Growth/Endocrine/Metabolic

Question 1

What is the most common cause of ambiguous genitalia in a newborn?

Answer 1

Congenital adrenal hyperplasia

Question 2

What is the inheritance pattern for congenital adrenal hyperplasia (CAH)?

Answer 2

Autosomal recessive

Question 3

Name the hormones released by the adrenal gland normally?

Answer 3

1. Cortisol
2. Testosterone
3. Aldosterone

Question 4

What is the most common cause of CAH? - which enzyme is absent?

Answer 4

Absence of the enzyme 21-hydroxylase

Question 5

What are the two sub-divisions of classical CAH?

Answer 5

1. Salt-losing form

2. Simple-virilising form

Question 6

What happens in congenital adrenal hyperplasia?

Answer 6

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

Question 7

How was the term ‘disorder of sexual development’ previously known?

Answer 7

Intersex conditions

Question 8

What are the various forms of DSD? (5)

Answer 8

1. 46, XX DSD
2. 46, XY DSD
3. Ovotesticular DSD
4. 46, XX testicular DSD
5. 46, XY complete gonadal dysgenesis

Question 9

Why is reconstructive surgery in DSD now delayed, compared to years ago when it used to be performed shortly after birth?

Answer 9

As early gender assignment may not reflect the psychological development and gender identity of the child, so it is deferred

Question 10

How does chromosomal sex determine the appearance of the genitalia?

Answer 10

Chromosomal sex prescribes gonadal sex, which in turn prescribes phenotypic sex. The gonad type determines whether the Mullerian or Wolffian ducts develop or regress.

Question 11

How does an embryo with a Y chromosome develop ovaries?

Answer 11

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.

Question 12

What is the most common cause of ambiguous genitalia in the newborn?

Answer 12

Congenital adrenal hyperplasia

Question 13

After CAH, what is the second most common cause of ambiguous genitalia?

Answer 13

Mixed gonadal dysgenesis (MGD)

Question 14

What does AMH stand for, and how can a deficiency of it cause inadequately virilised males?

Answer 14

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.

Question 15

When is it likely for phenotypic females with DSD to be diagnosed?

Answer 15

When presenting with primary amenorrhoea (females with 46, XY)

Question 16

Why is DSD a medical emergency?

Answer 16

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.

Question 17

What are the common findings in a newborn with a male appearance suggesting DSD? (3)

Answer 17

1. Severe hypospadias with bifid scrotum
2. Undescended testis with hypospadias
3. Bilateral non-palpable testes in a full-term apparently male infant

(and of course in a baby with indeterminate sex due to ambiguous genitalia)

Question 18

What are the common findings in a newborn with a female appearance suggesting DSD? (2)

Answer 18

1. Clitoral hypertrophy of any degree, non-palpable gonads
2. Vulva with single opening

(and of course in a baby with indeterminate sex due to ambiguous genitalia)

Question 19

What is the most commonly seen condition in a child with DSD?

Answer 19

A virilised female with 46 XX with CAH

Question 20

What questions are important to ask when taking a history from the mother/family of a child with DSD? (6)

Answer 20

1. Medication history including any exposure to androgens in a mother
2. Any history or signs of virilisation in the mother
3. A history of unexplained early or neonatal deaths
4. Any history of a DSD in other children
5. A history of parental consanguinity
6. Family history of: infertility, ambiguous genitalia, primary amenorrhoea, late puberty

Question 21

What is one of the most important investigations for suspected DSD?

Answer 21

Pelvic ultrasound

Question 22

What endocrine screening is often performed in a baby with suspected DSD? (4)

Answer 22

1. LH and FSH
2. ACTH, renin, aldosterone
3. Testosterone androstenedione, 17 alpha-hydroxyprogesterone
4. Synthetic ACTH stimulation test

Question 23

In terms of medical emergencies, how can CAH present? (3)

Answer 23

1. Adrenocortical crisis
2. Hyponatraemia
3. Hypoglycaemia

Question 24

What is phenylketonuria (PKU)?

Answer 24

It is an inborn error of amino acid metabolism, caused by absent or virtually absent phenylalanine hydroxylase (PAH) enzyme activity.

Question 25

What does phenylalanine hydroxylase (PAH) normally do and why is it important?

Answer 25

PAH enzyme converts dietary phenylalanine to tyrosine. The products of this metabolic pathway are important in the formation of catecholamines, neurotransmitters and melanin

Question 26

What happens to phenylalanine when it builds up in the system?

Answer 26

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.

Question 27

How is PKU screened for?

Answer 27

The heel-prick blood test

Question 28

What is the inheritance pattern for classical PKU and which chromosome is it on?

Answer 28

Autosomal recessive, chromosome 12

Question 29

How does PKU present? (6)

Answer 29

``` 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 ```

Question 30

In appearance, how do children with PKU present?

Answer 30

They tend to be very fair with pale blue eyes, compared to siblings and general family colouring

Question 31

What is the management of PKU? (4)

Answer 31

1. Specialist metabolic/paediatric clinic. 2. Dietary protein restriction combined with dietary substitutes of proteins containing a balanced mixture of amino acids including generous supply of tyrosine. 3. Regular assay of plasma phenylalanine levels 4. Strict diet during pregnancy for PKU patients as if untreated can cause microcephaly, intellectual disability and ADHD in unborn child.

Question 32

What are the complications of PKU? (5)

Answer 32

1. Developmental delay or intellectual disability developing later in life due to non-adherence to diet 2. Epilepsy 3. Severe behavioural disturbance 4. Subtle deficiencies in attention and organisational planning abilities 5. Agoraphobia

Question 33

What is the prognosis like for people with PKU?

Answer 33

Excellent if adhere to diet and other therapies

Question 34

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?

Answer 34

Grapes, Drapes, Grow, Blow 1. Testicular volume increases 2. Pubic hair grows 3. Grow taller 4. Ejac

Question 35

In girls during puberty, what is the order of development?

Answer 35

1. Breasts 2. Hair growth 3. Height 4. Menarche