J Clin Endocrinol Metab 43: 937, 1976 METHYLPHENIDATE INCREASES SERUM GROWTH HORMONE CONCENTRATIONS W.A. Brown, and B.W. Williams, Neuroendocrine Research Laboratory, VA Hospital, Davis Park, Providence, Rhode Island 02908 and Brown University Program in Medicine ABSTRACT: Serum growth hormone (GH) and cortisol concentrations were measured in 12 healthy, young men following oral administration of methylphenidate (20 mgm) or a placebo. Methylphenidate elicited unequivocal GH elevations in 9 of 12 subjects while only 2 subjects showed GH elevation following placebo, Cortisol concentrations were not affected by methylphenidate.
Methylphenidate (Ritalin) is widely used in the treatment of children with minimal brain dysfunction and for its stimulant properties as an adjunct in the treatment of depression. It is similar but not identical to amphetamine in its neuropharmacologic and behavioral effects. Methylphenidate releases catecholamines, preferentially dopamine, from nerve endings and may directly stimulate dopamine receptor sites (1,2). Growth hormone (GH) release in humans has been shown to be stimulated by pharmacologic agents which elevate brain levels of dopamine, which release dopamine from presynaptic nerve endings, and which directly stimulate dopamine receptor sites (3»*0« Intravenous methylamphetamine has been shown to elevate GH and cortisol concentrations while oral dexamphetamine has been shown to elevate serum cortisol but not serum GH concentrations (5). There are no published reports of the endocrine effects of methylphenidate. In view of its neuropharmacologic effects and its wide use in both children and adults, it seems important to investigate the effects of methylphenidate on endocrine regulation.
saline drip. Subjects were at bedrest. Forty-five minutes following venepuncture an identical capsule containing methylphenidate (20 mg) or placebo (lactose) was administered on a double-blind basis. Blood samples (10 cc) were drawn at -U5, -30, 0, 30, U5, 60, 75, 90, 105, and 120 minutes. Serum was assayed for GH by double-antibody radioimmunoassay (6) and for cortisol by a competitive protein binding method (7)« The intra-assay coefficient of variation (CV) for GH in our laboratory is 5.7$ and interassay CV is 7-5$. The intra-assay CV for cortisol is 7-7$ and interassay CV is 7«9%- Samples were measured in duplicate and all samples from the same session were measured in the same assay. RESULTS
Nine of twelve subjects showed a marked rise in GH (9.0 -> UO.O ng/ml) following methylphenidate, while only two subjects showed a rise in GH (7«5,> ^0.0 ng/ml) following placebo (p< .01 Fisher Exact Probability Test). All other control subjects maintained basal (< 3.5 ng/ml) GH concentrations. Elevations in GH began at 60 to 75 minutes following methylphenidate and peaked at 90 to 105 minutes. There were no significant differences in METHODS mean cortisol concentrations or pattern of change in cortisol concentration between Twelve healthy male volunteers, methylphenidate and placebo sessions with ages 21 to 37 (mean age 25) were given cortisol concentrations showing the expecmethylphenidate and placebo on two ted downward shift during both sessions. separate occasions in balanced order. During the second hour following methylExperimental sessions began at 8:30am. phenidate most subjects reported mild following an overnight fast. Blood transient feelings of euphoria and acsamples were drawn through a 19 gauge tivation. scalp-vein needle kept open with a slow
937
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 14 June 2015. at 14:12 For personal use only. No other uses without permission. . All rights reserved.
