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Frontiers in Clinical Diabetes and... 2023Robust experiment evidence suggests that prolactin can enhance beta-cell proliferation and increase insulin secretion and sensitivity. Apart from acting as an endocrine... (Review)
Review
Robust experiment evidence suggests that prolactin can enhance beta-cell proliferation and increase insulin secretion and sensitivity. Apart from acting as an endocrine hormone, it also function as an adipokine and act on adipocytes to modulate adipogenesis, lipid metabolism and inflammation. Several cross-sectional epidemiologic studies consistently showed that circulating prolactin levels positive correlated with increased insulin sensitivity, lower glucose and lipid levels, and lower prevalence of T2D and metabolic syndrome. Bromocriptine, a dopamine receptor agonist used to treat prolactinoma, is approved by Food and Drug Administration for treatment in type 2 diabetes mellitus since 2009. Prolactin lowering suppress insulin secretion and decrease insulin sensitivity, therefore dopamine receptor agonists which act at the pituitary to lower serum prolactin levels are expected to impair glucose tolerance. Making it more complicating, studies exploring the glucose-lowering mechanism of bromocriptine and cabergoline have resulted in contradictory results; while some demonstrated actions independently on prolactin status, others showed glucose lowering partly explained by prolactin level. Previous studies showed that a moderate increase in central intraventricular prolactin levels stimulates hypothalamic dopamine with a decreased serum prolactin level and improved glucose metabolism. Additionally, sharp wave-ripples from the hippocampus modulates peripheral glucose level within 10 minutes, providing evidence for a mechanistic link between hypothalamus and blood glucose control. Central insulin in the mesolimbic system have been shown to suppress dopamine levels thus comprising a feedback control loop. Central dopamine and prolactin levels plays a key role in the glucose homeostasis control, and their dysregulation could lead to the pathognomonic central insulin resistance depicted in the "ominous octet". This review aims to provide an in-depth discussion on the glucose-lowering mechanism of dopamine receptor agonists and on the diverse prolactin and dopamine actions on metabolism targets.
PubMed: 36993818
DOI: 10.3389/fcdhc.2023.935872 -
The Journal of Clinical Endocrinology... Aug 2023Prolactinomas are the most common pituitary tumor histotype, with microprolactinomas being prevalent in women and macroprolactinomas in men. Hyperprolactinemia is among... (Review)
Review
Prolactinomas are the most common pituitary tumor histotype, with microprolactinomas being prevalent in women and macroprolactinomas in men. Hyperprolactinemia is among the most common causes of hypogonadotropic hypogonadism in both sexes, prompting medical advice for hypogonadism (infertility, oligo-amenorrhea, impotence, osteoporosis/osteopenia) in both sexes, and for signs and symptoms of mass effects (hypopituitarism, visual loss, optic chiasm compression, cranial nerve deficits, headaches) predominantly in men. Diagnostic workup involves a single prolactin measurement and pituitary imaging, but some laboratory artifacts (ie, the "hook effect" and macroprolactin) can complicate or delay the diagnosis. The treatment of choice for prolactinomas is represented by dopamine agonists, mainly cabergoline, which are able to induce disease control, restore fertility in both sexes, and definitively cure one-third of patients, thus permitting treatment discontinuation. Pregnancy and menopause may promote spontaneous prolactin decline and anticipate cabergoline discontinuation in women. Surgery and/or radiotherapy are indicated in case of resistance to cabergoline not overcome by the increase in drug dose up to the maximally tolerated or the patient's personal choice of surgery. The evidence of resistance to cabergoline in invasive and proliferative tumors may indicate biological aggressiveness, thus requiring alternative therapeutic approaches mainly based on temozolomide use as monotherapy or combined with radiotherapy. In uncontrolled patients, new medical approaches (alternative hormonal treatments, cytotoxic drugs, peptide receptor radionuclide therapy, mTOR/Akt inhibitors, tyrosine kinase inhibitors, or immunotherapy) may be offered but the experience collected to date is still very scant. This article reviews different facets of prolactinomas and discusses approaches to the condition in more common clinical situations.
