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Cancers Feb 2024Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing's disease, can result in hypertension. However, whether prolactinoma is...
Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing's disease, can result in hypertension. However, whether prolactinoma is associated with this complication remains unknown. Moreover, the effect of treatment with surgery or drugs on blood pressure (BP) is unknown. Herein, a retrospective study reviewed 162 patients with prolactinoma who underwent transsphenoidal surgery between January 2005 and December 2022. BP measurements were performed 1 day before and 5 days after surgery. Accordingly, patients' medical characteristics were recorded. In addition, in situ rat and xenograft nude-mice prolactinoma models have been used to mimic prolactinoma. In vivo BP and serum prolactin (PRL) levels were measured after cabergoline (CAB) administration in both rats and mice. Our data suggest that surgery can effectively decrease BP in prolactinoma patients with or without hypertension. The BP-lowering effect was significantly associated with several variables, including age, sex, disease duration, tumor size, invasion, dopamine agonists (DAs)-resistance, recurrence, and preoperative PRL levels. Moreover, in situ and xenograft prolactinomas induced BP elevation, which was alleviated by CAB treatment without and with a statistical difference in rats and mice, respectively. Thus, surgery or CAB can decrease BP in prolactinoma, indicating that pre- and postoperative BP management becomes essential.
PubMed: 38398117
DOI: 10.3390/cancers16040726 -
Neuroendocrinology 2024Acromegaly patients, in addition to the most prominent physical and endocrine changes, also exhibit a higher risk of cognitive dysfunction. However, the reasons and...
INTRODUCTION
Acromegaly patients, in addition to the most prominent physical and endocrine changes, also exhibit a higher risk of cognitive dysfunction. However, the reasons and mechanisms underlying cognitive impairments in acromegaly patients remain unknown.
METHODS
Acromegalic rats were induced by subcutaneous injection of tumor cells, with continuous monitoring of the body weight and hormones to confirm the occurrence of acromegaly. Behavioral assessments, including open field test, novel object recognition test, and Barnes maze test, were conducted to evaluate the animals' cognitive function. Western blotting, immunohistochemistry, and immunofluorescence techniques were employed to examine changes in the hippocampal tau protein, Aβ, and associated signaling pathways.
RESULTS
The tumor cells secreting growth hormone increased the secretion of growth hormone, resulting in changes in body size and endocrine functions, thus causing acromegaly. The acromegaly model showed deficiencies in working memory and spatial memory. Hyperphosphorylation of tau protein was observed in the hippocampus of the acromegaly model, but no Aβ deposition was observed. The acromegaly model exhibits hippocampal growth hormone (GH) resistance, decreased expression of GH receptors, and subsequently reduced expression activity of the PI3K-Akt-GSK3β signaling pathway, which is responsible for the hyperphosphorylation of tau protein.
CONCLUSION
The prolonged elevation of GH and insulin-like growth factor 1 caused by acromegaly may lead to abnormalities in the SD rat's PI3K-Akt-GSK3β signaling pathway, subsequently resulting in hyperphosphorylation of the hippocampal tau protein and cognitive impairment.
Topics: Animals; Male; Rats; Acromegaly; Cognitive Dysfunction; Disease Models, Animal; Growth Hormone; Hippocampus; Insulin-Like Growth Factor I; Maze Learning; Phosphorylation; Rats, Sprague-Dawley; Signal Transduction; tau Proteins
PubMed: 38368872
DOI: 10.1159/000537813 -
Frontiers in Endocrinology 2024Acromegaly is caused by excessive growth hormone (GH) and insulin-like growth factor 1 (IGF1). Medical therapy plays a role as a treatment option for persistent disease...
BACKGROUND
Acromegaly is caused by excessive growth hormone (GH) and insulin-like growth factor 1 (IGF1). Medical therapy plays a role as a treatment option for persistent disease after non-curative surgery or as a first-line therapy when surgery is not feasible. Pasireotide-LAR (Pas-LAR) is recommended for patients with acromegaly as second-line treatment.
AIM
To evaluate the patients characteristics predictive of an adequate response to Pas-LAR and the long-term efficacy and safety of the Pas-LAR treatment.
