DOCSLIB.ORG

Partial Androgen Insensitivity Syndrome in 28 Newborn and Infant

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Partial Androgen Insensitivity Syndrome in 28 Newborn and Infant European Journal of Endocrinology (2011) 165 579–587 ISSN 0804-4643 CLINICAL STUDY ‘Idiopathic’ partial androgen insensitivity syndrome in 28 newborn and infant males: impact of prenatal exposure to environmental endocrine disruptor chemicals? Laura Gaspari1,2, Franc¸oise Paris1,2, Pascal Philibert2, Franc¸oise Audran2, Mattea Orsini3, Nade`ge Servant2, Laurent Maı¨moun2, Nicolas Kalfa2,4 and Charles Sultan1,2 1Unite´ d’Endocrinologie–Gyne´cologie Pe´diatrique, Service de Pe´diatrie 1, Hoˆpital Arnaud-de-Villeneuve and 2Service d’Hormonologie (De´veloppement et Reproduction), Hoˆpital Lapeyronie, CHU Montpellier et Universite´ Montpellier 1, Montpellier, France, 3De´partement d’Informatique Me´dicale, CHU de Nıˆmes et EA-2415 et Universite´ Montpellier, Montpellier, France and 4Service de Chirurgie Pe´diatrique, Hoˆpital Lapeyronie, CHU Montpellier, Montpellier, France (Correspondence should be addressed to C Sultan at Unite´ d’Endocrinologie–Gyne´cologie Pe´diatrique, Hoˆpital Arnaud-de-Villeneuve, CHU Montpellier et Universite´ Montpellier 1; Email: [email protected]) Abstract Objective: 46,XY disorders of sex differentiation (46,XY DSD) can be due to a testis determination defect, an androgen biosynthesis defect, or androgen resistance (complete or partial androgen insensitivity syndrome (PAIS), or 5a reductase deficiency). We aimed to evaluate the impact of a prenatal contamination by environmental xenoestrogens in ‘idiopathic’ PAIS-like phenotype. Subjects: We investigated 28 newborn/infant males with 46,XY DSD, normal androgen production, and no androgen receptor or steroid-5aR type II enzyme (SRD5A2) gene mutations. Methods: To exclude other genetic defects, we sequenced the steroidogenic factor 1 (SF1) and mastermind-like domain-containing 1 (MAMLD1) genes, which were recently found to be associated with the PAIS-like phenotype. Parents were interviewed about their environmental/occupational exposure to endocrine disrupting chemicals (EDCs) before/during the patients’ fetal life. Total estrogenic bioactivity of patient serum was analyzed by ultrasensitive bioassay. Results: All the patients had normal SF1 sequence and one patient showed a double polymorphism of MAMLD1. Eleven (39.3%) of the 28 patients had reported parental fetal exposure to EDCs. The mean estrogenic bioactivity in these 11 patients with fetal EDC exposure (6.65G8.07 pg/ml) versus 17 cases without contamination (1.27G0.34 pg/ml) and controls (1.06G0.44 pg/ml; P!0.05) was elevated. Conclusions: Our results indicate that the ‘idiopathic’ PAIS-like phenotype may in some cases be related to EDC contamination during fetal life. European Journal of Endocrinology 165 579–587 Introduction In our experience, the molecular diagnosis of PAIS is confirmed by androgen receptor (AR) gene abnorm- Differentiation of the male external genitalia requires ality in 85–90% of familial cases and only 10–15% of normal androgen production and adequate response of sporadic cases (5), although Ahmed et al. (7) reported a target tissues during fetal life (1). Male external genital positive mutational analysis of the AR gene in 28% of all malformation is related to either insufficient testoster- cases of PAIS (familialCsporadic cases). In addition, one production by fetal testis or partial androgen the clinical picture is not specific to the AR gene, and resistance of target organs (2–4). The etiology of other gene alterations may induce undervirilization in undervirilization in males includes gonadal dysgenesis, XY newborns despite normal androgen secretion (8). defects in androgen biosynthesis, and, most frequently, For example, steroid-5aR type II enzyme (SRD5A2) androgen resistance (1). deficiency may give rise to the typical clinical picture of All patients with undermasculinization should be first PAIS (8). The SRD5A2 defect is not usually considered, investigated for the basal or post-human chorionic however, because many pediatric endocrinologists gonadotropin (hCG) test level of plasma testosterone: a assume that it is limited to only certain ethnic groups low plasma testosterone level tends to indicate testicular (Dominican and New Guinean), despite a recent study dysgenesis or testosterone