The Clinical Characteristics of Macroprolactinemia / 대한내분비학회지

BACKGROUND: Prolactin has been identified by gel chromatography to exist is three different forms in human serum; monomeric prolactin(molecular mass 23kDa), big prolactin (molecular mass 50~60 kDa) and big big prolactin, otherwise known as macroprolactin(molecular mass 150~170kDa). The predominance of macroprolactinemia has long been known in idiopathic hyperprolactinemic patients with maintained fertility. In recent reports, 24% of microprolactinoma patients showed no menstrual disturbances, which was suggestive of macroprolactinemia. The purpose of this study was to evaluate: (1) the frequency of macroprolactinemia among idiopathic hyperprolactinemia and prolactinoma patients, (2) the difference in the clinical characteristics between hyperprolactinemia, with and without macroprolactinemia, among idiopathic hyperprolactinemia and prolactinoma patients, and (3) the follow-up prolactin level using the bromocriptine response. METHODS: We retrospectively analyzed the clinical characteristics and prolactin levels in 43 idiopathic hyperprolactinemia and 51 prolactinoma patients with a poor bromocriptine response. Macroprolactinemia was identified by the prolactin recovery of < 40% using the polyethylene glycol(PEG) precipitation test. RESULTS: (1) Of the 43 idiopathic hyperprolactinemia and 51 prolactinoma patients, 17(39.5%) and 9(17.6%), respectively, were macroprolactinemic(P<0.05). (2) Among the idiopathic hyperprolactinemia patients, galactorrhea combined with amenorrhea was significantly less frequent (P<0.05), with the 1- and 2-year follow-up prolactin levels being significantly higher in those with macroprolactinemia than monomeric prolactinemia(P<0.05). (3) Among the prolactinoma patients, amenorrhea was significantly less frequent(P<0.05), but asymptomatic cases were more frequent in those with macroprolactinemia than monomeric prolactinemia(P <0.05). The 1- and 2-year follow-up prolactin levels were significantly higher in those with macroprolactinemia than monomeric prolactinemia(P<0.05). CONCLUSION: The screening of macroprolactinemia should be considered in idiopathic hyperprolactinemia and prolactinoma patients with a poor bromocriptine response

The Clinical Characteristics of Macroprolactinemia / 대한내분비학회지

BACKGROUND: Prolactin has been identified by gel chromatography to exist is three different forms in human serum; monomeric prolactin(molecular mass 23kDa), big prolactin (molecular mass 50~60 kDa) and big big prolactin, otherwise known as macroprolactin(molecular mass 150~170kDa). The predominance of macroprolactinemia has long been known in idiopathic hyperprolactinemic patients with maintained fertility. In recent reports, 24% of microprolactinoma patients showed no menstrual disturbances, which was suggestive of macroprolactinemia. The purpose of this study was to evaluate: (1) the frequency of macroprolactinemia among idiopathic hyperprolactinemia and prolactinoma patients, (2) the difference in the clinical characteristics between hyperprolactinemia, with and without macroprolactinemia, among idiopathic hyperprolactinemia and prolactinoma patients, and (3) the follow-up prolactin level using the bromocriptine response. METHODS: We retrospectively analyzed the clinical characteristics and prolactin levels in 43 idiopathic hyperprolactinemia and 51 prolactinoma patients with a poor bromocriptine response. Macroprolactinemia was identified by the prolactin recovery of < 40% using the polyethylene glycol(PEG) precipitation test. RESULTS: (1) Of the 43 idiopathic hyperprolactinemia and 51 prolactinoma patients, 17(39.5%) and 9(17.6%), respectively, were macroprolactinemic(P<0.05). (2) Among the idiopathic hyperprolactinemia patients, galactorrhea combined with amenorrhea was significantly less frequent (P<0.05), with the 1- and 2-year follow-up prolactin levels being significantly higher in those with macroprolactinemia than monomeric prolactinemia(P<0.05). (3) Among the prolactinoma patients, amenorrhea was significantly less frequent(P<0.05), but asymptomatic cases were more frequent in those with macroprolactinemia than monomeric prolactinemia(P <0.05). The 1- and 2-year follow-up prolactin levels were significantly higher in those with macroprolactinemia than monomeric prolactinemia(P<0.05). CONCLUSION: The screening of macroprolactinemia should be considered in idiopathic hyperprolactinemia and prolactinoma patients with a poor bromocriptine response

