Cerebrospinal Fluid Prolactin: A Reflection of Abnormal Prolactin Secretion in Patients with Pituitary Tumors L E R O Y L. SCHROEDER,

1

JOHN C. JOHNSON,* A N D WILLIAM B. MALARKEY

Division of Endocrinology and Metabolism, and Department of Radiology,* Ohio State University Hospitals, Columbus, Ohio ABSTRACT. Cerebrospinal fluid prolactin levels were determined in 33 patients with pituitary disease, 3 pregnant women at term and 30 control subjects. Prolactin which was immunologically similar to the human prolactin standard was detected by radioimmunoassay in the CSF of most of these subjects. Elevated serum and CSF PRL concentrations were found in three pregnant subjects and in twelve patients with pituitary tumors. Ten patients with pituitary tumors had serum PRL concentrations greater than their corresponding CSF PRL levels. A significant correlation was noted between the elevated serum and CSF prolactin levels in the twelve hyperprolactinemic patients which suggested that the CSF prolactin concentration was influenced by

S

ERUM PROLACTIN (PRL) levels are frequently elevated in patients with pituitary tumors not associated with acromegaly or Cushing's disease (1-3). The hyperprolactinemia in these patients possibly reflects decreased prolactin inhibiting factor reaching the prolactin synthesizing cells of the pituitary and/or failure of the tumor to respond to this signal (4). Prolactin secretion from these neoplasms usually fails to increase normally following TRH (5-7), chlorpromazine (4,8) and sleep (3,9); however, it is usually suppressed by L-dopa (8, 10,11).

The presence of pituitary hormones in the CSF of man has previously been reported Received January 9, 1976. Supported in part by the Clinical Research Grant (RR-34) from the National Institutes of Health and the Alex R. McDonald Memorial Grant for Cancer Research from the American Cancer Society. ' Trainee in Endocrinology, supported by Training Grant (5TolAM05118-18) from the National Institute of Arthritis and Metabolic Diseases. Presented in part at the American Federation for Clinical Research Meeting, Chicago, Illinois, November, 1975. Reprint requests: William B. Malarkey, M. D., Ohio State University Hospitals, 410 West Tenth Avenue, Columbus, Ohio 43210.

the serum PRL level. Two patients with pituitary tumor however, had CSF prolactin concentrations higher than their serum levels, which suggested that direct secretion of prolactin from the tumor to the CSF can also occur. Three patients with chromophobe adenomas had normal serum PRL concentrations and elevated CSF prolactin levels which differentiated them from fifteen patients with the primary empty sella syndrome who had normal serum and CSF prolactin levels. The finding of normal CSF prolactin levels in the primary empty sella patients argues against the postulate that the diaphragma sellae significantly influences CSF pituitary peptide concentrations. (J Clin Endocrinol Metab 43: 1255, 1976)

(12,13). In order to pursue our investigation of PRL secretion in patients with pituitary tumors, we have evaluated the serum and cerebrospinal fluid (CSF) PRL and growth hormone (GH) levels of patients with various pituitary disorders. We were interested in evaluating the relationship between serum and CSF PRL and GH concentrations, as well as the diagnostic value of a CSF PRL determination. We have found that CSF prolactin levels are increased in patients with pituitary tumors and pregnancy, while they are normal in control subjects and in patients with the primary empty sella syndrome. Materials and Methods Protocol Serum and CSF specimens were collected from 66 patients undergoing pneumoencephalography (PEG) or myelography for diagnostic purposes. The patients undergoing PEG were kept NPO after 0800 h, and all procedures were done at 1300 h. Blood samples for serum PRL and GH determinations were obtained through an indwelling iv needle ten min before acquisition of the CSF specimen. The serum and CSF specimens were stored at —20 C until assayed for PRL and GH.

1255

The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 19 November 2015. at 16:24 For personal use only. No other uses without permission. . All rights reserved.

JCE & M • 1976 Vol 43 • No 6

SCHROEDER, JOHNSON AND MALARKEY

1256 Patients

Assays

We have studied 33 patients with pituitary disorders of whom 15 had the empty sella syndrome, 12 had chromophobe adenomas, 4 had acromegaly and 2 had Nelson's syndrome (Table 1). The most frequent signs and symptoms presented by these patients were amenorrhea, galactorrhea and visual field defects (see Table 1). All but one patient, #15 Table I, had suprasellar pituitary mass lesion demonstrated by pneumoencephalography (PEG). Fasting serum and cerebrospinal fluid was obtained from three pregnant patients at term who were undergoing spinal anesthesia for cesarean section and from fifteen female patients who presented with hypertension, headaches and/or abnormal sella turcica size by routine skull films. These latter patients had no clinical evidence of an endocrinopathy, and their PEG demonstrated the presence of air in the sella turcica. As control patients, we selected 30 patients who were undergoing myelography or pneumoencephalography for suspected herniated disks (n = 14), possible high cord tumors (n = 3), acoustic neuromas (n = 3), multiple sclerosis (n = 3), and patients (n = 7) being evaluated for midline brain tumors who were subsequently found to be normal.

Human growth hormone was assayed according to the method of Grodsky and Forsham (14). The serum and CSF prolactin determinations were performed according to the homologous radioimmunoassay method of Sinha et at. (15). The intra and interassay coefficients of variation for the assay in our laboratory were less than 11%. All specimens from individual patients were run in the same assay. The sensitivity of this assay was 1.0 ng/ml, and approximately 40% of our control subjects' CSF prolactin concentrations fell below this level. For purposes of statistical analysis, undetectable CSF PRL levels were assigned the lowest measureable PRL concentration. The significance of the difference between the means was evaluated by the Wilcoxon Rank Sum test with a P value of less than 0.05 being considered significant.

Results

Similarity of serum and CSF prolactin Serial dilutions of CSF from three patients with a suprasellar meningioma, idiopathic galactorrhea and a pituitary tumor were compared to dilutions of the human prolactin

TABLE 1. Characteristics of patients with pituitary tumors Patient no.

Sex

Age

Diagnosis

Prolactin t serum

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

F F F F F M M M F M F M F M M M F F

23 26 18 40 19 42 31 42 26 56 62 16 22 64 27 33 33 62

Chromophobe* adenoma Chromophobe adenoma Chromophobe adenoma Chromophobe adenoma Chromophobe adenoma Chromophobe adenoma Chromophobe adenoma Chromophobe adenoma Chromophobe adenoma Chromophobe adenoma Chromophobe adenoma Chromophobe adenoma Acromegaly Acromegaly Acromegaly Acromegaly Nelson's Nelson's

600 593 166 32.8 32.0 27.1 21.3 16.5 12.6 11.8 6.6 2400 111 43.6 27.5 5.8 20 20

Growth (ng/ml) hormone \ (ng/ml) CSF CSF serum 60 24.3 37.6 5.8 14.1 2.0 3.9 3.1 3.1 7.6 2.8 4000 119 9.0 9.2 1 1 1.9

Cerebrospinal fluid prolactin: a reflection of abnormal prolactin secretion in patients with pituitary tumors.

Cerebrospinal fluid prolactin levels were determined in 33 patients with pituitary disease, 3 pregnant women at term and 30 control subjects. Prolacti...
575KB Sizes 0 Downloads 0 Views