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    Home > Active Ingredient News > Endocrine System > The latest international "Position Statement on Prolactin-secreting Tumors" was released, compiled and shared by Professor Li Wangen's team

    The latest international "Position Statement on Prolactin-secreting Tumors" was released, compiled and shared by Professor Li Wangen's team

    • Last Update: 2022-04-28
    • Source: Internet
    • Author: User
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    This article is authorized by Professor Li Wangen to publish Yimaitong
    .

    Foreword: Prolactinoma is not uncommon in clinical endocrinology, and there is no domestic guideline or consensus in this field
    .

    The American Endocrine Society published a version of the Endocrine Society Clinical Practice Guidelines for the Diagnosis and Treatment of Hyperprolactinemia in 2011 (Melmed S, 2011), more than 10 years ago
    .

    Last month, the "European Journal of Endocrinology" published the "Position Statement of the Italian Association of Endocrinologists (AME) and the International Society of Clinical Endocrinology (ICCE) on Prolactin-secreting Tumors".
    Please advise
    .

    Compilation: Hu Zhuoqing Reviewed by Department of Endocrinology, Second Affiliated Hospital of Guangzhou Medical University: Prof.
    Wangen Li, Director of Department of Endocrinology, Second Affiliated Hospital of Guangzhou Medical University ➤ The level of agreement (LoA) ranges from 1 to 9, with 1 being the most divergent and 9 being the same Agree
    .

    ➤recommendation, abbreviated
    R.

    I.
    Diagnosis R 1.
    It is recommended to measure PRL levels in all clinically suspicious patients
    .

    These findings include oligomenorrhea, erectile dysfunction, galactorrhea or infertility in males/females, and abnormalities in the sellar region on MRI (LoA 9)
    .

    R 2.
    A detailed medical and medication history is recommended to rule out physiologic (including pregnancy and lactation), secondary, and iatrogenic hyperprolactinemia (LoA 9)
    .

    R 3.
    Confirmation of randomly elevated PRL levels is recommended unless the PRL has been significantly elevated (>80-100 ng/mL)
    .

    Insert an IV catheter and inject normal saline for 15-20 minutes before drawing blood for PRL (LoA 9)
    .

    R 4.
    It is recommended that all clinicians be aware of the PRL assays used and the units of measurement, etc.
    (LoA 8)
    .

    R 5.
    It is recommended to perform macroprolactin testing in the following patients: (1) asymptomatic; (2) clinically atypical; (3) inconsistent PRL results in different testing methods; (4) serum serum after dopamine agonist use PRL levels were not significantly decreased, and pituitary macroadenomas and PRL levels were in the range of 100-200 ng/mL (LoA 9)
    .

    R 6.
    It is recommended that in patients with pituitary macroadenomas (ie > 3 cm) with normal or mildly elevated PRL levels, the samples should be serially diluted before measuring PRL levels to rule out hook effects (LoA 8)
    .

    R 7.
    PRL levels are helpful in determining the etiology of hyperprolactinemia in patients with pituitary tumors, PRL levels >200-250 ng/mL are almost always caused by macroprolactinomas (LoA 8)
    .

    R 8.
    It is recommended to define a clear PRL starting level for patients with large prolactinomas (without a vague definition like "above 1000 ng/mL") to facilitate follow-up of drug therapy (LoA 8)
    .

    R 9.
    It is recommended to screen for hypopituitarism in the following two cases while diagnosing prolactinoma: (1) all macroadenomas; (2) suspected hypopituitary microadenomas
    .

    R 10.
    It is recommended that all PRL-secreting tumors be tested for insulin-like growth factor I at diagnosis (LoA 7.
    5)
    .

    R 11.
    It is recommended that for possible drug-induced hyperprolactinemia, gadolinium imaging should be performed only if the hyperprolactinemia persists after discontinuation or replacement of the suspected drug, or if the patient is clinically unable to discontinue the suspected drug Enhanced MRI (LoA 9)
    .