Comparison of Treatment Modalities in Hyperprolactinemia / 대한내분비학회지

BACKGROUND: Prolactinomas have been treated primarily with bromocriptine, a dopamine agonists, rather than by transsphenoidal pituitary adenomectomy. However, lower success rates, as well as intolerance or resistance to medical therapy, have been reported in some recent series. The purpose of this study was to compare the effects of surgery and bromocriptine in the treatment of prolactinomas patients. Also we investigated the natural history and effects of bromocriptine on patients with idiopathic hyperprolactinemia. METHEODS: We retrospectively compared the effects of treatment with surgery and with bromocriptine in 27 idiopathic hyperprolactinemia patients, 35 microprolactinoma patients and 61 macroprolactinoma patients. RESULTS: (1) In 14 patients with untreated idiopathic hyperprolactinemia, 8 (57%) achieved remission. In patients without remission, preoperative serum prolactin level was significantly higher than patients with remission (p<0.05). In 13 patients on bromocriptine, 11 (85%) achieved remission, while the other 2, taking bromocriptine irregularly because of side effects, had persistent hyperprolactinemia. (2) In 35 patients with microprolactinoma, 11 (30%) surgery as initial therapy and surgical remission was achieved in only 5 of the 11 (45%). In 23 patients on bromocriptine, 17 (74%) achieved remission. Among the 6 patients without remission, 5 patients took bromocriptine irregularly because of side effect. (3) In 61 patients with macroprolactinoma, 49 (80%) underwent surgery as initial therapy and surgical remission was achieved in only 9 of the 49 (18%). In 50 patients on bromocriptine, 30 (60%) achieved remission. Among the 20 patients without remission, 13 took bromocriptine irregularly because of side effect and 5 were resistant to bromocriptine. CONCLUSION: In idiopathic hyperprolactinemia, the requirement for medical treatment is doubtful because of a high tendency to ward spontaneous cure. In spite of the low success rate, surgery has been used as the primary therapy for prolactinoma in Korea. And yet, medical treatment with bromocriptine is superior to surgery. However, irrgular administration of medication due to drug side effects was the main cause of the low success rate. Therefore, the necessity for new drug development is emphasized

Reduction of Central Dopamine Release in Hyperprolactinemia / 대한내분비학회지

Background: Prolactin(PRL) secretion is tonically inhibited by doparnine that originates from the hypothalamic tuberoinfundibular tract and reaches the lactotroph via the hypophyseal portal vessel. Hyperprolactinemia associated with oligomenorrhea-amenorrhea, galactorrhea and/or infertility is mainly due to PRL-secreting pituitary adenoma(PA). The diagnosis of idiopathic hyperprolac- tinemia(IHP) is made, when hyperprolactinemia is sustained and all causes of hyperprolactinemia are excluded without radiological abnormality. It is not known, whether IHP and PA are two distinct entities or two subsequent phases of the same disease. The etiology of both disorders remains unresolved. We investigated that PRL hypersecretion in patients with IHP and PA may be the result of a defect in the central nervous system(CNS)-dopamine release, and that there may be some differences in pathogenesis of both diseases. Methods: We measured 24 hour-urinary dopamine, norepinephrine, epinephrine, and serum and 24 hour-urinary VMA(vanillyl rnandelic acid), HVA(homovanilic acid), DOPAC(3,4-dihydroxy phenylaceticacid), MHPG(3-methoxy 4-hydroxy phenylglycol) in 10 normal controls, 9 patients with IHP, and 17 patients with PA in the early follicular phase. Results: Urinary HVA and DOPAC concentrations, the major metabolites of CNS dopaminergic activity, were signficantly lower in both patients with IHP and PA compared with those in normal controls(p 0.05), whereas they were not different in both disease groups. Dopamine, norepine-phrine, epinephrine, MHPG concentrations were similar to those of the normal controls. Although VMA concentrations of both disease groups were significantly higher than those of normal controls, all of them were within normal range. Conelusion: Although our data are unable to establish the precise biochemical defect responsible for central dopamine deficiency in pathogensis of IHP and PA, we can support the presence of a pathological reduction of brain dopamine activity in IHP and PA.