Initial Serum Prolactin Research Articles

Broad clinical spectrum and diverse outcomes of prolactinoma with pediatric onset: medication-resistant and recurrent cases.

Prolactinoma is a benign tumor of the pituitary gland that rarely occurs in children and adolescents; thus, the clinical spectrum and long-term prognosis in these patients remain unknown. This study was performed to investigate the long-term outcomes of medical treatment and the prognostic factors for remission and relapse in children and adolescents with prolactinoma. Three male subjects and four female subjects between the ages of 7- and 17-years-old were included in this study. The mean initial serum prolactin level was 443 ± 251.8 ng/mL (range, 152-946 ng/mL). During the follow-up period (range, 0.6-20 years), a dopamine agonist was administered, and surgery or radiotherapy was performed in cases of resistance to medical treatment or relapse. Unlike female subjects with macroadenoma who often exhibit a good clinical course, two male subjects with early onset macroadenoma presented with visual disturbances. These subjects showed resistance to medical therapy and relapsed, eventually requiring surgical removal and radiotherapy; one of the subjects manifested a metastatic thrombus in the internal jugular vein. In conclusion, pediatric prolactinoma exhibits a broad clinical spectrum, a relatively high incidence of macroadenoma, resistance to medical therapy, and frequent tumor relapses. In addition, a poor prognosis appears to be correlated with male sex, age at disease onset, and histopathological characteristics.

Prolactinoma management: predictors of remission and recurrence after dopamine agonists withdrawal.

Prolactinomas are the most common functional pituitary tumour. Dopamine agonists (DA) are its principal treatment. The criteria that should guide therapy withdrawal and the factors that influence disease remission or relapse are not yet fully established. Our purpose is to evaluate the proportion of patients who attempted DA withdrawal, and to identify the factors that influence clinicians to try it. In addition, we aim to study the factors that are involved in prolactinoma remission/relapse after therapy withdrawal. We retrospectively evaluated 142 patients with prolactinoma diagnosis who had been treated exclusively with DA. Firstly, the patients were divided in two groups, according to whether DA withdrawal had been attempted, or not, and the factors that might predict clinicians' decision to discontinue the therapy were then analysed. Secondly, patients who attempted withdrawal were further divided into two subgroups, based on their remission or relapse status and predictors of remission were evaluated. DA withdrawal was attempted in 35.2% of our patients. Females, subjects with lower initial serum prolactin (PRL) levels, those with microadenomas and those with longer treatment duration all had a higher probability of seeing their therapy discontinued. In the withdrawal group, the remission rate was 72%. Macroprolactinomas relapse more often than microprolactinomas (p < 0.05). The recurrence group had higher median initial serum PRL levels and a lower mean duration of therapy, however these variables did not reach statistical significance. We found a low percentage of attempt of withdrawal of DA therapy in the subjects with prolactinoma. Our data confirms that DA therapy can be discontinued with a high remission rate. Tumour size was the main variable that affected the withdrawal outcome in our patients.

Serum Prolactin Concentrations in Relation to Hypopituitarism and Obesity in Children with Optic Nerve Hypoplasia

Background/Aims: The majority of children with optic nerve hypoplasia (ONH) develop hypopituitarism and many also become obese. These associated conditions are a major cause of morbidity and are possibly due to hypothalamic dysfunction. Because mild hyperprolactinemia often occurs in subjects with disorders of the hypothalamus, we examined whether hyperprolactinemia was present in children with ONH during the first 3 years of life and whether it was a marker for hypopituitarism and/or obesity. Methods: Data were retrospectively analyzed from a registry study of children with ONH. The initial serum prolactin was obtained prior to age 36 months (n = 125) and compared with pituitary function and body mass index at age 5. Results: 72% of subjects had an elevated initial serum prolactin and 60% had hypopituitarism. An elevated initial prolactin was associated with hypopituitarism (OR 2.58; 95% CI 1.16, 5.73), specifically with growth hormone deficiency (OR 2.77; 95% CI 1.21, 6.34). 31% of subjects had a body mass index ≥85th percentile, but this did not correlate with initial hyperprolactinemia. Conclusions: Early hyperprolactinemia correlates with the presence of hypopituitarism in children with ONH, but it is not a reliable prognosticator of hypopituitarism. Additionally, hyperprolactinemia does not predict future weight excess.

