Dose Of Cabergoline Research Articles

Giant prolactinoma in Asian-Indians: A single-center experience from Western India

PurposeGiant prolactinomas (GP) are rare tumors accounting for 4.3% of prolactinomas, with paucity of literature from India. We aim to describe clinical, biochemical, radiological, and treatment outcomes in a large series of Asian-Indian patients with GP. MethodsA single-center retrospective analysis of GPs (n=84), age-based (adults: 66 versus pediatric: 18) and gender-based (males: 64 versus females: 20) comparison was done. ResultsThe mean age at presentation was 34.1±13years, and 64 (76.2%) were males. Males were younger at presentation (32.1±12.2 versus 40.1±13.8years, P: 0.01). The majority presented with mass-effect-related manifestations (visual disturbances: 91.6%, headache: 84.5%) and/or hypogonadism (98.7%). At baseline, largest tumor dimension was 5.3±1.0cm, and serum prolactin was 8343 (3865.5–12,306) ng/mL; most (94.6%) had gonadal axis involvement. Dopamine-agonist (DA) as first-line therapy (45/67, 67.2%) achieved normoprolactinemia (maximum cabergoline dose: 2.0±1.2mg/week) in 36/45 (80%) and tumor response (≥50% reduction) in 36/37 (97.3%) patients at the last follow-up (median duration: 33 [14.5–53.5]months). Notably, gonadal axis recovery was poor (6/30, 20%) despite normoprolactinemia post-DA monotherapy. At latest follow-up, secondary hypothyroidism (32.5% versus 82.6%, P: 0.001) and central hypocortisolism (5.6% versus 42.9%, P: 0.007) were less frequent in DA monotherapy (n=43) than in multimodal therapy group (n=23). The proportion of males (94.4% versus 71.2%, P: 0.04) was higher in the pediatric age group, with DA-induced (first-line) normoprolactinemia observed in 66.7% of them. ConclusionGP has male predominance, DA as first-line therapy normalized prolactin in four-fifths of patients with better preservation of HPT and HPA axes in patients with DA monotherapy.

FRI322 Lack Of Tumor Size Change With Long-term Cabergoline For Prolactinoma

Abstract Disclosure: S. Bendaram: None. V. Kantorovich: None. Introduction: Prolactinomas are the most common tumors of the pituitary gland and account for about 40% of all Pituitary adenomas, of which 10% are macroprolactinomas measuring >1 cm. Dopamine Agonists (DAs) normalize the prolactin levels and aid in shrinkage of the tumor size. We present two cases of Macroprolactinomas with biochemical response to DAs but no shrinkage in size as expected. Case 1: 75-year-old male with history of hypertension, left frontal MCA stroke with residual aphasia who underwent brain MRI for a recent TIA, was found to have a new 2.3 x 1.9 x 2.4 cm mass in the pituitary fossa invading the right cavernous sinus, concerning for a pituitary macroadenoma. Prolactin levels were 4152 ng/ml on dilution study, low testosterone with inappropriately normal LH/FSH. He denied any symptoms from compression, hyperprolactinemia or hypogonadism. After starting Cabergoline 0.25 mg biweekly, repeat levels in 2 weeks showed a decline in prolactin levels to 808.7 ng/ml. Visual Field (VF) testing was abnormal but was unreliable due to high fixation losses. Same dose of cabergoline was continued, with decline in prolactin further to 37.8 ng/ml, while a repeat MRI Brain showed no substantial change in the size of the mass. Cabergoline was doubled, and a repeat MRI still demonstrated same size of the mass, despite prolactin levels decreasing to below normal range. Case 2: 62-year-old male with history of macroprolactinoma for >3 years, but non-adherent to medications, who presented to his PCP with persistent occipital headaches, and was referred to Endocrinology due to repeat MRI brain revealing interval increase in the size of sellar and suprasellar mass measuring 2.2 x 2.2 x 2.9 cm in size consistent with macroadenoma with mass-effect on the optic chiasm and prechiasmatic optic nerves. Evaluation of pituitary panel revealed prolactin levels of 1352 ng/ml, low testosterone and LH, while the rest of the labs were normal. He was started on cabergoline 0.5 mg biweekly, and a repeat prolactin level after a single dose of cabergoline improved to 469 ng/ml. He was continued on the same dose with prolactin dropping to 2.6 ng/ml in 2 months, and further to 1.8 ng/dl after 10 months of treatment. Initial VF testing also demonstrated some degree of defect with compression of optic chiasm. Repeat MRI 3 months after initiation of cabergoline revealed interval decrease in size of macroadenoma to 2.1 cm in the largest dimension, which stayed the same on the recent imaging. Discussion: DAs like Cabergoline are first line therapy for prolactinomas. Fibrotic changes from long standing adenomas might be a possibility causing resistance to shrinkage of tumor, however it would be interesting to know if any specific molecular mechanisms that could be involved. In tumors with significant mass effect or those not responding to MT, Surgery is the preferred next step, and neurosurgery evaluation is necessary for further management. Presentation: Friday, June 16, 2023

