-
Case report: Complete restoration of the HPA axis function in Cushing's disease with drug treatment.Frontiers in Endocrinology 2024This report describes a rare case of a 20-year-old man with an ACTH- and prolactin-secreting invasive pituitary macroadenoma causing hyperprolactinemia and Cushing's...
This report describes a rare case of a 20-year-old man with an ACTH- and prolactin-secreting invasive pituitary macroadenoma causing hyperprolactinemia and Cushing's disease. He was later found to have an AIP mutation. Treatment with cabergoline (1.5 mg weekly) normalized prolactin concentrations and induced a major shrinkage of the adenoma. Not only was urinary free cortisol normalized for more than 14 years, but also the treatment induced normal hypothalamo-pituitary-adrenal (HPA) axis function as illustrated by the reappearance of a normal cortisol/ACTH circadian rhythm, cortisol suppression to dexamethasone, and disappearance of the excessive and aberrant responses to CRH and desmopressin, respectively. This case is the first description of complete restoration of the physiological characteristics of the HPA axis by a medication during the treatment of Cushing's disease. Although exceptional, it illustrates that drugs targeting the pituitary adenoma can bring true complete remission of Cushing's disease.
Topics: Male; Humans; Young Adult; Adult; Hypothalamo-Hypophyseal System; Pituitary ACTH Hypersecretion; Hydrocortisone; Prolactin; Pituitary-Adrenal System; Pituitary Neoplasms; Adrenocorticotropic Hormone
PubMed: 38390203
DOI: 10.3389/fendo.2024.1337741 -
Frontiers in Surgery 2024Usually, prolactinomas are treated with dopamine agonists (DA). Surgery is considered an option when the patient cannot bear or does not respond positively to DA therapy.
INTRODUCTION
Usually, prolactinomas are treated with dopamine agonists (DA). Surgery is considered an option when the patient cannot bear or does not respond positively to DA therapy.
AIM
This study aims to determine the early and late outcomes of surgery, with particular emphasis on developing prognostic factors for surgical treatment and analyzing risk factors affecting the recurrence of hyperprolactinemia and prolactinoma.
MATERIAL AND METHODS
This retrospective study was conducted at the Feofaniya Clinical Hospital of the State Administration of Affairs (Kyiv, Ukraine), evaluating 109 patients' records from 2009 to 2019. The main patients' inclusion criteria were: serum prolactin (PRL) level of more than 100 ng/ml, presence of pituitary adenoma (PA) on MRI, histologically approved PA by microscopy. According to the size of the prolactin-secreting PA (PSPAs) the selected 109 patients were divided into two groups: micro- (≤10 mm, = 75) and macroadenoma group (10-40 mm, = 34).
RESULTS
1 month after the operation, PRL levels decreased by 87% ( < 0.001), 12 months-by 93% ( < 0.001). After receiving surgery and DA therapy for 12 months 77.1% of patients achieved biochemical remission. Out of the total number of patients observed, 15.6% ( = 17) had a Knosp score greater than 3. Additionally, in the macroadenoma group, the percentage of patients with a Knosp score greater than 3 was 41,2%, which was significantly higher as compared to the microadenoma group (4%, < 0.001). In patients with microadenomas a weak reverse correlation between patients' age ( = -0.258, < 0.026) and positive with tumor size ( = 0.251, < 0.030) was revealed. In the macroadenoma group significant association was found only between preoperative serum PRL level and tumor size ( = 0.412, < 0.016). The preoperative PRL can be used as a diagnostic marker for lack of early biochemical remission in patients with PSPAs with diagnostic accuracy 66.9%.
CONCLUSIONS
This study found that primary transsphenoidal surgery is an effective treatment in reaching PRL level control in patients with both micro- and macroprolactinomas. The correct and thorough selection of candidates for surgery is crucial to achieve postoperative serum PRL normalization in the vast majority of patients.
