This study aims at improving knowledge about the diagnosis of growth hormone deficiency (GHD) and treatment with growth hormone (GH), with the goal of providing information on the presence of new biomarkers, such as miRNAs, for diagnostic and therapeutic purposes, with the goal of establishing a personalized GH treatment scheme, optimizing resources, reducing costs, and improving outcomes.

In 200 prepubertal and pubertal subjects with the suspicion of GHD, the levels of three specific circulating miRNas will be measured to establish whether they can be used for the diagnosis of GH deficiency. In subjects with isolated idiopathic GHD (IIGHD), short statured patients born SGA, Noonan and Turner syndromes, and SHOX deficiency, we will also assess the changes of the identified miRNAs before and after 3 months on GH therapy to verify an early growth prediction model for growth response at 12 months on treatment. Finally, we plan to identify any differences in these miRNAs at 3 months on treatment using daily GH versus weekly (long-acting) GH.

Inclusion Criteria for aim 1:

• Children with short stature and suspicion of GHD
• Subjects with organic GH deficiency

Exclusion criteria for aim 1:

-Subjects with underlying genetic conditions and chronic diseases

Inclusion Criteria for aim 2-3-5:

• patients having confirmed GHD enrolled for aim 1
• patients with growth failure and born SGA (>4 yr of age)
• patients with Noonan and Turner syndrome and growth failure
• patients with short stature homeobox-containing gene deficiency (SHOXD) and growth failure

Inclusion Criteria for aim 4:

- Isolated idiopathic prepubertal naive GHD subjects on long-acting versus daily GH therapy

All patients will be investigated in routine practice during the normal workup for short stature and stunted growth. Treatment will be also delivered accordind to standard care indications and as established by regulatory agencies in Italy.