JEADV
LETTERS TO THE EDITOR
Diffuse hair loss associated with hyperprolactinaemia: report of three cases Editor Hyperprolactinaemia can be physiological (e.g. pregnancy), pharmacological, disease-induced (e.g. prolactin-producing tumours, hypothalamic disease, hypothyroidism, renal insufficiency), or idiopathic.1 Hair loss associated with hyperprolactinaemia has been recognized for a long time,2 but frequently overlooked in clinical practice. Hereby, we report three patients with diffuse hair loss related to hyperprolactinaemia, among them one with macroprolactinoma, another on risperidone due to drug abuse and the other with psychiatric disorders taking multiple antipsychotics. Case 1: A 24-year-old woman came to us complaining about progressing hair loss for 3 years. Physical examination revealed a diffuse hair thinning remarkably in the parietal regions (Fig. 1). Trichogram anaylsis showed increased telogen hair shedding (23% frontal and 25% occipital). Endocrinological work-up disclosed a high serum level of prolactin (478.9, normal: 4.8– 23.3 ng/mL), mild hypothyroidism, normal testosterone and suppressed levels of luteinising hormone and follicle stimulating hormone. A macroprolactinoma (2.7 9 2 9 1.9 cm) without mass effect on optic chiasm was found on magnetic resonance imaging study. Case 2: A 21-year-old male patient was referred to us due to acute exacerbation of hair loss for several months. He had been put on risperidone to tackle psychological problems caused by drug abuse of lysergic acid diethylamide and ecstasy (3,4-methylenedioxy-N-methylamphetamine, MDMA). Trichogram examination showed mild increase in telogen hair (frontal 18% and occipital 24%) and a significantly higher percentage of dystrophic hair especially in the occipital scalp (19%). Laboratory study showed a mildly increased prolactin serum level (47.4 ng/ mL) with otherwise inconspicuous data in endocrinology. Case 3: A 26-year-old woman of African origin presented to us in 2010 with a history of accelerating progression of diffuse hair loss for 5 years, most severe on the frontal scalp (Fig. 2). Depression and paranoid schizophrenia was diagnosed in 2004, and since 2007 she had been put on risperidone, haloperidol and clozapine. A high ratio of telogen hair at 36% was seen in the trichogram. Laboratory results including radiologic findings were all within normal range except for an increased prolactin level at 83 ng/mL. Three possible causes may interact to induce
JEADV 2015, 29, 607–616
Figure 1 24-year-old woman with a macroprolactinoma and hyperprolactinaemia showed a remarkably diffuse hair thinning in the parietal regions.
and aggravate her hair loss: androgenetic alopecia, hyperprolactinaemia and tractional alopecia. Prolactin is primarily synthesized in the pituitary but is also expressed along with its receptor in human skin and scalp hair follicles.3 In vitro, prolactin can inhibit hair shaft elongation and induce premature catagen formation, along with reduced proliferation and increased apoptosis of hair bulb keratinocytes.3 Prolactin can stimulate adrenal steroidogenesis, leading to hyperandrogenaemia associated with hyperprolactinaemia. Clinical manifestations can appear at levels of 50 to 100 ng/mL, such as galactorrhoea, amenorrhoea and impotence. However, the threshold leading to hair loss remains unclear, while women appear to be more vulnerable (personal observation). As dopamine is physiologically the predominant inhibitor of prolactin, drugs blocking the endogenous dopamine receptors can cause hyperprolactinaemia, most common among them are antipsychotics such as haloperidol, chlorpromazine, thioridazine and thiotixene.4 With chronic use of antipsychotics, 40–90% of patients maintain elevated prolactin levels. Risperidone, a
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
608
hyperprolactinemia is very likely. It is to note that MDMA, as used in the case 2, can also increase the plasma levels of prolactin.11 In conclusion, our cases provide further evidence that hyperprolactinaemia can be associated with diffuse hair loss. Atypical antipsychotics, especially risperidone, can cause hyperprolactinaemia. Screening for prolactin in patients with diffuse hair loss of unclear medical history is warranted. M. Ziai,1 L. Cifuentes,1 M. Grosber,1,2 M. McIntyre,1 H. Prucha,1 J. Ring,1 W. Chen1,* €t Department of Dermatology and Allergy, Technische Universita €nchen, Munich, Germany, 2Department of Dermatology, Free Mu University of Brussels, Brussels, Belgium *Correspondence: W. Chen. E-mail: [email protected] 1
