(1) Atypical genitalia in a genetic female with clitoromegaly and labial fusion, indicating virilization;
(2) Hyperpigmentation around the nipple and genitalia;
(3) Biochemical findings of elevated 17-OHP, ACTH and DHEA with low cortisol, consistent with 21-hydroxylase deficiency;
(4) Hyponatremia and hyperkalemia, suggestive of salt wasting form of CAH.
The child
AIS is a genetic condition where affected people have male chromosomes and male gonads with complete or partial feminization of the external genitals
An inherited X-linked recessive disease with a mutation in the Androgen Receptor (AR) gene resulting in:Functioning Y sex chromosome and abnormality on X chromosome
Congenital Adr Hyperplasia (CAH) can appear at any age from birth to puberty where it can lead to ambiguous genitalia. It is due to absolute or relative deficiency of 17 Hydroxylase or 21 Hydroxylase enzyme.
AIS is a genetic condition where affected people have male chromosomes and male gonads with complete or partial feminization of the external genitals
An inherited X-linked recessive disease with a mutation in the Androgen Receptor (AR) gene resulting in:Functioning Y sex chromosome and abnormality on X chromosome
Congenital Adr Hyperplasia (CAH) can appear at any age from birth to puberty where it can lead to ambiguous genitalia. It is due to absolute or relative deficiency of 17 Hydroxylase or 21 Hydroxylase enzyme.
Seminar on critical Congenital heart disease Dr Habibur Rahim | Dr Faria YasminDr. Habibur Rahim
Seminar on critical Congenital heart disease Dr Habibur Rahim | Dr Faria Yasmin
Duct-dependent systemic circulations
Critical aortic stenosis
Coarctation of the aorta
Interruption of aortic arch
Hypoplastic left heart syndrome
Duct-dependent pulmonary circulations
Pulmonary atresia Critical pulmonary stenosis
Tricuspid atresia
Tetralogy of Fallot
Ebstein’s anomaly
Parallel non-mixing circulation
Transposition of great arteries
Other
Total anomalous pulmonary venous connection (TAPVC)
Double outlet right ventricle
Single ventricle
Truncus arteriosus
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
1. Welcome To Seminar
Dr. Fatema Begum Sadia,Year-5
Dr. Faria Yasmin,Year-3
Resident , Department Of Neonatology
2. Case scenario- 1
B/O Mousumi, outborn ,2nd issue of non
consanguineous parents presented with:
• Atypical pattern of external genitalia more female
pattern, clitoromegaly (1.6 cm), urethral opening at
the base of clitoris ,partial fusion of labioscrotal fold
with a vaginal opening present ,skin hyperpigmented.
• Hypertension & hyperpigmentation around nipple &
umbilicus. Other wise the Child was normal.
3. Case scenario-2
Abu sufiyan, 15 days old, 1st issue of non-
consanguinous parents presented with the
complaints of atypical pattern of external
genitalia [ more male pattern, phallus size about
2.2 cm, hypospadias’s present, both testes are in
the scrotum, scrotum is bifid, scrotal skin is more
pigmented. Otherwise the baby was normal.
4. What are the abnormalities of these babies?
What may be the cause of these abnormalities?
What should be the approach?
6. Outline:
• Introduction
• Development & Function of Gonads
• Definition of DSD & Nomenclature
• Etiological classification of DSD
• Evaluation of DSD Patient
• Investigations
• Treatment of DSD
• Counseling
7. Introduction
• The Birth of a baby is an exiting event.
• If a baby born with Genitalia that cannot be readily identified as
either male or female inevitably precipitates a crisis for the parents.
8. Disorders of Sex Development (DSD):
• DSD is a condition “in which development of chromosomal, gonadal or
anatomical sex is atypical.”
• Discrepancy between external genitalia & internal gonad.
• Atypical genitalia are present when the sex of an infant is not readily
apparent after examination of the external genitalia.
• It is increasingly preferable to use the term “atypical genitalia” rather
than “ambiguous genitalia”
9. Development of the Gonads
• Genetic sex (XX or XY) is determined at fertilization .
• Gonadal sex- is determined by 7th weeks of gestation from
undifferentiated, bipotential fetal gonad that arises from a thickening of
the urogenital ridge & develops into either ovary or testis.
• Phenotypic sex is established at the end of first trimester.
11. Figure: Indifferent stages of the external genitalia.
A. Approximately 4 weeks. B. Approximately 6 weeks.
Figure: Development of external genitalia in the male at 10
weeks.
Figure: Development of the external genitalia in the
female at 5 months A and in the newborn B.