    R 12.
    Careful clinical neuroradiological evaluation is recommended to avoid false positive diagnosis (LoA 9)
    .

    R 13.
    It is recommended to review MRI within 3-6 months for patients with macroprolactinomas and within 1 year for patients with microprolactinomas after starting dopamine agonists
    .

    If there is no response to treatment or new symptoms develop, early follow-up should be considered (LoA 9)
    .

    R 14.
    It is recommended to limit the use of gadolinium during follow-up (especially for macroadenomas) (LoA 8)
    .

    R 15.
    It is recommended to consider prolactinoma based on family history of prolactinoma, early age of onset (less than 20 years) and aggressive growth (ie, uncontrolled tumor growth despite appropriate treatment) or concomitant endocrine disorders.
    No possibility of hereditary prolactinoma (LoA 8.
    5) 2.
    Treatment 1.
    General R 16.
    Multidisciplinary diagnosis and treatment (MDT) of tumors is recommended, especially large prolactinomas (this should be a strong recommendation, but due to limitations of reality, the proposal was downgraded) (LoA 8)
    .

    R 17.
    Referral to a specialist in pituitary surgery is recommended when neurosurgery is considered (LoA 9)
    .

    R 18.
    Recommend transsphenoidal adenoma resection as a viable option for any patient with resectable adenoma (microprolactinoma or encapsulated macroprolactinoma), preferably in consultation with an endocrinologist and neurosurgeon.
    Physician joint assessment (LoA 9)
    .

    R 19.
    Transsphenoidal adenoma resection is recommended when treatment is required and the patient is unwilling to receive long-term medical therapy (LoA 9)
    .

    R 20.
    Treatment with a dopamine agonist (cabergoline) is recommended at the lowest effective dose to suppress PRL hypersecretion and tumor volume (LoA 9)
    .

    R 21.
    Recommend bromocriptine for cabergoline-intolerant patients who are not candidates for surgery and in countries where cabergoline is not available or resource-poor (LoA 8)
    .

    R 22.
    It is recommended that patients starting cabergoline treatment and their caregivers be alerted to possible impulse control disturbances (also known as intention control disturbances) and regularly asked about psychiatric symptoms during long-term treatment (LoA 8.
    5)
    .

    R 23.
    Recommend regular cardiac auscultation and ultrasonography in patients with a heart murmur or with a weekly cabergoline dose of more than 2 mg, without ignoring causes of valve involvement other than endocrine factors (LoA 7)
    .

    2.
    For Microadenomas R 24.
    The aim of the proposed treatment is to reverse the clinical manifestations, mainly hypogonadism (LoA 9)
    .

    R 25.
    If hypogonadism or galactorrhea is not a problem, it can be clinically observed; for women not planning to become pregnant, oral estrogen-progestin contraceptives may also be used (LoA 8.
    5)
    .

    R 26.
    Surgery is recommended for patients with dopamine agonist resistance or intolerance (LoA 9)
    .

    R 27.
    Advise postmenopausal women to discontinue dopamine agonists (LoA 7.
    5)
    .

    3.
    For macroadenomas R 28.
    Regardless of tumor size or the severity of neurological and ophthalmic damage, cabergoline is recommended as first-line therapy under strict clinical and laboratory monitoring to rapidly improve neuro-ophthalmic symptoms (LoA ).
    9)
    .

    R 29.
    Recommend adrenal gland surgery by a pituitary surgeon for patients with severe neuro-ophthalmic impairment that does not improve rapidly with dopamine agonists (within 2 weeks), or who are resistant or intolerant to dopamine agonists, or who are reluctant to choose dopamine agonist therapy.
    Tumor resection (LoA 9)
    .

    R 30.
    Careful and close follow-up of patients with partial responses to dopamine agonists is recommended, with prompt referral to neurosurgery when the efficacy of dopamine agonist therapy has disappeared (LoA 9)
    .