M. Ziai and L. Cifuentes contributed equally to this work.
References Figure 2 A 26-year-old woman with progressive frontoparietal alopecia, probably caused by multiple factors, namely, androgenetic alopecia, tractional alopecia and hyperprolactinaemia associated with psychosis and antipsychotic drugs.
combined serotonin/dopamine receptor antagonist, can cause prolactin elevations even higher than seen with the typical antipsychotics. The endocrinological side-effects have been noticed in 1–10% of patients treated with risperidone.5 The occurrence rate of hyperprolactinaemia associated with other therapeutic agents is as follows: antipsychotics 31%, antidepressants 26%, H2-receptor antagonists 5% and other drugs 10%.6 However, the real prevalence of hair loss caused by dopaminergic psychotropic drugs remains to be determined. Epilepsy, affective disorders and psychosis themselves may be a risk factor for metabolic syndrome.7,8 Neuroleptics, such as carbamazepine and phenytoin, can alter the metabolism of sex steroid hormones, while association between valproic acid and a frequent occurrence of polycystic ovary syndrome and hyperandrogenism in women with epilepsy has been well demonstrated.7 There is also increasing concern that antipsychotic drugs, particularly second-generation atypical antipsychotics (such as risperidone and clozapine used in case 3), have metabolic consequences, including hyperandrogenaemia and insulin resistance.8,9 Antipsychotics can modulate hormone release from the hypothalamic–pituitary–gonadal axis, altering the metabolism of sex hormones and their binding proteins.10 In our case 3, an exacerbation of a preexistent androgenetic alopecia through
JEADV 2015, 29, 607–616
1 Majumdar A, Mangal NS. Hyperprolactinemia. J Hum Reprod Sci 2013; 6: 168–175. 2 Orfanos CE, Hertel H. Disorder of hair growth in hyperprolactinemia. Z Hautkr 1988; 63: 23–26. 3 Foitzik K, Krause K, Conrad F, Nakamura M, Funk W, Paus R. Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression. Am J Pathol 2006; 168: 748–756. 4 Cookson J, Hodgson R, Wildgust HJ. Prolactin, hyperprolactinaemia and antipsychotic treatment: a review and lessons for treatment of early psychosis. J Psychopharmacol 2012; 26: 42–51. 5 Holzer L, Eap CB. Risperidone-induced symptomatic hyperprolactinaemia in adolescents. J Clin Psych 2006; 26: 167–171. 6 Petit A, Piednoir D, Germain ML, Trenque T. Drug-induced hyperprolactinemia: a case-non-case study from the national pharmacovigilance database. Therapie 2003; 58: 159–163. 7 Verrotti A, D’Egidio C, Coppola G, Parisi P, Chiarelli F. Epilepsy, sex hormones and antiepileptic drugs in female patients. Expert Rev Neurother 2009; 9: 1803–1814. 8 Yogaratnam J, Biswas N, Vadivel R, Jacob R. Metabolic complications of schizophrenia and antipsychotic medications- an updated review. East Asian Arch Psychiatry 2013; 23: 21–28. 9 Reddy SM, Goudie CT, Agius M. The metabolic syndrome in untreated schizophrenia patients: prevalence and putative mechanisms. Psychiatr Danub 2013; 25(Suppl 2): S94–S98. 10 Hasnain M, Fredrickson SK, Vieweg WV, Pandurangi AK. Metabolic syndrome associated with schizophrenia and atypical antipsychotics. Curr Diab Rep 2010; 10: 209–216. 11 Harris DS, Baggott M, Mendelson JH, Mendelson JE, Jones RT. Subjective and hormonal effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology 2002; 162: 396–405. DOI: 10.1111/jdv.12407
© 2014 European Academy of Dermatology and Venereology
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
LETTERS TO THE EDITOR
