Retarded Growth, and Normal GH


Question

I have a case of a female child (7.5 yr-old) with short stature relative to familial channel (channel 3%, ht 115cm) without low weight (10-25%, wt 20.5kg) with severe bone age retardation (2yr at chronological age of 6yr and 3yr at chronological age of 7.5 yr).

She was born with ht 49cm and wt 3250g. She shifted her growth channel from 90% at age of two yr to 25% at 4-5yr and then stabilized in the 3% channel between 6 to 7.5yr old. She had a well-registered low growth velocity from 4 to 5yr of age (4cm/yr, channel <3%) but current normal velocity (6cm/yr, channel 25%).

Medical history and physical examination did not suggest chronic illness, malnourishment or congenital syndromes.

She had normal response of GH to clonidine test (0.1 to 10.78) and normal basal evaluation: RBC, WBC, AST, ALT, creatinine, stool fat, IGF-1 163; IGFBP3 3.8; TSH 1.8; FT4 1.27; anti-endomisium IgA and IgG (-). Calcium was evaluated when she was 6yr old and was normal. Alkaline phosphatase and karyotype were not analyzed.

What do you suggest for differential diagnosis and workout on such a severe bone age retardation? Dr. Marcelo Miranda O. Lima, Campinas - SP - Brazil

Response

Regarding her evaluation, it seems that you have been quite thorough. In the laboratory analyses, did you obtain an ESR? Did you measure total IgA to ensure that the negative endomesial IgA is reliable? Additionally, I would like to see a normal urinalysis, normal liver functions, including albumin. On the CBC, did you have a normal MCV? You did not obtain a karyotype, and I would consider one if the above tests are all negative—although I think that the likelihood of Turner syndrome is quite low. Is there a family history of similar growth ? Of medical problems ? Is she taking any medication now—or in the past ? Have physical and cognitive development been normal since birth ?

The fairly realistic differential at this point includes the iron deficiency, zinc deficiency, skeletal dysplasias, pseudohypoparathyroidism (or pseudopseudo), psychosocial dwarfism and constitutional delay of growth.

The early growth pattern suggests that this is not GH deficiency, and your lab work clearly supports this. Over how long a period has her growth velocity been 6 cm/yr ? If sustained, and IF this is without pubertal/sex hormone influence, then this is very reassuring—and supports an extremely exaggerated constitutional delay of growth as the cause.

An assessment of her growth curve--normal in utero /early growth followed by poor growth after the infancy, and now normal—suggests that she had some type of abnormality from age 2-6 years, and that she has (mostly or completely) recovered; note that her bone age advanced two years in the first six years of her life, and then one year from chronological age 6 to 7.5 years.

In addition to the above, I would continue to follow her closely, to ensure that her growth stays normal, and that puberty does not occur early. I would not suggest treating her at this time ( e.g. with growth hormone) as her current growth velocity may indicate some degree of spontaneous catch-up growth. I suspect that most height prediction algorithms will overestimate her adult height (due to her severe bone age delay), and I would caution against excessively optimistic height predictions. Michael P. Wajnrajch, MD