Growth/Endocrine/Metabolic Flashcards
What is the most common cause of ambiguous genitalia in a newborn?
Congenital adrenal hyperplasia
What is the inheritance pattern for congenital adrenal hyperplasia (CAH)?
Autosomal recessive
Name the hormones released by the adrenal gland normally?
- Cortisol
- Testosterone
- Aldosterone
What is the most common cause of CAH? - which enzyme is absent?
Absence of the enzyme 21-hydroxylase
What are the two sub-divisions of classical CAH?
- Salt-losing form
2. Simple-virilising form
What happens in congenital adrenal hyperplasia?
The adrenal glands are abnormally enlarged, and so produce excessive amounts of androgens (male steroid hormones) leading to abnormal sexual developments in females affected with the disease
How was the term ‘disorder of sexual development’ previously known?
Intersex conditions
What are the various forms of DSD? (5)
- 46, XX DSD
- 46, XY DSD
- Ovotesticular DSD
- 46, XX testicular DSD
- 46, XY complete gonadal dysgenesis
Why is reconstructive surgery in DSD now delayed, compared to years ago when it used to be performed shortly after birth?
As early gender assignment may not reflect the psychological development and gender identity of the child, so it is deferred
How does chromosomal sex determine the appearance of the genitalia?
Chromosomal sex prescribes gonadal sex, which in turn prescribes phenotypic sex. The gonad type determines whether the Mullerian or Wolffian ducts develop or regress.
How does an embryo with a Y chromosome develop ovaries?
The part of the Y chromosome which is sex-determining is on the short arm. If this area of the Y chromosome is missing the gonad develops into an ovary instead of testis.
What is the most common cause of ambiguous genitalia in the newborn?
Congenital adrenal hyperplasia
After CAH, what is the second most common cause of ambiguous genitalia?
Mixed gonadal dysgenesis (MGD)
What does AMH stand for, and how can a deficiency of it cause inadequately virilised males?
AMH is anti-mullerian hormone and is critical for male differentiation of the genital ducts. AMH is produced by the sertoli cells of the testis and suppressive development of the Mullerian duct. If AMH is deficient, there will be persistent Mullerian duct syndrome.
When is it likely for phenotypic females with DSD to be diagnosed?
When presenting with primary amenorrhoea (females with 46, XY)
Why is DSD a medical emergency?
For physical, social and psychological reasons. Immediate referral to an experienced MDT is essential. Also 75% of infants with CAH have salt-wasting nephropathy which can cause hypotension, collapse and death.
What are the common findings in a newborn with a male appearance suggesting DSD? (3)
- Severe hypospadias with bifid scrotum
- Undescended testis with hypospadias
- Bilateral non-palpable testes in a full-term apparently male infant
(and of course in a baby with indeterminate sex due to ambiguous genitalia)
What are the common findings in a newborn with a female appearance suggesting DSD? (2)
- Clitoral hypertrophy of any degree, non-palpable gonads
- Vulva with single opening
(and of course in a baby with indeterminate sex due to ambiguous genitalia)
What is the most commonly seen condition in a child with DSD?
A virilised female with 46 XX with CAH
What questions are important to ask when taking a history from the mother/family of a child with DSD? (6)
- Medication history including any exposure to androgens in a mother
- Any history or signs of virilisation in the mother
- A history of unexplained early or neonatal deaths
- Any history of a DSD in other children
- A history of parental consanguinity
- Family history of: infertility, ambiguous genitalia, primary amenorrhoea, late puberty
What is one of the most important investigations for suspected DSD?
Pelvic ultrasound
What endocrine screening is often performed in a baby with suspected DSD? (4)
- LH and FSH
- ACTH, renin, aldosterone
- Testosterone androstenedione, 17 alpha-hydroxyprogesterone
- Synthetic ACTH stimulation test
In terms of medical emergencies, how can CAH present? (3)
- Adrenocortical crisis
- Hyponatraemia
- Hypoglycaemia
What is phenylketonuria (PKU)?
It is an inborn error of amino acid metabolism, caused by absent or virtually absent phenylalanine hydroxylase (PAH) enzyme activity.
What does phenylalanine hydroxylase (PAH) normally do and why is it important?
PAH enzyme converts dietary phenylalanine to tyrosine. The products of this metabolic pathway are important in the formation of catecholamines, neurotransmitters and melanin
What happens to phenylalanine when it builds up in the system?
Phenylalanine leads to the formation of phenylpyruvic acid and phenylethylamine which are thought to be neurotoxic above a threshold concentration. If untreated, it can lead to general learning disability.
How is PKU screened for?
The heel-prick blood test
What is the inheritance pattern for classical PKU and which chromosome is it on?
Autosomal recessive, chromosome 12
How does PKU present? (6)
Most children appear normal at birth and diagnosis usually occurs through abnormal result in the heel-prick test If undetected, may present with: 1. Progressive developmental delay 2. Deterioration in motor skills and cognitive ability (MRI evidence demyelination) 3. Recurrent vomiting 4. Eczematous skin 5. Seizures 6. Severe behavioural disturbance
In appearance, how do children with PKU present?
They tend to be very fair with pale blue eyes, compared to siblings and general family colouring
What is the management of PKU? (4)
- Specialist metabolic/paediatric clinic.
- Dietary protein restriction combined with dietary substitutes of proteins containing a balanced mixture of amino acids including generous supply of tyrosine.
- Regular assay of plasma phenylalanine levels
- Strict diet during pregnancy for PKU patients as if untreated can cause microcephaly, intellectual disability and ADHD in unborn child.
What are the complications of PKU? (5)
- Developmental delay or intellectual disability developing later in life due to non-adherence to diet
- Epilepsy
- Severe behavioural disturbance
- Subtle deficiencies in attention and organisational planning abilities
- Agoraphobia
What is the prognosis like for people with PKU?
Excellent if adhere to diet and other therapies
In puberty in boys, what is the order of development in terms of pubic hair, growth, testicular volume increasing, and what is the helpful, if not somewhat vulgar, mnemonic to remember?
Grapes, Drapes, Grow, Blow
- Testicular volume increases
- Pubic hair grows
- Grow taller
- Ejac
In girls during puberty, what is the order of development?
- Breasts
- Hair growth
- Height
- Menarche