Ref: Langman’s Medical Embryology, 12th Edition
12. Figure: Genes responsible for Gonadal differentiation
Ref: Langman’s Medical Embryology, 12th Edition
13. Proposed Revised Nomenclature:
PREVIOUS PROPOSED
Intersex Disorders of sex development
(DSD)
Male pseudohermaphrodite 46, XY DSD
Female pseudohermaphrodite 46, XX DSD
True hermaphrodite Ovotesticular DSD
XX male or XX sex reversal 46,XX testicular DSD
XY sex reversal
46,XY complete gonadal
dysgenesis
European Society for Paediatric Endocrinology (ESPE) : 2006
14. INCIDENCE:
• 1 in 5000
• CAH is the most frequent cause of atypical genitalia in
the newborn, constituting approximately 60% of all
DSDs.
• BSMMU ENDOCRINOLOGY CLINIC (2020)
Total New case DSD CAH
3454 347 23 13(56%)
15. NICU, BSMMU
Year Total admitted patient DSD
2019 1848 (1789 +59) 3 (0.2%)
2020 1241 (1219+22) 5 (0.4%)
16. Etiologic Classification of Disorders of Sex Development (DSD):
Disorder of sexual development (DSD)
46,XX DSD 46,XY DSD Ovo-testicular DSD
Sex chromosome
DSD
17. 46,XX DSD
1. Androgen Exposure
Congenital adrenal hyperplasia(CAH): 21-OH, 11β-OH, 3β- HSD
Tumor: Virilizing maternal adrenal or ovarian tumor.
Maternal drugs: e.g. Danazol, Progestins etc.
2. Disorder of Ovarian Development
XX gonadal dysgenesis
Testicular DSD
3. Undetermined Origin
Associated with genitourinary and gastrointestinal tract defects
18. 46,XY DSD
1) Deficiency of Testicular Hormones
• Leydig cell aplasia
• 3β-HSD II deficiency
• 17-Hydroxylase/17, 20-lyase deficiency
2) Defect in Androgen Action
• Androgen Insensitivity Syndromes
• DHT Deficiency (5 –α- reductase deficiency)
3) Defects in Testicular Development
• Denys-Drash syndrome
• WAGR syndrome
• Mutation in SRY gene
• XY Gonadal agenesis
19. • In ovotesticular DSD, both ovarian and testicular tissues are present, either
in the same or in opposite gonad.
• Genotype :
• 46XX - 70% ,
• 46XY - 10%
• Mosaics 46XX/45XO/46XY/multiple X/multiple Y - 20%
• Affected patients have ambiguous genitals, varying from normal female with
only slight enlargement of the clitoris to almost normal male external
genitals.
• Palpable Gonad: Ovotestis which may be bilateral. If unilateral, the
contralateral gonad is usually an ovary but may be a testis.
Ovotesticular DSD
20. • 45,X (Turner syndrome and variants)
• 47,XXY (Klinefelter syndrome and variants)
• 45,X/46,XY (mixed gonadal dysgenesis, sometimes a cause of
ovotesticular DSD)
Sex chromosome DSD
21. CONGENITAL ADRENAL HYPERPLASIA
It is a group of AR disorders of cortisol biosynthesis characterized by
a deficiency of one of the adrenal enzymes.
Enzyme deficiency results in-
• Reduction in end-products such as cortisol deficiency
• Accumulation of hormone precursors
• Increased ACTH production.
22. Figure: Adrenal metabolic pathways related to normal sex development
Ref: Gomella’s Neonatology, 8th Edition
23. Pathophysiology
• Congenital Adrenal Hyperplasia
1. 46 XX DSD
a) 21α –Hydroxylase (21α –OH) deficiency
b) 11β –Hydroxylase (11β –OH) deficiency
c) 3β –hydroxysteroid dehydrogenase II (3β –HSD II) deficiciency
2. 46 XY DSD
a) 3β-HSD II deficiency
b) 17-Hydroxylase (17α-OH)/17,20-lyase deficiency
25. 21- hydroxylase deficiency most common 90%
• Three forms of 21- hydroxylase deficiency.
1. Classic-
salt wasting-75%
Simple virilizing-25%
2. Non-classic or late onset-
26. Clinical features of 21-hydroxylase deficiency:
•Female- born with ambiguous genitalia (clitoromegaly, labial fusion)
with normal development of ovary and female internal genital
structure.
•Male- external genital normal.
•Common for both male & female:
•Symptoms of salt wasting- anorexia, vomiting, wt loss,
dehydration, shock.
