Table 2.

Summary of RCT and longitudinal studies of the effects of GHD and rhGH therapy in adolescents with CO-GHD.

Reference	N	MPHD/IGHD	Age (years)	Design	Groups	rhGH doses	TB	LS	Body composition	CVS risks	Glucose metabolism	QOL
(39) (56)	18	15/3	20.2±1	2 years RCT	n=9 on rhGH n=10 on placebo	3.6IU/day	–	–	↑ 6% in LM in rhGH ↓ 6% FM in rhGH	↔	↓ IS in rhGH	↔a
(4) (40)	24	20/4	17±1.4	1 year RCT	n=12 on rhGH n=12 no rhGH	17μg/kg/day	↑ 6% -BMC in rhGH	↑ 5% BMC in rhGH	↑ (6%) LM in rhGH ↔ FM	↔		–
(16)	64	52/12	23±4.2	2 years RCT	n=20 on adult GH n=23 on paed GH n=21 Placebo	12.5 and 25.0μg/kg/day	↑ 3.3% BMD adult GH ↑ 5% BMD in paed-GH ↑ 1.3% BMD placebo	–	↑ LM of 13.4% in rhGH vs 3.1% in placebo	↔	–	↔b
(15) (41) (65)	92	72/20	19±2.8	2 years RCT	n=59 on adult -GH n=58 on pead-GH n=32 on Placebo	12.5 and 25.0μg/kg/day	↑ 9% BMC in rhGH ↑ 5% BMC in placebo ↑ 5% BMD in rhGH ↑ 3% BMD in placebo	–	↑ 14% LM in rhGH vs 2% in no GH ↓ FM	↔	–	↔c
(20)	58	25/33	15.8	2 years RCT	n=25 on rhGH n=15 on placebo n=18 GH-sufficient	20μg/kg/day	↔ BMD across all groups at baseline and after 2 years	↔	↔ In LM ↔ In FM	↔	↔ HOMA-IR-QUICKI	↔b
(47)	10	5/5	17–20	1 year long	n=10 on rhGH n=10 control	8–10μg/kg/day	–	–	–	+ effect on lipids ↔ in IMT in GHD ↓ IMT in GH-sufficient	↑ HOMA in rhGH ↓ HOMA in GH-sufficient	–
(48)	23	9/14	15–20		n=15 on rhGH n=8 GH-sufficient n=23 control
(17) (27)	160	35/125	18–25	2 years, RCT	n=109 on rhGH n=51 no rhGH	0.2–0.4mg/day	↔ BMD ↑ Cortical thickness ↓ Endosteal diameter	↑ 3.5% BMD in rhGH	–	–	–	–
(21)	40	12/28	15.6–17.3	2 years long	n=23 on rhGH n=17 no rhGH	0.4–1.3mg/day	↔ BMD SDS	↔ BMAD	↓ LM ↑ FM in untreated	–	–	–

^aGeneral Health Questionnaires (GHQ); ^bAGHDA; ^cQLS-H questionnaires. ↑, increase; ↓, decrease; ↔, no significant changes or different; long, longitudinal; RCT, randomised control trial; n, number of patients; rhGH, recombinant human growth hormone; BMD, bone mineral density; BMAD, bone mineral apparent density ; BMC, bone mineral content; LM, lean mass; FM, fat mass; LS, lumbar spine; TB, total body; CO, childhood-onset GH deficiency; IGHD, Isolated growth hormone deficiency; MPHD, multiple pituitary hormone deficiencies; CVS, cardiovascular system; IMT, intima-media thickness; HOMA-IR, homeostasis model assessment-insulin resistance; IS, insulin sensitivity; QUICKI, quantitative insulin sensitivity check index.