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Cureus Nov 2023Many antipsychotic (AP) medications work by reducing dopamine levels. As hyperdopaminergia is known to cause psychosis, antipsychotics work to relieve these symptoms by... (Review)
Review
Many antipsychotic (AP) medications work by reducing dopamine levels. As hyperdopaminergia is known to cause psychosis, antipsychotics work to relieve these symptoms by antagonizing dopamine receptors and lowering dopamine levels. Dopamine is also a known negative modulator of the prolactin pathway, which allows for drug agents like dopamine agonists (DAs) to be incredibly effective in managing tumors that secrete excess prolactin (prolactinomas). While the effects of DAs on prolactinoma size and growth have been studied for decades, the effects of APs on prolactinoma size remain to be seen. We hope to investigate the effects of APs on prolactinomas by conducting a thorough PubMed search, including patients with diagnosed prolactinoma on concurrent AP therapy. Our search led to 27 studies with a total of 32 patients. We identified themes regarding seven antipsychotics: risperidone, haloperidol, amisulpride, thioridazine, aripiprazole, olanzapine, and clozapine. Risperidone, haloperidol, amisulpride, and thioridazine caused a significant increase in prolactin in most cases where they were used, and prolactin decreased after their discontinuation. For example, risperidone discontinuation resulted in a decrease in prolactin levels by an average of 66%, while haloperidol, amisulpride, and thioridazine discontinuation lowered prolactin by an average of 82%, 72%, and 89.7%, respectively. However, there were some exceptions in regard to risperidone, haloperidol, and thioridazine, where prolactin levels were not as severely affected. Aripiprazole, olanzapine, and clozapine all had significant reductions in prolactin levels when patients were switched from another antipsychotic, such as risperidone or haloperidol. The average percent decrease in prolactin when switched to aripiprazole was 67.65%, while it was 54.16% and 68% for olanzapine and clozapine, respectively. The effect of individual antipsychotics on prolactinoma size was difficult to ascertain, as imaging was not obtained (or indicated) after every antipsychotic switch, and many patients were taking dopamine agonists concurrently. Therefore, it would be difficult to ascertain which factor affected size more. Also, some patients received surgery or radiotherapy, which completely negated our ability to make any assertions about the effects of certain pharmacological agents. Although it is difficult to ascertain the role that antipsychotic medications play in the formation of prolactinoma, we have found that the cessation of certain antipsychotic medications may lead to a reduction in prolactin levels and possibly the presence of a measurable prolactinoma.
PubMed: 38143631
DOI: 10.7759/cureus.49342 -
Neuropathology : Official Journal of... Jun 2024A dopamine agonist administered for prolactinoma treatment and pituitary stimulation tests are reported as risk factors for pituitary apoplexy. We report a case of an...
A dopamine agonist administered for prolactinoma treatment and pituitary stimulation tests are reported as risk factors for pituitary apoplexy. We report a case of an 82-year-old patient who suffered from pituitary apoplexy in an endocrinologically silent adenoma during lanreotide administration. The patient was diagnosed with a pancreatic neuroendocrine tumor with lymph node metastasis and treated with lanreotide for two years. An endoscopic endonasal transsphenoidal approach was used for tumor and hematoma removal. The specimen showed growth hormone and prolactin positivity and was diagnosed as pit1-lineage plurihormonal adenoma. The tumor also showed positivity for somatostatin receptor 2. Thus, lanreotide treatment is a risk factor for pituitary apoplexy even in silent adenoma.
Topics: Humans; Pancreatic Neoplasms; Somatostatin; Neuroendocrine Tumors; Aged, 80 and over; Pituitary Apoplexy; Adenoma; Peptides, Cyclic; Male; Pituitary Neoplasms; Antineoplastic Agents
PubMed: 38099404
DOI: 10.1111/neup.12959 -
Annals of Medicine and Surgery (2012) Dec 2023Secretory pituitary macroadenoma also known as prolactinoma are benign neoplasm comprising very minimal cases of intracranial masses. Among the various presentation...
INTRODUCTION AND IMPORTANCE
Secretory pituitary macroadenoma also known as prolactinoma are benign neoplasm comprising very minimal cases of intracranial masses. Among the various presentation suggestive of panhypopituitarism, psychosis, and features of schizophrenia is very rarely seen. In the majority of cases, neurosurgical intervention for the excision of tumor is considered a standard treatment modality but conservative management with dopamine agonist and steroids have also been shown to provide an optimal level of care also improving the quality of level of patient.