FRI318 A Case Of Mixed Growth Hormone And Prolactin-secreting Giant Pituitary Macroadenoma

Abstract Disclosure: A. Khan: None. I. Alpertunga: None. V. Kantorovich: None. Introduction Co-secretion of prolactin (PRL) and growth hormone (GH) from a single pituitary adenoma is an established entity in the medical literature and present in about 5% of the cases. Guidelines recommend to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the time of initial diagnosis. Our case describes the management of a giant pituitary macroadenoma co-secreting PRL and GH. Case A 20-year-old male with history significant for schizophrenia presented with visual disturbances and discharge from his left nipple. His prolactin level (PRL) was noted to be elevated at 12,396 (4.0-15.2) ng/ml on work-up during recent prior investigation. On physical exam, he had bilateral temporal visual field deficit as well as dysfunction in upward gaze of left eye. Head imaging showed a 7.5 x 6.2 x 5 cm associated with remodeling of the sella turcica and expanding into the suprasellar space and significant mass-effect on the adjacent frontal lobes bilaterally, mild mass-effect on the adjacent optic chiasm with significant surrounding vasogenic edema and compressing the bilateral anterior cerebral arteries. Patient was started on low dose cabergoline in caution of prevention of possibility of rapid response-related significant volume contraction of the tumor with possibility of reactive edema. The dose of cabergoline was rapidly titrated up to 3 mg bi-weekly with minimal prolactin fluctuation of PRL between 12,000 and 16,000 ng/ml. Because of mild atypical acromegalic facial features, patient had GH axis assessment. IGF-1 level came back elevated at 529 (83-456) ng/ml with a high IGF Binding Protein- 3 of 8.9 (2.9-7.2) mg/l. He was started on octreotide titrated up to a dose of 150 mcg three times daily. Repeat MRI brain did not show tumor shrinkage. Subsequently, patient underwent bifrontal craniotomy for resection/debulking of parasellar tumor. PRL dropped to 931 ng/ml immediately after surgery. At the time of writing, pathology of the tumor and repeat IGF-1 level is pending. Patient was monitored closely in the ICU with a steroid taper postoperatively. Discussion Dopamine agonists are the first-line therapy for medical treatment of hyperprolactinemia but can also suppress GH and IGF-1 levels. However, in acromegaly, cabergoline is utilized mostly for small adenomas with mild elevation of IGF-1. In our case, we decided to use a combination of cabergoline and somatostatin receptor analog, octreotide. However, given the giant adenoma with very high PRL and IGF-1 levels, patient showed a poor response to medical therapy, and given the impending threat to patient’s vision, he underwent surgical debulking. Our case highlights the management of a giant, mixed hormone-secreting pituitary adenoma. Presentation: Friday, June 16, 2023