PubMed: 38375408
DOI: 10.3389/fsurg.2024.1283179 -
Frontiers in Endocrinology 2024Prolactinomas (PRLomas) constitute approximately half of all pituitary adenomas and approximately one-fifth of them are diagnosed in males. The clinical presentation of... (Review)
Review
Prolactinomas (PRLomas) constitute approximately half of all pituitary adenomas and approximately one-fifth of them are diagnosed in males. The clinical presentation of PRLomas results from direct prolactin (PRL) action, duration and severity of hyperprolactinemia, and tumor mass effect. Male PRLomas, compared to females, tend to be larger and more invasive, are associated with higher PRL concentration at diagnosis, present higher proliferative potential, are more frequently resistant to standard pharmacotherapy, and thus may require multimodal approach, including surgical resection, radiotherapy, and alternative medical agents. Therefore, the management of PRLomas in men is challenging in many cases. Additionally, hyperprolactinemia is associated with a significant negative impact on men's health, including sexual function and fertility potential, bone health, cardiovascular and metabolic complications, leading to decreased quality of life. In this review, we highlight the differences in pathogenesis, clinical presentation and treatment of PRLomas concerning the male sex.
Topics: Female; Male; Humans; Prolactinoma; Hyperprolactinemia; Quality of Life; Pituitary Neoplasms; Adenoma
PubMed: 38370355
DOI: 10.3389/fendo.2024.1338345 -
CNS Neuroscience & Therapeutics Feb 2024Prolactinomas are the most prevalent functional pituitary neuroendocrine tumors (PitNETs), and they are invasive to surrounding anatomic structures. The detailed...
CONTEXT
Prolactinomas are the most prevalent functional pituitary neuroendocrine tumors (PitNETs), and they are invasive to surrounding anatomic structures. The detailed mechanisms of invasion are not yet clear.
OBJECTIVE
We explored the role of PBK phosphorylation in the proliferation and invasion of prolactinomas and its possible mechanism.
RESULTS
We report that PBK directly binds to and is phosphorylated at Thr9 by cyclin-dependent kinase 5 (CDK5), which promotes GH3 cell EMT progression and proliferation. Phosphorylation of PBK at Thr9 (pPBK-T9) by CDK5 enhances the stability of PBK. p38 is one of the downstream targets of PBK, and its phosphorylation is reduced as pPBK-T9 increases in vivo and in vitro. Furthermore, we found that pPBK-T9 is highly expressed in invasive PitNETs and was significantly correlated with invasion by univariate and multivariate analyses.
CONCLUSIONS
Phosphorylation of PBK at Thr9 by CDK5 promotes cell proliferation and EMT progression in prolactinomas.
Topics: Humans; Cell Proliferation; Cyclin-Dependent Kinase 5; Phosphorylation; Pituitary Neoplasms; Prolactinoma; Neoplasm Invasiveness
PubMed: 38363020
DOI: 10.1111/cns.14629 -
Acta Endocrinologica (Bucharest,... 2023Dopamine agonists (DA) are first line treatment for prolactinomas. Optic chiasm herniation can rarely occur during therapy, while brain herniation is very uncommon.
BACKGROUND
Dopamine agonists (DA) are first line treatment for prolactinomas. Optic chiasm herniation can rarely occur during therapy, while brain herniation is very uncommon.
CASE REPORTS
A 34 yo woman presented with headaches and vision changes. Prolactin (PRL) was 4300 ng/mL. MRI showed a 4.5 cm pituitary adenoma with chiasm compression. After 3 months, PRL decreased to 201 ng/mL while patient was taking CAB 0.75 mg twice a week. MRI showed ~30% tumor reduction with medial temporal lobe herniation and encephalocele. CAB was stopped and she underwent surgical debulking and encephalocele repair. Histopathology confirmed prolactin tumor. CAB 0.75 mg twice a week was resumed.A 50 yo man had incidental detection of a sellar mass after trauma. MRI showed 3.6 cm tumor with minimal contact of right optic nerve, and PRL 3,318 ng/ml. He received CAB 0.5mg twice a week with PRL improvement to 26 ng/mL after 1 month. After 2 months ophthalmology exam showed new left superotemporal depression. PRL was 68 ng/mL and MRI showed 35% mass reduction and new inferior displacement tethering of the chiasm. CAB dose was decreased to 0.25 mg twice a week.
CONCLUSION
Our cases illustrate that rapid biochemical and radiographic response to DA therapy in large prolactinomas warrants close clinical and neuro-ophthalmologic follow-up. We recommend repeating the MRI 3 months after initiation of DA therapy or sooner in case of new mass effect manifestations. Decision regarding DA dose reduction or chiasmopexy for visual field deficits needs to be multi-disciplinary and on a case-to-case basis.