CASE PRESENTATION
A 42-year-old Asian male presented with a history of talking to self, delusion of persecution, over talkativeness, hallucination, increased suspiciousness, and history of lost and found in the streets where he was working as a migrant worker. The patient was initially managed in line of schizophrenia with the antipsychotics drug of choice. On further assessment there was no improvement of psychiatric symptoms but they further deteriorated with additional neuropsychiatric symptoms; hence, MRI brain was carried out. Following which, the diagnosis of pituitary macroadenoma was confirmed and further more hormonal analysis was done, which showed findings suggestive of panhypopituitarism. The patient was then managed conservatively with dopamine agonist and steroids, which showed rapid improvement of psychiatric symptoms with a massive reduction in the size of the pituitary macroadenoma.
CLINICAL DISCUSSION
With the incidence of 100 per million cases pituitary adenomas are considered locally invading with the characteristic compression of the surrounding structure, presenting as visual hallucinations, olfactory hallucinations, episodes of losing time, apathy, and features suggestive of adrenal insufficiency, hypogonadotrophic hypogonadism, and symptoms secondary to hormonal imbalance such as hypothyroidism. Psychiatric symptomatic presentations are considered a very rare presentation in cases of pituitary macroadenoma. Also, psychiatric features and symptoms of psychosis are associated with prolcatinomas through idiopathic mechanism and the basic casualty has not been established. Surgical intervention such as trans-sphenoidal resection of the mass can be undertaken in case where mass effects is present but long-term remission and prognosis is found not to be fruitful. Conservative treatment with dopamine agonist such as cabergoline and steroids also plays a meaningful role in abrupt management in such cases.
CONCLUSION
Pituitary macroadenoma presenting as a patient of schizophrenia is noted very rarely in medical literature; hence, investigations in view of neurosurgical diagnosis in cases presenting as psychosis should be considered for ideal holistic management. Conservative management can also be a breakthrough treatment modality in complete recovery of pituitary macroadenoma.
PubMed: 38098557
DOI: 10.1097/MS9.0000000000001413 -
Frontiers in Endocrinology 2023To summarize the clinical characteristics of 4 male prolactinoma patients with severe obesity.
OBJECTIVE
To summarize the clinical characteristics of 4 male prolactinoma patients with severe obesity.
METHODS
The clinical data of all the patients were retrospectively analyzed.
RESULTS
All the patients visited our hospital for severe obesity at the age of 16-30 years old with their body mass index (BMI) of 37.9-55.9 kg/m. All the patients were obese since childhood, even at birth. Hyperprolactinemia (72.3-273.0 ng/ml) was found during the etiological screening of obesity and MRI revealed pituitary adenomas. Additionally, all of them had multiple obesity related complications, such as hyperinsulinemia and dyslipidemia. Treatment of dopamine agonists (DAs) effectively normalized their prolactin level and the pituitary MRI reexamination after 6 months of DAs treatment showed the shrinkage of the pituitary adenomas in 3 patients. Their weight also decreased in different degrees (2.70~19.03% lower than the baseline) with improved metabolic profiles.
CONCLUSION
Serum prolactin level should be screened in obese patients, especially those with severe obesity.
Topics: Infant, Newborn; Humans; Male; Child; Adolescent; Young Adult; Adult; Prolactinoma; Pituitary Neoplasms; Dopamine Agonists; Prolactin; Obesity, Morbid; Retrospective Studies; Obesity; Adenoma
PubMed: 38093965
DOI: 10.3389/fendo.2023.1285477 -
Clinical Neurology and Neurosurgery Jan 2024First-line prolactin-secreting tumor (PST) management typically involves treatment with dopamine agonists and the role of surgery remains to be further explored. We...
OBJECTIVE
First-line prolactin-secreting tumor (PST) management typically involves treatment with dopamine agonists and the role of surgery remains to be further explored. We examined the international experience of 12 neurosurgical centers to assess the patient characteristics, safety profile, and effectiveness of surgery for PST management.
METHODS
Patients surgically treated for PST from January 2017 through December 2020 were evaluated for surgical characteristics, outcomes, and safety.
RESULTS
Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PST were macroadenomas. Minor complications were seen in 39.3% of patients and major complications were in 4.4%. The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. At 3-6 months, local control on imaging was achieved in 94.8% of cases and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. On multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly protective against early endocrinological cure. Knosp classification was highly predictive of residual tumor or PST recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01). There was noted institutional variation in clinical factors and outcomes.