biosynthesis defects; con- demonstrating that SRD5A2 gene analysis should versely, normal/high plasma testosterone orients be performed when no AR mutation is identified (8).In toward the diagnosis of partial androgen insensitivity addition, steroidogenic factor 1 (SF1) or mastermind-like syndrome (PAIS) (1, 4–6). domain-containing 1 (MAMLD1) gene abnormalities q 2011 European Society of Endocrinology DOI: 10.1530/EJE-11-0580 Online version via www.eje-online.org Downloaded from Bioscientifica.com at 09/24/2021 10:04:58PM via free access 580 L Gaspari and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2011) 165 have been detected in rare cases of 46,XY disorders of Patients and methods sex differentiation (46,XY DSD) with normal testoster- one production. Participants Unfortunately, a defect in testosterone action cannot Forty-seven males from the neonatal period to 1 year be identified in the majority of undervirilized patients of age with nonsyndromic 46,XY DSD were included with normal androgen secretion (5–7), leading to the in this study. All cases were referred to our Pediatric diagnosis of ‘idiopathic’ PAIS-like phenotype (1).Inthese Endocrine Clinic at the University Hospital of Montpel- cases, other possible mechanisms should be investigated. lier (France). The study was approved by the Ethics It has been demonstrated in animal models and humans Committee of the University Hospital of Montpellier, and that exogenous chemicals with estrogenic and anti- all participating parents gave written informed consent androgenic activities can disturb the androgen/estrogen to all hormonal (included total estrogenic bioactivity) balance in the developing male fetus and thus impact and genetic investigations. external genital differentiation (9–11). In addition, most All patients were French with Mediterranean environmental pollutants are known to exhibit both origin (France, Italian, Spanish, Portuguese, or North estrogenic and anti-androgenic activities on stable human African) and none presented familial clustering of cell lines expressing the estrogen receptors a (ERa or male external genital malformations, defined as the ESR1) and b (ERb or ESR2), or the AR (12).These presence of these malformations in other probands chemicals with endocrine disrupting properties are often and first-degree relatives. All 47 newborns and infants industrial and agricultural by- and end-products, and they with undervirilization were oriented toward male are now referred to as endocrine disrupting chemicals gender. Figure 1 shows the distribution of the 47 (EDCs). Several authors have documented an increasing patients on the basis of endocrine and molecular trend in male external genital malformations in animals analysis. In our group, 16 patients presented low and humans over the last several decades and have basal plasma testosterone and an insufficient response focused on these EDCs as suspected causes (9–11, 13–18). to hCG stimulation. Accordingly, the diagnosis of In this work, we present arguments for the potential testicular dysgenesis was raised and confirmed in six role of EDCs in the pathophysiology of ‘idiopathic’ cases by the identification of SF1, WT1,orSOX9 gene PAIS-like phenotype through investigation of prenatal mutations (6/16 cases). The remaining 31 new- contamination by EDCs in relation to parental envir- borns/infants with normal/high plasma testosterone onmental/occupational exposure. In addition, since production were diagnosed as PAIS and further environmental pollutants are known for their estro- investigated for AR and SRD5A2 gene mutations. We genic activity and can be released progressively from identified three defects in the AR gene (3/31 cases), the adipose tissue where they accumulate (10, 11), while no SRD5A2 gene abnormality was detected. we assumed that the total estrogenic bioactivity would Twenty-eight newborns/infants from this group of 31 serve as a good marker for fetal contamination by EDCs. PAIS patients were thus considered as presenting an We thus measured it in the patients’ serum with an ‘idiopathic’ PAIS-like phenotype and were further ultrasensitive bioassay that we developed. investigated in this study. 