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Growth Hormone Deficiency Causing Micropenis:Peter A Growth Hormone Deficiency Causing Micropenis:Peter A. Lee, MD, PhD, a Tom Mazur, PsyD, Lessons b Christopher P. Houk, MD, Learned c Robert M. Blizzard, MD d From a Well-Adjusted Adultabstract This report of a 46, XY patient born with a micropenis consistent with etiology from isolated congenital growth hormone deficiency is used to (1) raise the question regarding what degree testicular testosterone exposure aDepartment of Pediatrics, College of Medicine, Penn State to the central nervous system during fetal life and early infancy has on the University, Hershey, Pennsylvania; bCenter for Psychosexual development of male gender identity, regardless of gender of rearing; (2) Health, Jacobs School of Medicine and Biomedical suggest the obligatory nature of timely full disclosure of medical history; Sciences, University at Buffalo and John R. Oishei Children’s Hospital, Buffalo, New York; cDepartment of (3) emphasize that virtually all 46, XY infants with functional testes and Pediatrics, Medical College of Georgia, Augusta University, a micropenis should be initially boys except some with partial androgen Augusta, Georgia; and dDepartment of Pediatrics, College of Medicine, University of Virginia, Charlottesville, Virginia insensitivity syndrome; and (4) highlight the sustaining value of a positive long-term relationship with a trusted physician (R.M.B.). When this infant Dr Lee reviewed and discussed the extensive medical records with Dr Blizzard, reviewed presented, it was commonly considered inappropriate to gender assign an pertinent medical literature, and wrote each draft infant male whose penis was so small that an adult size was expected to be of the manuscript with input from all coauthors; inadequate, even if the karyotype was 46, XY, and testes were functional. Dr Mazur reviewed the literature and wrote a chronologic history outline with particular attention Concomitantly, female gender assignment was considered the appropriate to the psychological aspects and comments with decision, believing that parental rearing in the assigned gender was suggestions on each draft of the manuscript; considered the major factor determining established adult gender identity. Dr Houk reviewed and discussed the extensive Full disclosure of medical information was considered inappropriate. medical records in person with Drs Blizzard and Lee, commented and outlined pertinent information Progress in appreciating the complexities of gender identity development, from this case, and reviewed and commented on which is not yet completely understood, and sexuality, coping ability, each draft of the manuscript; Dr Blizzard, who and outcome data has resulted in a change of practice in initial gender cared for this patient for the first 35 years of the patient’s life, created an extensive collection assignment. A 46, XY individual with functional testes and verified androgen of notes and comments regarding this patient, responsiveness should be assigned and reared as male, regardless of discussed information to be included in this report, penis size. Without androgen responsiveness, the multiple factors must be and approved the manuscript being submitted; and all authors approved the final manuscript as carefully considered and disclosed. submitted. DOI: https:// doi. org/ 10. 1542/ peds. 2017- 4168 CASE SUMMARY Accepted for publication Apr 2, 2018 gender by parents and caregivers, Address correspondence to Peter A. Lee, MD, PhD, Milton S. Hershey Medical Center, PO Box 850, 500 A 46, XY individual born with a gender adjustment problems developed, and at age 29 years, after University Dr, Hershey, PA 17033-085. E-mail: plee@ stretched penis length of 1.5 cm was psu.edu reassigned female at 5 months of full medical history disclosure, this patient self-reassigned as male. This PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, life. Risks of female reassignment 1098-4275). were discussed; parents signed a patient is now a self-supporting, Copyright © 2018 by the American Academy of detailed hand-written consent. Testes socially active, married, sexually active, – Pediatrics were removed, and the penis was unequivocal heterosexual man. refashioned as a clitoris. With Figs 1 5, During childhood, developmental To cite: Lee PA, Mazur T, Houk CP, et al. Growth we provide a chronological summary milestones were normal, and gender Hormone Deficiency Causing Micropenis: Lessons in which we detail the life events for identity appeared female, but Learned From a Well-Adjusted Adult. Pediatrics. this 39-year-old well-adjusted man. poor self-concept, inattentiveness, 2018;142(1):e20174168 Despite multiple genital surgeries and and hyperactivity were noted a long-term commitment to a female (retrospectively, this perhaps