Topics: Male; Pregnancy; Humans; Female; Prolactinoma; Cabergoline; Prolactin; Ergolines; Pituitary Neoplasms; Dopamine Agonists; Hypogonadism
PubMed: 36974474
DOI: 10.1210/clinem/dgad174 -
Faculty Reviews 2023Pituitary adenomas (PAs) are common intracranial tumors. Despite their benign nature, PAs may cause a significant burden of disease, leading to either hormonal... (Review)
Review
Pituitary adenomas (PAs) are common intracranial tumors. Despite their benign nature, PAs may cause a significant burden of disease, leading to either hormonal disturbances or local compression. A subset of PAs presents an aggressive behavior that remains difficult to predict, and in rare cases they metastasize. Therefore, early diagnosis and treatment are important. Advances in molecular pathology have improved the understanding of their pathogenesis and offer opportunities to identify and target novel pathways. Improved imaging and functional molecular techniques precisely detect even very small tumors and guide targeted treatment. Transsphenoidal surgery is the first-line treatment for the majority of PAs, and advances in the field of endoscopic neurosurgery offer excellent outcomes. Dopamine agonists (DAs) are traditionally the first-line treatment for prolactinomas. For patients with acromegaly, first- and second-generation somatostatin analogues (SSAs) are applied when surgery is not successful or not indicated. For Cushing's disease (CD), drugs targeting adrenal steroidogenesis, somatostatin receptors in the pituitary, and glucocorticoid receptors are used to treat hypercortisolism in patients with persistent or recurrent CD, for those who are not good surgical candidates, and as a bridge treatment for those who have undergone radiation treatment until cortisol levels are controlled. Temozolomide (TMZ) is the first-line chemotherapy for aggressive PAs, but new experimental therapies, like the anti-vascular endothelial growth factor (anti-VEGF) therapy, mechanistic target of rapamycin (mTOR) inhibitors, tyrosine kinase inhibitors, and cell cycle and checkpoint inhibitors, are now available. Radiotherapy is offered to patients with residual, recurrent, or progressive tumors. Modern techniques in radiotherapy planning and delivery are able to deliver high doses to the target tissue while sparing vital structures. As we familiarize ourselves with the biological behavior of PAs and our therapeutic armamentarium expands, the next goal is to tailor and personalize treatment to each individual patient so as to achieve the best outcome.
PubMed: 36968144
DOI: 10.12703/r/12-6 -
Minerva Surgery Oct 2023We aimed to compare the treatment outcomes of neuroendoscopic and microscopic trans-sphenoidal pituitary adenomectomies, as well as the effects on hormone levels and...
BACKGROUND
We aimed to compare the treatment outcomes of neuroendoscopic and microscopic trans-sphenoidal pituitary adenomectomies, as well as the effects on hormone levels and clinical symptoms.
METHODS
A total of 82 patients with pituitary adenomas that were surgically resected from June 2018 to March 2021 were selected and divided into a group receiving neuroendoscopic trans-sphenoidal pituitary adenomectomy (group A, N.=40), and the other group receiving microscopic surgery (group B, N.=42). Surgery-related indices, hormone levels before discharge and alleviation of symptoms 24 weeks after surgery were compared.
RESULTS
Both groups had significantly different degrees of tumor resection (P<0.05). The proportion of cases receiving total adenomectomy in group A significantly exceeded that of group B (P<0.05). The surgical time of group A was significantly longer than that of group B (P<0.05). Group A had significantly shorter mean hospitalization stay than that of group B (P<0.05). The postoperative hormone levels of both groups decreased significantly differently (P<0.05). Before discharge, the hormone recovery rate of group A significantly surpassed that of group B (P<0.05). The hormone levels of cases with prolactinoma, adrenocorticotropic hormone adenoma and growth hormone adenoma in group A dropped more significantly than those of group B did (P<0.05).