SAT616 Differentiating Resistant Prolactinoma From Macroprolactinemia

Abstract Disclosure: S. Lacount: None. P. Belany: None. Introduction: Prolactinomas are the most common secretory tumor of the pituitary gland. Hyperprolactinemia can present as hypogonadism, infertility, galactorrhea, or it may remain asymptomatic. In asymptomatic hyperprolactinemia, macroprolactinemia and other secondary causes should be considered and ruled out. Prolactinomas treated with dopamine agonists typically respond well, with decreasing tumor size and prolactin level reduction. We present a case of a prolactinoma not responding biochemically or anatomically to maximum doses of dopamine agonists, concerning for resistant prolactinoma versus macroprolactinemia. Clinical Case: A 62 y.o. male with PMH of HTN, HLD and CAD who presented with fatigue and headaches in 2009. Initial work-up showed an elevated prolactin level to 178 ng/mL (reference range 2.0-18.0 ng/mL). MRI pituitary showed a 1.8 x 1.9 x 1.5 cm mass but without optic chiasmal compression. Patient refused medications and opted to pursue endoscopic endonasal approach (EEA), which was completed in March 2009. Pathology and hormonal immunostains confirmed prolactinoma. Due to persistently elevated prolactin levels following EEA, cabergoline was started. Follow-up MRI Pituitary in November 2012 showed stable heterogeneous residual tissue without tumor recurrence. Despite escalating cabergoline doses (up to 8 mg weekly), his prolactin levels remained slightly elevated (50 ng/mL) after surgery with unchanged symptoms from presentation. Due to the association of cabergoline and cardiac valve disease development, his dose was decreased back down to 0.5 mg twice weekly. Given his persistent asymptomatic hyperprolactinemia that was nonresponsive to high-dose cabergoline, there was consideration for macroprolactinemia causing a falsely high level. Screening polyethylene glycol (PEG) precipitation test in November 2022 was normal. MRI pituitary in December 2022 showed a progressive sellar lesion with increased size and cavernous sinus invasion near the carotid artery. Patient was referred to neurosurgery in January 2023 for further evaluation of potential resistant prolactinoma. Due to the MRI findings and persistently elevated prolactin levels, he will undergo repeat EEA in May 2023 for treatment of resistant prolactinoma. Conclusion: Dopamine agonists are very effective in treating prolactinomas. In asymptomatic hyperprolactinemia, PEG precipitation is an inexpensive test to screen for macroprolactinemia. Once macroprolactinemia and other secondary causes are ruled out, resistant prolactinoma can be considered. Resistant prolactinoma is defined by failure to achieve normoprolactinemia and at least 50% reduction in tumor size on maximum-tolerated therapy. Risk factors for resistant prolactinoma include larger tumor volume and male gender. Treatment options include different or increased dopamine agonist doses, radiotherapy and resection. Presentation: Saturday, June 17, 2023

Evaluation of pulmonary side effects in prolactinoma patients treated with cabergoline.

Cabergoline (CAB) is the most used dopamine agonist in the treatment of prolactinomas. Studies related to the treatment of Parkinson's disease have shown that dopamine agonists can lead to fibrotic syndromes affecting the heart and the lung. The aim of this study was to evaluate the possible pulmonary side effects of CAB in prolactinoma patients. Chest X-ray imaging and pulmonary function parameters like forced vital capacity (FVC), total lung capacity (TLC), and diffusion capacity for carbon monoxide (DLCO) were evaluated in 73 prolactinoma patients. The cumulative dose of CAB and the total duration of CAB use were also calculated, and all data were reviewed retrospectively. The median cumulative CAB dose was 192 mg, and the median duration of CAB use was 64 months. Only 13 patients (17%) among this cohort had abnormal DLCO results that could be an indirect sign of pulmonary fibrosis. These abnormal DLCO results were found not to be associated with cumulative CAB dose in these 13 patients. CAB appears to be safe in terms of pulmonary functions with a median cumulative dose of 192 mg in prolactinoma patients.

