Paeds: Endocrinology (2)

Question 1

Causes of delayed puberty with short stature

Answer 1

• Turner’s syndrome
• Prader-Willi syndrome
• Noonan’s syndrome

Question 2

Causes of delayed puberty with normal stature

Answer 2

• polycystic ovarian syndrome
• androgen insensitivity
• Kallman’s syndrome
• Klinefelter’s syndrome

Question 3

Ages for classification of late puberty (both genders)

Answer 3

Question 4

Ages at which a girl and a boy may be classified as ‘extreme’ delay in puberty

Answer 4

Girl → >14 y old

Boy → >16 y old

Question 5

What’s the danger of congenital hypothyroidism?

Answer 5

If not diagnosed and treated within the first four weeks it causes irreversible cognitive impairment

Question 6

Features of congenital hypothyroidism

Answer 6

• prolonged neonatal jaundice
• delayed mental & physical milestones
• short stature
• puffy face
• macroglossia
• hypotonia

Question 7

Screening for congenital hypothyroidism

Answer 7

Children are screened at 5-7 days using the heel prick test

Question 8

What’s a secondary hypothyroidism?

• where is the problem
• levels of TFTs

Answer 8

• problem is at the hypothalamus or pituitary gland
• Low levels of plasma TSH
• Low levels of plasma Thyroxine

*Requires the levels of FT4 and TSH for diagnosis

Question 9

Would UK Neonatal Screening Programme pick up secondary hypothyroidism?

Answer 9

No.

If there is clinical suspicion of hypothyroidism, a full assessment of thyroid function is mandatory

Question 10

How testing for congenital hypothyroidism is done in the UK?

Answer 10

• Midwife obtains sample on day 5-8 regardless of health and sends blood spot card by 1st class post clearly identified as newborn screening blood spot
• Laboratory analyses for blood spot TSH
• Each laboratory defines a cut off point which identifies an abnormal result
• Normal result, parents informed
• Abnormal result referred to clinician for confirmation

Question 11

Causes of hypothyroidism in children

Answer 11

The most common cause of hypothyroidism in children (juvenile hypothyroidism) is autoimmune thyroiditis.

Other causes include

• post total-body irradiation (e.g. in a child previous treated for acute lymphoblastic leukaemia)
• iodine deficiency (the most common cause in the developing world)

Question 12

Structure of adrenal gland

Answer 12

Question 13

How to assess BMI in children?

Answer 13

• BMI assessment more difficult in children than adults
• body mass index (BMI) varies with age
• BMI percentile charts are therefore needed to make an accurate assessment

Question 14

What to do next if BMI of a child is at:

• 91st centile or above
• 98th centile or above

Answer 14

• 91st centile or above → consider tailored clinical intervention if BMI
• 98th centile or above → consider assessing for comorbidities

Question 15

Causes of obesity in children

Answer 15

• lifestyle factors → the most common cause of obesity in children
• growth hormone deficiency
• hypothyroidism
• Down’s syndrome
• Cushing’s syndrome
• Prader-Willi syndrome

Question 16

Epidemiology of obesity in children

Answer 16

• Asian children: four times more likely to be obese than white children
• female children
• taller children: children with obesity are often above the 50th percentile in height

Question 17

Consequences of obesity in children

Answer 17

• orthopaedic problems: slipped upper femoral epiphyses, Blount’s disease (a development abnormality of the tibia resulting in bowing of the legs), musculoskeletal pains
• psychological consequences: poor self-esteem, bullying
• sleep apnoea
• benign intracranial hypertension
• long-term consequences: increased incidence of type 2 diabetes mellitus, hypertension and ischaemic heart disease

Question 18

Genetics and obesity (simply)

Answer 18

genetics plays a part but does not pre-destine us to be obese

Question 19

Relationship of GH and IGF-1

Answer 19

• GH (via a complex cascade) initiates the release of IGF-I within many tissues but predominantly the liver and at the growth plate
• IGF-I acts in an autocrine and paracrine manner via the IGF-I receptor to stimulate cell proliferation and longitudinal growth

Question 20

What other hormones can affect GH-IGF-1 system?

Answer 20

Many other hormones can affect the GH-IGF-I system or directly affect cell proliferation at the growth plate including:

• thyroid hormone
• vitamin D
• corticosteroids

Question 21

What is the trigger for puberty to start?