METHODS
Data from 19 patients with active acromegaly, who were and resistant or intolerant to first-line medical therapy and were switched to pas-LAR have been retrospectively collected. We compared the baseline clinical and biochemical characteristics of patients who were found to respond to Pas-LAR therapy (responders, n=14) with those of patients who did not respond (non-responders, n=5). We then evaluated the Pas-LAR efficacy and safety during long-term follow-up in responders.
RESULTS
IGF1 normalization occurred in 71.4% of responders after one injection. IGF1 levels, [median(interquartile range) of the upper limit of the normal range (ULN) fold increase] were higher in non-responders compared to responders within the initial month of therapy [1.40(1.30-2.34) vs 0.70(0.55-1.25), respectively, p=0.009] and after three [1.77(1.74-2.29) vs 0.94(0.82-1.13), respectively, p=0.029] and six months [1.68(1.33-1.72) vs 1.00(0.65 -1.28), respectively, p=0.002]. Out of 6 patients with symptomatic headache (all in responder group), 5 and 1 reported the resolution and improvement of headache, respectively, already after the first injection. Median HbA1c levels tended to increase from baseline to 6 months both in responder (36 mMol/Mol to 42 mMol/Mol) and non-responder patients (45 mMol/Mol to 48 mMol/Mol). During long term follow up, in the responder group 2 new patients developed diabetes. Tumor shrinkage was observed in 6 out of 7 evaluated responders, with no cases of size increase during the long-term follow-up.
CONCLUSION
Pas-LAR is effective and safe and the early identification of responders is possible just after the first administration.
Topics: Humans; Acromegaly; Retrospective Studies; Human Growth Hormone; Treatment Outcome; Headache; Somatostatin
PubMed: 38362280
DOI: 10.3389/fendo.2024.1344728 -
Frontiers in Endocrinology 2024
Topics: Humans; Acromegaly; Treatment Outcome; Human Growth Hormone; Comorbidity
PubMed: 38348419
DOI: 10.3389/fendo.2024.1351350 -
Diabetes, Metabolic Syndrome and... 2024Uric acid (UA) is the end product of purine metabolism in the human, and the imbalance between production and excretion results in the disturbance of serum uric acid... (Review)
Review
Uric acid (UA) is the end product of purine metabolism in the human, and the imbalance between production and excretion results in the disturbance of serum uric acid (SUA). There is evidence suggesting that pituitary-target gland hormones can affect UA metabolism through regulating the activity of xanthine oxidase and UA transporters. Related endocrine diseases including thyroid dysfunction, polycystic ovary syndrome, acromegaly and Cushing's syndrome are often accompanied by elevated UA levels. In addition to the direct influence of abnormal hormones, obesity and insulin resistant play a pivotal role. Diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion also present with abnormal SUA levels due to the action of antidiuretic hormone. However, certain evidence within the population is disputed. This review summarized the effects of pituitary-target gland hormones on UA metabolism, and preliminarily described the related mechanisms, offering a theoretical foundation for assessing SUA in endocrine disorders as well as guiding its management.
PubMed: 38343584
DOI: 10.2147/DMSO.S448547 -
International Journal of Molecular... Feb 2024Several genetic investigations were conducted to identify germline and somatic mutations in somatotropinomas, a subtype of pituitary tumors. To our knowledge, we report...
Several genetic investigations were conducted to identify germline and somatic mutations in somatotropinomas, a subtype of pituitary tumors. To our knowledge, we report the first acromegaly patient carrying a pathogenic variant: c.2410G>A (rs79658334), p.Val804Met. Alongside the fact that the patient's father and daughter carried the same variant, we investigated the clinical significance of this variant in the context of somatotropinomas and other endocrine tumors, reviewing the mutations' oncogenic mechanisms. The aim was to search for new targets to precisely manage and treat acromegaly. Our case describes a new phenotype associated with the pathogenic variant, represented by aggressive acromegaly, and suggests consideration for mutation screening if NGS for well-established PitNET-associated gene mutations renders negative.