Abstract #1407996: Co-secreting Pituitary Tumors: A Clinical Challenge

Co-secreting pituitary adenomas are rare, with complex clinical presentation and challenging long-term management. We present a small case series of co-secreting pituitary tumors, highlighting the importance of evaluating all pituitary hormones in the setting of a pituitary adenoma. Case 1: Active acromegaly with a functioning pituitary FSHoma A 46-year-old married male, presented with bilateral vision loss, headache, and weight gain for the last 18 months. He had also noticed enlarging hands and decreased libido. He was obese (BMI of 32.2 Kg/m2). Red reflex was present in the right eye, while temporal hemianopia was noted in the left eye. He had phenotypic features of acromegaly, had enlarged testicles measuring more than 25mls bilaterally. Acromegaly and FSHoma were confirmed with raised IGF-1 levels (733.70 ng/ml) and FSH levels, checked twice (108.9 & 107 mIU/ml respectively) with low LH (2.40 mIU/ml) and T (1.27 pg/ml); PRL, ACTH, and TSH were normal. MRI pituitary revealed a large mass measuring ∼ 2.9 x 3.6 x 4.7 cm. He was referred for pituitary surgery but was lost to follow-up thereafter. Case 2, 3, 4, 5: Acromegaly with co-secretion of prolactin Two single females, aged 18, and 33; one married, aged 33, and a 23-year-old single male presented with enlarging hands and feet and weight gain. All females had secondary amenorrhoea and galactorrhoea. A male patient and two of the females also had headaches and visual disturbances. The youngest of them did not have any classical signs of acromegaly but had bitemporal hemianopia. The male patient had right-sided temporal hemianopia. They all had raised IGF-1 levels (1195.0, 701.0, 1136.0, & 516.7ng/mL). PRL levels were 458.1, 303.0, 53.0, and 1825 ng/ml. Their LH, FSH, and FT4 levels were low. All had normal ACTH and Cortisol levels. MRI pituitary revealed pituitary macroadenomas. All were started with cabergoline and referred for surgery. Only the youngest patient underwent surgery. The other three declined surgery for the time being and were started on monthly long-acting Octreotide. Case 6: Prolactinoma with late co-secretion of growth hormone A 40-year-old female, with a history of micro prolactinoma diagnosed in 2004, recently presented in 2021 with complaints of enlarging hands and feet. There was no history of headache or visual symptoms. She presented, 16 years ago with secondary amenorrhoea with isolated hyperprolactinemia. Her MRI showed a pituitary mass measuring 1.2 x1.6 cm. Since that time, she was on cabergoline. She also had subtle signs of acromegaly. Showed raised IGF-1 (410.0) and GH nadir of 3.12mcg/L after a 75 g oral glucose challenge. Her FSH, LH, Estradiol, FT4, and cortisol were normal, while PRL was raised (49.6 ng/ml). Her cabergoline dose was increased and was referred for Trans-sphenoidal surgery. The literature review revealed a very rare synchronous presentation of acromegaly and FSH-secreting pituitary adenoma. FSH and FSHoma is specified in the etiology of macroorchidism, as present in our case. Up to 25% of GH adenomas co-secrete prolactin. The Third Type occurs due to Primitive acidophilic stem cell adenomas with dual hormone secretion from a single cell.

Medical Therapies in Prolactinomas Patients Resistant to Bromocriptine

Prolactinoma is the most common pituitary tumor. Bromocriptine(BRC) is a dopamine receptor agonist(DAs), which is one of the medical treatments for prolactinomas. However, about a quarter of patients are resistant to BRC. The aim of this article is to explore medical treatment for prolactinoma patients who are resistant to BRC, including increasing the dose of BRC and substituting drugs (cabagoline, temozolomide). Since prolactinomas is predominantly microadenoma, medical therapy based on DAs is the first-line treatment. Cabergoline (CAB), belong to DAs, is progressively substituted for BRC because of its excellent tolerability and better efficacy. In addition, small percentage of patients with prolactinomas are aggressive, this means that they are naturally resistant to DAs. High doses of CAB and standard doses of TMZ are treatments for aggressive prolactinoma, however, the use of high-dose CAB has been linked to an increased risk of cardiac valvopathy in patients with both Parkinson's disease and prolactinoma. Hence, TMZ, last conservative treatment, is recommended for this subset of patients.

De Novo Psychiatric Disorders in a Woman With Giant Prolactinoma Treated With Cabergoline

Dopamine agonists are the first-line treatment of prolactinomas. The risk of developing de novo psychiatric symptoms during dopamine agonist therapy is low. Herein, we report the case of a 42-year-old woman with a giant prolactinoma who developed a psychiatric disorder after 1 day of cabergoline therapy initiation. She presented with amenorrhea, galactorrhea, headaches, and disturbed vision. Biological investigations revealed hyperprolactinemia (2975 ng/ml) with gonadotropin deficiency. Pituitary MRI showed a giant pituitary adenoma. The patient was treated with cabergoline at the dose of 1 mg twice weekly. One day after the treatment initiation, she developed acute delirium with temporospatial disorientation and compulsive medication use. These symptoms disappeared 1 week after the reduction of the dose of cabergoline. Patients with hyperprolactinemia receiving an initial high dose of cabergoline may develop changes in mood and behavior regardless of prior psychiatric history.

