Table 3. Open in new tab Response to...

	1	2^a	4^b	8	11^c	12^d	20	23	24^e	Total
Variant	p.(Arg107Glyfs*31)	p.(Lys117Asn)	p.(Arg141Pro)	p.(Ala204Glu)	p.(Ala271Pro)	p.(Phe279Leu)
At start of rhGH therapy
Age, y	12.4	11.5	15.2	4.6	4.6	11.7	4.9	7.0	9.9	9.1 ± 3.9
Sex	Female	Male	Male	Male	Female	Female	Male	Male	Male
Height (SDS)	−3.2	−2.9	−2.5	−2.9	−3.4	−3.2	−3.0	−2.6	−3.3	−3.0 ± 0.3
HV, cm/y	4.4	4.0	4.5	8.1	5.3	4.0	6	4.6	4.6	5.1 ± 1.3
PAH, SDS	−2.9	−3.3	−2.4	—	−3.8	−2.2	—	—	−3.3	−3.0 ± 0.6
BA delay, y	1.4	0.0	0.5	—	0.6	1.8	—	—	1.2	0.9 ± 0.7
Tanner stage	3	1	3-4	1	1	1	1	1	1
IGF-I, SDS	−2.1	−0.7	−1.7	−1.4	−2.0	−1.1	0.0	−1.7	−1.0	−1.3 ± 0.7
Starting dose, mg/kg.d	—	0.037	0.032	0.043	—	0.028	—	0.028	0.035	0.034 ± 0.006
After 1 y of rhGH
Height gain, SDS	0.6	0.4	0.7	1.6	1.5	0.8	0.7	0.5	1.1	0.9 ± 0.4
PAH gain, SDS	0.6	0.7	2.2	—	—	0.6	—	—	0.9	1.0 ± 0.7
HV 0-1 y, cm/y	9.3	7.8	9.1	12.1	11.8	9.3	8.8	8.1	11.2	9.7 ± 1.6
BA delay, y	1.0	0.4	3.1	—	—	1.8	—	—	0.2	1.3 ± 1.2
Dose after 1 y, mg/kg.d	—	0.035	0.020	0.036	—	0.026	—	0.053	0.032	0.034 ± 0.011
After 2 y of rhGH
Height gain SDS 0-2 y	1.1		1.4	2.1	1.6		1.2			1.5 ± 0.4
PAH gain SDS 0-2 y	1.6		2.4	—	—		—			2.0 ± 0.6
HV 1-2 y, cm/y	6.4		6.9	8.2	7.1		9.9			7.7 ± 1.4
BA delay, y	2.0		3.5	1.1	—		—			2.2 ± 1.2
Dose after 2 y, mg/kg.d	0.036		0.012	0.037	—		—			0.028 ± 0.014
At stop of rhGH therapy
Age, y			18.8		14.53
Height, SDS^f			−0.6		−1.7
BA delay, y			—		—
Tanner stage			5		5

2^a

4^b

11^c

12^d

24^e

Total

Variant

p.(Arg107Glyfs*31)

p.(Lys117Asn)

p.(Arg141Pro)

p.(Ala204Glu)

p.(Ala271Pro)

p.(Phe279Leu)

At start of rhGH therapy

Age, y

12.4

11.5

15.2

4.6

11.7

4.9

7.0

9.9

9.1 ± 3.9

Sex

Female

Male

Female

Male

Height (SDS)