Macroprolactinemia in Patients Presenting With Stalk Compressing Masses

Introduction Decreased dopaminergic inhibition of prolactin secretion by hypothalamus or stalk compressive masses can induce hyperprolactinemia. Macroprolactin may be the dominant form of prolactin in any case of hyperprolactinemia. The aim of this study was to evaluate the association of macroprolactinemia in patients presenting with hyperprolactinemia caused by stalk compressive masses. Patients and Methods We evaluated a series of 37 patients with hyperprolactinemia because of hypothalamus or stalk compressive masses. In patients with significant hyperprolactinemia (>35 μg/L in women and >30 μg/L in men), serum prolactin measured again, after incubation with poly ethylene glycol (PEG). Macroprolactinemia was diagnosed if the serum prolactin after PEG was ≤40% of initial serum prolactin. In 2 patients with macroprolactinemia, prolactin measured again before and after PEG, 2 months after surgery. Results Serum prolactin was significantly high in 18 (48.6%) patients. Macroprolactinemia proved in 3 patients (8.1%) after PEG incubation. In 2 of 3 patients surgery was performed. Prolactin level decreased after surgery in them but not to normal levels. After PEG test macroprolactinemia persisted but monomeric prolactin decreased to normal level only in 1 patient with complete resection, but remained elevated in the second one with significant remnant. Conclusions Macroprolactinemia may be the cause of hyperprolactinemia in stalk compressive masses. Macroprolactin forms after production and release of monomeric form from the pituitary.

Is surgical intervention frequently required for medically managed macroprolactinomas? A study of spontaneous cerebrospinal fluid rhinorrhea

Background The frequency of spontaneous CSF rhinorrhea in macroprolactinoma patients is poorly documented and was previously thought to be a very rare occurrence. Methods Thirty patients with macroprolactinomas (>1.0 cm diameter) identified from the Swansea neuroendocrine database were studied retrospectively. Results At presentation, the median serum prolactin was 28 354 (range, 1844 to >6 000 000) mU/L; radiologically, 4 adenomas were invading the cavernous sinus, one the sphenoid sinus and 5 both the cavernous and sphenoid sinus. After commencement of medical therapy, 4 subjects developed CSF rhinorrhea requiring surgical correction; all 4 had tumors invading both the cavernous and sphenoid sinus and an initial serum prolactin more than 75 000 mU/L. One subject developed an acute psychosis, and a man who presented with delayed puberty committed a serious sexual offense. Conclusions Serious adverse effects are not uncommon in medically treated macroprolactinoma patients. Subjects with adenomas invading the sphenoid sinus have a high risk of developing CSF rhinorrhea that requires neurosurgical intervention.

USING A NONLINEAR CROSSED RANDOM EFFECTS MODEL WITH THREE-WAY TREATMENT STRUCTURE FOR DESCRIBING CIRCADIAN PATTERNS OF SERUM PROLACTIN CONCENTRATIONS IN HEAT STRESSED HOLSTEINS

A modified Gaussian model with three-level crossed and nested random effects is used to describe circadian patterns of serum prolactin concentrations in a crossover experiment. Testing of three-way treatment effects and carryover effects are incorporated with the model building process as is the within-group correlation. We found that the interaction between environment and parity had significant effect (p<0.05) on both initial serum prolactin concentration and range of the prolactin concentration. There was no significant effect of recombinant bovine somatotropin (rbST) on either the initial value or concentration of serum prolactin. The inclusion of carryover effects in the model significantly improves the fit of the multilevel nonlinear mixed effects model. We present in detail a general approach to nonlinear crossed random effects model building and three-way treatment effects testing.

Use of nonergot alkaloid-producing endophytes for alleviating tall fescue toxicosis in sheep.

