Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, 80131 Naples, Italy.
Dipartimento di Sanità Pubblica, Università Federico II di Napoli, 80131 Naples, Italy.
J Clin Endocrinol Metab. 2023 Aug 18;108(9):2400-2423. doi: 10.1210/clinem/dgad174.
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.
催乳素瘤是最常见的垂体瘤组织类型，微催乳素瘤在女性中更为常见，而大催乳素瘤在男性中更为常见。高催乳素血症是两性促性腺激素低下性性腺功能减退症的最常见原因之一，促使对两性性腺功能减退症（不育、少经或闭经、阳萎、骨质疏松/骨量减少）提出医学建议，并对男性主要出现的肿块效应的迹象和症状（垂体功能减退、视力丧失、视交叉受压、颅神经缺陷、头痛）提出建议。诊断性检查包括单次催乳素测量和垂体成像，但一些实验室假象（即“钩状效应”和大催乳素）会使诊断变得复杂或延迟。催乳素瘤的治疗选择是多巴胺激动剂，主要是卡麦角林，它能够诱导疾病控制，恢复两性的生育能力，并使三分之一的患者得到明确治愈，从而可以停止治疗。怀孕和绝经可能会促进催乳素的自发下降，并预期女性在停止使用卡麦角林。如果药物剂量增加到最大耐受剂量仍不能克服对卡麦角林的耐药性，或者患者选择手术，则需要手术和/或放疗。在侵袭性和增殖性肿瘤中对卡麦角林耐药的证据可能表明存在生物学侵袭性，因此需要替代的治疗方法，主要基于替莫唑胺的单独使用或联合放疗。在未得到控制的患者中，可以提供新的治疗方法（替代激素治疗、细胞毒性药物、肽受体放射性核素治疗、mTOR/Akt 抑制剂、酪氨酸激酶抑制剂或免疫疗法），但迄今为止收集的经验仍然非常有限。本文回顾了催乳素瘤的不同方面，并讨论了在更常见的临床情况下对该疾病的处理方法。