−3.2

−2.9

−2.5

−2.9

−3.4

−3.2

−3.0

−2.6

−3.3

−3.0 ± 0.3

HV, cm/y

4.4

4.0

4.5

8.1

5.3

4.0

4.6

5.1 ± 1.3

PAH, SDS

−2.9

−3.3

−2.4

—

−3.8

−2.2

—

−3.3

−3.0 ± 0.6

BA delay, y

1.4

0.0

0.5

—

0.6

1.8

—

1.2

0.9 ± 0.7

Tanner stage

3-4

IGF-I, SDS

−2.1

−0.7

−1.7

−1.4

−2.0

−1.1

0.0

−1.7

−1.0

−1.3 ± 0.7

Starting dose, mg/kg.d

—

0.037

0.032

0.043

—

0.028

—

0.028

0.035

0.034 ± 0.006

After 1 y of rhGH

Height gain, SDS

0.6

0.4

0.7

1.6

1.5

0.8

0.7

0.5

1.1

0.9 ± 0.4

PAH gain, SDS

0.6

0.7

2.2

—

0.6

—

0.9

1.0 ± 0.7

HV 0-1 y, cm/y

9.3

7.8

9.1

12.1

11.8

9.3

8.8

8.1

11.2

9.7 ± 1.6

BA delay, y

1.0

0.4

3.1

—

1.8

—

0.2

1.3 ± 1.2

Dose after 1 y, mg/kg.d

—

0.035

0.020

0.036

—

0.026

—

0.053

0.032

0.034 ± 0.011

After 2 y of rhGH

Height gain SDS 0-2 y

1.1

1.4

2.1

1.6

1.2

1.5 ± 0.4

PAH gain SDS 0-2 y

1.6

2.4

—

2.0 ± 0.6

HV 1-2 y, cm/y

6.4

6.9

8.2

7.1

9.9

7.7 ± 1.4

BA delay, y

2.0

3.5

1.1

—

2.2 ± 1.2

Dose after 2 y, mg/kg.d

0.036

0.012

0.037

—

0.028 ± 0.014

At stop of rhGH therapy

Age, y

18.8

14.53

Height, SDS^f

−0.6

−1.7

BA delay, y

—

Tanner stage

	1	2^a	4^b	8	11^c	12^d	20	23	24^e	Total
Variant	p.(Arg107Glyfs*31)	p.(Lys117Asn)	p.(Arg141Pro)	p.(Ala204Glu)	p.(Ala271Pro)	p.(Phe279Leu)
At start of rhGH therapy
Age, y	12.4	11.5	15.2	4.6	4.6	11.7	4.9	7.0	9.9	9.1 ± 3.9
Sex	Female	Male	Male	Male	Female	Female	Male	Male	Male
Height (SDS)	−3.2	−2.9	−2.5	−2.9	−3.4	−3.2	−3.0	−2.6	−3.3	−3.0 ± 0.3
HV, cm/y	4.4	4.0	4.5	8.1	5.3	4.0	6	4.6	4.6	5.1 ± 1.3
PAH, SDS	−2.9	−3.3	−2.4	—	−3.8	−2.2	—	—	−3.3	−3.0 ± 0.6
BA delay, y	1.4	0.0	0.5	—	0.6	1.8	—	—	1.2	0.9 ± 0.7
Tanner stage	3	1	3-4	1	1	1	1	1	1
IGF-I, SDS	−2.1	−0.7	−1.7	−1.4	−2.0	−1.1	0.0	−1.7	−1.0	−1.3 ± 0.7
Starting dose, mg/kg.d	—	0.037	0.032	0.043	—	0.028	—	0.028	0.035	0.034 ± 0.006
After 1 y of rhGH
Height gain, SDS	0.6	0.4	0.7	1.6	1.5	0.8	0.7	0.5	1.1	0.9 ± 0.4
PAH gain, SDS	0.6	0.7	2.2	—	—	0.6	—	—	0.9	1.0 ± 0.7
HV 0-1 y, cm/y	9.3	7.8	9.1	12.1	11.8	9.3	8.8	8.1	11.2	9.7 ± 1.6
BA delay, y	1.0	0.4	3.1	—	—	1.8	—	—	0.2	1.3 ± 1.2
Dose after 1 y, mg/kg.d	—	0.035	0.020	0.036	—	0.026	—	0.053	0.032	0.034 ± 0.011
After 2 y of rhGH
Height gain SDS 0-2 y	1.1		1.4	2.1	1.6		1.2			1.5 ± 0.4
PAH gain SDS 0-2 y	1.6		2.4	—	—		—			2.0 ± 0.6
HV 1-2 y, cm/y	6.4		6.9	8.2	7.1		9.9			7.7 ± 1.4
BA delay, y	2.0		3.5	1.1	—		—			2.2 ± 1.2
Dose after 2 y, mg/kg.d	0.036		0.012	0.037	—		—			0.028 ± 0.014
At stop of rhGH therapy
Age, y			18.8		14.53
Height, SDS^f			−0.6		−1.7
BA delay, y			—		—
Tanner stage			5		5

Table 3.

Open in new tab

Response to recombinant human growth hormone treatment in patients with (likely) pathogenic variants in GHSR

