0021-972X/91/7306-1281$03.00/0 Journal of Clinical Endocrinology and Metabolism Copyright© 1991 by The Endocrine Society
Vol. 73, No. 6 Printed in U.S.A.
Pulsatile Glycoprotein Hormone Secretion in Glycoprotein-Producing Pituitary Tumors* M. H. SAMUELS, P. HENRY, B. K. KLEINSCHMIDT-DEMASTERS, K. LILLEHEI, AND E. C. RIDGWAY Division of Endocrinology, University of Texas Health Sciences Center (M.H.S.), San Antonio, Texas 782847877; and the Divisions of Endocrinology and Metabolism (P.H., E.C.R.), Neuropathology (B.K.K.-DJ, and Neurosurgery (K.L.), University of Colorado Health Sciences Center, Denver, Colorado 80262
ABSTRACT. To study patterns of hormone production and secretion in glycoprotein-producing pituitary tumors, 12 patients with such tumors underwent the following studies. Preoperatively, all patients had serum TSH, LH, FSH, and a-subunit levels measured every 15 min for 24 h. Hormone pulses were located by cluster analysis, and pulse parameters were compared to those in healthy young men, healthy young women, healthy postmenopausal women, and subjects with primary hypothyroidism. After surgery, immunocytochemistry for the four glycoproteins was performed on all tumors, and Northern blot analysis was performed in six tumors with probes for the four subunits. By immunocytochemistry, 42% of the tumors were positive for
T
HE PITUITARY glycoproteins include TSH, LH, FSH, and a-subunit. Many clinically nonfunctioning pituitary tumors synthesize these hormones (1, 2), as shown by elevated serum hormone levels (2, 3), immunocytochemistry (4, 5), cell culture (2, 6, 7), and mRNA analysis (8). However, many aspects of dynamic hormone secretion in these tumors remain to be studied. Under normal conditions and in states of excess hormone secretion due to primary thyroid or gonadal deficiency, the pituitary glycoproteins are secreted in pulses (9). Recent case reports have suggested that glycoproteins were also secreted episodically in a few patients with glycoprotein tumors (10-12), although formal pulse analysis was not carried out. This raises fascinating questions regarding the origin and control of such pulses, but systematic study of these tumors is necessary to explore such questions. To determine whether pulsatile hormone secretion occurs in glycoprotein tumors, we studied 12 patients Received January 7,1991. Address requests for reprints to: Dr. M. H. Samuels, Department of Medicine, Division of Endocrinology, University of Texas Health Sciences Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7877. * This work was supported in part by Adult GCRC Grant MOl-RR00051 and NIH Grants DK-36843-03 (to M.H.S.) and CA-47411-01 and DK-36843 (to E.C.R.).
TSHjS, 83% for LHfr 75% for FSH0, and 92% for a-subunit. Preoperative serum hormone levels varied widely between patients and were not well correlated with the intensity of immunocytochemical staining. Northern blot analysis did not appear to be as sensitive as immunocytochemistry for detection of the glycoproteins. All patients had pulsatile glycoprotein secretion, with pulses of normal frequency but varied amplitude. These results suggest that in patients with glycoprotein tumors, hormone pulses may be an integral part of autonomous secretion, or that hypothalamic control is involved in glycoprotein secretion and, perhaps, in the pathogenesis of these tumors. {J Clin Endocrinol Metab 73: 1281-1288, 1991)
with glycoprotein-producing pituitary macroadenomas. In each case, pulsatile hormone secretion was assessed preoperatively, and immunocytochemistry was performed postoperatively; in addition, mRNA analysis was performed on excised tumor tissue in 6 cases.
Materials and Methods Patients Twelve patients (eight men and four women, aged 34-74 yr) with pituitary macroadenomas that had positive immunostaining for one or more of the pituitary glycoproteins were studied at the University of Colorado Health Science Center (Table 1). One patient had previously undergone unsuccessful surgery (patient 7); no patient had undergone radiation therapy. Two patients had TSH-induced hyperthyroidism [one was the subject of a previous report (13)]; while the other patients had no clinical signs of excess hormone production. None of the patients had hypothyroidism, hypoadrenalism, or diabetes insipidus. Seven patients (five men and two women) had untreated central hypogonadism, while a third woman (patient 6) had low estradiol levels consistent with her postmenopausal status, but low LH levels, suggesting central hypogonadism. Four of the hypogonadal patients had mild hyperprolactinemia (range, 2772 ng/L; normal, 1-20 /tg/L). Clinical studies All patients had preoperative basal blood samples drawn for hormone measurements, and then blood was drawn every 15
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JCE & M • 1991 Vol 73 • No 6
SAMUELS ET AL.
TABLE 1. Patient characteristics, serum hormone levels, immunocytochemistry, and mRNA analysis in 12 pituitary macroadenomas Immunocytochemistry
Patient no., age (yr), sex
Serum T (nmol/L) or E2 (pmol/L)
TSH (mU/L)
LH (IU/L)
FSH (IU/L)
a (ng/mL)
1.40.F 2,38,M 3,54,M 4,74,M 5,39,M 6,59,F 7,35,F 8.34.M 9,57,M 10,46,M 11.65.M 12,35,F
294 (E2) 6.2 (T) 29.9 (T) 6.9 (T) 5.1 (T)
Vol. 73, No. 6 Printed in U.S.A.