Answer 21

• Puberty’s trigger lies in hypothalamus → secretion of gonadotropin-releasing hormone (GnRH)
• GnRH → stimulates the pituitary gland → release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
• LH and FSH → signal ovaries and testes to begin releasing the appropriate sex hormones → estrogens and testosterone, which launch the other signs of puberty in the body

Question 22

Hormone release during late pre-pubertal years

Answer 22

• During the late pre-pubertal years gonadotrophin releasing hormone (GnRH) are secreted with increasing frequency, initially during sleep
• In the early stages FSH secretion is in excess of LH but as the amplitude of GnRH pulses increase LH secretion becomes predominant

Question 23

What’s the earliest sign of puberty in females

Answer 23

Breast development or ‘thelarche’ is the earliest sign of puberty and coincides with pubertal growth spurt

Question 24

What’s first sign of puberty in males?

Answer 24

The first sign of puberty in boys is change in testicular volume from 3 mls to 4 mls

Question 25

Prognosis for delayed puberty

Answer 25

Many children with delayed puberty will eventually go through an otherwise normal puberty, just at a late age

Question 26

Benign causes of delayed puberty

Answer 26

* child is just maturing more slowly than average, a condition called **constitutional delay of puberty** **​\*** This condition often runs in families * young girls who undergo intense physical training for a sport, such as running or gymnastics, start puberty later than normal

Question 27

Indications for reviewing a patient with delayed puberty

Answer 27

* No breast development in girls by age 13 * No menstruation for five or more years after the first appearance of breast tissue * No testicles development by age 14 in boys * Incompletely developed male organs by five years after they first start to develop

Question 28

Management of Turner's syndrome

Answer 28

There's no cure for Turner syndrome, but certain treatments can help cope with the symptoms and effects of this condition: * Hormone treatments with **growth hormone** and/or other hormones can improve growth and help girls achieve taller heights in adulthood * **Estrogen replacement** around the age of 12 or 13 may be initiated to stimulate the development of secondary sexual characteristics, such as breasts, and menstruation * If structural heart defects are present, **cardiac surgery** may be needed

Question 29

Is Turner's syndrome inherited?

Answer 29

Most cases of Turner syndrome are not inherited. * chromosomal abnormality occurs as a random event during the formation of reproductive cells (eggs and sperm) in the affected person's parent * an error in cell division called nondisjunction can result in reproductive cells with an abnormal number of chromosomes Mosaic Turner syndrome is also not inherited * it occurs as a random event during cell division in early fetal development → as a result, some of an affected person's cells have the usual two sex chromosomes, and other cells have only one copy of the X chromosome

Question 30

Biochemical characteristics of Addison's disease

Answer 30

* hyponatremia * hypoglycaemia * hyperkalaemia * unexplained eosinophilia * mild prerenal azotaemia (accumulation of urea and creatinine in the body)

Question 31

Causes of congenital hypothyroidism

Answer 31

* anatomic defect in the gland * an inborn error of thyroid metabolism * iodine deficiency

Question 32

Signs and symptoms of congenital hypothyroidism

Answer 32

* Infants with congenital hypothyroidism are usually born at term or after term * Often, affected infants are described as "good babies" because they rarely cry and they sleep most of the time  Decreased activity  Large anterior fontanelle  Poor feeding and weight gain  Small stature or poor growth  Jaundice  Decreased stooling or constipation  Hypotonia  Hoarse cry

Question 33

Physical findings O/E of congenital hypothyroidism

Answer 33

The physical findings of hypothyroidism may or may not be present at birth. Signs include:  Coarse facial features  Macroglossia  Large fontanelles  Umbilical hernia  Mottled, cool, and dry skin  Developmental delay  Pallor  Myxedema  Goiter

Question 34

Diagnosis of congenital hypothyroidism

Answer 34

Diagnosis of primary hypothyroidism * decreased levels of serum thyroid hormone (**total or free T4**) and elevated levels of thyroid-stimulating hormone (**TSH)** * if maternal antibody-mediated hypothyroidism is suspected→ **maternal and neonatal antithyroid antibodies**

Question 35

In neonate, does a combination of low T4 and normal TSH require treatment?

Answer 35

The combination of low or low-normal serum total T4 levels and a serum TSH within the reference range suggests *thyroid-binding globulin (TBG) deficiency*. This congenital disorder causes no pathologic consequence but should be recognized to avoid unnecessary thyroid hormone administration (i.e. when thinking about congenital hypothyroidism).