46, XY DSD newborns/infants n = 47 Low basal/post-hCG plasma testosterone Normal/high basal/post-hCG plasma testosterone = testicular dysgenesis or = PAIS-phenotype testosterone biosynthesis defects n = 31 n = 16 SF1, WT1, and SOX9 No gene mutations AR gene mutation No AR, SRD5A2, SF1, gene mutations n = 10 n = 3 or MAMLD1 gene mutations n = 6 = 'idiopathic' PAIS-phenotype n = 28 EDCs fetal exposure No EDCs fetal exposure n = 11 n = 17 Increased total Normal total Increased total Normal total estrogenic estrogenic estrogenic estrogenic Figure 1 Distribution of the 47 under- bioactivity bioactivity bioactivity bioactivity virilized newborns/infants on the basis of n = 9 n = 2 n = 2 n = 15 endocrine and molecular analysis. www.eje-online.org Downloaded from Bioscientifica.com at 09/24/2021 10:04:58PM via free access EUROPEAN JOURNAL OF ENDOCRINOLOGY (2011) 165 ‘Idiopathic’ PAIS and endocrine disruptors 581 Clinical examination Occupational exposure to environmental pollutants was assessed from the answers to questions on paid Pediatric endocrinologists examined the infants in employment and jobs that entail the use of pesticides warm conditions (room temperature
Load more

Recommended publications
  • Hypospadias by Ronald S
    Kapi‘olani Pediatric Urology Hypospadias By Ronald S. Sutherland, M.D., F.A.A.P., F.A.C.S. What is hypospadias? Defined as a congenital deformity where the urethral opening is located beneath the penis rather then the tip, hypospadias ranges from a mild to severe deformity. The more common form is the distal variety, with the opening toward the front of the penis, which can usually be repaired with pleasing cosmetic results. More severe forms may be associated with the opening located at the base of the penis or further back near the anus. Usually hypospadias is also present with downward curvature of the penis (chordee), and a flattening of the foreskin with a hood-like covering. Occasionally the scrotum is also malformed and appears higher around the penis. Hypospadias can be found in a variety of congenital syndromes, including those with cardiac, renal, and testicular anomalies. (see next page) What causes hypospadias? Hypospadias develops early in gestation and occurs for unknown reasons, although there is slight familial tendency. Recent evidence suggests that the incidence is increasing and may be linked to environmental and genetic disruptions during the period when genital development is particularly sensitive to sex-steroid hormone imbalances. Occasionally, hypospadias can be detected by prenatal ultrasound. No pre-natal treatment or intervention is available. Parents should not request a circumcision for their newborn son with hypospadias because the foreskin may be necessary to assist with surgical repair. Sometimes hypospadias is not recognized until after the circumcision is completed. These cases are usually mild forms that can be repaired without the use of foreskin.
    [Show full text]
  • Hypospadias Repair
    Patient and Family Education Hypospadias Repair What causes it? What is hypospadias? Incomplete development of the urethra causes Hypospadias is a birth defect of the penis. hypospadias. It can occur in families. The The urethral opening, the hole where the urine comes out, is not in the normal position. reason for it happening is usually not known. Instead of the tip, it is on the undersurface of Why is it important to recognize the penis. Boys with hypospadias are usually hypospadias? missing the underside of their foreskin so An abnormally placed urethral opening does that the foreskin forms a hood. For this not allow the urine to pass as it s hould. A reason, most boys born with boy with hypospadias urinates with a hypospadias are not circumcised. There is stream that is often directed downward often a bend or curve (called chordee) in the rather than out and away from the body. This penis when the boy has an erection. causes wet pants and shoes. This condition, Hypospadias may be mild, moderate, or when left uncorrected, may make future severe depending on how far back the opening sexual intercourse difficult, or is and how much curvature is present. The impossible. more severe forms of hypospadias are usually associated with worsening degrees of chordee. Can it be corrected? Yes, surgery can correct the problem. These operations are best done between 6 and 18 months of age. The repair is usually performed in one surgery. If the hypospadias is severe, it may be necessary to have more than one surgery. The Normal position for urethra surgery usually lasts 1-3 hours and the patient goes home the same day.