ODP334 Must we Wait for the Development of Metastasis to be Able to Distinguish Dopamine Resistant Aggressive Prolactinoma from Prolactin Producing Pituitary Carcinomas? Case Report and Literature Review

Abstract Background Prolactinomas, the most prevalent type of neuroendocrine disease, account for approximately 40% of all pituitary adenomas. In the vast majority of cases, these are benign tumors with excellent clinical response to medical therapy with dopamine agonist agents such as bromocriptine and cabergoline. Rarely medical treatment fails to normalize prolactin levels and/or decrease the size of the tumor, posing a challenge to the clinician. Case presentation 40-year-old man who underwent resection of a 7.4 cm pituitary prolactinoma via frontal craniotomy followed by radiotherapy. He developed panhypopituitarism and was placed on chronic hormonal replacement therapy plus high dose cabergoline. Two years later he presented with recurrence of his disease and was diagnosed with an unresectable 4.9 cm pituitary adenoma showing cortical breakthrough of the sellar floor, invasion into the optic chiasm, erosion of the posterior sphenoid walls, extension into the sphenoid sinuses and posteriorly into the pons, midbrain and third ventricle, as well as complete encasement of the distal, superior cerebellar and posterior cerebral arteries. The patient underwent endoscopic trans sphenoidal partial tumor resection and CSF leak repair. Pathology revealed a pituitary prolactinoma with Ki-67 of up to 8% and positive p53 immunostaining. His cabergoline dose was adjusted to 0.5 mg PO daily and he was also started on Sandostatin 20 mg IM monthly as well as appropriate hormonal replacement of the other deficient pituitary hormonal axes. Follow up imaging revealed stability of the lesion. The patient continues to do clinically well and actively follows with endocrinology and neurosurgery with serial brain MRIs and laboratory workup. Discussion The histological and biochemical characteristics of aggressive prolactin secreting tumors has been reported to be of minimal utility in distinguishing benign from malignant lesions. Tumors can only be diagnosed as carcinomas after they have metastasized and they can only be classified as aggressive after treatment failure or unusual growth, which creates a disadvantage for the prognosis and management of these patients. Clinicians are in need of better guidelines that can help them identify the rare cases that might warrant more aggressive clinical interventions beyond dopamine agonists such as surgery, radiation, temozolomide, somatostatin receptor agonists and others, with the hope of delaying or preventing the development of metastasis. Case reports of atypical presentations of aggressive prolactinomas such as the one here presented, can help broaden our understanding of the predictable signs of poor prognosis. Presentation: No date and time listed

ODP328 Longitudinal Multidisciplinary Approach for Cabergoline-Resistant Aggressive Prolactinoma Complicated by Multiple Endocrine Neoplasia Type 1

Abstract Background Cabergoline-resistant prolactinomas comprise approximately 10% of all prolactinomas, and sometimes show aggressive features including invasion or higher proliferation profiles. The treatment for such cabergoline-resistant aggressive prolactinomas is challenging and requires a multidisciplinary approach. Clinical case: A 47-year-old woman was diagnosed with hyperprolactinemia after complaining of menstrual irregularities at 20 years old. No neoplastic lesion was identified in the suprasellar region, and 0.25 mg/week cabergoline was initiated. At 35 years’ old, an adenoma was suspected on the right side of the pituitary gland, though plasma prolactin values were sustained without any clinical symptoms. When the patient was 46 years old, her prolactin levels elevated to 202 ng/ml, and magnetic resonance imaging showed a tumor invaded bilateral cavernous sinuses. Because prolactin levels and tumor size continued to increase despite increasing the cabergoline dose to 1 mg/week, endoscopic transsphenoidal surgery was performed. The tumor nearly total removal, the postoperative prolactin levels decreased to 00, but started to increase again in a short period of time. Pathologic assessment revealed a high Ki-67 index (20%) and diffusely positive prolactin alongside negative expression of other anterior hormones. The tumor remained in the cavernous sinus and postoperative prolactin levels tended to increase over time. Cabergoline was restarted and increased to 7mg/week, although prolactin levels were not suppressed. Magnetic resonance imaging and computed tomography scanning showed no metastasis, and octreotide scintigraphy revealed no abnormal accumulation except for the tumor in the cavernous sinus. Radiation therapy was administered to the remaining tumor, and prolactin levels gradually decreased. Thereafter, hypercalcemia and high intact parathyroid hormone levels were found in the presence of left-inferior parathyroid enlargement, leading to a diagnosis of multiple endocrine neoplasia type 1 (MEN1). The patient had no family history of endocrine disease. MEN1 gene mutation was not detected by direct sequencing. Discussion Functional pituitary adenomas including prolactinomas and growth hormone-producing pituitary adenomas are usually benign with a Ki-67 index of approximately 1%, little mitosis, and slow progression 1) . However, pituitary adenomas in MEN1 patients have a higher rate of drug resistance and histological invasiveness than sporadic adenomas, which results in a higher postoperative recurrence rate and a lower normalization rate of approximately 40% 2) . For this case, close monitoring for tumor growth and metastasis was essential.

