Idiopathic short stature

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Idiopathic short stature (ISS) refers to extreme short stature that does not have a diagnostic explanation (idiopathic designates a condition that is unexplained or not understood) after an ordinary growth evaluation. The term has been in use since at least 1975[1] without a precise percentile or statistical definition of "extreme".

In 2003 Eli Lilly and Company offered a more precise definition of ISS when the pharmaceutical company submitted clinical trial data to the U.S. Food and Drug Administration (FDA) requesting approval to advertise their brand of growth hormone for the treatment of ISS.[2] They proposed a definition of a height more than 2.25 standard deviations below mean, roughly equal to the shortest 1.2% of the population.

Other researchers have described a cutoff of 2.0 standard deviations.[3]


Since 2003 this diagnosis has become controversial.

  • Does it make sense to define a disease solely as a certain percentage of the population if there is little perceptible difference between a person just above the cutoff and another person just below the cutoff?
  • How many of the people in the lowest 2% of the population are not simply "idiopathic" but rather have subtler disorders of growth hormone or IGF1 production or responsiveness or any of hundreds of other known or unknown conditions not readily detected by an "ordinary" growth evaluation?
  • Should insurance or government (the other 99% of the population) pay US$100,000 or more (which is the estimated cost[4]) to treat someone to move them from the first percentile to perhaps the 10th? Would that just transfer the disadvantages to those in what was previously the "2nd" percentile?
  • Even if treatment successfully changes height to the 5th or 10th percentile, does it actually improve the person's life in any measurable way? There is some evidence that hormone treatment may not result in a significant improvement in psychosocial functioning.[5]


Medical Therapy

The use of insulin-like growth factor 1[6] or aromatase inhibitors[7] have been proposed as an alternative to growth hormone.

Related Chapters


  1. Sizonenko PC, Rabinovitch A, Schneider P, Paunier L, Wollheim CB, Zahnd G (1975). "Plasma growth hormone, insulin, and glucagon responses to arginine infusion in children and adolescents with idiopathic short stature, isolated growth hormone deficiency, panhypopituitarism, and anorexia nervosa". Pediatr. Res. 9 (9): 733–8. PMID 1105371.
  2. Leschek EW, Rose SR, Yanovski JA; et al. (2004). "Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial". J. Clin. Endocrinol. Metab. 89 (7): 3140–8. doi:10.1210/jc.2003-031457. PMID 15240584.
  3. Bonioli E, Tarò M, Rosa CL; et al. (2005). "Heterozygous mutations of growth hormone receptor gene in children with idiopathic short stature". Growth Horm. IGF Res. 15 (6): 405–10. doi:10.1016/j.ghir.2005.08.004. PMID 16213173.
  4. Lee JM, Davis MM, Clark SJ, Hofer TP, Kemper AR (2006). "Estimated cost-effectiveness of growth hormone therapy for idiopathic short stature". Arch Pediatr Adolesc Med. 160 (3): 263–9. doi:10.1001/archpedi.160.3.263. PMID 16520445.
  5. Visser-van Balen H, Sinnema G, Geenen R (2006). "Growing up with idiopathic short stature: psychosocial development and hormone treatment; a critical review". Arch. Dis. Child. 91 (5): 433–9. doi:10.1136/adc.2005.086942. PMID 16632673.
  6. Savage MO, Camacho-Hübner C, David A; et al. (2007). "Idiopathic short stature: will genetics influence the choice between GH and IGF-I therapy?". Eur. J. Endocrinol. 157 Suppl 1: S33–7. doi:10.1530/EJE-07-0292. PMID 17785695.
  7. Damiani D, Damiani D (2007). "Pharmacological management of children with short stature: the role of aromatase inhibitors". J Pediatr (Rio J). 83 (5 Suppl): S172–7. doi:10.2223/JPED.1699. PMID 17901908.

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