PubMed: 38356985
DOI: 10.4183/aeb.2023.339 -
Neurologia Medico-chirurgica Apr 2024Prolactin-producing pituitary tumor (PRLoma) is the most prevalent functional pituitary tumor. If the tumor becomes large, vision can be impaired. In contrast to other...
Prolactin-producing pituitary tumor (PRLoma) is the most prevalent functional pituitary tumor. If the tumor becomes large, vision can be impaired. In contrast to other pituitary tumors, cabergoline (CAB) is extremely effective for PRLoma and has become the first-line treatment. In this study, we examined our experience with the pharmacological and surgical management of PRLomas with visual impairment (VI) to determine whether VI could be a surgical indication. Further, we discussed the function of surgery in situations where the gold standard of PRLoma treatment was CAB administration. Of the 159 patients with PRLomas (age, 13-77 [mean = 36.3] years; men, 29; women, 130) at Tokyo Women's Medical University Hospital from 2009 to 2021, 18 (age, 15-67 [mean = 35.8] years; men, 12; woman, 6) had VI (subjectively, 12; objectively, 6). They started CAB treatment immediately (maximum dose: 0.5 to 6 mg/week; average: 2.17 mg/week). VI improved in 16 patients (88.9%) but did not improve in 2 (11.1%) requiring surgeries. One of the two patients had a parenchymal tumor resistant to CAB, and the other had a cystic tumor due to intratumoral bleeding. Consequently, CAB is the first-line treatment for PRLomas with VI because of its significantly high rate of improvement. However, close and rigorous surveillance is necessary for cases resistant to CAB, and the correct decision is required regarding surgical interventions at proper timing and appropriate surgical approaches considering the purpose of surgery.
Topics: Male; Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Aged; Pituitary Neoplasms; Prolactinoma; Prolactin; Ergolines; Antineoplastic Agents; Cabergoline; Vision Disorders; Dopamine Agonists
PubMed: 38355129
DOI: 10.2176/jns-nmc.2023-0184 -
Problemy Endokrinologii Jan 2024The main treatment option of prolactin-secreting pituitary adenomas is dopamine agonist therapy, which demonstrates prolactin level normalizing and reducing the size of...
The main treatment option of prolactin-secreting pituitary adenomas is dopamine agonist therapy, which demonstrates prolactin level normalizing and reducing the size of an adenoma in the majority of cases. However, significant amount of patients - about 20% - poorly responds even to high doses of dopamine agonists that is explained by the resistance to therapy. The occurrence of pharmacodynamic characteristics is one of the causes responsible for the development of resistance to typical therapy. Clinical manifestations of persistent hyperprolactinemia are due to following pathological factors: hormonal hypersecretion and the mass-effect of pituitary adenoma. Prevention of irreversible changes is possible only with timely detection of resistance and determination of the optimal personalized treatment algorithm.We report a clinical case of dopamine-agonist resistant microprolactinoma. Patient's health stabilisation, normal level of prolactin and reduction in size of adenoma were achieved due to administration of combined treatment with tamoxifen and dopamine agonists. Hyperprolactinaemia occurring because of prolactin-secreting pituitary adenoma and associated adverse effects are significant problem, decreasing quality of life and demographics in general. This underlines the importance of figuring out causes and identifying predictors of the therapy resistance.The results of the study, illustrated by a clinical example, are presented in the present paper.
Topics: Humans; Prolactinoma; Dopamine Agonists; Prolactin; Quality of Life; Pituitary Neoplasms; Hyperprolactinemia; Adenoma
PubMed: 38311996
DOI: 10.14341/probl13351 -
AACE Clinical Case Reports 2024To report a case of adenomyosis in a woman with hyperprolactinemia which resolved after initiation of dopamine agonist therapy.
BACKGROUND/OBJECTIVE
To report a case of adenomyosis in a woman with hyperprolactinemia which resolved after initiation of dopamine agonist therapy.