Pulsatile Glycoprotein Hormone Secretion in Glycoprotein-Producing Pituitary Tumors* M. H. SAMUELS, P. HENRY, B. K. KLEINSCHMIDT-DEMASTERS, K. LILLEHEI, AND E. C. RIDGWAY Division of Endocrinology, University of Texas Health Sciences Center (M.H.S.), San Antonio, Texas 782847877; and the Divisions of Endocrinology and Metabolism (P.H., E.C.R.), Neuropathology (B.K.K.-DJ, and Neurosurgery (K.L.), University of Colorado Health Sciences Center, Denver, Colorado 80262
ABSTRACT. To study patterns of hormone production and secretion in glycoprotein-producing pituitary tumors, 12 patients with such tumors underwent the following studies. Preoperatively, all patients had serum TSH, LH, FSH, and a-subunit levels measured every 15 min for 24 h. Hormone pulses were located by cluster analysis, and pulse parameters were compared to those in healthy young men, healthy young women, healthy postmenopausal women, and subjects with primary hypothyroidism. After surgery, immunocytochemistry for the four glycoproteins was performed on all tumors, and Northern blot analysis was performed in six tumors with probes for the four subunits. By immunocytochemistry, 42% of the tumors were positive for
T
HE PITUITARY glycoproteins include TSH, LH, FSH, and a-subunit. Many clinically nonfunctioning pituitary tumors synthesize these hormones (1, 2), as shown by elevated serum hormone levels (2, 3), immunocytochemistry (4, 5), cell culture (2, 6, 7), and mRNA analysis (8). However, many aspects of dynamic hormone secretion in these tumors remain to be studied. Under normal conditions and in states of excess hormone secretion due to primary thyroid or gonadal deficiency, the pituitary glycoproteins are secreted in pulses (9). Recent case reports have suggested that glycoproteins were also secreted episodically in a few patients with glycoprotein tumors (10-12), although formal pulse analysis was not carried out. This raises fascinating questions regarding the origin and control of such pulses, but systematic study of these tumors is necessary to explore such questions. To determine whether pulsatile hormone secretion occurs in glycoprotein tumors, we studied 12 patients Received January 7,1991. Address requests for reprints to: Dr. M. H. Samuels, Department of Medicine, Division of Endocrinology, University of Texas Health Sciences Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7877. * This work was supported in part by Adult GCRC Grant MOl-RR00051 and NIH Grants DK-36843-03 (to M.H.S.) and CA-47411-01 and DK-36843 (to E.C.R.).
TSHjS, 83% for LHfr 75% for FSH0, and 92% for a-subunit. Preoperative serum hormone levels varied widely between patients and were not well correlated with the intensity of immunocytochemical staining. Northern blot analysis did not appear to be as sensitive as immunocytochemistry for detection of the glycoproteins. All patients had pulsatile glycoprotein secretion, with pulses of normal frequency but varied amplitude. These results suggest that in patients with glycoprotein tumors, hormone pulses may be an integral part of autonomous secretion, or that hypothalamic control is involved in glycoprotein secretion and, perhaps, in the pathogenesis of these tumors. {J Clin Endocrinol Metab 73: 1281-1288, 1991)
with glycoprotein-producing pituitary macroadenomas. In each case, pulsatile hormone secretion was assessed preoperatively, and immunocytochemistry was performed postoperatively; in addition, mRNA analysis was performed on excised tumor tissue in 6 cases.
Materials and Methods Patients Twelve patients (eight men and four women, aged 34-74 yr) with pituitary macroadenomas that had positive immunostaining for one or more of the pituitary glycoproteins were studied at the University of Colorado Health Science Center (Table 1). One patient had previously undergone unsuccessful surgery (patient 7); no patient had undergone radiation therapy. Two patients had TSH-induced hyperthyroidism [one was the subject of a previous report (13)]; while the other patients had no clinical signs of excess hormone production. None of the patients had hypothyroidism, hypoadrenalism, or diabetes insipidus. Seven patients (five men and two women) had untreated central hypogonadism, while a third woman (patient 6) had low estradiol levels consistent with her postmenopausal status, but low LH levels, suggesting central hypogonadism. Four of the hypogonadal patients had mild hyperprolactinemia (range, 2772 ng/L; normal, 1-20 /tg/L). Clinical studies All patients had preoperative basal blood samples drawn for hormone measurements, and then blood was drawn every 15
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The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 12 May 2015. at 15:57 For personal use only. No other uses without permission. . All rights reserved.
1282
JCE & M • 1991 Vol 73 • No 6
SAMUELS ET AL.
TABLE 1. Patient characteristics, serum hormone levels, immunocytochemistry, and mRNA analysis in 12 pituitary macroadenomas Immunocytochemistry
Patient no., age (yr), sex
Serum T (nmol/L) or E2 (pmol/L)
TSH (mU/L)
LH (IU/L)
FSH (IU/L)
a (ng/mL)
1.40.F 2,38,M 3,54,M 4,74,M 5,39,M 6,59,F 7,35,F 8.34.M 9,57,M 10,46,M 11.65.M 12,35,F
294 (E2) 6.2 (T) 29.9 (T) 6.9 (T) 5.1 (T)