    [Show full text]
  • Background Briefing Document from the Consortium of Sponsors for The
    BRIEFING BOOK FOR Pediatric Advisory Committee (PAC) Prepared by Alan Rogol, M.D., Ph.D. Prepared for Consortium of Sponsors Meeting Date: April 8th, 2019 TABLE OF CONTENTS LIST OF FIGURES ................................................... ERROR! BOOKMARK NOT DEFINED. LIST OF TABLES ...........................................................................................................................4 1. INTRODUCTION AND BACKGROUND FOR THE MEETING .............................6 1.1. INDICATION AND USAGE .......................................................................................6 2. SPONSOR CONSORTIUM PARTICIPANTS ............................................................6 2.1. TIMELINE FOR SPONSOR ENGAGEMENT FOR PEDIATRIC ADVISORY COMMITTEE (PAC): ............................................................................6 3. BACKGROUND AND RATIONALE .........................................................................7 3.1. INTRODUCTION ........................................................................................................7 3.2. PHYSICAL CHANGES OF PUBERTY ......................................................................7 3.2.1. Boys ..............................................................................................................................7 3.2.2. Growth and Pubertal Development ..............................................................................8 3.3. AGE AT ONSET OF PUBERTY.................................................................................9 3.4.
    [Show full text]
  • Case Report Full Text Online At
    Case Report Full text online at http://www.jiaps.com Penile agenesis A. K. Bangroo, Ramji Khetri, Sashi Tiwari St Stephen's Hospital, Tis Hazari, Delhi Correspondence: AK Bangroo, 103, Administrative block, St. Stephens Hospital, Tis Hazari, Delhi-110054, India. E-mail: [email protected] ABSTRACT Penile agenesis is an extremely rare disorder with profound urological and psychological consequences. The goal of treatment is an early female gender assignment and feminizing reconstruction of the perineum. KEY WORDS: Aphallia, Penile agenesis, Ambiguous genitalia Penile agenesis (PA) is an extremely rare developmental the scrotal folds which were preserved for subsequent anomaly with the reported incidence of 1 in 30 million genital reconstruction. births[1]. PA is believed to result from either the absence of the genital tubercle, or its failure to develop.[2] Several DISCUSSION investigators claim the absence of corpora cavernosa and corpora spongiosum as a prerequisite for the diagnosis of The earliest case report of aphallia was by Imminger in penile agenesis.[3] Except for the reported XX-XY mosaic, 1853[2] since then only 75 cases have been reported in the patients have 46 XY karyotypes.[4] More than half of these literature[6]. Skoog and Belman[5] suggested three variants, have associated anomalies, including developmental de­ based on urethral position in relationship to the anal fects of the caudal axis, genitourinary and gastrointestinal sphincter, as: Postsphincteric; Presphincteric tract anomalies.[5] The scrotum, testes and testicular func­ (Prostatorectal fistula) and Urethral atresia. More proxi­ tion are usually normal[2]. mal the bladder outlet, greater is the likelihood of other anomalies and death.[5] CASE REPORT A two-day-old 3.2 kg genotypic male (46XY) neonate was brought, by a social organization, to our hospital with the complaint of absence of penis, and passage of meco­ nium mixed with urine through rectum.
