resection allows a precise adenomectomy with preservation of normal pituitary function and low complication rates. Although it was initially popular as the treatment of choice in prolactinoma therapy, transsphenoidal adenomectomy had recurrence rates of hyperprolactinemia ranging from 26 to 50% in large surgical series. Although more recent reports with rigorous long-term follow-up review contained reduced postoperative recurrence rates (12-15%), 14,32,49 dopamine agonist drugs are now the treatment of choice for most patients with hyperprolactinemia. Administration of bromocriptine, a semisynthetic ergot alkaloid and long-acting dopamine agonist, results in normalization of prolactin levels in more than 80% of patients with controlled prolactinoma growth. Bromocriptine inhibits secretion and synthesis of prolactin and proliferation of lactotroph cells within the anterior pituitary. Although prolactinoma cells usually remain sensitive to bromocriptine, the drug does not cure these adenomas; discontinu-ation of therapy often results in recurrent hyperprolactinemia. Although prolactinomas are the most common secretory pituitary tumor, giant pituitary adenomas are a rare subcategory of pituitary lesions. Overall, population of giant pituitary adenomas raise distinct and complex management issues because of frequent involvement of the CS and other parasellar and basal forebrain structures. Giant pituitary adenomas with evidence of invasion on neuroimaging have a variable clinical course. On one end of the spectrum, there have been reports of adenomas infiltrating the CS, and on the other, adenomas with a stable course and no growth for years have been observed. The growth rate and growth potential of these tumors has not yet been elucidated. Originally described as having large suprasellar extension and associated with very high morbidity and mortality rates, 4,19,23,53 giant pituitary adenomas are now associated with improved outcomes provided by microsurgical techniques and instrumentation. Giant prolactinomas stand out clinically among this group of giant pituitary tumors, not only in their known frank invasiveness, 1,39 but also in their presumed hyperresponsiveness to pharmocotherapy. 34,37 Although case reports and anecdotal descriptions of giant prolactinomas exist in the surgical literature, there are no published Object. Giant prolactinomas are rare tumors whose treatment and outcome has only been addressed in isolated case reports. The authors document the long-term follow-up findings and clinical outcome in a group of patients with giant prolactinomas.
Clinical Features, Therapeutic Trends, and Outcome of Giant Prolactinomas: A Single-Center Experience Over a 12-Year Period
Clinical Medicine Insights: Endocrinology and Diabetes
Background: Management of giant prolactinomas presents a different challenge than the management of traditional prolactinomas. Objective: The aim of this study was to report the largest long-term single-center study of giant prolactinomas to analyze their clinical features; define epidemiological characteristics, comorbidities, complications, treatment outcomes; and to demonstrate our experience with long-term cabergoline (CAB) treatment of these giant tumors. Methods: A retrospective case study and clinical review of patients presenting with giant prolactinomas in the pituitary clinic at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, in the period between 2006 and 2018 were included in the study. Of the charts reviewed, 33 patients (24 men; 9 women) with age of diagnosis between 18 and 63 years (mean = 37.21 years) met the selection criteria for giant prolactinomas. Result: The most common presenting features include headache (87.8%), visual defects (69.7%), and hypogonadism...
Long-term Follow-up of 84 Patients With Giant Prolactinomas—A Swedish Nationwide Study
The Journal of Clinical Endocrinology & Metabolism
Purpose To describe the clinical presentation and treatment outcomes in a nationwide cohort of patients with giant prolactinomas. Methods Register-based study of patients with giant prolactinomas [serum prolactin (PRL) > 1000 µg/L, tumor diameter ≥40 mm] identified in the Swedish Pituitary Register 1991-2018. Results Eighty-four patients [mean age 47 (SD ±16) years, 89% men] were included in the study. At diagnosis, the median PRL was 6305 µg/L (range 1450-253 000), the median tumor diameter was 47 mm (range 40-85), 84% of the patients had hypogonadotropic hypogonadism, and 71% visual field defects. All patients were treated with a dopamine agonist (DA) at some point. Twenty-three (27%) received 1 or more additional therapies, including surgery (n = 19), radiotherapy (n = 6), other medical treatments (n = 4), and chemotherapy (n = 2). Ki-67 was ≥10% in 4/14 tumors. At the last follow-up [median 9 years (interquartile range (IQR) 4-15)], the median PRL was 12 µg/L (IQR 4-126), and...