Cabergoline-Induced Hypoprolactinemia May Attenuate Cardiometabolic Effects of Atorvastatin: A Pilot Study

Introduction: Hypoprolactinemia, which is usually a consequence of treatment with inadequate high doses of dopaminergic agents, is a poorly understood clinical condition. The aim of the current study was to investigate whether the cardiometabolic effects of statin therapy differ between patients with low prolactin production and patients with normal levels of this hormone. Methods: We studied two groups of cabergoline-treated premenopausal women with hypercholesterolemia matched for age, plasma lipids, cabergoline dose, and treatment duration: 11 women with hypoprolactinemia (group A) and 15 women with plasma levels of this hormone within the reference range (group B). The control group (C) included 25 dopaminergic-naïve normoprolactinemic women, matched for age and lipid levels. Plasma lipids, insulin sensitivity, and levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D were measured before and after 14-week treatment with atorvastatin (20 mg daily). Results: Patients with hypoprolactinemia were more insulin-resistant, had lower values of total testosterone and free androgen index, and had higher levels of hsCRP and fibrinogen than individuals with normal prolactin levels. Although atorvastatin reduced total and LDL cholesterol and hsCRP in all study groups, this effect was stronger in groups B and C than in group A. Only in groups B and C, the drug decreased uric acid, fibrinogen, and homocysteine and increased 25-hydroxyvitamin D. In turn, only in group A, atorvastatin worsened insulin sensitivity and reduced free androgen index. Conclusion: Coexisting hypoprolactinemia may have an unfavorable impact on the pleiotropic effects of statins.

Effect of Cabergoline Treatment on Disease Control in Acromegaly Patients.

The aim of this study was to evaluate the efficacy of cabergoline in normalizing plasma IGF-I levels in acromegaly patients with elevated IGF-I levels after surgery and/or SRL therapy. Acromegaly patients (n: 143) were evaluated retrospectively. Patients with elevated IGF-I levels after surgery and/or SRLs therapy and a fixed dose of SRLs treatment for the last six months with no history of radiotherapy in the last three years were included in the study (n: 12). Previous treatment regimens, baseline PRL and IGF-I levels (ULNR), sella MRI, and immunohistochemical findings were evaluated. Cabergoline was used as an add on (n: 11) or single medical treatment (n: 1). The median duration of treatment with SRL alone was 12 months (range 6-48 months). The mean IGF-I value before cabergoline therapy was 1.45±0.4 ULNR. The mean cabergoline dose and duration of treatment were 1.55±0.75 mg/week and 9±6.3 months, respectively. IGF-I normalization was only achieved in patients with serum IGF-I concentration<1.5×ULNR before the onset of cabergoline treatment (n: 9). In some of the patients with IGF-I normalization, baseline prolactin levels were normal (n: 3). Immunopositivity for prolactin in adenoma tissue was found in three patients with IGF-I normalization. Cabergoline therapy is effective in the normalization of IGF-I levels even in normoprolactinemic acromegaly patients when IGF-I levels are mildly or moderately elevated during SRL therapy.