CONCLUSIONS
Compared with microscopic surgery, neuroendoscopic trans-sphenoidal pituitary adenomectomy worked more effectively, induced fewer postoperative complications and better promoted the postoperative recovery of hormone levels.
PubMed: 36951674
DOI: 10.23736/S2724-5691.23.09779-4 -
Cureus Feb 2023The management of dopamine agonist (DA)-resistant prolactinomas unresponsive to second and third-line treatment is challenging and requires alternative medical therapy.... (Review)
Review
The management of dopamine agonist (DA)-resistant prolactinomas unresponsive to second and third-line treatment is challenging and requires alternative medical therapy. The presence of estrogen receptors on pituitary tumors, and the variable behavior of pituitary tumors in the presence of estrogen, prompted investigation of the role of anti-estrogen in the treatment of DA-resistant prolactinomas. The goal of this paper is to perform a systematic review of the role of tamoxifen in the treatment of DA-resistant prolactinomas. A systematic review was conducted. Inclusion criteria were case reports, case series, and experimental studies using tamoxifen in DA-resistant prolactinomas. Exclusion criteria included review articles, DA-sensitive prolactinomas, and those that were not previously treated with DA. Data were analyzed using descriptive statistics. For continuous data, the mean was used. For dichotomous data, frequencies and percentages were used. Data on 22 patients were extracted from the seven included studies. Twenty patients (90.9%) responded positively to the use of tamoxifen with a mean reduction in prolactin levels of 57.4%. Ten patients (45.5%) showed normalization of prolactin post-tamoxifen administration. Regression of tumor size and stability of tumor growth were reported in four out of 22 cases (18.2%). Combination therapy with DA and tamoxifen increased DA sensitivity and had a clinically significant inhibitory effect on prolactin secretion. Furthermore, tamoxifen may be considered an effective adjuvant for tumor size control. Therefore, further studies are needed to draw more clinically and statistically robust conclusions.
PubMed: 36950000
DOI: 10.7759/cureus.35171 -
Pituitary Jun 2023A small subset of lactotroph adenomas is resistant to dopamine agonists (DA) and can also demonstrate aggressive or even malignant behavior. The implicated mechanisms... (Review)
Review
A small subset of lactotroph adenomas is resistant to dopamine agonists (DA) and can also demonstrate aggressive or even malignant behavior. The implicated mechanisms are not clearly defined. Management can be challenging and requires a multidisciplinary approach. In DA resistant prolactinomas, switching to another DA could be the first option to consider. Further strategies include surgery and radiotherapy used alone or in combination. In cases of aggressive or malignant prolactinomas, temozolomide could be offered. Immune checkpoint inhibitors have been also recently proposed as an alternative approach. The place of other treatments (e.g., metformin, selective estrogen modulators, somatostatin analogues, tyrosine kinase inhibitors, inhibitors of mammalian target of rapamycin and peptide radio-receptor therapy) remains to be carefully assessed.
Topics: Humans; Prolactinoma; Pituitary Neoplasms; Dopamine Agonists; Temozolomide; Somatostatin
PubMed: 36928728
DOI: 10.1007/s11102-023-01305-8 -
Journal of Medical Case Reports Mar 2023Resistance to dopamine agonists is not uncommonly seen in prolactinomas. However, development of resistance to dopamine agonists after an initial period of robust... (Review)
Review
BACKGROUND
Resistance to dopamine agonists is not uncommonly seen in prolactinomas. However, development of resistance to dopamine agonists after an initial period of robust treatment response is rare, and only 39 cases have been reported in the past four decades. We describe a Chinese man with this rare condition and explored the postulated mechanisms that may explain this phenomenon. We compiled similar cases that were previously reported and compared their etiology, progress, and response to treatment. On the basis of these cases, we derived a list of differential diagnoses to consider in patients with secondary resistance to dopamine agonists.