JCE & M • 1976 Vol 43 • No 4
RAPID COMMUNICATIONS
938
SERUM GROWTH HORMONE FOLLOWING METHYLPHENIDATE AND PLACEBO (ng/ml, N = 12) + sem
Time (minutes)
Methylphenidate
Placebo
75
90**
105**
120**
9-9
12.9
25.2
26.3
2U.U
2.9
U.I
3.9
k.Q
5.1
5-0
5-3
U.9
6.5
6.0
5.5
5.0
U.5
3.1
2.7
2.8
3.3
3.2
3.2
2.5
-1*5
-30
0*
30
U5
60
2.8
k.O
7.8
6.7
6.7
1.1
1.1*
2.8
2.7
5.1
3.3
k.l
.61 1.2
1.7
The slightly elevated mean baseline values reflect the fact that half the subjects showed baseline elevations in GH (probably stress related) prior to both placebo and methylphenidate. Following methylphenidate, but not placebo, such subjects showed a subsequent GH peak. ** t test p
Methylphenidate (Ritalin) is widely used in the treatment of children with minimal brain dysfunction and for its stimulant properties as an adjunct in the treatment of depression. It is similar but not identical to amphetamine in its neuropharmacologic and behavioral effects. Methylphenidate releases catecholamines, preferentially dopamine, from nerve endings and may directly stimulate dopamine receptor sites (1,2). Growth hormone (GH) release in humans has been shown to be stimulated by pharmacologic agents which elevate brain levels of dopamine, which release dopamine from presynaptic nerve endings, and which directly stimulate dopamine receptor sites (3»*0« Intravenous methylamphetamine has been shown to elevate GH and cortisol concentrations while oral dexamphetamine has been shown to elevate serum cortisol but not serum GH concentrations (5). There are no published reports of the endocrine effects of methylphenidate. In view of its neuropharmacologic effects and its wide use in both children and adults, it seems important to investigate the effects of methylphenidate on endocrine regulation.
saline drip. Subjects were at bedrest. Forty-five minutes following venepuncture an identical capsule containing methylphenidate (20 mg) or placebo (lactose) was administered on a double-blind basis. Blood samples (10 cc) were drawn at -U5, -30, 0, 30, U5, 60, 75, 90, 105, and 120 minutes. Serum was assayed for GH by double-antibody radioimmunoassay (6) and for cortisol by a competitive protein binding method (7)« The intra-assay coefficient of variation (CV) for GH in our laboratory is 5.7$ and interassay CV is 7-5$. The intra-assay CV for cortisol is 7-7$ and interassay CV is 7«9%- Samples were measured in duplicate and all samples from the same session were measured in the same assay. RESULTS
Nine of twelve subjects showed a marked rise in GH (9.0 -> UO.O ng/ml) following methylphenidate, while only two subjects showed a rise in GH (7«5,> ^0.0 ng/ml) following placebo (p< .01 Fisher Exact Probability Test). All other control subjects maintained basal (< 3.5 ng/ml) GH concentrations. Elevations in GH began at 60 to 75 minutes following methylphenidate and peaked at 90 to 105 minutes. There were no significant differences in METHODS mean cortisol concentrations or pattern of change in cortisol concentration between Twelve healthy male volunteers, methylphenidate and placebo sessions with ages 21 to 37 (mean age 25) were given cortisol concentrations showing the expecmethylphenidate and placebo on two ted downward shift during both sessions. separate occasions in balanced order. During the second hour following methylExperimental sessions began at 8:30am. phenidate most subjects reported mild following an overnight fast. Blood transient feelings of euphoria and acsamples were drawn through a 19 gauge tivation. scalp-vein needle kept open with a slow
937
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 14 June 2015. at 14:12 For personal use only. No other uses without permission. . All rights reserved.
JCE & M • 1976 Vol 43 • No 4
RAPID COMMUNICATIONS
938
SERUM GROWTH HORMONE FOLLOWING METHYLPHENIDATE AND PLACEBO (ng/ml, N = 12) + sem
Time (minutes)
Methylphenidate
Placebo
75
90**
105**
120**
9-9
12.9
25.2
26.3
2U.U
2.9
U.I
3.9
k.Q
5.1
5-0
5-3
U.9
6.5
6.0
5.5
5.0
U.5
3.1
2.7
2.8
3.3
3.2
3.2
2.5
-1*5
-30
0*
30
U5
60
2.8
k.O
7.8
6.7
6.7
1.1
1.1*
2.8
2.7
5.1
3.3
k.l
.61 1.2
1.7
The slightly elevated mean baseline values reflect the fact that half the subjects showed baseline elevations in GH (probably stress related) prior to both placebo and methylphenidate. Following methylphenidate, but not placebo, such subjects showed a subsequent GH peak. ** t test p
