JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 25, Number 3, 2015 ª Mary Ann Liebert, Inc. Pp. 277–278 DOI: 10.1089/cap.2014.0094
Possible Exogenous Growth Hormone Induced Mood Disorder with Mixed Features in a Child Taha Can Tuman,1 Zehra Topal,1 Nuran Demir,1 Ozden Arisoy,1 Sarper Taskiran,2 and Ali Evren Tufan, MD1
To the Editor:
T
he incidence of growth hormone (GH) deficiency in infants is reported to be 1 in 3800 live births (Rogol and Hayden 2014). Growth failure caused by GH deficiency is treated with exogenous hormone replacement (Rogol and Hayden 2014). Treatment with GH in childhood is generally without serious complications, and the most common side effects reported are headaches, dizziness, joint/muscle pains, and fluid retention (Fuller and Sjatovic 2007). Here, we report a case of mood disorder with mixed features in a prepubertal child, which was thought to be possibly related to exogenous GH replacement. Case Report The patient was an 11-year-old male who had been brought to our department with complaints of ‘‘insomnia, talkativeness, increased energy, and spending.’’ He was inattentive, hyperactive, and euphoric, and it was reported that ‘‘he felt he could do anything.’’ Upon questioning, it was learned that the complaints had been present continuously for the past 3 months. The patient’s grades had suffered, and within the past month he had verbalized suicidal ideations to his teachers. Mental status examination revealed auditory hallucinations, and grandiose delusions alternating with depressive ruminations and limited insight. Past medical and psychiatric history were unremarkable, except growth failure that had led to a referral to the pediatrics department 4 months earlier. The patient was diagnosed with GH deficiency, and somatropin injections (0.5 mg/day) had been commenced 3 months earlier and titrated to 0.7 mg/day in the past month. Apart from mild inattention and irritability, no distinct depressive episode had been reported prior to treatment with GH. Family history was negative for psychopathology. Neurological examination ruled out papillary edema, and no signs or symptoms of intracranial hypertension were reported. Laboratory evaluations as well as electroencephalogram (EEG) were normal. Psychometric evaluation with the Childhood Mania Scale as completed by the parents revealed a score of 35 (chief complaints: auditory hallucinations, paranoid ideations, impulsivity, grandiosity, pressured speech, insomnia, increased energy, euphoria, and irritability). The baseline evaluation with Young Mania Rating Scale (YMRS) yielded a score of 38. Childhood Depression Inventory and other measures could not be completed because of the patient’s excessive agita-
tion. Children’s Global Assessment Scale (CGAS) revealed moderate impairment (score: 45). Consequently, the patient was diagnosed with mood disorder with mixed features caused by somatropin according to Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria (American Psychiatric Association 1994). The pediatrics team and the parents of the patient refused a trial of somatropin cessation therefore treatment was started with risperidone 0.5 mg/day, later titrated to 1 mg/day, while the somatropin dose was reduced to 0.5 mg/day. A follow-up visit after 2 weeks revealed a YMRS score of 24 and a CGAS score of 55 (variable functioning). Because the patient continued to have persisting grandiose delusions and depressive ruminations, valproate 200 mg/day was added. At the 4th and 12th weeks, the patient’s YMRS scores were noted to be 20 and 15, respectively, and depressive ruminations, suicidality, and frank grandiosity remitted, whereas mood was somewhat elevated with hyperactivity and slight irritability. Discussion Here, we report a case of mood disorder with mixed features in a prepubertal child. An evaluation with the Naranjo Algorithm yielded a score of 4 (possible adverse drug reaction) (Naranjo et al. 1981) and the patient responded partially to a trial of antipsychotics and mood stabilizers. Because of the lack of a somatropin washout trial, we could not ascertain causality. The relationship of mood disorder to somatropin treatment may be spurious, and may reflect an underlying vulnerability to stress, although the lack of family history and prior episodes argues otherwise. Alternatively, somatropin treatment in our case may have caused a mixed episode, presumably via elevated insulin-like growth factor (IGF)-1 and its effects on monoaminergic transmission. Recent observations of elevated IGF-1 in bipolar patients may support this proposition (Kim et al. 2013; Li et al. 2014). Our results should be confirmed with future studies. Disclosures No competing financial interests exist. References American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association; 1994.
1
Department of Child and Adolescent Psychiatry, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey. Department of Psychiatry, Koc University Medical Faculty, Istanbul, Turkey. Part of this case report was presented as a poster at the 6th International Congress of Psychopharmacology and the 2nd International Symposium on Child and Adolescent Psychopharmacology (April 4–20, 2014, Antalya, Turkey). 2
277
278 Fuller MA, Sajatovic M: Drug Information Handbook for Psychiatry: A Comprehensive Reference of Psychotropic, Non-psychotropic, and Herbal Agents, 6th ed. Hudson, OH: LexiComp; 2007. Kim Y-K, Na K-S, Hwang J-A, Yoon H-K, Lee H-J, Hahn S-W, Lee B-H, Jung H-Y: High IGF-1 in patients with bipolar I Disorder: A trait marker? J Affect Disord 151:738- 743, 2013. Li X, Zhang T, He S, Hong B, Chen Z, Peng D, Wu Y, Wen H, Lin Z, Fang Y, Jiang K: Elevated serum levels of FGF-2, NGF and IGF-1 in patients with manic episode of bipolar disorder. Psychiatry Res 218:54–60, 2014. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ: A reliable method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30:239–245, 1981.
TUMAN ET AL. Rogol AD, Hayden GF: Etiologies and early diagnosis of short stature and growth failure in children and adolescents. J Pediatr 164 Suppl 5:S1–S14, 2014.