    R 31.
    It is recommended that in most cases only annual follow-up assessment of the PRL is safe in those who respond well to dopamine agonist therapy (after a normal PRL and tumor shrinkage)
    .

    It is safe to have an MRI every year or more
    .

    If PRL levels remain normal, MRI may even be skipped (LoA 8)
    .

    R 32.
    Urgent evaluation by an otolaryngologist or neurosurgeon is recommended in the presence of a nasal CSF leak (LoA 9)
    .

    R 33.
    It is recommended that dopamine agonists be discontinued only in patients with complete resolution of large prolactinomas (or tumor shrinkage of at least 50%) and persistently low PRL levels to normal levels after dopamine agonist tapering during long-term treatment , with careful quarterly follow-up of PRL levels and gonadal status (LoA 7.
    5)
    .

    R 34.
    It is recommended not to discontinue dopamine agonists in patients with large prolactinoma who have been receiving long-term dopamine agonist therapy if the tumor has not shrunk significantly or the PRL level cannot be reduced to normal (LoA 9)
    .

    R 35.
    Radiation therapy is recommended for patients with large prolactinomas uncontrolled by dopamine agonists and surgery (LoA 9)
    .

    R 36.
    It is recommended that regardless of the radiological technique chosen, it should be performed in a multidisciplinary pituitary team (LoA 9)
    .

    R 37.
    It is recommended that when feasible and technically feasible, radiosurgery should be used instead of fractionated RT, unless the tumor is too close to the optic nerve pathway or tends to diffusely infiltrate surrounding anatomical structures (LoA 9)
    .

    R 38.
    Annual long-term follow-up is recommended to assess the efficacy and safety of RT (LoA 9)
    .

    III.
    SPECIAL ISSUES 1.
    Children R 39.
    Dopamine agonist therapy is recommended for children with prolactinomas to preserve normal pituitary function, and neurosurgical therapy can be used as a Alternative (LoA 9)
    .

    2.
    Gonadal Replacement, Contraception, Fertility, and Amenorrhea R 40.
    It is recommended for men with persistent hypogonadism that early testosterone replacement therapy should be initiated within 3-6 months of dopamine agonist initiation, as long as the PRL is gradually decreasing ( LoA 9)
    .

    R 41.
    It is recommended that every hypogonadal woman with macroprolactinoma be evaluated for gonadal replacement therapy (LoA 9)
    .

    R 42.
    It is recommended that hormone replacement therapy be continued in women with hypogonadism until at least the age of physiological menopause (LoA 9)
    .

    R 43.
    Estrogen is recommended as a safe option for women with microprolactinomas or macroprolactinomas who respond well to dopamine agonist therapy and who require contraception (LoA 8.
    5)
    .

    R 44.
    It is recommended to restore fertility with gonadotropins when needed (LoA 9)
    .

    R 45.
    It is recommended to plan pregnancy (LoA 9)
    .

    R 46.
    It is recommended that pregnant patients be provided with adequate information and have easy access to endocrine counselling (LoA 9)
    .

    R 47.
    Dopamine agonist therapy (preferably cabergoline, to improve tolerance) is recommended when a pregnancy is planned and discontinued when pregnancy is confirmed (LoA 9)
    .

    R 48.
    It is recommended not to check PRL levels during pregnancy (LoA 9)
    .

    R 49.
    In patients with microprolactinomas or macroprolactinomas with small residual intrasellar residues, only clinical follow-up is performed throughout pregnancy
    .

    (LoA 9)
    .

    R 50.
    It is recommended that patients with macroprolactinoma undergo clinical and pituitary function and neuro-ophthalmologic evaluations in the first, second, and third trimesters of pregnancy (LoA 9)
    .

    R 51.
    MRI of the pituitary gland is not recommended during stable pregnancy and early postpartum (LoA 9)
    .

    R 52.
    Neuro-ophthalmic evaluation, MRI without gadolinium contrast, and evaluation of pituitary function are recommended for patients with symptoms of mass compression during pregnancy (LoA 9)
    .