    [Show full text]
  • EAU Pocket Guidelines on Male Hypogonadism 2013
    GUIDELINES ON MALE HYPOGONADISM G.R. Dohle (chair), S. Arver, C. Bettocchi, S. Kliesch, M. Punab, W. de Ronde Introduction Male hypogonadism is a clinical syndrome caused by andro- gen deficiency. It may adversely affect multiple organ func- tions and quality of life. Androgens play a crucial role in the development and maintenance of male reproductive and sexual functions. Low levels of circulating androgens can cause disturbances in male sexual development, resulting in congenital abnormalities of the male reproductive tract. Later in life, this may cause reduced fertility, sexual dysfunc- tion, decreased muscle formation and bone mineralisation, disturbances of fat metabolism, and cognitive dysfunction. Testosterone levels decrease as a process of ageing: signs and symptoms caused by this decline can be considered a normal part of ageing. However, low testosterone levels are also associated with several chronic diseases, and sympto- matic patients may benefit from testosterone treatment. Androgen deficiency increases with age; an annual decline in circulating testosterone of 0.4-2.0% has been reported. In middle-aged men, the incidence was found to be 6%. It is more prevalent in older men, in men with obesity, those with co-morbidities, and in men with a poor health status. Aetiology and forms Male hypogonadism can be classified in 4 forms: 1. Primary forms caused by testicular insufficiency. 2. Secondary forms caused by hypothalamic-pituitary dysfunction. 164 Male Hypogonadism 3. Late onset hypogonadism. 4. Male hypogonadism due to androgen receptor insensitivity. The main causes of these different forms of hypogonadism are highlighted in Table 1. The type of hypogonadism has to be differentiated, as this has implications for patient evaluation and treatment and enables identification of patients with associated health problems.
    [Show full text]
  • A MRI Diagnosis of Congenital Urogenital Anomalies in 27 Years
    Journal of Advances in Radiology and Medical Imaging Volume 4 | Issue 1 ISSN: 2456-5504 Case Report Open Access A MRI Diagnosis of Congenital Urogenital Anomalies in 27 Years Old Man D’Amato D*, Ranalli T, Tatulli D, Bocchinfuso F, Manenti G, Valente F and Bizzaglia M Diagnostic and Interventional Radiology, Policlinico Tor Vergata, University of Rome “Tor Vergata”, Rome, Italy *Corresponding author: D’Amato D, Diagnostic and Interventional Radiology, Policlinico Tor Vergata, University of Rome “Tor Vergata”, Viale Oxford 181, Rome, Italy, Tel: +393207034690, E-mail: [email protected] Citation: D’Amato D, Ranalli T, Tatulli D, Bocchinfuso F, Manenti G, et al. (2019) A MRI Diagnosis of Congenital Urogenital Anomalies in 27 Years Old Man. J Adv Radiol Med Image 4(1): 102 Received Date: April 04, 2019 Accepted Date: August 26, 2019 Published Date: August 28, 2019 Abstract Congenital anorchia is an uncommon clinical condition. Etiology and pathogenetic mechanisms are often unknown. Although some patients with anorchia present with ambiguous external genitalia or micropenis, most have a normal phenotype. XY Disorders of Sex Development classifications are numerous and success rate in establishing a precise diagnosis is far lower than in XX karyotype. We report the case of a young man, with 46 XY karyotype showing various uro-genital abnormalities. A definitive diagnosis was not established due to the complex clinical presentation. Ultrasonography and Magnetic Resonance Imaging techniques were useful tools in the definition of uro-genital anomalies and gonadal development in this complex scenario. Keywords: Anorchia; Cryptorchidism; Urogenital Anomalies; DSD; MRI List of abbreviations: MRI: Magnetic Resonance Imaging; US: Ultrasonography; DSD: Disorders of Sex Development, FSH: Follicle- Stimulating Hormone; HCG: Human Chorionic Gonadotropin; LH: Luteinizing Hormone; AMH Antimüllerian Hormone; LHRH LH- Releasing Hormone; SD: Standard Deviation Introduction The disorders of sexual differentiation constitute a challenging area for both diagnostic and therapeutic impact.