Diffuse hair loss associated with hyperprolactinaemia: report of three cases Editor Hyperprolactinaemia can be physiological (e.g. pregnancy), pharmacological, disease-induced (e.g. prolactin-producing tumours, hypothalamic disease, hypothyroidism, renal insufficiency), or idiopathic.1 Hair loss associated with hyperprolactinaemia has been recognized for a long time,2 but frequently overlooked in clinical practice. Hereby, we report three patients with diffuse hair loss related to hyperprolactinaemia, among them one with macroprolactinoma, another on risperidone due to drug abuse and the other with psychiatric disorders taking multiple antipsychotics. Case 1: A 24-year-old woman came to us complaining about progressing hair loss for 3 years. Physical examination revealed a diffuse hair thinning remarkably in the parietal regions (Fig. 1). Trichogram anaylsis showed increased telogen hair shedding (23% frontal and 25% occipital). Endocrinological work-up disclosed a high serum level of prolactin (478.9, normal: 4.8– 23.3 ng/mL), mild hypothyroidism, normal testosterone and suppressed levels of luteinising hormone and follicle stimulating hormone. A macroprolactinoma (2.7 9 2 9 1.9 cm) without mass effect on optic chiasm was found on magnetic resonance imaging study. Case 2: A 21-year-old male patient was referred to us due to acute exacerbation of hair loss for several months. He had been put on risperidone to tackle psychological problems caused by drug abuse of lysergic acid diethylamide and ecstasy (3,4-methylenedioxy-N-methylamphetamine, MDMA). Trichogram examination showed mild increase in telogen hair (frontal 18% and occipital 24%) and a significantly higher percentage of dystrophic hair especially in the occipital scalp (19%). Laboratory study showed a mildly increased prolactin serum level (47.4 ng/ mL) with otherwise inconspicuous data in endocrinology. Case 3: A 26-year-old woman of African origin presented to us in 2010 with a history of accelerating progression of diffuse hair loss for 5 years, most severe on the frontal scalp (Fig. 2). Depression and paranoid schizophrenia was diagnosed in 2004, and since 2007 she had been put on risperidone, haloperidol and clozapine. A high ratio of telogen hair at 36% was seen in the trichogram. Laboratory results including radiologic findings were all within normal range except for an increased prolactin level at 83 ng/mL. Three possible causes may interact to induce
JEADV 2015, 29, 607–616
Figure 1 24-year-old woman with a macroprolactinoma and hyperprolactinaemia showed a remarkably diffuse hair thinning in the parietal regions.
and aggravate her hair loss: androgenetic alopecia, hyperprolactinaemia and tractional alopecia. Prolactin is primarily synthesized in the pituitary but is also expressed along with its receptor in human skin and scalp hair follicles.3 In vitro, prolactin can inhibit hair shaft elongation and induce premature catagen formation, along with reduced proliferation and increased apoptosis of hair bulb keratinocytes.3 Prolactin can stimulate adrenal steroidogenesis, leading to hyperandrogenaemia associated with hyperprolactinaemia. Clinical manifestations can appear at levels of 50 to 100 ng/mL, such as galactorrhoea, amenorrhoea and impotence. However, the threshold leading to hair loss remains unclear, while women appear to be more vulnerable (personal observation). As dopamine is physiologically the predominant inhibitor of prolactin, drugs blocking the endogenous dopamine receptors can cause hyperprolactinaemia, most common among them are antipsychotics such as haloperidol, chlorpromazine, thioridazine and thiotixene.4 With chronic use of antipsychotics, 40–90% of patients maintain elevated prolactin levels. Risperidone, a
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
608
hyperprolactinemia is very likely. It is to note that MDMA, as used in the case 2, can also increase the plasma levels of prolactin.11 In conclusion, our cases provide further evidence that hyperprolactinaemia can be associated with diffuse hair loss. Atypical antipsychotics, especially risperidone, can cause hyperprolactinaemia. Screening for prolactin in patients with diffuse hair loss of unclear medical history is warranted. M. Ziai,1 L. Cifuentes,1 M. Grosber,1,2 M. McIntyre,1 H. Prucha,1 J. Ring,1 W. Chen1,* €t Department of Dermatology and Allergy, Technische Universita €nchen, Munich, Germany, 2Department of Dermatology, Free Mu University of Brussels, Brussels, Belgium *Correspondence: W. Chen. E-mail: [email protected] 1
