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The Lancet. Diabetes & Endocrinology Dec 2021Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a... (Review)
Review
Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a consensus workshop comprising more than 50 academic researchers and clinical experts to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, data from 2015 to present about screening and diagnosis; surgery, medical, and radiation therapy; and disease-related and treatment-related complications of Cushing's disease summarised in recorded lectures were reviewed by all participants. During the meeting, concise summaries of the recorded lectures were presented, followed by small group breakout discussions. Consensus opinions from each group were collated into a draft document, which was reviewed and approved by all participants. Recommendations regarding use of laboratory tests, imaging, and treatment options are presented, along with algorithms for diagnosis of Cushing's syndrome and management of Cushing's disease. Topics considered most important to address in future research are also identified.
Topics: Consensus; Cushing Syndrome; Humans; Pituitary ACTH Hypersecretion; Pituitary Gland
PubMed: 34687601
DOI: 10.1016/S2213-8587(21)00235-7 -
Frontiers in Endocrinology 2022Over the last years, the metabolic role of PRL has emerged. PRL excess is known to promote weight gain, obesity, metabolic syndrome, and impairment in gluco-insulinemic... (Review)
Review
Over the last years, the metabolic role of PRL has emerged. PRL excess is known to promote weight gain, obesity, metabolic syndrome, and impairment in gluco-insulinemic and lipid profiles, likely due to the suppression of physiologic dopaminergic tone. Prolactin receptors and dopamine receptors type 2 have been demonstrated to be expressed on both human pancreatic β- cell and adipocytes, supporting a key role of prolactin and dopamine in peripheral metabolic regulation. Medical treatment with the dopamine agonists bromocriptine and cabergoline has been demonstrated to decrease the prevalence of metabolic syndrome and obesity, and significantly improve gluco-insulinemic and lipid profiles. In hyperprolactinemic men with concomitant hypogonadism, correction of hyperprolactinaemia and testosterone replacement has been proven to restore metabolic impairment. In turn, low prolactin levels have also been demonstrated to exert a detrimental effect on weight gain, glucose and lipid metabolism, thus leading to an increased prevalence of metabolic syndrome. Therefore, PRL values ranging from 25 to 100 mg/L, in absence of other recognizable pathological causes, have been proposed to represent a physiological response to the request for an increase in metabolic activity, and nowadays classify the so-called HomeoFIT- PRL as a promoter of metabolic homeostasis. The current review focuses mainly on the effects of hyperprolactinemia and its control by medical treatment with DAs on the modulation of food intake, body weight, gluco-insulinemic and lipid profile. Furthermore, it provides the latest knowledge about the metabolic impact of hypoprolactinemia.
Topics: Bromocriptine; Cabergoline; Dopamine; Dopamine Agonists; Glucose; Humans; Hyperprolactinemia; Lipids; Male; Metabolic Syndrome; Obesity; Prolactin; Receptors, Dopamine; Receptors, Prolactin; Testosterone; Weight Gain
PubMed: 36237192
DOI: 10.3389/fendo.2022.1015520 -
The Journal of Clinical Investigation Nov 2009Dysregulated growth hormone (GH) hypersecretion is usually caused by a GH-secreting pituitary adenoma and leads to acromegaly - a disorder of disproportionate skeletal,... (Review)
Review
Dysregulated growth hormone (GH) hypersecretion is usually caused by a GH-secreting pituitary adenoma and leads to acromegaly - a disorder of disproportionate skeletal, tissue, and organ growth. High GH and IGF1 levels lead to comorbidities including arthritis, facial changes, prognathism, and glucose intolerance. If the condition is untreated, enhanced mortality due to cardiovascular, cerebrovascular, and pulmonary dysfunction is associated with a 30% decrease in life span. This Review discusses acromegaly pathogenesis and management options. The latter include surgery, radiation, and use of novel medications. Somatostatin receptor (SSTR) ligands inhibit GH release, control tumor growth, and attenuate peripheral GH action, while GH receptor antagonists block GH action and effectively lower IGF1 levels. Novel peptides, including SSTR ligands, exhibiting polyreceptor subtype affinities and chimeric dopaminergic-somatostatinergic properties are currently in clinical trials. Effective control of GH and IGF1 hypersecretion and ablation or stabilization of the pituitary tumor mass lead to improved comorbidities and lowering of mortality rates for this hormonal disorder.
