45. Endocrine Disorders of Growth and Development

Question 1

When do children need further assessment of growth?

What are the 4 aspects of short stature evaluation?

What are some reasons for proportionate or disproprotionate growth failure/short stature?

Answer 1

Weight/height/BMI is below the 0.4th centile, unless already fully investigated earlier OR if height centile is >3 centile spaces below the mid-parental centile OR a drop in height centile position of >2 centile spaces.

Height centile vs weight centile, When started (utero/infancy/childhood/puberty), Body proportions (1⁰ or 2⁰ growth disorder), Presenting signs (ISS (idiopathic short stature)/specific diagnosis).

Proportionate: psycosocial growth retardation, Turner syndrome, chronic renal insufficiency, GI disease, nutritional deficiency, hypo/hyperthyroidism. GH insensitivity/resistance/deficiency, idiopathic short stature.

Disproportionate: skeletal dysplasia: achondroplasia, hypochondroplasia, rickets

Question 2

What is this condition and the clinical phenotype?

Answer 2

Turner syndrome: a female is partly or completely missing an X chromosome.

Phenotype: short stature, SHOX haplo-insufficiency, gonadal dysgenesis, webbed neck, shield chest, widely spaced nipples, cubitus valgus, lymphodema of hands, shortening of 4th/5th metacarpal, knock-knees.

Question 3

What are the recommended tests for systemic disorders?

Describe GH secretion.

What is the GH-IGF axis?

Answer 3

FBC, ESR, Na, K, Cl, bicarbonate, Ca, phosphate, alkaline phosphatase, blood urea nirtogen, creatinine, ILGF-1, ILGF binding protein-3, IgA, tissue transglutaminase, TSH, FT4, karyotype (female only).

CNS -> hypothalamus releases GHRH -> somatotroph cells in anterior pituitary release GH. Somatostatin regulates GHRH release. GH = main regulator of growth in childhood.

GH causes IGF-1 to be produced in the liver and other target tissues, which binds to IGF-1 receptors on target tissues and growth plates, causing growth. IGF-1 release also inhibts further GH release from the anterior pituitary.

Question 4

What are some height-promoting treatment options?

What ages do boys and girls go through puberty?

Answer 4

rhGH (recombinant human GH), oxandrolone ( synthetic, orally active anabolic-androgenic steroid). rhCH seems to be most effective if used until max attainable height, but treatment cost estimated £164,000 and uncertain psychological benefit/harm. Observation and reassurance.

Girls: 8-13y. Boys: 9.5-14y.

Question 5

How is delayed puberty investigated?

What could the following results suggest, and what could second line investigations be for:

a) low/normal serum LH and FSH for early Tanner stages and normal growth rate for bone age.
b) low/normal serum LH and FSH for early Tanner stages and slow growth rate for bone age.
c) elevated FSH after 13y in girls or 14y in boys.

Answer 5

First line evaluation: family history of delayed puberty, history of chronic disease e.g. cryptorchidism, anorexia, growth rate, Tanner stage, testis volume, tests (biochem, bone age X-ray), basal serum LH, FSH, IGF-I, prolactin and testosterone (boys).

a) GnRH deficiency or CDGP (constitutional delay of growth and puberty) -> 2^nd line: GnRH test, hCG stimulation test, serum inhibin B, olefactory funciton test, genetic screening.
b) Functional hypogonadotropic hypogonadism -> low BMI -> GI disorder or undefeeding . Normal BMI -> hypothyreosis, hyper-PRL, GHD. HIgh BMI -> iatrogenic (corticoids). All = examine furhter for chronic diseases.
c) 1⁰ hypogonadism -> 2^nd line: karyotype (girl) or serum inhibinB (boys).