    R 53.
    Recommend reintroduction of dopamine agonists (preferably cabergoline) in symptomatic macroprolactinoma patients during pregnancy for rapid symptom relief and maintenance after delivery (LoA 9)
    .

    R 54.
    Vaginal delivery is recommended for patients with microprolactinomas (unless otherwise recommended by the obstetrician), with a specific analysis of the mode of delivery for patients with macroprolactinomas (LoA 9)
    .

    R 55.
    It is recommended that women with prolactinomas in stable pregnancy be able to breastfeed and delay the resumption of dopamine agonist therapy
    .

    (LoA 9)
    .

    R 56.
    Recommend non-hormonal contraception after delivery or after cessation of breastfeeding to allow assessment of PRL levels in all women within 3-6 months and follow-up MRI for large prolactinomas (LoA 8)
    .

    R 57.
    Recommend restarting dopamine agonist therapy in women with recurrent postpartum symptomatic hyperprolactinemia (LoA 9)
    .

    R 58.
    It is recommended that postmenopausal patients with microprolactinoma discontinue dopamine agonists, monitor annually if PRL is elevated, and perform MRI if PRL is progressively elevated (LoA 8)
    .

    R 59.
    It is recommended that postmenopausal patients with macroprolactinoma continue dopamine agonist therapy at the lowest dose that controls tumor growth, with follow-up based on clinical status (LoA 9)
    .

    3.
    Miscellaneous R 60.
    It is recommended that the treatment of prolactinomas is not altered by breast cancer (LoA 9)
    .

    R 61.
    It is recommended to assess PRL levels (LoA 8) before initiating neuroleptic medication
    .

    R 62.
    It is recommended that endocrinologists and psychiatrists work closely together to manage patients with psychiatric disorders and hyperprolactinemia (LoA 9)
    .

    R 63.
    Dopamine agonist therapy is recommended for patients with prolactinoma treated with antipsychotics, with an individualized assessment of efficacy and safety (LoA 8)
    .

    R 64.
    An assessment of bone health is recommended to determine whether to initiate bone-active therapy (LoA 9)
    .

    4.
    Dopamine agonist resistance and aggressive disease R 65.
    Strict follow-up is recommended for all patients with large prolactinomas, mainly men, because of their higher risk of instability in their disease course (LoA 9)
    .

    R 66.
    It is recommended that the team of pituitary specialists rapidly employ multiple modalities of therapy (reoperation + radiation therapy + dopamine agonists) in cases of dopamine agonist resistance or escape or uncontrolled tumor growth (LoA 9)
    .

    R 67.
    Recommend treatment with temozolomide in patients with dopamine agonist-resistant macroprolactinomas who are unsuccessful with surgery and/or radiotherapy, or who have established metastases (LoA 9)
    .

    R 68.
    Recommend that temozolomide be discontinued after the third cycle of treatment in patients with progressive disease (LoA 8.
    5)
    .

    R 69.
    An experimental approach is recommended for aggressive patients who do not respond to temozolomide (LoA 8)
    .

    The translator introduces Dr.
    Hu Zhuoqing, attending physician, Department of Endocrinology, Second Affiliated Hospital of Guangzhou Medical University
    .

    Experts introduce Professor Li Wangen, chief physician and doctoral supervisor
    .

    Director of Endocrinology Department of the Second Affiliated Hospital of Guangzhou Medical University, Vice Chairman of Diabetes Branch of Guangdong Medical Association
    .

    Designing a "dumb plan" for long-acting insulin adjustment in hospitalized patients [Clin Ther.
    2014;36(9):1269-75; Adv Ther.
    2016;33(2):178-85.
    These two papers were included in the Canadian 2018 Diabetes Guidelines Citation, Can J Diabetes 42 (2018) S115–S123] and Screening Outpatients for Long-Acting Insulin Adjustment "For Dummies"
    .

    Originally published in Eur J Endocrinol.
    2022 Feb 3;186(3):P1-P33.
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