Topics: Acromegaly; Animals; Growth Hormone; Growth Hormone-Secreting Pituitary Adenoma; Humans; Insulin-Like Growth Factor I; Morbidity; Signal Transduction
PubMed: 19884662
DOI: 10.1172/JCI39375 -
Neuroendocrinology 2019An appropriate diagnostic evaluation is essential for the most appropriate treatment to be performed. Currently, macroprolactinemia is the third most frequent cause of... (Review)
Review
An appropriate diagnostic evaluation is essential for the most appropriate treatment to be performed. Currently, macroprolactinemia is the third most frequent cause of nonphysiological hyperprolactinemia after drugs and prolactinomas. Up to 40% of macroprolactinemic patients may present with hypogonadism symptoms, infertility, and/or galactorrhea. Thus, the screening for macroprolactin is indicated not only for asymptomatic subjects but also for those without an obvious cause for their prolactin (PRL) elevation. Before submitting patients to macroprolactin screening and pituitary magnetic resonance imaging, one should rule out pregnancy, drug-induced hyperprolactinemia, primary hypothyroidism, and renal failure. The magnitude of PRL elevation can be useful in determining the etiology of hyperprolactinemia. PRL values >250 ng/mL are highly suggestive of prolactinomas and virtually exclude nonfunctioning pituitary adenomas (NFPAs) and other sellar masses as the etiology of hyperprolactinemia. However, they can also be found in subjects with macroprolactinemia, drug-induced hyper-prolactinemia or chronic renal failure. By contrast, most patients with NFPAs, drug-induced hyperprolactinemia, macroprolactinemia, or systemic diseases present with PRL levels <100 ng/mL. However, exceptions to these rules are not rare. Indeed, up to 25% of patients harboring a microprolactinoma or a cystic macroprolactinoma may also have PRL <100 ng/mL. Falsely low PRL levels may result from the so-called "hook effect," which should be considered in all cases of large (≥3 cm) pituitary adenomas associated with normal or mildly elevated PRL levels (≤250 ng/mL). The hook effect may be unmasked by repeating PRL measurement after a 1:100 serum sample dilution.
Topics: Female; Humans; Hyperprolactinemia; Male
PubMed: 30889571
DOI: 10.1159/000499694 -
Orphanet Journal of Rare Diseases Jun 2008Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the... (Review)
Review
Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The prevalence is estimated at 1:140,000-250,000. It is most often diagnosed in middle-aged adults (average age 40 years, men and women equally affected). Due to insidious onset and slow progression, acromegaly is often diagnosed four to more than ten years after its onset. The main clinical features are broadened extremities (hands and feet), widened thickened and stubby fingers, and thickened soft tissue. The facial aspect is characteristic and includes a widened and thickened nose, prominent cheekbones, forehead bulges, thick lips and marked facial lines. The forehead and overlying skin is thickened, sometimes leading to frontal bossing. There is a tendency towards mandibular overgrowth with prognathism, maxillary widening, tooth separation and jaw malocclusion. The disease also has rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis. In the majority of cases, acromegaly is related to a pituitary adenoma, either purely GH-secreting (60%) or mixed. In very rare cases, acromegaly is due to ectopic secretion of growth-hormone-releasing hormone (GHRH) responsible for pituitary hyperplasia. The clinical diagnosis is confirmed biochemically by an increased serum GH concentration following an oral glucose tolerance test (OGTT) and by detection of increased levels of insulin-like growth factor-I (IGF-I). Assessment of tumor volume and extension is based on imaging studies. Echocardiography and sleep apnea testing are used to determine the clinical impact of acromegaly. Treatment is aimed at correcting (or preventing) tumor compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. Transsphenoidal surgery is often the first-line treatment. When surgery fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogs and/or radiotherapy can be used. The GH antagonist (pegvisomant) is used in patients that are resistant to somatostatin analogs. Adequate hormonal disease control is achieved in most cases, allowing a life expectancy similar to that of the general population. However, even if patients are cured or well-controlled, sequelae (joint pain, deformities and altered quality of life) often remain.
Topics: Acromegaly; Adult; Female; Human Growth Hormone; Humans; Male; Middle Aged; Pituitary Neoplasms; Prevalence; Radiography
PubMed: 18578866
DOI: 10.1186/1750-1172-3-17 -
The Journal of Clinical Endocrinology... Apr 2020The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013.
OBJECTIVE
The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013.
PARTICIPANTS
The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration.
EVIDENCE
This evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities.
CONSENSUS PROCESS
Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system.
CONCLUSIONS
Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality.
Topics: Acromegaly; Comorbidity; Consensus; Humans; Practice Guidelines as Topic; Quality of Life
PubMed: 31606735
DOI: 10.1210/clinem/dgz096 -
Neuroendocrinology 2019
Topics: Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma
PubMed: 31167201
DOI: 10.1159/000500723 -
American Journal of Health-system... May 2021This article aims to evaluate management options for antipsychotic-induced hyperprolactinemia and associated treatment considerations such as efficacy, tolerability,...
PURPOSE
This article aims to evaluate management options for antipsychotic-induced hyperprolactinemia and associated treatment considerations such as efficacy, tolerability, drug interactions, contraindications, and dosing regimens.