Nonergot alkaloid-producing endophytes from New Zealand were inserted into tall fescue (Festuca arundinacea) cultivars in an attempt to address the problem of fescue toxicosis in grazing sheep. A 3-yr grazing study was conducted to determine lamb performance and to evaluate toxicosis in lambs grazing nonergot alkaloid-producing endophyte-infected (AR542 or AR502), endophyte-free (E-), or wild-type toxic endophyte-infected (E+) Jesup tall fescue or nonergot alkaloid-producing endophyte-infected (AR542) Georgia-5 tall fescue. Replicated 0.11-ha tall fescue paddocks were established at the central Georgia Branch Station during September 1997 and stocked with lambs from spring 1998 through autumn 2000. Mean ergot alkaloid concentrations were higher (P < 0.01) in E+ forage than in AR542, AR502, and E- tall fescue, and ergot alkaloid concentrations in E- plants and plants infected with AR542 and AR502 were low. Forage availability did not differ (P = 0.92) across treatments during autumn and was higher (P < 0.05) in Georgia-5 AR542 than in Jesup AR502 and E+ pastures. Initial serum prolactin (PRL) concentrations did not differ (P = 0.58) across treatments during autumn, but were higher on Jesup AR542 than E+ during spring. Post-treatment serum PRL concentrations were depressed (P < 0.01) on E+ compared with AR542, AR502, and E- in both spring and autumn. Signs of heat stress were observed in E+ lambs during periods of high ambient temperatures. Mean post-treatment rectal temperature and mean stocking rate exhibited treatment x year interactions (P < 0.05). Lamb ADG was higher (P < 0.05) on AR542, AR502, and E- than on E+ tall fescue. Similarly, gain/hectare was higher (P < 0.015) on AR542, AR502, and E- than on E+. Tall fescue pastures containing AR542 and AR502 endophytes yielded lamb performance that did not differ from that on E- tall fescue and which was superior to performance on E+ tall fescue. Depressed PRL concentrations and elevated rectal temperatures as indicators of toxicosis were evident only in lambs grazing E+ tall fescue, suggesting that nonergot alkaloid-producing endophyte-infected tall fescue is a viable alternative for alleviating tall fescue toxicosis.

An Unusual Form of Big, Big (Macro) Prolactin in a Pregnant Patient

It is well recognized that circulating prolactin may exist in several forms, including little (monomeric), big, and big, big (macroprolactin) prolactin with molecular masses of 23, 50, and 150–170 kDa, respectively (1). We report the case of a 30-year-old woman who initially attended her primary care physician because of the onset of painful irregular periods. Her cycle usually was regular, but she had had an 8-week interval of amenorrhea, followed by a particularly painful bleed for which she sought medical advice. Before this, and subsequently, her menstruation had been completely regular with a 28-day cycle. She had no other problems. The patient’s initial serum prolactin was recorded as 15 800 mIU/L (∼530 μg/L) in a Bayer Immuno 1TM assay (Bayer Corporation). Other investigations at the time were entirely normal. When the subject was monitored 2 months later, she was symptomless and menstruating regularly; her serum prolactin, using the same assay as before, was 8440 mIU/L (∼270 μg/L). Pituitary imaging by magnetic resonance was normal. She had, of choice, never been pregnant. Because of the patient’s lack of symptoms, normal pituitary imaging, and regular cycles, further analytical investigations were carried out on a sample of her serum. After polyethylene glycol (PEG) precipitation, the recovery of prolactin was low, indicating the presence of macroprolactin (2), and 15% of her total prolactin was estimated to be monomeric prolactin. …

Macroprolactinaemia: validation and application of the polyethylene glycol precipitation test and clinical characterization of the condition.

The clinical characteristics and natural history of macroprolactinaemia are yet to be fully established and there is currently no widely accepted simple in vitro test for routine identification of the condition. This study was designed to further validate the polyethylene glycol (PEG) precipitation test with assessment of percentage prolactin recovery (%R), for the detection of macroprolactinaemia and clinically characterize cases identified using the test. Analytical validation and application of the PEG precipitation test for diagnosis of macroprolactinaemia and a retrospective case-notes review of some of the patients identified with the condition. Sera from 188 patients with elevated serum prolactin (PRL) concentrations were screened for macroprolactinaemia. Seventeen of the patients who were under follow-up at the local teaching hospital and were identified to have macroprolactinaemia were systematically characterized clinically. Prolactin was measured in sera, fractions from gel filtration chromatography and supernatant obtained after PEG precipitation, by the DELFIA fluoroimmunoassay. CLINICAL ENDPOINTS: Initial serum PRL and symptoms and their response to dopamine agonist therapy; imaging of the pituitary gland; serum PRL and symptoms after cessation of dopamine agonist therapy; course of serum PRL and symptoms without dopamine agonist therapy. The within-batch coefficient of variation (CV) of the PEG precipitation test ranged between 2.8 and 7.3% while the between-batch CV ranged between 3.4 and 9.7%. Intra-individual variability up to five months was 9.9%. A prolactin recovery </= 40% was indicative of macroprolactinaemia, while the condition was unlikely to be present at values > 50%. The prevalence of macroprolactinaemia was 15% without sex difference. Clinical characterization of 17 patients showed modest initial serum PRL concentrations and there was imaging evidence of a coexisting pituitary adenoma in three of them. Dopamine agonist therapy resulted in substantial falls in serum PRL and this was associated with improvement or resolution of symptoms in some patients. Stoppage of dopamine agonist resulted in rebound hyperprolactinaemia in all cases. Spontaneous improvement in symptoms occurred in three patients but hyperprolactinaemia persisted in all those who were not on treatment. The PEG precipitation test with assessment of 'free' prolactin has been shown to be reproducible and sensitive for the detection of macroprolactinaemia. Many of the patients who had macroprolactinaemia presented with at least one symptom of the hyperprolactinaemic syndrome. Dopaminergic therapy may influence the course of both serum PRL and symptoms in some of these patients.