    [Show full text]
  • Battle of Sex Hormones in Genitalia Anomalies
    COMMENTARY COMMENTARY Battle of sex hormones in genitalia anomalies Liang Maa,b,1 exposures to antiandrogen or estrogenic com- aDivision of Dermatology, Department of Medicine, Washington University School of pounds can lead to a range of penile anoma- Medicine, St. Louis, MO 63110; and bDepartment of Developmental Biology, Washington lies similar to human CPAs (2). However, University School of Medicine, St. Louis, MO 63110 how and when EDCs may influence normal external genitalia development is not very clear. In PNAS, Zheng et al. (3) use a state- To cope with their transition to a terrestrial anomalies (CPAs), including ambiguous gen- of-the-art conditional androgen receptor lifestyle, vertebrates had to extensively modify italia, hypospadias, chordee, and micropenis, (AR) knockout mouse model to show that their reproductive organs to facilitate repro- represent one of the most common birth de- disruption of androgen signaling at different duction on land (1). The mammalian penis fects, second only to congenital cardiac de- developmental stages can produce the full represents such a pinnacle in mammalian fects. Hypospadias is an arrest in urethra spectrum of CPAs. The authors go on to evolution, which enabled internal fertilization development, such that the urethra opening show that androgen and estrogen signaling and successful land invasion. There are two is located anywhere along the ventral side of antagonize each other during neonatal mouse phases of external genitalia development in the penile shaft instead of at the glans penis. i genital development and identify a signaling mammals: ( ) an ambisexual stage, in which Chordee is the abnormal bending of the penis, molecule, Indian hedgehog (Ihh), as a novel male and female embryos undergo the same resulting from tethering of urethral epithelium AR target required for penile masculinization.
    [Show full text]
  • Evaluation of Additional Anomalies in Concomitance of Hypospadias And
    Türkiye Çocuk Hastalıkları Dergisi 222 Özgün Araştırma Original Article Turkish Journal of Pediatric Disease Evaluation of Additional Anomalies in Concomitance of Hypospadias and Undescended Testes Hipospadias ve İnmemiş Testis Birlikteliğinde Ek Anomali Sıklığının Değerlendirilmesi Ufuk ATES, Gülnur GÖLLÜ, Nil YAŞAM TAŞTEKİN, Anar QURBANOV, Günay EKBERLİ, Meltem BİNGÖL KOLOĞLU, Emin AYDIN YAĞMURLU, Tanju AKTUĞ, Hüseyin DİNDAR, Ahmet Murat ÇAKMAK Ankara University Medical School, Pediatric Surgery Department, Pediatric Urology Division, Ankara, Turkey ABSTRACT Objective: Hypospadias is a common genitourinary system (GUS) anomaly in boys occurring in 1 of 200 to 300 live births. Undescended testes is frequently detected among accompanying anomalies in cases with hypospadias. Especially in proximal hypospadias and bilateral cases, this association may indicate sexual differentiation disorders. The aim of the study was to evaluate the togetherness of additional anomalies in hypospadiac children with undescended testes. Material and Methods: Between 2007 and 2016, data of 392 children who underwent surgery for hypospadias were evaluated retrospectively. Urethral meatus was present at scrotal and penoscrotal in 65 cases (16.6%) and glanular, coronal, subcoronal and midpenile in 327 cases (83.4%). The cases were divided into two groups as those with both testes in the scrotum and those with undescended testes, and the anomalies were recorded. Results: The mean age of the children with proximal hypospadias was 21 months (6-240 months). Of the children with proximal hypospadias, 26 (40%) had undescended testes and 39 (60%) had testes in the scrotum. Undescended testes were detected bilaterally in 17 patients (65.4%) and unilaterally in nine patients (34.6%) in the undescended testes group.
    [Show full text]
  • 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.
    [Show full text]
  • Hyperplasia (Growth Factors
    Adaptations Robbins Basic Pathology Robbins Basic Pathology Robbins Basic Pathology Coagulation Robbins Basic Pathology Robbins Basic Pathology Homeostasis • Maintenance of a steady state Adaptations • Reversible functional and structural responses to physiologic stress and some pathogenic stimuli • New altered “steady state” is achieved Adaptive responses • Hypertrophy • Altered demand (muscle . hyper = above, more activity) . trophe = nourishment, food • Altered stimulation • Hyperplasia (growth factors, . plastein = (v.) to form, to shape; hormones) (n.) growth, development • Altered nutrition • Dysplasia (including gas exchange) . dys = bad or disordered • Metaplasia . meta = change or beyond • Hypoplasia . hypo = below, less • Atrophy, Aplasia, Agenesis . a = without . nourishment, form, begining Robbins Basic Pathology Cell death, the end result of progressive cell injury, is one of the most crucial events in the evolution of disease in any tissue or organ. It results from diverse causes, including ischemia (reduced blood flow), infection, and toxins. Cell death is also a normal and essential process in embryogenesis, the development of organs, and the maintenance of homeostasis. Two principal pathways of cell death, necrosis and apoptosis. Nutrient deprivation triggers an adaptive cellular response called autophagy that may also culminate in cell death. Adaptations • Hypertrophy • Hyperplasia • Atrophy • Metaplasia HYPERTROPHY Hypertrophy refers to an increase in the size of cells, resulting in an increase in the size of the organ No new cells, just larger cells. The increased size of the cells is due to the synthesis of more structural components of the cells usually proteins. Cells capable of division may respond to stress by undergoing both hyperrtophy and hyperplasia Non-dividing cell increased tissue mass is due to hypertrophy.