SUMMARY
Hyperprolactinemia is a common adverse effect of antipsychotics. First-line management includes reducing the dose of the offending antipsychotic, discontinuing the antipsychotic, or switching to another antipsychotic associated with a lower risk of hyperprolactinemia. However, these options are not always practical and are associated with a risk of relapse of the psychiatric illness. Other management options include adjunctive aripiprazole, dopamine agonists (cabergoline and bromocriptine), metformin, and herbal supplements. A search of Embase, PubMed, and Google Scholar using key terms such as hyperprolactinemia, prolactin, antipsychotic, treatment guidelines, aripiprazole, dopamine agonist, cabergoline, bromocriptine, metformin, herbals, supplements, and medications was conducted for literature retrieval. Upon evaluation of the available literature we found the following: (1) aripiprazole is safe and effective in lowering prolactin levels within normal limits; (2) adjunctive cabergoline and bromocriptine decrease elevated prolactin levels, while cabergoline may be more effective in reducing prolactin but can also be associated with a more serious adverse effect of cardiac valvular abnormalities; (3) metformin causes a mild reduction of prolactin levels; and (4) there are limited data to support use of herbal medications (chamomile, Peony-Glycyrrhiza decoction, and shakuyaku-kanzo-to) in antipsychotic-induced hyperprolactinemia.
CONCLUSION
There are treatments available for antipsychotic-induced hyperprolactinemia in patients who are unable to alter their current antipsychotic regimen. However, there remains a need for additional short- and long-term studies to determine the efficacy and safety of these treatment strategies, given that patients taking antipsychotics typically require chronic, life-long treatment for their illnesses.
Topics: Antipsychotic Agents; Aripiprazole; Humans; Hyperprolactinemia; Mental Disorders; Prolactin
PubMed: 33954421
DOI: 10.1093/ajhp/zxab065 -
Ugeskrift For Laeger Dec 2018Acromegaly is a rare and disabling disease with a plethora of symptoms and signs attributed to sustained elevations and actions of growth hormone and insulin-like growth...
Acromegaly is a rare and disabling disease with a plethora of symptoms and signs attributed to sustained elevations and actions of growth hormone and insulin-like growth factor 1. Acromegaly is characterised by excessive somatic growth and multiple comorbidities in addition to occasional compression of the optic nerve and hypopituitarism due to the underlying adenoma. The course of the disease is insidious, and a diagnostic delay of 5-10 years is typical, and this pre-diagnostic period is also associated with increased morbidity. Effective treatment is available, once the diagnosis is established.
Topics: Acromegaly; Adenoma; Comorbidity; Delayed Diagnosis; Human Growth Hormone; Humans
PubMed: 30520722
DOI: No ID Found -
Translational Psychiatry Jul 2022Antipsychotic-induced hyperprolactinemia (AP-induced HPRL) occurs overall in up to 70% of patients with schizophrenia, which is associated with hypogonadism and sexual... (Meta-Analysis)
Meta-Analysis
Antipsychotic-induced hyperprolactinemia (AP-induced HPRL) occurs overall in up to 70% of patients with schizophrenia, which is associated with hypogonadism and sexual dysfunction. We summarized the latest evidence for the benefits of prolactin-lowering drugs. We performed network meta-analyses to summarize the evidence and applied Grading of Recommendations Assessment, Development, and Evaluation frameworks (GRADE) to rate the certainty of evidence, categorize interventions, and present the findings. The search identified 3,022 citations, 31 studies of which with 1999 participants were included in network meta-analysis. All options were not significantly better than placebo among patients with prolactin (PRL) less than 50 ng/ml. However, adjunctive aripiprazole (ARI) (5 mg: MD = -64.26, 95% CI = -87.00 to -41.37; 10 mg: MD = -59.81, 95% CI = -90.10 to -29.76; more than 10 mg: MD = -68.01, 95% CI = -97.12 to -39.72), switching to ARI in titration (MD = -74.80, 95% CI = -134.22 to -15.99) and adjunctive vitamin B6 (MD = -91.84, 95% CI = -165.31 to -17.74) were associated with significant decrease in AP-induced PRL among patients with PRL more than 50 ng/ml with moderated (adjunctive vitamin B6) to high (adjunctive ARI) certainty of evidence. Pharmacological treatment strategies for AP-induced HPRL depends on initial PRL level. No effective strategy was found for patients with AP-induced HPRL less than 50 ng/ml, while adjunctive ARI, switching to ARI in titration and adjunctive high-dose vitamin B6 showed better PRL decrease effect on AP-induced HPRL more than 50 ng/ml.
Topics: Antipsychotic Agents; Aripiprazole; Humans; Hyperprolactinemia; Network Meta-Analysis; Prolactin; Vitamin B 6
PubMed: 35790713
DOI: 10.1038/s41398-022-02027-4