Cardiometabolic profile of young women with hypoprolactinemia

PurposeUnlike hyperprolactinemia, clinical significance of prolactin deficiency remains poorly understood. The aim of this study was to assess the cardiometabolic profile of patients with low prolactin levels.MethodsThe study population consisted of three groups of young women. Two groups were chronically treated with cabergoline but differed in prolactin levels, which were either abnormally low (group A; n = 16) or within the reference range (group B, n = 23). Group C, serving as a control group, included 28 drug-naïve women with normal prolactin levels. The dose of cabergoline in group A was then tapered down. Glucose homeostasis markers, plasma lipids and circulating levels of hormones, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine, as well as the carotid intima-media thickness were assessed at baseline and 6 months later.ResultsCompared with subjects with normal prolactin levels, women with hypoprolactinemia had higher levels of 2-h postchallenge glucose, glycated hemoglobin, triglycerides, uric acid, hsCRP and fibrinogen, lower values of HDL-cholesterol, total testosterone and free androgen index, as well as reduced insulin sensitivity. No differences in these variables were observed between groups B and C. Apart from prolactin normalization, cabergoline dose reduction reversed all laboratory disturbances reported in group A.ConclusionThe obtained results suggest that hypoprolactinemia in women of reproductive age may increase cardiometabolic risk.

Resistant prolactinomas: a case series of 26 patients.

Prolactin (PRL)-secreting tumors are the most common functional pituitary adenomas. They usually respond to dopamine agonist (DA) treatment, with PRL normalization and adenoma shrinkage. Our aim was to characterize patients with prolactinoma resistant to DA treatment. This retrospective case series included patients diagnosed with DA-resistant prolactinomas between 1993-2017 in three medical centers. Resistance was defined as PRL levels above three times the upper limit of normal (ULN) despite a weekly dose of ≥2 mg cabergoline (CAB). Clinical and biochemical information, and response to treatment, were retrieved from medical records. Twenty-six patients were identified; 20 males. Of 25 macroadenomas, three were giant tumors (>40 mm) and 15 (57.7%) were invasive. The mean age at diagnosis was 31.8 ± 14.9 years (range: 13-62). The median maximal CAB dose was 3.5 mg/week (IQR, 2.5-5). Half the patients received only CAB in escalating doses, nine received CAB and underwent transsphenoidal surgery, and four underwent surgery and radiotherapy in addition to CAB treatment. PRL levels at baseline between patients treated only with CAB and those operated were (91.6 [51.1-296.7] vs. 73.1 [22.6-170.9] XULN p = 0.355), and under maximal CAB dose PRL levels between patients treated only with CAB and those operated were similar (5.77 [1.27-11.27] vs 5.27 (2.9-26) XULN p = 0.317). At the last visit patients who received combined therapy achieved lower PRL levels than those treated with DA only (5.22 [1.7-21.6] vs 1.1 [0.44-3.99] XULN p = 0.017) PRL normalization was attained in seven patients and levels below 3 × ULN in fourteen patients; the overall response was 56%. Resistant prolactinomas usually require a multi-modal treatment strategy. We were able to control 14/25 (56%) of resistant tumors.

Efficacy and safety of long-term high doses of cabergoline in prolactin secreting tumor

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

Challenging management of giant prolactinomas in men: from efficient small dose of cabergoline to SSA, neurosurgery and Temozolomide

Challenging management of giant prolactinomas in men: from efficient small dose of cabergoline to SSA, neurosurgery and Temozolomide

Aggressive giant prolactinoma: a case report

BackgroundManaging treatment-resistant aggressive giant prolactinoma can be challenging, as the diagnosis is often complex, and treatment beyond dopamine agonists, surgery, and radiotherapy is limited.Case presentationA 21-year-old Malay woman first presented to our hospital at the age of 16 years with 1-year history of reduced vision and 2 years of amenorrhea. Her baseline prolactin level was 255,894 µIU/mL with secondary hypogonadism, and pituitary magnetic resonance imaging revealed a giant prolactinoma (2.8 × 3.2 × 4.2 cm3) with suprasellar extension and optic chiasmal compression. She was initially treated with cabergoline, and reductions in the prolactin level and tumor mass were achieved, leading to vision improvement and resumption of normal menstruation. However, she developed recurrent tumor growth and hyperprolactinemia, causing relapse of symptoms, and she needed surgery. Eventually, despite three tumor debulking surgeries and escalation of cabergoline doses up to 1 mg/day, her tumor progressed with aggressive characteristics. Following a multidisciplinary meeting, the patient is initiated on temozolomide therapy after considering the long-term side effects of radiotherapy in her case.ConclusionThis case highlights the importance of early identification of treatment-resistant prolactinoma and the need for a multidisciplinary approach in managing aggressive prolactinoma in young patients, particularly regarding timely implementation of temozolomide therapy.

