Endocrinology: Rickets; Growth Deficiency; Delayed Puberty Flashcards
What is the simplified pathophysiology of rickets? [3]
Which populations are at higher risks of rickets? [4]
Vitamin D is a hormone (not technically a vitamin) created from cholesterol by the skin in response to UV radiation.
Inadequate vitamin D leads to a lack of calcium and phosphate in the blood
- Since calcium and phosphate are required for the construction of bone, low levels result in defective bone mineralisation
Low calcium causes a secondary hyperparathyroidism as the parathyroid gland tries to raise the calcium level by secreting parathyroid hormone. Parathyroid hormone stimulates increased reabsorption of calcium from the bones. This causes further problems with bone mineralisation.
Those at higher risk:
- Patients with darker skin require a longer period of sun exposure to generate the same quantity of vitamin D
- Patients with malabsorption disorders (such as inflammatory bowel disease) are more likely to have vitamin D deficiency.
- CKD: The kidneys are essential in metabolising vitamin D to its active form, therefore vitamin D deficiency is common in chronic kidney disease.
- Limited exposure to sunlight
- Low Ca & P diets
- Medications like glucocorticoids and ARVs
TOM TIP: Think about the risk factors for vitamin D deficiency in your exams and clinical practice. Patients with rickets are likely to have risk factors such as darker skin, low exposure to sunlight, live in colder climates and spend the majority of their time indoors.
Patients with vitamin D deficiency and rickets may not have any symptoms. Potential symptoms are [6]
Bone deformities that can occur in rickets include: [4]
Patients with vitamin D deficiency and rickets may not have any symptoms. Potential symptoms are:
* Lethargy
* Bone pain
* Swollen wrists
* Bone deformity
* Poor growth
* Dental problems
* Muscle weakness
* Pathological or abnormal fractures
Bone deformities that can occur in rickets include:
* Bowing of the legs, where the legs curve outwards
* Knock knees, where the legs curve inwards
* Rachitic rosary, where the ends of the ribs expand at the costochondral junctions, causing lumps along the chest
* Craniotabes, which is a soft skull, with delayed closure of the sutures and frontal bossing
* Delayed teeth with under-development of the enamel
Investigations for Rickets?
Serum 25-hydroxyvitamin D is the laboratory investigation for vitamin D.
- A result of less than 25 nmol/L establishes a diagnosis vitamin D deficiency, which can lead to rickets.
Xray is required to diagnose rickets.
- X-rays may also show osteopenia (more radiolucent bones).
Bone profile
* Serum calcium may be low
* Serum phosphate may be low
* Serum alkaline phosphatase may be high
* Parathyroid hormone may be high
Why are breastfed babies more at risk of rickets? [1]
How do you avoid this? [1]
Prevention is the best management for rickets. Breastfed babies are at higher risk of vitamin D deficiency compared with formula fed babies, as formula feed is fortified with vitamin D.
- Breastfeeding women and all children should take a vitamin D supplement. NICE clinical knowledge summaries recommend supplements containing 400 IU (10 micrograms) per day for children and young people.
How do you treat vitamin D deficiency in children? [1]
How do you treat rickets? [2]
Children with vitamin D deficiency can be treated with vitamin D (ergocalciferol). The doses for treatment of vitamin D deficiency depend on the age (see the BNF).
- The dose for children between 6 months and 12 years is 6,000 IU per day for 8 – 12 weeks.
Children with features of rickets should be referred to a paediatrician.
- Vitamin D and calcium supplementation is used to treat rickets.
- Surgical Intervention: In severe cases where there are bone deformities, surgical correction might be necessary. This includes procedures like osteotomies and epiphysiodesis.
Describe what is meant by Familial Hypophosphatemia (X-linked Hypophosphatemic Rickets)? [1]
How does it differ to diet linked rickets? [2]
This genetic disorder leads to phosphate wasting at the renal level resulting in hypophosphatemia. It shares many clinical features with nutritional rickets including stunted growth, bowing of the legs, and dental anomalies.
- However, unlike nutritional rickets where serum phosphate levels normalise with supplementation, familial hypophosphatemia does not respond to vitamin D therapy alone due to renal phosphate wasting.
- Another distinguishing feature is that it presents with normal or even slightly elevated levels of alkaline phosphatase as opposed to the significantly increased levels seen in nutritional rickets.
The most common cause of hypothyroidism in children [1]
The most common cause of hypothyroidism in children (juvenile hypothyroidism) is autoimmune thyroiditis.
What is meant by congenital hypothyroidism? [1]
How is it detected? [1]
Congenital hypothyroidism is where the child is born with an underactive thyroid gland.
- This occurs in around 1 in 3000 newborns. It can be the result of an underdeveloped thyroid gland (dysgenesis) or a fully developed gland that does not produce enough hormone (dyshormonogenesis).
- Very rarely it can be the result of a problem with the pituitary or hypothalamus. This usually occurs without any other problems and the cause is not clear.
Congenital hypothyroidism is screened for on the newborn blood spot screening test. Where it is not picked up a birth, patients can present with:
What is the most common cause of acquired hypothyroidism in children? [1]
How would you detect? [1]
The most common cause of acquired hypothyroidism is autoimmune thyroiditis, also known as Hashimoto’s thyroiditis.
- It is associated with antithyroid peroxidase (anti-TPO) antibodies and antithyroglobulin antibodies
Describe the basic physiology of the release of GH [2]
Growth hormone is produced by the anterior pituitary gland
- It is responsible for stimulating cell reproduction and the growth of organs, muscles, bones and height.