M. Ziai and L. Cifuentes contributed equally to this work.
References Figure 2 A 26-year-old woman with progressive frontoparietal alopecia, probably caused by multiple factors, namely, androgenetic alopecia, tractional alopecia and hyperprolactinaemia associated with psychosis and antipsychotic drugs.
combined serotonin/dopamine receptor antagonist, can cause prolactin elevations even higher than seen with the typical antipsychotics. The endocrinological side-effects have been noticed in 1–10% of patients treated with risperidone.5 The occurrence rate of hyperprolactinaemia associated with other therapeutic agents is as follows: antipsychotics 31%, antidepressants 26%, H2-receptor antagonists 5% and other drugs 10%.6 However, the real prevalence of hair loss caused by dopaminergic psychotropic drugs remains to be determined. Epilepsy, affective disorders and psychosis themselves may be a risk factor for metabolic syndrome.7,8 Neuroleptics, such as carbamazepine and phenytoin, can alter the metabolism of sex steroid hormones, while association between valproic acid and a frequent occurrence of polycystic ovary syndrome and hyperandrogenism in women with epilepsy has been well demonstrated.7 There is also increasing concern that antipsychotic drugs, particularly second-generation atypical antipsychotics (such as risperidone and clozapine used in case 3), have metabolic consequences, including hyperandrogenaemia and insulin resistance.8,9 Antipsychotics can modulate hormone release from the hypothalamic–pituitary–gonadal axis, altering the metabolism of sex hormones and their binding proteins.10 In our case 3, an exacerbation of a preexistent androgenetic alopecia through
JEADV 2015, 29, 607–616
1 Majumdar A, Mangal NS. Hyperprolactinemia. J Hum Reprod Sci 2013; 6: 168–175. 2 Orfanos CE, Hertel H. Disorder of hair growth in hyperprolactinemia. Z Hautkr 1988; 63: 23–26. 3 Foitzik K, Krause K, Conrad F, Nakamura M, Funk W, Paus R. Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression. Am J Pathol 2006; 168: 748–756. 4 Cookson J, Hodgson R, Wildgust HJ. Prolactin, hyperprolactinaemia and antipsychotic treatment: a review and lessons for treatment of early psychosis. J Psychopharmacol 2012; 26: 42–51. 5 Holzer L, Eap CB. Risperidone-induced symptomatic hyperprolactinaemia in adolescents. J Clin Psych 2006; 26: 167–171. 6 Petit A, Piednoir D, Germain ML, Trenque T. Drug-induced hyperprolactinemia: a case-non-case study from the national pharmacovigilance database. Therapie 2003; 58: 159–163. 7 Verrotti A, D’Egidio C, Coppola G, Parisi P, Chiarelli F. Epilepsy, sex hormones and antiepileptic drugs in female patients. Expert Rev Neurother 2009; 9: 1803–1814. 8 Yogaratnam J, Biswas N, Vadivel R, Jacob R. Metabolic complications of schizophrenia and antipsychotic medications- an updated review. East Asian Arch Psychiatry 2013; 23: 21–28. 9 Reddy SM, Goudie CT, Agius M. The metabolic syndrome in untreated schizophrenia patients: prevalence and putative mechanisms. Psychiatr Danub 2013; 25(Suppl 2): S94–S98. 10 Hasnain M, Fredrickson SK, Vieweg WV, Pandurangi AK. Metabolic syndrome associated with schizophrenia and atypical antipsychotics. Curr Diab Rep 2010; 10: 209–216. 11 Harris DS, Baggott M, Mendelson JH, Mendelson JE, Jones RT. Subjective and hormonal effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology 2002; 162: 396–405. DOI: 10.1111/jdv.12407
© 2014 European Academy of Dermatology and Venereology
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