Giant prolactinoma: case report and review of literature
Journal of Diabetes & Metabolic Disorders, 2013
Invasive giant prolactinoma" is a large prolactinoma (>4 cm in dimension) presenting with serum prolactin levels of >1000 ng/dL and mass related clinical symptoms. Here we report a patient with a giant prolactinoma presented with central hypogonadism, suppressed adrenal and thyroid function, supra sellar extension, visual field impairment and high prolactin level. The patient was treated with cabergoline, levothyroxin and prednisolone. After 18 months, tumor size markedly reduced, associated with adrenal function and visual field improvement, but central hypogonadism and secondary hypothyroidism persisted. Previous studies showed normalization of thyrotropin secretion after treatment but it remained low in our patient even after 18 months follow up.
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Endocrinology & Metabolic Syndrome, 2015
Background: Prolactin is a well-known hormone that mainly functions as a milk producer. Its secretion by lactotroph cells in the pituitary gland (anterior pituitary) is under regulation by different effectors, mainly by Dopamine. However, under non-physiologic circumstances, Prolactin can be over secreted (hyper-prolactinemia) either due to primary (such as pituitary adenoma) or secondary (such as hypothyroidism, infections and systemic diseases) causes. Since prolactin has actions on glucose and lipid metabolisms, hyper-prolactinemia can result in insulin resistance and worsening of lipid profile. In case of prolactinoma, Prolactin can be co-secreted with Growth Hormone in 25% of cases (since lactotroph cells as well as somatotroph cells share common genetic origin), which can have a detrimental additive effect on insulin sensitivity and lipid profile. Case description: We describe a case of a young male patient with background of type 2 diabetes mellitus (T2DM) (which was not well controlled on oral hypoglycemic agents) and dyslipidemia (which was controlled with Atorvastatin) presented with progressive nausea, vomiting, dizziness and abdominal pain and was admitted initially as a case of DKA. After induction of therapy, the patient was stabilized but then his mental status deteriorated significantly. Computerized Tomography (CT) of the head revealed a giant pituitary mass. Hormonal workups were immediately sent which showed markedly elevated prolactin (PRL) level and slightly elevated growth hormone level as well as IGF-1. The elevation of PRL along with the findings of Magnetic Resonance Imaging (MRI) of pituitary gland, confirmed the diagnosis of giant invasive prolactinoma, which explained his insulin resistance and therefore his presentation. Conclusion: DKA is a rare presentation of pituitary prolactinoma and should be considered if occurred in a patient with co-existing CNS manifestations.
Surgical treatment of prolactinomas--our experience
Collegium antropologicum, 2014
The dilemma of whether to apply surgical or drug treatment to prolactinomas has been ongoing for the past 30 years. The aim of this study is to compare the early postoperative values of prolactin (PRL) in two groups of patients with prolactinomas: those who underwent primary surgical-treatment, and those who underwent surgery after a dopamine agonist (DA) therapy. We present the results of surgical treatment on a series of 161 patients with prolactinomas. Surgery was the primary treatment in 65 patients, while 96 patients had surgery following a long-term treatment with a DA. All surgically treated prolactinomas were operated in the standard transsphenoidal, microsurgical approach. The criteria for hyperprolactinemia remission was a PRL level under 25 ng/ml. Early normalization of PRL was achieved in 92% of those patients who underwent primary surgical-treatment, yet it was achieved in only 42% of patients who were operated on after receiving a long-term drug treatment with a DA. Th...
Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients
European Journal of Endocrinology, 2008
Objective: Medical therapy with dopamine agonists (DA) is the primary treatment of choice in most patients with prolactinomas. 'Classical' surgical indications are intolerance or lack of efficiency of DA therapy. Focusing on a possible shift of recent indications, we retrospectively analyzed our results of surgical treatment in prolactinomas. Patients and methods: Between 1990 and 2005, we have operated on 212 consecutive patients with prolactinomas. Surgical indications were divided into 'classical' indications and 'modern' indications defined as cystic prolactinomas or patients with microprolactinomas who individually decided on a primary surgical treatment. Results: Initial overall remission was accomplished in 53.2% including giant prolactinomas. However, in microadenomas, the remission rate was significantly higher with 91.3%. Overall remission at the latest follow-up was 42.7%, but 72.5% in intrasellar tumors, 80% in cystic prolactinomas, and 84.8% in microprolactinomas. The overall recurrence rate was 18.7%. Relapse of hyperprolactinemia in microprolactinomas was 7.1%. In our series, continually less patients were surgically treated for 'classical' indications. By contrast, the number of patients who individually decided on a primary surgical therapy has increased considerably. Conclusion: Remission rates after surgical treatment of prolactinomas remain excellent, particularly in microadenoma and intrasellar macroadenomas, whereas morbidity of transsphenoidal surgery is low in the hands of experienced pituitary surgeons. Our remission rates not only confirm the already interdisciplinarily accepted surgical indications, but also emphasize the value of primary transsphenoidal surgery as a discussion-worthy alternative to dopaminergic therapy in young patients with microprolactinomas or cystic tumors.