- It stimulates the release of insulin-like growth factor 1 (IGF-1) by the liver, which is also important in promoting growth in children and adolescents.
Describe the differences in causes between congenital and acquired growth hormone deficiency [2]
Congenital growth hormone deficiency
- results from a disruption to the growth hormone axis at the hypothalamus or pituitary gland.
- It can be due to a known genetic mutation such as the GH1 (growth hormone 1) or GHRHR (growth hormone releasing hormone receptor) genes
- or due to another condition such as empty sella syndrome where the pituitary gland is under-developed or damaged.
Acquired growth hormone deficiency:
- can be secondary to infection, trauma or interventions such as surgery.
How may GHD present at birth? [3]
How many GHD present later in childhood? [4]
Growth hormone deficiency may present at birth or in neonates with:
* Micropenis (in males)
* Hypoglycaemia
* Severe jaundice
Older infants and children can present with:
* Poor growth, usually stopping or severely slowing from age 2-3
* Short stature
* Slow development of movement and strength
* Delayed puberty
* Obesity
Investigation, diagnosis and management will be made by specialists in paediatric endocrinology using which tests? [1]
Describe this test [1]
Growth hormone stimulation test:
- glucagon, insulin, arginine and clonidine can be used to stimulate release of growth hormone
- Growth hormone levels are monitored regularly for 2-4 hours
- In growth hormone deficiency there will be a poor response to stimulation.
Growth hormone deficiency is related to numerous other conditions. Which tests would you conduct to assess for these? [4]
Test for other associated hormone deficiencies, for example thyroid and adrenal deficiency
MRI brain for structural pituitary or hypothalamus abnormalities
Genetic testing for associated genetic conditions such as Turner syndrome and Prader–Willi syndrome
Xray (usually of the wrist) or a DEXA scan can determine bone age and help predict final height
Mx of Growth Hormone Deficiency? [3]
Daily subcutaneous injections of growth hormone (somatropin)
Treatment of other associated hormone deficiencies
Close monitoring of height and development
How would you determine what delayed puberty is in boys [1] and girls [1]
No testicular enlargement by 14 years of age,
Whereas in girls, it’s often determined by the lack of breast development by 13 years.
What are three common causes of delayed puberty? [3]
This condition can be caused by various factors including constitutional delay, hypogonadotropic hypogonadism and hypergonadotropic hypogonadism
The investigation of delayed puberty involves a structured approach to identify underlying causes and guide appropriate management.
Initial investigations should focus on first-line tests, followed by more specific assessments if necessary.
What are the first line tests and what do they show? [5]
Bone Age Assessment:
- A radiograph of the left hand and wrist is typically performed to evaluate skeletal maturity.
- Bone age significantly behind chronological age may indicate constitutional delay of growth and puberty (CDGP).
Serum Gonadotropins:
- Measurement of luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels can distinguish between hypogonadotropic hypogonadism (low or normal LH/FSH) and hypergonadotropic hypogonadism (elevated LH/FSH).
Sex Steroid Levels:
- Serum testosterone in males or estradiol in females helps assess gonadal function.
- Low levels are indicative of delayed puberty.
Thyroid Function Tests:
- Evaluate thyroid-stimulating hormone (TSH) and free thyroxine (T4) to rule out hypothyroidism, which can contribute to delayed puberty.
Karyotype Analysis:
- Particularly indicated in females with primary amenorrhoea, to diagnose conditions such as Turner syndrome
If initial investigations indicate an abnormality or if the diagnosis remains unclear with regards to delayed pubery, further investigations may be warranted.
Describe these [4]
Pituitary Function Tests:
- Assess other pituitary hormones including adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin, and cortisol levels to evaluate for panhypopituitarism or isolated deficiencies.
MRI Brain/Pituitary:
- Indicated if central causes such as a pituitary tumour or structural abnormalities are suspected based on clinical findings or hormonal assays.
Kallmann Syndrome:
- Genetic testing for mutations in genes associated with this condition should be considered if anosmia is present alongside hypogonadotropic hypogonadism.
Celiac Disease:
- Serological testing for tissue transglutaminase antibodies may be necessary in cases where malabsorption syndromes are suspected contributors to delayed puberty.
How can you manange constitutional delay of growth and puberty (CDGP)? [2]
reassurance about late development often suffices
Consider short-term sex steroid treatment to induce puberty if psychosocial distress is significant.
- Use oral testosterone in boys and ethinylestradiol in girls for a limited period (6-12 months).
How do you treat delayed puberty in the cases of permanent hypogondatropic hypogonadism due to structural hypothalamic/pituitary disease or genetic defects?
How do you treat delayed puberty in the cases of primary gonadal failure (hypergonadotropic hypogonadism)? [1]
permanent hypogondatropic hypogonadism due to structural hypothalamic/pituitary disease or genetic defects
- long-term sex steroid replacement
- In males, testosterone can be used; in females, a combination of oestrogen and progesterone.
primary gonadal failure (hypergonadotropic hypogonadism)
- lifelong sex steroid replacement therapy is required for induction of puberty and maintenance of secondary sexual characteristics
Klinefelter’s syndrome is associated with karyotype [1]
Klinefelter’s syndrome is associated with karyotype 47, XXY.
Describe the clinical features of Klinefelters [6]
- Often taller than average
- Lack of secondary sexual characteristics
- Small, firm testes
- Infertile
- Gynaecomastia - increased incidence of breast cancer
- Elevated gonadotrophin levels but low testosterone