signals Downloaded from www.aappublications.org/news by guest on September 23, 2021 PEDIATRICS Volume 142, number 1, July 2018:e20174168 CASE REPORT “ ” herself lesbian (although sexual orientation itself is not evidence of incorrect gender assignment, this may indicate a struggle with female gender), and related and identified with other similar-aged lesbians (Fig 4). At 22, she reestablished physician contact and indicated that she had previously told doctors what she thought they wanted to hear, rather than how she felt. She still refused hormonal therapy (indication of not wanting female characteristics), was gender-neutral in appearance, FIGURE 1 and began requesting full medical Timeline of events and observations for birth to 6 years (arrows are used to highlight key events). FSH, follicle-stimulating hormone; hCG, human chorionic gonadotropin; IGF-1, insulin-like growth history and records. As was common factor1; LH, luteinizing hormone. in this era, records had not been made available consistent with the perception that disclosure might foster more psychological problems. Finally, at age 29, her medical history was reviewed and explained by R.M.B. over several sessions (Fig 5). This disclosure was followed by an immediate gender change to male similar to a case in which a person with a diagnosis of partial androgen insensitivity syndrome (pAIS) changed gender from male to female 1 upon learning of her medical history. Mastectomy was undertaken, and testosterone therapy was initiated. FIGURE 2 After full replacement was achieved, Timeline of events and observations for ages 6.5 to 9 years (arrows are used to highlight key events). orgasmic ability was restored. GH deficiency was reverified, and adult GH replacement therapy was begun. His birth certificate was reissued that a struggle with female gender The patient delayed the male. Now, multiple years after these began during childhood). With Figs 1 recommended onset of estrogen changes, this man continues to be and 2, we outline the medical history; therapy for several years (further gainfully employed, is socially active, genital anatomy; gender assignment; evidence of a struggle with female – maintains fulfilling relationships growth hormone (GH) testing; gender), beginning sex steroids at – with family and friends, has enjoyed pregonadectomy hypothalamic age 11.5 years with vaginoplasty physical intimacy, including 2 pituitary testicular function; the at 14 years. Concerns included an long-term romantic relationships dramatic fivefold phallic growth from atypical reproductive anatomy, with women that included male- 6 mm to 3 cm during GH therapy; noncompliance with estrogen typical sexual activities (with the behavioral, psychological, functional therapy (sign of a gender struggle) inherent limitations imposed by difficulties; and recurrent problems and prescribed vaginal dilation, penile absence), and by his mid-30s from previous genital surgery. and desire for sexual hair (Fig was married. This may imply that, Concerns involved genital differences 3). In early adulthood, during a although fetal testicular testosterone compared with other girls (again 3-year interval without physician was insufficient to stimulate fetal perhaps this signals that a struggle contact, the patient worked as a penis growth in the face of GH with female gender began during nursing assistant, refused hormones deficiency, testosterone exposure childhood), and clitoral erections. and/or medications, declared to the central nervous system (CNS) Downloaded from www.aappublications.org/news by guest on September 23, 2021 2 LEE et al uncertainty, particularly in how individual personality factors, such as resilience, influence outcomes. It is still true that this type of variability in behavioral outcomes makes a perfect gender assignment impossible in all cases. With this current case report, we point to the need for cautious and careful case-by-case management for these patients and, when possible, for such management to be performed FIGURE 3 by open-minded3 multidisciplinary Timeline of events and observations for ages 10 to 16 years (arrows are used to highlight key events). teams. ADHD, attention-deficit/hyperactivity disorder; FSH, follicle-stimulating hormone; GI, gender idenity; LH, luteinizing hormone. Etiologies of micropenis commonly include pituitary gonadotropin deficiency, androgen4 biosynthetic defects, and pAIS. Classic teaching is used to instruct us that fetal and neonatal penis growth is primarily driven by androgen stimulation (via dihydrotestostrone). Isolated GH deficiency is typically not1, mentioned5 as a cause of micropenis, although penis growth has been reported among patients with GH deficiency6 who received GH therapy. Authors of textbook chapters may mention isolated GH deficiency
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