•Hyponatremia , hyperkalemia, acidosis and often hypoglycaemia
present
29. 17 α-hydroxylase def./ associate with 17-20-lyase def
•Decreased/absent- Androgen & cortisol.
•Increased DOC- ↑↑ BP, Hypokalemia and Suppression of renin.
•Affected male incompletely virilized; present as Female phenotype.
30. Defect in androgen action:
• Results in failure of the external genitalia to undergo male
differentiation because of the lack of DHT.
• The outcome is a neonate with female or atypical genitalia but
with a 46XY karyotype, normally developed testes, and male
internal duct.
5α-REDUCTASE DEFICIENCY:
31. • Also called testicular feminization
• The AISs are the most common forms of male DSD.
• Can be caused by defect in androgen receptor or an unknown defect with
normal receptor.
• Two Types :
• Complete AIS : Genetic male(XY) appears with labial testes &
otherwise normal female external genitalia.
• Partial AIS : incomplete virilization of a male, more common.
Androgen Insensitivity Syndromes (AIS):
32. Gonadal dysgenesis:
Pure gonadal dysgenesis:
• Presence of a streak gonad bilaterally (complete gonadal dysgenesis)
or unilaterally (partial gonadal dysgenesis).
• Streak gonads in Y-positive patients carry a significant risk for tumor
development.
Mixed gonadal dysgenesis:
• Presence of a unilateral functioning testis and a contralateral streak
gonad.
• All patients have a Y chromosome and some degree of virilization of
the external genitalia;
• High risk of gonadal malignancy in mid to late childhood.
33. Defects in testicular development:
DENYS-DRASH SYNDROME :
Nephropathy with ambiguous genitals and bilateral
Wilms tumor.
WAGR SYNDROME :
• Consists of Wilms tumor, aniridia, genitourinary
malformations, and mental retardation.
35. .
1. Family history of
- Familial genital ambiguity
- CAH
- Cryptorchidism
- Hypospedias
- Pubertal delay,Amenorrhea,Infertility
- Consanguinity
2. History of maternal drug exposure ( Particularly androgen)
3. H/O maternal virilization in pregnancy
4. History of Neonatal/early infancy death
5. Vomiting/ dehydration of sibling(possibility of CAH)
6. H/O any corrective genital surgery
7. Genetic syndrome
History
36. Physical examination
General examination
• Any dismorphic features ( Syndromes & chromosomal anomaly)
• Vitals, to see any evidence of salt wasting ( CAH) – Low BP, F/O
dehydration , shock
• Hyperpigmentation of skin and areola
Per abdomen : Any abdominal mass
37. Physical examination
Genitalia examination
Phallus length: Stretched phallic length (Normal should be
>= 2cm)
Clitoral length ( < 1cm)
Urethral meatus: hypospadiasis, chordee
Presence of vaginal opening
Labioscrotal fold: Pigmentation and symmetry of the
scrotum or labioscrotal fold.
Labia majora – normally unfused but may show variable
degree of post fusion.
Scrotum – Fused or bifid, rugosity suggest androgen effect
Gonadal size, position and descent
Inguinal hernia
39. Investigations
For chromosome analysis
• Karyotyping
To find-out etiology:
Hormone analysis
• S. Cortisol
• S. ACTH
• Rapid ACTH stimulation test
• 17 Hydroxyprogesterone
• Dehydroepiandosterone sulfate ( DHEA-S)
• S. Testosterone
• S. Testosterone & S. Dihydrosterone ( DHT) ratio at basal and after 24 hour of successive 3 days
injection of ꞵ-hcg.