CASE PRESENTATION
A 63-year-old Chinese man presented with blurred vision and was subsequently diagnosed with a macroprolactinoma. He had initial response to cabergoline but developed secondary resistance to it after 5 years. The prolactinoma continued to grow, and his serum prolactin remained markedly elevated despite adherence to escalating dosages of cabergoline up to 6 mg/week. The patient finally underwent transsphenoidal surgery and was found to have a sparsely granulated lactotroph tumor with Ki-67 index of 5%. Postoperatively, there was improvement in his serum prolactin level, although he still required treatment with cabergoline at 6 mg/week.
CONCLUSIONS
Surgery can facilitate disease control in patients with prolactinomas that develop secondary resistance to dopamine agonists. Malignant prolactinoma is an important differential diagnosis in this group of patients, especially when serum prolactin remains markedly elevated despite resolution or stability of the primary pituitary lesion, suggesting a metastatic source of prolactin secretion.
Topics: Male; Humans; Middle Aged; Prolactinoma; Dopamine Agonists; Cabergoline; Ergolines; Prolactin; Pituitary Neoplasms
PubMed: 36927797
DOI: 10.1186/s13256-023-03820-5 -
Cureus Feb 2023Pituitary composite tumors consisting of metastasis within an adenoma are rare and aggressive entities. We present a case of esophageal adenocarcinoma metastasis at a...
Pituitary composite tumors consisting of metastasis within an adenoma are rare and aggressive entities. We present a case of esophageal adenocarcinoma metastasis at a prolactinoma presenting in a unique fashion and highlight how this case could contribute to a better understanding and early recognition of this condition. The patient was a 65-year-old male who presented with partial palsy of the third and sixth cranial nerves. He had a history of treated esophageal adenocarcinoma. He also had a known small parasellar lesion, with an elevated prolactin. Investigations showed a rapid progression of the parasellar lesion and normalization of prolactin. Partial surgical resection was performed, and pathology confirmed metastasis of the known digestive tract neoplasia. Although extremely rare, dual pathology of pituitary metastasis within adenomas should be considered in the differential diagnosis of sellar masses. Atypical behavior of benign adenomas, including rapid growth, spontaneous normalization of prolactin, or progression despite medical treatment should prompt medical teams to reconsider their diagnosis.
PubMed: 36909111
DOI: 10.7759/cureus.34676 -
Surgical Neurology International 2023A giant prolactinoma extending to the suprasellar area and causing hydrocephalus may be life-threatening and should be treated promptly. A case of a giant prolactinoma...
BACKGROUND
A giant prolactinoma extending to the suprasellar area and causing hydrocephalus may be life-threatening and should be treated promptly. A case of a giant prolactinoma with acute hydrocephalus that underwent transventricular neuroendoscopic tumor resection followed by cabergoline administration is presented.
CASE DESCRIPTION
A 21-year-old man had a headache lasting for about a month. He gradually developed nausea and disturbance of consciousness. Magnetic resonance imaging showed a contrast-enhanced lesion that extended from the intrasellar space to the suprasellar space and into the third ventricle. The tumor obstructed the foramen of Monro and caused hydrocephalus. A blood test showed marked elevation of prolactin (16,790 ng/mL). The tumor was diagnosed as a prolactinoma. The tumor in the third ventricle had formed a cyst, and the cyst wall blocked the right foramen of Monro. The cystic component of the tumor was resected using an Olympus VEF-V flexible neuroendoscope. The histological diagnosis was pituitary adenoma. The hydrocephalus improved rapidly and his consciousness became clear. After the operation, he was started on cabergoline. The tumor size subsequently decreased.
CONCLUSION
Prompt partial resection of the giant prolactinoma by transventricular neuroendoscopy resulted in early improvement of hydrocephalus with less invasiveness, allowing subsequent treatment with cabergoline.
PubMed: 36895233
DOI: 10.25259/SNI_1060_2022