CONCLUSION
Our results evaluate a modern, multicenter, global series of PST. These data can serve as a benchmark to compare with DA therapy and other surgical series. Further study and longer term outcomes could provide insight into how patients benefit from surgical treatment.
Topics: Humans; Female; Young Adult; Adult; Middle Aged; Male; Adenoma; Prolactin; Dopamine Agonists; Pituitary Neoplasms; Treatment Outcome; Neoplasm Recurrence, Local; Retrospective Studies; Follow-Up Studies; Prolactinoma
PubMed: 38091700
DOI: 10.1016/j.clineuro.2023.108079 -
Journal of Endocrinological... May 2024
PubMed: 38079105
DOI: 10.1007/s40618-023-02247-5 -
Endocrine Connections Feb 2024Pituitary dysfunction following mild traumatic brain injury can have serious physical and psychological consequences, making correct diagnosis and treatment essential....
OBJECTIVE
Pituitary dysfunction following mild traumatic brain injury can have serious physical and psychological consequences, making correct diagnosis and treatment essential. To the best of our knowledge, this study is the first to study the prevalence of pituitary dysfunction following mild traumatic brain injury in an all-female population following detailed endocrinological work-up after screening for pituitary dysfunction in female athletes.
DESIGN
This is a retrospective cohort study.
METHODS
Hormone screening blood tests, including serum blood values for thyroid-stimulating hormone, free thyroxin, insulin-like growth factor 1, prolactin, cortisol, follicle-stimulating hormone, luteinizing hormone, estrogen and progesterone, were taken in 133 female athletes. Results were repeatedly outside the reference value in 88 women necessitating further endocrinological evaluation. Two of those were lost to follow-up, and further endocrinological evaluation was performed in 86 participants.
RESULTS
Six women (4.6%, n = 131) were diagnosed with hypopituitarism, four (3.1%) with central hypothyroidism and two with growth hormone deficiency (1.5%). Ten women (7.6%) had hyperprolactinemia, and four (3.1%) of them had prolactinoma. Medical treatment was initiated in 13 (9.9%) women. Significant prognostic factors were not found.
CONCLUSIONS
As 12.2% of female athletes with a history of mild traumatic brain injury had pituitary dysfunction (hypopituitarism 4.6%, hyperprolactinemia 7.6%), we conclude that pituitary dysfunction is an important consideration in post-concussion care. Hyperprolactinemia in the absence of prolactinoma may represent pituitary or hypothalamic injury following mild traumatic brain injury.
SIGNIFICANCE STATEMENT
Mild traumatic brain injury (mTBI) has become a growing public health concern as 50 million people worldwide sustain a traumatic brain injury annually, with mTBI being the most common (70-90%). As studies on mTBI have focused on mostly male populations this study aims to explore pituitary dysfunction (PD) in female athletes following mTBI. To the best of our knowledge, it is the first all-female study on PD following mTBI. The study found that 12.2% of the participating women had PD after mTBI. Six (4.6%) had hypopituitarism and ten (7.6%) had hyperprolactinemia. These findings suggest that PD following mTBI is an important consideration that endocrinologists and other medical staff working with athletes need to be aware of.
PubMed: 38078923
DOI: 10.1530/EC-23-0363 -
Frontiers in Endocrinology 2023Germline loss-of-function variants in , encoding peptidylglycine α-amidating monooxygenase (PAM), were recently discovered to be enriched in conditions of pathological...
INTRODUCTION
Germline loss-of-function variants in , encoding peptidylglycine α-amidating monooxygenase (PAM), were recently discovered to be enriched in conditions of pathological pituitary hypersecretion, specifically: somatotrophinoma, corticotrophinoma, and prolactinoma. PAM is the sole enzyme responsible for C-terminal amidation of peptides, and plays a role in the biosynthesis and regulation of multiple hormones, including proopiomelanocortin (POMC).
METHODS
We performed exome sequencing of germline and tumour DNA from 29 individuals with functioning pituitary adenomas (12 prolactinomas, 10 thyrotrophinomas, 7 cyclical Cushing's disease). An unfiltered analysis was undertaken of all variants with population prevalence <5%.