CASE REPORT
A 35-year-old woman with a history of Graves' disease was referred for evaluation of hyperthyroidism in March 2020. She was started on methimazole and thyroid function normalized. The patient also had a history of a pituitary microadenoma and was previously treated with cabergoline which was stopped after 12 months as she became pregnant.In July 2020, the patient began to have polymenorrhea. Hyperprolactinemia was thought to be an unlikely cause as it most often causes hypogonadotropic hypogonadism with amenorrhea. A pelvic ultrasound demonstrated a bulky uterus with adenomyosis. Gynecology recommended treating adenomyosis by lowering her prolactin levels. She was started on cabergoline 0.25 mg weekly in October 2021. Within 2 months of initiation of cabergoline, she had resolution of symptoms and radiological resolution of adenomyosis.
DISCUSSION
Prolactin has been implicated in the pathogenesis of adenomyosis, endometriosis and leiomyomas suggesting that a decrease in prolactin levels may suppress these lesions. The pathogenesis of adenomyosis has been related to direct prolactin effects in the promotion of gland/cell proliferation and function.
CONCLUSION
We conclude that prolonged elevation in prolactin may result in the development of adenomyosis and subsequent prolonged abnormal uterine bleeding. Dopamine agonists, like cabergoline, inhibit the synthesis and secretion of prolactin from the pituitary gland and may have a role in the management of adenomyosis in patients with hyperprolactinemia.
PubMed: 38303768
DOI: 10.1016/j.aace.2023.11.002 -
Journal of Neurological Surgery. Part... Feb 2024Pituitary tumor treatment is hampered by the relative rarity of the disease, absence of a multicenter collaborative platform, and limited translational-clinical...
Pituitary tumor treatment is hampered by the relative rarity of the disease, absence of a multicenter collaborative platform, and limited translational-clinical research partnerships. Prior studies offer limited insight into the formation of a multicenter consortium. The authors describe the establishment of a multicenter research initiative, Registry of Adenomas of the Pituitary and Related Disorders (RAPID), to encourage quality improvement and research, promote scholarship, and apply innovative solutions in outcomes research. The challenges encountered during the formation of other research registries were reviewed with those lessons applied to the development of RAPID. RAPID was formed by 11 academic U.S. pituitary centers. A Steering Committee, bylaws, data coordination center, and leadership team have been established. Clinical modules with standardized data fields for nonfunctioning adenoma, prolactinoma, acromegaly, Cushing's disease, craniopharyngioma, and Rathke's cleft cyst were created using a Health Insurance Portability and Accountability Act-compliant cloud-based platform. Currently, RAPID has received institutional review board approval at all centers, compiled retrospective data and agreements from most centers, and begun prospective data collection at one site. Existing institutional databases are being mapped to one central repository. The RAPID consortium has laid the foundation for a multicenter collaboration to facilitate pituitary tumor and surgical research. We sought to share our experiences so that other groups also contemplating this approach may benefit. Future studies may include outcomes benchmarking, clinically annotated biobank tissue, multicenter outcomes studies, prospective intervention studies, translational research, and health economics studies focused on value-based care questions.
PubMed: 38274483
DOI: 10.1055/a-1978-9380 -
Diagnostics (Basel, Switzerland) Jan 2024Plurihormonal pituitary neuroendocrine tumors (PitNETs) are rare forms of tumors that express more than one hormone. The most common association is between growth...
Plurihormonal pituitary neuroendocrine tumors (PitNETs) are rare forms of tumors that express more than one hormone. The most common association is between growth hormone (GH) and prolactin (PRL), but other unusual combinations have been reported, such as GH and ACTH. Usually, the clinical dominance in these cases is related to GH hypersecretion. In these cases, immunohistochemistry (IHC) of transcription factors (TFs) is very useful for an accurate diagnosis. We included 42 patients diagnosed with pituitary neuroendocrine tumors (PitNETs): 37 patients with a confirmed diagnosis of acromegaly, and 5 patients with prolactinomas. All patients underwent transsphenoidal surgical intervention. We correlated the immunohistochemical features of plurihormonal PitNETs with clinical, hormonal, and imaging data. Tumor specimens were histologically and immunohistochemically examined. Based on the 2022 WHO classification, using IHC, 13 patients exhibited positive staining for more than one hormone, while unusual combinations like GH + ACTH and PRL + ACTH were also identified in other cases. Unusual cell combinations that produce hormones unrelated histogenetically, biochemically, or through regulatory mechanisms can appear and may display aggressive behavior, persistent disease, and high recurrence. We have not identified a clear correlation with the prognosis of these rare PitNETs.
PubMed: 38248047
DOI: 10.3390/diagnostics14020170