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Clinical management of prolactinomas: a ten-year experience
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A ten-year experience on 36 patients bearing macroprolactinomas (MP) and 86 others bearing microprolactinomas (mP) is reported in this study. Different therapeutical approaches were used: 1) trans-sphenoidal surgery in 24 patients with MP and in 25 with mP; 2) medical therapy with the oral form of bromocriptine (BRC) in all the 24 patients with MP previously subjected to surgery, in 48 patients with mP ab initio, and in 16 out of 25 patients with mP previously subjected to surgery; 3) medical therapy with the long-acting injectable forms of BRC in 12 MP- and 13 mP-bearing patients, and 4) conventional radiotherapy in 12 of the 24 patients with MP previously subjected to surgery. The follow-up, performed five years after surgery, showed that: a) all the 24 patients with MP but one had normal PRL levels during BRC administration, with a rebound of hyperprolactinemia in all cases after withdrawal; b) during the treatment BRC caused normalization of PRL in 15 of the 16 mP-bearing patien...
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Background The management of giant prolactinomas remains a major challenge, despite dopamine agonists being the first line of treatment, owing to its efficacy to normalize prolactin levels and reduce tumor volume. The aim of this study is to characterize the therapeutic aspects, manifestations and outcomes of 16 cases of giant prolactinomas admitted at a single tertiary center in Riyadh, Saudi Arabia. Methods Retrospective data collection involving 16 Saudi patients diagnosed with giant prolactinoma at the Pituitary Clinic in King Fahad Medical City, Riyadh, Saudi Arabia between January 2006 and July 2012. Results A total of 16 patients (ten males; six females) with age of diagnosis between 21 and 55 years (mean 34.9 years) were included in the analysis. The most common presenting features include headache, visual defects and sexual dysfunction. Baseline mean serum prolactin level were extremely high for both sexes which eventually decreased by as much as 97 % after cabergoline treatment. Serum prolactin concentrations completely normalized in six patients and significantly decreased in five patients 3-5 times that of normal range. Tumor volume also decreased by an average of 86 % for males and 87 % for females.
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Management of Giant Prolactinomas: Evaluation of the Role of Surgery and Medical Treatment
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Management of Giant Prolactinomas: Evaluation of the Role of Surgery and Medical Treatment ... Waleed F. El-Saadany, MD, Osama S. Abdel Aziz, MD, Alaa Abdel Raouf, MD and Nabil Abdel Rahman, MD Department of Neurosurgery, Faculty of Medicine, Alexandria University
THERAPY OF ENDOCRINE DISEASE: The challenges in managing giant prolactinomas
European Journal of Endocrinology, 2014
Giant prolactinomas are rare tumours, representing only 2–3% of all prolactin (PRL)-secreting tumours and raising special diagnostic and therapeutic challenges. Based on several considerations developed in this review, their definition should be restricted to pituitary adenomas with a diameter of 40 mm or more, significant extrasellar extension, very high PRL concentrations (usually above 1000 μg/l) and no concomitant GH or ACTH secretion. Giant prolactinomas are much more frequent in young to middle-aged men than in women, with a male to female ratio of about 9:1. Endocrine symptoms are often present but overlooked for a long period of time, and diagnosis is eventually made when neurologic complications arise from massive extension into the surrounding structures, leading to cranial nerve palsies, hydrocephalus, temporal epilepsy or exophthalmos. PRL concentrations are usually in the range of 1000–100 000 μg/l, but may be underestimated by the so-called ‘high-dose hook effect’. As ...
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Hormone and Metabolic Research
The aim of the study was to evaluate the clinical features and long-term therapeutic outcome of giant prolactinoma (gPRLoma) in men and to compare them with those of a group of male patients with non-gPRL macroprolactinomas (non-gPRLomas). A retrospective and multicenter study of gPRLomas in men diagnosed in a 20-year period was performed. Clinical data and treatment outcome were registered. The diagnosis of gPRLoma was established when the maximal tumor diameter was ≥40 mm or the tumor had ≥20 mm of suprasellar extension associated to hyperprolactinemia (PRL>1000 ng/ml). Non-gPRLoma was considered when tumor diameter was ≥ 10 mm and<40 mm associated to hyperprolactinemia (PRL≥200 ng/ml). Twenty-three patients with gPRLoma (age 38.3±13.5 years) followed for at least 3 months (follow-up 87.1±60.5 months, range 3–211 months) were evaluated. A group of 42 patients with non-gPRLoma (age 42±16.6 years; NS; follow-up 89±65.9 months, range 3–222 months; NS) served as a control group...
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