40. Investigations
Imaging
1. USG of whole abdomen
• To find out presence,localization and characteristics of gonad
• To see internal female genital organ- uterus,fallopian tube
• To see the hyperplasia of adrenal gland
2. CT/MRI of pelvic organ
3. Genitourethrography / Urogenital sinogram: Before surgery
4. Diagnostic laparoscopy: To Identify testis and to take tissue for biopsy
41. Investigations
To find out association
Serum electrolytes
Hyperkalemia and Hyponatremia
(21-hydroxylase deficiency)
Hypoglycemia (21-hydroxylase deficiency)
Hypokalemia (11β-hydroxylase deficiency)
Molecular genetic analysis
• FISH for SRY gene analysis
• CYP 21
• DNA analysis
42. Virilization of a genetic female (by excessive maternal or fetal androgen
in CAH)
Hormone assay
17-OHP (Increase in CAH)
S. Cortisol (Decrease in CAH)
S. ACTH (Increase in CAH)
Testosterone, DHT, androstenedione (Increase in CAH)
If Karyotyping is 46XX
43. If Karyotyping is 46XY
Testosterone, DHT, androstenedione (A high Testosterone to
DHT ratio suggests 5 α reductase deficiency)
Testosterone , LH & FSH
Increased- Androgen insensitivity syndrome
Decreased in Gonadal Dysgenesis
HCG stimulation test
44. Interpretation:
Rise in testosterone- Normal
Absent response with elevated LH/FSH- Primary gonadal failure
Rise in testosterone with no rise in Di-hydrotestosterone-
5 α reductase deficiency
An absent testosterone with elevation of androstenedione
suggests- block in testosterone synthesis
Other Endocrine screening
Anti-mullerian hormone and inhibin B levels
HCG stimulation test
45. Prenatal diagnosis of CAH
• Done by chorionic villus sampling and amniocentesis
• DNA analysis to for sex determination & CYP21 gene analysis from
chorionic villus sampling
• 17-OH-progesterone & androstenedione in amniotic fluid is used for
antenatal diagnosis
Ref:New et al,Inborn errors of adrenal steroidogenesis. Molecular and Cellular
Endocrinology2003;211(12):75-84
47. B/O Mousumi, Atypical pattern of external genitalia ,
hyperpigmentation around nipple & genitalia. Other
wise the Child was normal.
O/E- stable vitals, no signs of dehydration
hyperpigmented nipple,
skin pigmentation present
Genitalia exam-
-Clitoromegaly measuring about 1.6 cm
-partial fusion of labioscrotal fold
-urethral opening was at the base of clitoris, vaginal
orifice present,
-hyperpigmented
-gonad was not palpable
Case scenario 1
48. 17-OHP- ↑26.50 ng/ml
S. ACTH-↑ 132.40 pg/ml
S. Cortisol- ↓140.50 nmol/L
DHEA- –↑ 651µg/dl
S electrolyte : Na -125 mmol/l
K -9.5 mmol/l
Cl - 93 mmol/l
TCO2 -16.4 mmol/l
USG of pelvic organ- There is a small structure
measuring about 1.31 cm in length and 0.50 cm in
AP diameter simulating a uterus behind urinary
bladder.
None of the ovaries could be well identified
No testis could be visualized.
Karyotyping- 46XX
Diagnosed as 46 due to
Congenital Adrenal
Hyperplasia ( 21 alpha
hydroxylase deficiency).
Baby was discharged with
oral Hydrocortisone 10
mg/sqm/day
49. Abu sufiyan, 15 days old, 1st issue of non-
consanguinous parents presented with the complaints
of atypical pattern of external genitalia , more male
pattern
O/E- stable vitals, no signs of dehydration
Genitalia exam-
Atypical genitalia more in male pattern, phallus present
length was measuring about 2.2 cm, urethral opening
was single and present under surface of phallus, both
testes were in the scrotum, scrotum was bifid, scrotal
skin was more pigmented.
Case scenario 2
50. S. Cortisol – 126.30 nmol/L
S. ACTH – 26.30 pg/ml
17 OHP – 0.31 ng/ml
DHEA-S – 13.50 µg/dlS.
Testosterone – 68.84 ng/dl
S electrolyte: Na -140 meq/l
Cl -103 meq/l
K – 4.3 meq/l
TCO2 -22 meq/l
USG of pelvic organ-
USG of pelvic organ- No mullerian structure
was found.
Karyotyping- 46XY
Diagnosed as 46XYDSD due
to Androgen insensitivity
syndrome or
Dihydrotestosterone
deficiency
Baby was discharged with
advice of EBF.
51. Early diagnosis of classic CAH is critical to save lives, and
diagnosing nonclassic CAH is important to prevent unnecessary
suffering. Molecular genetic analysis of CYP21A2 is useful in
confirming the diagnosis, providing genetic counseling, and
predicting prognoses. Genotype is well correlated with the clinical
severity of 21OHD. However, further research is needed to identify
modifier genes in 21OHD, which could explain the phenotypic
variability of androgen effects.
54. Treatment Principles of CAH
• Treatment is life-long
• Treatment goals are
To normalize electrolytes & hormone levels by
using glucocorticoids & mineralocorticoids
replacement.
To maintain growth velocity & skeletal
maturation.
55. Acute Medical Management
• Fluid therapy in babies with salt losing crisis : 0.9% sodium chloride 10
ml/kg as IV bolus, followed by a continuous IV infusion of 0.9% or 0.45%
saline 1.5-2 times of maintanence fluid.
• If the patient is hypoglycemic, 2ml/Kg of 10% dextrose.