LOW‐DOSE PITUITARY IRRADIATION FOR ACROMEGALY

External radiotherapy has been used as primary treatment for acromegaly in 29 patients and in combination with surgery in 41 patients in whom growth hormone levels remained elevated postoperatively. Fourteen further patients who did not receive radiotherapy have also been studied, four of whom had undergone surgical treatment. Radiotherapy schedules consisted of 20 Gy in eight fractions over 11 days (n = 23) or 35-40 Gy in 15 fractions over 21 days (n = 47). Growth hormone hypersecretion was either unchanged or increased with time in non-irradiated patients. In those patients who underwent radiotherapy, the likelihood of the mean GH level during GTT falling to less than 5 mU/l was unaffected by the total dose of radiation administered. However, patients with a pre-radiotherapy GH level of less than 30 mU/l showed a significantly increased probability of achieving a post- radiotherapy GH level less than 5 mU/l (P = 0.002). Previous surgery, initial serum prolactin and the age or sex of the patient did not predict the successful outcome of radiotherapy. In view of the known dose dependency of radiation-induced hypopituitarism, lower radiation dose schedules (20 Gy; eight fractions in 11 days) can be used in acromegaly with some benefit, especially in younger patients. However, all patients should undergo operative removal of as much GH-secreting tissue as possible, in order to lower GH levels and increase the probability of achieving a cure following radiotherapy.

Bromocriptine-unresponsive prolactin macroadenoma in a prepubertal female

Macroprolactinomas occur rarely in prepubertal children. A prepubertal 11 10/12-year-old female with a macroprolactinoma presented with a diagnosis of anorexia nervosa. Findings included severe headaches, anorexia, weight loss, and growth failure. The initial serum prolactin level was 2,916 ng/ml. This value fell after beginning treatment witli bromocriptine, but later rose despite a doubling of the dose. Transsphenoidal surgical resection was performed and postoperative radiation given. The use of bromocriptine, surgical resection, and radiation therapy in the treatment of macroprolactinomas are discussed.

To treat or not to treat: hyperprolactinemia

ABSTRACT Physicians are overtreating hyperprolactinemia, says Michele C. S. Koppelman, MD, of the National Institute of Child Health and Development (NICHD), Bethesda, Md.At the recent meeting of the Endocrine Society in San Francisco, Koppelman reported on a follow-up study of 25 female patients with long-standing, untreated hyperprolactinemia. Most of the patients' conditions remained stable or improved clinically over the years, and some showed apparent regression of pituitary adenomas.On average, the onset of the patients' symptoms predated the follow-up study by 11.3 years and the diagnoses of hyperprolactinemia by 5.3 years. Half of the women had had initial serum prolactin levels higher than 200 ng/mL, and two thirds had had levels exceeding 100 ng/mL. In 15 patients, skull x-ray films and polytomography of the pituitary fossa had shown abnormalities in the sella turcica. None of the patients with these abnormalities had visual field defects, but several had headaches.At the

Cyproheptadine in the management of the galactorrhea-amenorrhea syndrome.

We evaluated long-term treatment with the antiserotonergic agent cyproheptadine in the management of the galactorrhea-amenorrhea syndrome. Fifteen women with a mean initial serum prolactin of 37 +/- 7 ng/mL received 16 to 24 mg of cyproheptadine daily; they had a significant decrease in prolactin concentration at 8 and at 16 weeks (P less than 0.01). Gonadotropin responses were variable, but no significant changes were recorded during treatment. Ten of the 15 women had menstrual bleeding while receiving cyproheptadine, seven had decreased galactorrhea, and two had cessation of galactorrhea. The side effects of treatment were transient drowsiness and weight gain. We conclude that long-term treatment of the galactorrhea-amenorrhea syndrome with cyproheptadine is effective in lowering serum prolactin in patients with mildly elevated or normal levels. Its effect on fertility remains to be ascertained.