Topics: Humans; Acromegaly; Germ-Line Mutation; Multiple Endocrine Neoplasia Type 2a; Mutation; Phenotype; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms
PubMed: 38339173
DOI: 10.3390/ijms25031895 -
Journal of Feline Medicine and Surgery Feb 2024Diabetes mellitus is the second-most common feline endocrinopathy, affecting an estimated 1/200 cats. While the underlying causes vary, around 15-25% of cats with... (Review)
Review
PRACTICAL RELEVANCE
Diabetes mellitus is the second-most common feline endocrinopathy, affecting an estimated 1/200 cats. While the underlying causes vary, around 15-25% of cats with diabetes mellitus develop the condition secondarily to progressive growth hormone (GH)-induced insulin resistance. This typically results in a form of diabetes that is challenging to manage, whereby the response to insulin is very variable or high doses are required to achieve even minimal diabetic control.
CLINICAL CHALLENGES
Although uncontrolled chronic excessive GH may result in phenotypic changes that raise suspicion for acromegaly, many cats with hypersomatotropism (HST) do not have these changes. In these situations, a clinician's index of suspicion may be increased by the presence of less dramatic changes such as marked polyphagia, stertor or uncontrolled diabetes mellitus. The current diagnostic test of choice is demonstration of a markedly increased serum insulin-like growth factor 1 (IGF1) concentration, but some affected cats will have only a marginal increase; additionally, chronic insulin administration in cats results in an increase in serum IGF1, making the diagnosis less clear cut and requiring additional confirmatory tests.
EVIDENCE BASE
Over the past two decades, HST has increasingly been recognised as an underlying cause of diabetes mellitus in cats. This review, which focuses on diagnosis and treatment, utilises data from observational studies, clinical trials and case series, as well as drawing on the experience of the authors in managing this condition.
Topics: Cats; Animals; Acromegaly; Growth Hormone; Diabetes Mellitus; Insulin; Cat Diseases
PubMed: 38323402
DOI: 10.1177/1098612X241226690 -
BMC Endocrine Disorders Jan 2024Management of recurrent acromegaly is challenging for both neurosurgeons and endocrinologists. Several treatment options including repeat surgery, medical therapy, and...
BACKGROUND AND OBJECTIVE
Management of recurrent acromegaly is challenging for both neurosurgeons and endocrinologists. Several treatment options including repeat surgery, medical therapy, and radiation are offered for such patients. The efficacy of these modalities for the treatment of recurrence has not been studied previously in the literature. In this study, we aim to systematically review the existing cases of recurrence and come to a conclusion regarding the appropriate treatment in such cases.
METHOD
A systematic review was performed through PubMed, Scopus, Web of Science, and Cochrane database to identify studies reporting the treatment outcome of recurrent acromegaly patients. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the included studies were reviewed for primary and secondary treatment, complications, and outcomes of the secondary treatment.
RESULTS
The systematic review retrieved 23 records with 95 cases of recurrent acromegaly. The mean time of recurrence was 4.16 years after the initial treatment. The most common primary treatment was surgery followed by radiotherapy. The remission rate was significantly higher in medical and radiotherapy compared to surgical treatment.
CONCLUSION
In cases of recurrent acromegaly, the patient may benefit more from radiotherapy and medical therapy compared to surgery. As the quality of evidence is low on this matter feature studies specifically designed for recurrent patients are needed.
Topics: Humans; Acromegaly; Treatment Outcome; Reoperation
PubMed: 38279102
DOI: 10.1186/s12902-023-01533-w -
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 -
Frontiers in Neuroscience 2023Plurihormonal pituitary adenoma (PPA) is a type of pituitary tumor capable of producing two or more hormones and usually presents as an aggressive, large adenoma. As... (Review)
Review
Plurihormonal pituitary adenoma (PPA) is a type of pituitary tumor capable of producing two or more hormones and usually presents as an aggressive, large adenoma. As yet, its pathogenesis remains unclear. This is the first study to systematically summarize the underlying pathogenesis of PPA. The pathogenesis is related to plurihormonal primordial stem cells, co-transcription factors, hormone co-expression, differential gene expression, and cell transdifferentiation. We conducted a literature review of PPA and analyzed its clinical characteristics. We found that the average age of patients with PPA was approximately 40 years, and most showed only one clinical symptom. The most common manifestation was acromegaly. Currently, PPA is treated with surgical resection. However, recent studies suggest that immunotherapy may be a potentially effective treatment.
PubMed: 38260014
DOI: 10.3389/fnins.2023.1323883