Address correspondence to: Evren Ali Tufan, MD Department of Child and Adolescent Psychiatry Faculty of Medicine Abant Izzet Baysal University Bolu Turkey E-mail: [email protected]
Possible Exogenous Growth Hormone Induced Mood Disorder with Mixed Features in a Child Taha Can Tuman,1 Zehra Topal,1 Nuran Demir,1 Ozden Arisoy,1 Sarper Taskiran,2 and Ali Evren Tufan, MD1
To the Editor:
T
he incidence of growth hormone (GH) deficiency in infants is reported to be 1 in 3800 live births (Rogol and Hayden 2014). Growth failure caused by GH deficiency is treated with exogenous hormone replacement (Rogol and Hayden 2014). Treatment with GH in childhood is generally without serious complications, and the most common side effects reported are headaches, dizziness, joint/muscle pains, and fluid retention (Fuller and Sjatovic 2007). Here, we report a case of mood disorder with mixed features in a prepubertal child, which was thought to be possibly related to exogenous GH replacement. Case Report The patient was an 11-year-old male who had been brought to our department with complaints of ‘‘insomnia, talkativeness, increased energy, and spending.’’ He was inattentive, hyperactive, and euphoric, and it was reported that ‘‘he felt he could do anything.’’ Upon questioning, it was learned that the complaints had been present continuously for the past 3 months. The patient’s grades had suffered, and within the past month he had verbalized suicidal ideations to his teachers. Mental status examination revealed auditory hallucinations, and grandiose delusions alternating with depressive ruminations and limited insight. Past medical and psychiatric history were unremarkable, except growth failure that had led to a referral to the pediatrics department 4 months earlier. The patient was diagnosed with GH deficiency, and somatropin injections (0.5 mg/day) had been commenced 3 months earlier and titrated to 0.7 mg/day in the past month. Apart from mild inattention and irritability, no distinct depressive episode had been reported prior to treatment with GH. Family history was negative for psychopathology. Neurological examination ruled out papillary edema, and no signs or symptoms of intracranial hypertension were reported. Laboratory evaluations as well as electroencephalogram (EEG) were normal. Psychometric evaluation with the Childhood Mania Scale as completed by the parents revealed a score of 35 (chief complaints: auditory hallucinations, paranoid ideations, impulsivity, grandiosity, pressured speech, insomnia, increased energy, euphoria, and irritability). The baseline evaluation with Young Mania Rating Scale (YMRS) yielded a score of 38. Childhood Depression Inventory and other measures could not be completed because of the patient’s excessive agita-
tion. Children’s Global Assessment Scale (CGAS) revealed moderate impairment (score: 45). Consequently, the patient was diagnosed with mood disorder with mixed features caused by somatropin according to Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria (American Psychiatric Association 1994). The pediatrics team and the parents of the patient refused a trial of somatropin cessation therefore treatment was started with risperidone 0.5 mg/day, later titrated to 1 mg/day, while the somatropin dose was reduced to 0.5 mg/day. A follow-up visit after 2 weeks revealed a YMRS score of 24 and a CGAS score of 55 (variable functioning). Because the patient continued to have persisting grandiose delusions and depressive ruminations, valproate 200 mg/day was added. At the 4th and 12th weeks, the patient’s YMRS scores were noted to be 20 and 15, respectively, and depressive ruminations, suicidality, and frank grandiosity remitted, whereas mood was somewhat elevated with hyperactivity and slight irritability. Discussion Here, we report a case of mood disorder with mixed features in a prepubertal child. An evaluation with the Naranjo Algorithm yielded a score of 4 (possible adverse drug reaction) (Naranjo et al. 1981) and the patient responded partially to a trial of antipsychotics and mood stabilizers. Because of the lack of a somatropin washout trial, we could not ascertain causality. The relationship of mood disorder to somatropin treatment may be spurious, and may reflect an underlying vulnerability to stress, although the lack of family history and prior episodes argues otherwise. Alternatively, somatropin treatment in our case may have caused a mixed episode, presumably via elevated insulin-like growth factor (IGF)-1 and its effects on monoaminergic transmission. Recent observations of elevated IGF-1 in bipolar patients may support this proposition (Kim et al. 2013; Li et al. 2014). Our results should be confirmed with future studies. Disclosures No competing financial interests exist. References American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association; 1994.
1
Department of Child and Adolescent Psychiatry, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey. Department of Psychiatry, Koc University Medical Faculty, Istanbul, Turkey. Part of this case report was presented as a poster at the 6th International Congress of Psychopharmacology and the 2nd International Symposium on Child and Adolescent Psychopharmacology (April 4–20, 2014, Antalya, Turkey). 2
277
278 Fuller MA, Sajatovic M: Drug Information Handbook for Psychiatry: A Comprehensive Reference of Psychotropic, Non-psychotropic, and Herbal Agents, 6th ed. Hudson, OH: LexiComp; 2007. Kim Y-K, Na K-S, Hwang J-A, Yoon H-K, Lee H-J, Hahn S-W, Lee B-H, Jung H-Y: High IGF-1 in patients with bipolar I Disorder: A trait marker? J Affect Disord 151:738- 743, 2013. Li X, Zhang T, He S, Hong B, Chen Z, Peng D, Wu Y, Wen H, Lin Z, Fang Y, Jiang K: Elevated serum levels of FGF-2, NGF and IGF-1 in patients with manic episode of bipolar disorder. Psychiatry Res 218:54–60, 2014. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ: A reliable method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30:239–245, 1981.
TUMAN ET AL. Rogol AD, Hayden GF: Etiologies and early diagnosis of short stature and growth failure in children and adolescents. J Pediatr 164 Suppl 5:S1–S14, 2014.
Address correspondence to: Evren Ali Tufan, MD Department of Child and Adolescent Psychiatry Faculty of Medicine Abant Izzet Baysal University Bolu Turkey E-mail: [email protected]