	1	2^a	4^b	8	11^c	12^d	20	23	24^e	Total
Variant	p.(Arg107Glyfs*31)	p.(Lys117Asn)	p.(Arg141Pro)		p.(Ala204Glu)			p.(Ala271Pro)	p.(Phe279Leu)
At start of rhGH therapy
Age, y	12.4	11.5	15.2	4.6	4.6	11.7	4.9	7.0	9.9	9.1 ± 3.9
Sex	Female	Male	Male	Male	Female	Female	Male	Male	Male
Height (SDS)	−3.2	−2.9	−2.5	−2.9	−3.4	−3.2	−3.0	−2.6	−3.3	−3.0 ± 0.3
HV, cm/y	4.4	4.0	4.5	8.1	5.3	4.0	6	4.6	4.6	5.1 ± 1.3
PAH, SDS	−2.9	−3.3	−2.4	—	−3.8	−2.2	—	—	−3.3	−3.0 ± 0.6
BA delay, y	1.4	0.0	0.5	—	0.6	1.8	—	—	1.2	0.9 ± 0.7
Tanner stage	3	1	3-4	1	1	1	1	1	1
IGF-I, SDS	−2.1	−0.7	−1.7	−1.4	−2.0	−1.1	0.0	−1.7	−1.0	−1.3 ± 0.7
Starting dose, mg/kg.d	—	0.037	0.032	0.043	—	0.028	—	0.028	0.035	0.034 ± 0.006
After 1 y of rhGH
Height gain, SDS	0.6	0.4	0.7	1.6	1.5	0.8	0.7	0.5	1.1	0.9 ± 0.4
PAH gain, SDS	0.6	0.7	2.2	—	—	0.6	—	—	0.9	1.0 ± 0.7
HV 0-1 y, cm/y	9.3	7.8	9.1	12.1	11.8	9.3	8.8	8.1	11.2	9.7 ± 1.6
BA delay, y	1.0	0.4	3.1	—	—	1.8	—	—	0.2	1.3 ± 1.2
Dose after 1 y, mg/kg.d	—	0.035	0.020	0.036	—	0.026	—	0.053	0.032	0.034 ± 0.011
After 2 y of rhGH
Height gain SDS 0-2 y	1.1		1.4	2.1	1.6		1.2			1.5 ± 0.4
PAH gain SDS 0-2 y	1.6		2.4	—	—		—			2.0 ± 0.6
HV 1-2 y, cm/y	6.4		6.9	8.2	7.1		9.9			7.7 ± 1.4
BA delay, y	2.0		3.5	1.1	—		—			2.2 ± 1.2
Dose after 2 y, mg/kg.d	0.036		0.012	0.037	—		—			0.028 ± 0.014
At stop of rhGH therapy
Age, y			18.8		14.53
Height, SDS^f			−0.6		−1.7
BA delay, y			—		—
Tanner stage			5		5

	1	2^a	4^b	8	11^c	12^d	20	23	24^e	Total
Variant	p.(Arg107Glyfs*31)	p.(Lys117Asn)	p.(Arg141Pro)		p.(Ala204Glu)			p.(Ala271Pro)	p.(Phe279Leu)
At start of rhGH therapy
Age, y	12.4	11.5	15.2	4.6	4.6	11.7	4.9	7.0	9.9	9.1 ± 3.9
Sex	Female	Male	Male	Male	Female	Female	Male	Male	Male
Height (SDS)	−3.2	−2.9	−2.5	−2.9	−3.4	−3.2	−3.0	−2.6	−3.3	−3.0 ± 0.3
HV, cm/y	4.4	4.0	4.5	8.1	5.3	4.0	6	4.6	4.6	5.1 ± 1.3
PAH, SDS	−2.9	−3.3	−2.4	—	−3.8	−2.2	—	—	−3.3	−3.0 ± 0.6
BA delay, y	1.4	0.0	0.5	—	0.6	1.8	—	—	1.2	0.9 ± 0.7
Tanner stage	3	1	3-4	1	1	1	1	1	1
IGF-I, SDS	−2.1	−0.7	−1.7	−1.4	−2.0	−1.1	0.0	−1.7	−1.0	−1.3 ± 0.7
Starting dose, mg/kg.d	—	0.037	0.032	0.043	—	0.028	—	0.028	0.035	0.034 ± 0.006
After 1 y of rhGH
Height gain, SDS	0.6	0.4	0.7	1.6	1.5	0.8	0.7	0.5	1.1	0.9 ± 0.4
PAH gain, SDS	0.6	0.7	2.2	—	—	0.6	—	—	0.9	1.0 ± 0.7
HV 0-1 y, cm/y	9.3	7.8	9.1	12.1	11.8	9.3	8.8	8.1	11.2	9.7 ± 1.6
BA delay, y	1.0	0.4	3.1	—	—	1.8	—	—	0.2	1.3 ± 1.2
Dose after 1 y, mg/kg.d	—	0.035	0.020	0.036	—	0.026	—	0.053	0.032	0.034 ± 0.011
After 2 y of rhGH
Height gain SDS 0-2 y	1.1		1.4	2.1	1.6		1.2			1.5 ± 0.4
PAH gain SDS 0-2 y	1.6		2.4	—	—		—			2.0 ± 0.6
HV 1-2 y, cm/y	6.4		6.9	8.2	7.1		9.9			7.7 ± 1.4
BA delay, y	2.0		3.5	1.1	—		—			2.2 ± 1.2
Dose after 2 y, mg/kg.d	0.036		0.012	0.037	—		—			0.028 ± 0.014
At stop of rhGH therapy
Age, y			18.8		14.53
Height, SDS^f			−0.6		−1.7
BA delay, y			—		—
Tanner stage			5		5

Abbreviations: BA, bone age; GH, growth hormone; GnRH, gonadotropin-releasing hormone; HV, annualized height velocity; IGF-I, insulin-like growth factor-I; PAH, predicted adult height; SDS, SD scores.

^aTesticular volume 6 to 8 mL at latest visit, 1 year after start of GH.

^bAromatase inhibitor from ages 13.0 to 17.8 years.

^cThelarche at 7.5 years, GnRH analogue from 7.5 to 12.3 years.

^dThelarche at 12.4 years, started GnRH analogue.

^eGonadarche at 12.2 years.

^fSDS for adult height (reference age, 21 years).

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