    [Show full text]
  • Micropenis Associated with Testicular Agenesis
    Arch Dis Child: first published as 10.1136/adc.50.3.247 on 1 March 1975. Downloaded from Short reports 247 REFERENCES Patients Barnes, N. D., Joseph, J. M., Atherden, S. M. and Clayton, B. E. (1972). Functional tests of adrenal axis in children with Case 1. The second child of unrelated parents, born measurement of plasma cortisol by competitive protein binding. after a normal term pregnancy. At birth it was difficult Archives of Disease in Childhood, 47, 66. to decide the infant's sex. A minute penis consisting of Deane, H. W., and Masson, G. M. C. (1951). Adrenal cortical a small prepuce-like skin tag devoid of palpable erectile changes in rats with various types of experimental hypertension. .ournal of Clinical Endocrinology, 11, 193. tissue was present (Fig. 1). The urethral orifice could Fanconi, G. (1954). Tubular insufficiency and renal dwarfism. not be seen but urine was passed from this area. Testes Archives of Disease in Childhood, 29, 1. could not be felt in the small, fleshy scrotum. Physical Howse, P. M., Rayner, P. H. W., Williams, J. W., and Rudd, B. T. (1974). Growth hormone secretion during sleep in short examination was otherwise normal. children: a continuous sampling study. Archives of Disease in Childhood, 49, 246. James, V. H. T., Townsend, J., and Fraser, R. (1967). Comparison of fluorimetric and isotopic procedures for the determination of plasma cortisol. journal of Endocrinology, 37, xxviii. Mattingly, D. (1962). A simple fluorimetric method for the estimation of free 1 1-hydroxycorticoids in human plasma. Journal of Clinical Pathology, 15, 374.
    [Show full text]
  • Anne Tamar-Mattis, JD* Advocates for Informed Choice
    Report to the Inter-American Commission on Human Rights: Medical Treatment of People with Intersex Conditions as a Human Rights Violation Anne Tamar-Mattis, JD* Advocates for Informed Choice March 13, 2013 I. Introduction Americans born with intersex conditions, or variations of sex anatomy, face a wide range of violations to their sexual and reproductive rights, as well as the rights to bodily integrity and individual autonomy. Beginning in infancy and continuing throughout childhood, children with intersex conditions are subject to irreversible sex assignment and involuntary genital normalizing surgery, sterilization, medical display and photography of the genitals, and medical experimentation. In adulthood, and sometimes in childhood, people with intersex conditions may also be denied necessary medical treatment. Moreover, intersex individuals suffer life-long physical and emotional injury as a result of such treatment. These human rights violations often involve tremendous physical and psychological pain and arguably rise to the level of torture or cruel, inhuman, or degrading treatment (CIDT).† The treatment experienced by American intersex people is a violation of the American Convention on Human Rights. The Convention recognizes torture and cruel, inhuman, or degrading treatment (CIDT) as human rights abuses. Under Article V, “(1) Every person has the right to have his physical, mental, and moral integrity respected. (2) No one shall be subjected to torture or to cruel, inhuman, or degrading punishment or treatment.” §1-2. In order to demonstrate why specific medical practices are human rights abuses against intersex people, we have applied Article 16 of the Convention Against Torture (CAT), and interpretations by the European Court of Human Rights and the mandate of the Special Rapporteur on Torture (SRT).
    [Show full text]