Dopamine agonist for the rapid improvement of visual field defects in giant and macro-prolactinomas

To evaluate effect of first-line dopamine agonist (DA) therapy as an alternative to surgery for visual field defect (VFD) recovery in giant and macro-prolactinoma. In this retrospective study, 125 patients with giant and macro-prolactinoma, except those with a history of previous surgery or radiotherapy, were evaluated. Those who underwent visual field examinations using the Humphrey Visual Field analyser upon initial assessment and after treatment were included for analysis. Twelve patients with VFD were included. The effects of DA therapy on both VFD and tumor size were evaluated within the first three months. There were twelve patients analysed: three females and nine males, five giant and seven macroprolactinomas; eight patients received cabergoline (CAB) and four patients received bromocriptine (BRC). The mean adenoma diameter was 35±13mm (range 15-60), and the mean PRL level was 3,523ng/dL (range 312-11,703). Eight patients (67%) complained of blurred vision, while four patients (33%) reported no visual symptoms. After a median duration of three weeks, the VFD completely resolved in ten patients (83%) but only partially improved in two (17%). The mean initial doses of CAB and BRC that provided VFD improvement were 0.5±0.2mg/week and 6.3±1.4mg/day, respectively. After a mean duration of 2.2±0.9months, the mean decrease in adenoma size was 43.6±24.5% (range 10-95%). The use of DA as a first-line treatment for at least one month before deciding on surgery is recommended in giant and macro-prolactinomas with VFD. Surgery should be considered only in cases with DA resistance or persistent visual impairment despite medical therapy.

Comparative evaluation on the effect of selected ergot-derived dopamine on some female reproductive hormones in Wistar rats

Background: Hormonal imbalance can occur during some disease conditions, while in some other cases, an increase or decrease in the levels of the female hormones in the body might be associated with adverse effects from drugs and may also pose the risk of infertility and Ovarian cancers when these drugs are abused. Although the dopamine agonists have been helpful in ameliorating some disease conditions, it could also cause an adverse effect on the reproductive hormones and other organs of the body. Objective: This study comparatively evaluated the effect of Bromocriptine and Cabergoline on some female reproductive hormones. Methodology: This study was carried out using twenty-five rats grouped into five groups of five rats in each. Group one was the control group, Group 2 and 3 were low and high dose of Bromocriptine, while Group 4 and 5 were low and high dose Cabergoline. The drugs were administered twenty-four hourly and lasted for 21 days. Blood samples were collected for hormonal assay. Results: The results for the bioassay of FSH, LH, PROG, PRO and Estrogen revealed that both low and high dose of Bromocriptine and Cabergoline administered to the Wistar rats caused an increase in the concentration of FSH, LH, Progesterone, Prolactin and Estrogen. The level of Prolactin and Estrogen increased significantly at 0.05 level. However, a decrease was observed in prolactin and estrogen level when administered High dose bromocriptine and Low dose cabergoline respectively. Conclusion: This assessment therefore suggests that both Cabergoline and Bromocriptine had no adverse effects on the female reproductive hormones, however, Cabergoline may pose greater effectiveness than bromocriptine, hence adherence to prescription is necessary for effectiveness.

Abstract- Poster

Introduction:Prolactinoma is a noncancerous tumor of the pituitary gland and causes the pituitary to make excess prolactin. Dopamine agonists are main stay of treatment. Atypical depression is a subtype of major depression that involves several specific symptoms, including increased appetite or weight gain, sleepiness or excessive sleep, marked fatigue, mood swings strongly reactive to environmental circumstances, and rejection senstivity.Case report:A 28-year-old female came to OPD with complaints of irritability, sleepiness, marked fatigue and occasional crying spells for 20 days. On history its reveled that she has been diagnosed with prolactinoma 3½ years ago, used cabergoline. After 6 months off medication the prolactin levels raised again (>200 ng/ml) and MRI confirming prolactinoma, she was restarted on cabergoline 0.5mg where she developed mood symptoms after 2 months, treated by decreasing the dose of cabergoline and low dose sertraline for 4 weeks with significant improvement.Conclusion:Pituitary adenomas and their treatment can individually and together can present with psychiatric manifestations. So, there is a need for us to evaluate and monitor for signs and symptoms of depression, anxiety and psychosis in pituitary tumors.