RESULTS
We identified five coding, non-synonymous variants of interest amongst seven individuals (six germline, one somatic). The five variants comprised four missense variants and one truncating variant, all heterozygous. Each variant had some evidence of pathogenicity based on population prevalence, conservation scores, predictions and/or prior functional studies. The yield of predicted deleterious variants was thus 7/29 (24%). The variants predominated in individuals with thyrotrophinomas (4/10, 40%) and cyclical Cushing's disease (2/7, 29%), compared to prolactinomas (1/12, 8%).
CONCLUSION
This is the second study to demonstrate a high yield of suspected loss-of-function, predominantly germline, variants in individuals with pathological pituitary hypersecretion. We have extended the association with corticotrophinoma to include the specific clinical entity of cyclical Cushing's disease and demonstrated a novel association between variants and thyrotrophinoma. variants might act as risk alleles for pituitary adenoma formation, with a possible genotype-phenotype relationship between truncating variants and altered temporal secretion of cortisol.
Topics: Humans; ACTH-Secreting Pituitary Adenoma; Adenoma; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Prolactinoma
PubMed: 38075079
DOI: 10.3389/fendo.2023.1305606 -
Cancers Dec 2023The most common genetic drivers of pituitary neuroendocrine tumors (PitNETs) lie within mutational hotspots, which are genomic regions where variants tend to cluster.... (Review)
Review
The most common genetic drivers of pituitary neuroendocrine tumors (PitNETs) lie within mutational hotspots, which are genomic regions where variants tend to cluster. Some of these hotspot defects are unique to PitNETs, while others are associated with additional neoplasms. Hotspot variants in and are the most common genetic causes of acromegaly and Cushing's disease, respectively. Although it has been proposed that these genetic defects could define specific clinical phenotypes, results are highly variable among studies. In contrast, hotspot variants are associated with a familial syndrome of cancer predisposition, and only exceptionally occur as somatic changes. A small number of non--driven corticotropinomas are due to somatic hotspot variants in or ; the latter is a well-known mutational hotspot in cancer. Finally, somatic variants affecting a hotspot in have been associated with multiple cancers and, more recently, with prolactinomas. Since the associations of , , and hotspot variants with PitNETs are very recent, their effects on clinical phenotypes are still unknown. Further research is required to fully define the role of these genetic defects as disease biomarkers and therapeutic targets.
PubMed: 38067388
DOI: 10.3390/cancers15235685 -
Journal of Clinical Densitometry : the... 2024No meta-analysis has holistically analysed and summarized the effect of prolactin excess due to prolactinomas on bone mineral metabolism. We undertook this meta-analysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
No meta-analysis has holistically analysed and summarized the effect of prolactin excess due to prolactinomas on bone mineral metabolism. We undertook this meta-analysis to address this knowledge-gap.
METHODS
Electronic databases were searched for studies having patients with hyperprolactinemia due to prolactinoma and the other being a matched control group. The primary outcome was to evaluate the differences in BMD Z-scores at different sites. The secondary outcomes of this study were to evaluate the alterations in bone mineral density, bone mineral content and the occurrence of fragility fractures.
RESULTS
Data from 4 studies involving 437 individuals was analysed to find out the impact of prolactinoma on bone mineral metabolism. Individuals with prolactinoma had significantly lower Z scores at the lumbar spine [MD -1.08 (95 % CI: -1.57 - -0.59); P < 0.0001; I = 54 % (moderate heterogeneity)] but not at the femur neck [MD -1.31 (95 % CI: -3.07 - 0.45); P = 0.15; I = 98 % (high heterogeneity)] as compared to controls. Trabecular thickness of the radius [MD -0.01 (95 % CI: -0.02 - -0.00); P = 0.0006], tibia [MD -0.01 (95 % CI: -0.02 - -0.00); P=0.03] and cortical thickness of the radius [MD -0.01 (95 % CI: -0.19 - -0.00); P = 0.04] was significantly lower in patients with prolactinoma as compared to controls. The occurrence of fractures was significantly higher in patients with prolactinoma as compared to controls [OR 3.21 (95 % CI: 1.64 - 6.26); P = 0.0006] Conclusion: Bone mass is adversely affected in patients with hyperprolactinemia due to prolactinoma with predominant effects on the trabecular bone.
Topics: Humans; Prolactinoma; Bone Density; Hyperprolactinemia; Absorptiometry, Photon; Cancellous Bone; Fractures, Bone; Radius; Femur Neck; Pituitary Neoplasms; Minerals
PubMed: 38064881
DOI: 10.1016/j.jocd.2023.101453