Growth Disorders Flashcards
What are the major causes of growth failure?
Systemic dz i.e. Celiac (reverses with gluten free diet), Chrons
Dysmorphic syndromes i.e. Turner’s syndrome = XO Karyotype; short stature bc SHOX deficiency present on short arms of X and Y chromosomes –> dysmorphic features, ovarian failure, coarcation of aorta, renal abnormalities, autoimmune dz, cognitive difficulties; responds well to GH
Hormonal disorders: TH deficiency, glucocorticoid excess, androgen or estrogen excess (premature epiphyseal closure), GH deficiency or nonresponsiveness, IGF-1 deficiency or nonresponsiveness
What can cause GH deficiency?
Midline brain defects
Destructive processes
Genetic mutations
Idiopathic
What else can cause growth failure thats similar to GH deficiency?
IGF-1 deficiency= Laron syndrome
You can also have problems in cytoplasmic signalling, intranuclear signalling etc. (pre/post receptor defects)
i.e. GH receptor, IGF1 receptor
What can cause large newporbs/tall children?
Normal variants
Hyperinsulinism - diabetes mellitus causing LGA babies, PHHI (congenital hyperinsulinism)
Dysmorphic syndromes: Marfan’s, homocysteinuria
Growth hormone excess
Abnormal secretion of sex steroids
Beckwith wiedeman syndrome?
Most common of overgrowth disorders
Overexpressoin of IGF-2 gene
Fetal organomegaly, neonatal hypoglycemia from hyperinsulinism, omphalocoele, embryonal tumors, hemihyperplasia
How can androgens & estrogens cause tall stature?
Sex steroids increase the rate of growth & the rate of bone maturation: precocious puberty –> tall childhood stature but short adult stature bc of premature epiphyseal closure
Estrogen deficiency will delay bone maturation & enable ongoing growth & resultant tall stature
Aromatase deficiency
Estrogen - necessary for epiphyseal plate closure
If they don’t have it, they keep growing!
Now aromatase inhibitors are under clinical investigation for use in treatment of short stature in boys
Adult: GH excess: cause, sx, tx
Excess: due to acromegaly
Sx: acral enlargement (hands, feet, heel pad thicker), coarse features, sweating, menstrual disorders, HA, arthritis, carpal tunnel syndrome, diabetes/impaired gluc intolerance, impaired potency/libido, htn, visual field defect, obstructive sleep apnea, galactorrhea, coronary artery d, maxilofacial features (enlarged nose, chin, mandible, macroglossia, spreading of teeth)
Check: GH levels after oral glucose (should be suppressed…if it’s not, suspect acromgealy)
Serum IGF-1 level- might be elevated
Tx: transphenoidal surgery, medical therapy
Adjunctive therapy after surgery for larger tumors (dopamine agonists, somatostatin analogs, GH receptor antagonist), radiotherapy
Somatostatin analogs
Lanerotide
Octreotide
Inhibit GH synthesis
GH antagonist
Pegvisomant: GH molecule that acts as a receptor antagonist
blocks GH receptors
IGF-I levels fall & clinical sx of acromegaly improve
Goals of therapy for acromegaly?
Biochemical congrol: GH suppression, IGF-I normalization
Relieve signs & sx
Reduce tumor size & mass effect
Preserve pituitary function
Minimal side effects
What can cause GH deficiency in adults?
Pituitary tumor
craniopharyngioma
Idiopathic
CNS tumor
Empty sella syndrome
Sheehan’s syndrome
Head trauma
Hypophysitis
Surgery
Granulomatous dz
Irradiation
Other
Clinical consequences of adult onset GH deficiency?
Increased cholesterol & other cv risk markers i.e. crp
Anbormal body composition: increased central body fat
Decreased bone density
Decreased quality of life
Therapy= daily, subcutaneous injections of human growth hormone –> modest improvements in the effects of GH deficiency listed above