• Correction of electrolyte imbalance (Hyperkalaemia, Hyponatremia)
• I.V Hydrocortisone
• If HTN : Start Anti hypertensive
56. Long Term Therapy
Glucocorticoids
Replacement
Hydrocortisone 15-20
mg/m2/day divided in 3
oral doses.
Dose should doubled
during crisis & stressful
conditions.
Mineralocorticoids
Treatment
Fludrocortisone acetate 0.05-
0.1 mg once daily orally
It will restore the sodium-
potassium balance
Hormone replacement therapy: for induction of puberty
57. Surgical Management
• Some female infants with adrenal hyperplasia are only mildly virilized and
may not require corrective surgery if they receive adequate medical
therapy to prevent further virilization
• Traditional approach is clitoris is embeded under the skin
• Vaginoplasty : If there is urogenital sinus.
• Removal of gonads : Dysgenesis
58. Newer Treatment Options
• Continuous Subcutaneous Hydrocortisone Infusions (CSHI)
• Inhibitors of Adrenal Androgen Synthesis (ketoconazole)
• Androgen Receptor Antagonists (Flutamide)
• Aromatase Inhibitors (AIs) (Testolactone)
• 5-α Reductase Inhibitors (Finasteride and Dutasteride)
• Gene Therapy
• Stem Cell Transplantation
• Bilateral Adrenalectomy
Ref: New et al,Inborn errors of adrenal steroidogenesis. Molecular and Cellular
Endocrinology.2003;211(12):75-84
59. Combination treatment
At the National Institutes of Health, a long-term randomized clinical
trial investigated a new treatment regimen combining a reduced
hydrocortisone dose, an anti-androgen, and an aromatase
inhibitor.
Ref: White and Speiser et al,Updates on Congenital Adrenal Hyperplasia.New
England Journal of Medicine.2003;349(8):776-88
60. New treatment approaches currently under investigation include
combination therapy to block androgen action and inhibit estrogen
production, and bilateral adrenalectomy in the most severely affected
patients
Ref: Gunther et al.‘Prophylactic Adrenalectomy of a Three-Year-Old Girl with
Congenital Adrenal Hyperplasia:Pre- and Postoperative Studies’.The Journal
of Clinical Endocrinology & Metabolism.2015.82(10).3324–3327
61. Follow Up
• Too little glucocorticoid : Results in symptoms of adrenal
insufficiency (e.g., anorexia, nausea, vomiting, abdominal pain,
asthenia) and will result in progressive virilization
• Excess glucocorticoid : excess weight gain, cushingoid features,
hypertension, hyperglycemia, cataracts, and growth failure
62. Prognosis
Early adequate therapy : Short stature, sexual precocity & metabolic
effects are not seen .
Late diagnosis & inadequate therapy may cause:
• Death of newborns with salt-losing types & if patients are not provided
with stress doses of glucocorticoid in times of illness, trauma, or
surgery.
• Psychological problems in girls with ambiguous genitalia.
• Short stature and infertility
65. To determine the sex, physicians should consider….
• Genetic and phenotypic sex
• Fertility potential
• Capacity for normal sexual function
• Endocrine function
• Potential for malignant change
• Parental opinion / preference (Full informed consent)
66. REVIEW ARTICLE| VOLUME 12, ISSUE 6, P418-425, DECEMBER 01, 2016
Fertility in disorders of sex development: A review
J.P. Van Batavia,T.F. Kolon
Journal of Pediatric Urology
Patients with some CAH may have functioning gonads with viable germ cells
but an inability to achieve natural fertility secondary to incongruent internal
or external genitalia,
other patients may have phenotypically normal genitalia but infertility due
to abnormal gonad development.
Infertility is seen in complete AIS .
Fertility is rare in pure or mixed gonadal dysgenesis, ovotesticular disorder,
Klinefelter syndrome.
67. Tony Briffa has PAIS.
Briffa is worlds first
intersex mayor.
Independent councillor,
mayor, deputy mayor in
the city of Hobsons
bay, Victoria.
Lady Colin
Campbell – Jamaican
born British writer.
Best seller books in
1992.
Sarah Gronert-
retired german tennis
player
Got award of best
world ranking of 164
on May 2012.
Not the end of life
68. ULTIMATE GOAL
To provide the framework for a child to develop into well
adjusted, psychosocially stable individual who identified with
and is happy in the chosen sex.
69. KEY MESSAGES
• Always think , Could this neonate have salt wasting CAH?
• Remember the risk of testicular cancer.
• Take the possible step to avoid assigning the neonate to the
wrong sex.