Table 4, Clinical evidence summary: Dose A (20 mg 0800 h, 10 mg 1600 h) vs Dose B (10 mg 0800 h and 1600 h) vs Dose C (10 mg 0800 h and 5 mg 1600 h) – SF-36 Outcomes - Routine pharmacological management of secondary and tertiary adrenal insufficiency

Table 4Clinical evidence summary: Dose A (20 mg 0800 h, 10 mg 1600 h) vs Dose B (10 mg 0800 h and 1600 h) vs Dose C (10 mg 0800 h and 5 mg 1600 h) – SF-36 Outcomes

Outcomes	№ of participants (studies) Follow-up	Certainty of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
SF36 - Physical functioning - A vs B Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Physical functioning - A vs B was 79.5 points	MD 9 points higher (9.74 lower to 27.74 higher)
SF36 - Physical functioning - A vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Physical functioning - A vs C was 80.5 points	MD 8 points higher (10.99 lower to 26.99 higher)
SF36 - Physical functioning - B vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Physical functioning - B vs C was 80.5 points	MD 1 points lower (22.26 lower to 20.26 higher)
SF36 - Role Physical – A vs B Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Role Physical - A vs B was 62.5 points	MD 15 points higher (17.36 lower to 47.36 higher)
SF36 - Role Physical - A vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Role Physical - A vs C was 55 points	MD 22.5 points higher (14.15 lower to 59.15 higher)
SF36 - Role Physical - B vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Role Physical - B vs C was 55 points	MD 7.5 points higher (28.29 lower to 43.29 higher)
SF36 - Bodily pain - A vs B Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Bodily pain - A vs B was 82.5 points	MD 2.6 points higher (16.67 lower to 21.87 higher)
SF36 - Bodily pain - A vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Bodily pain - A vs C was 76.5 points	MD 8.6 points higher (10.2 lower to 27.4 higher)
SF36 - Bodily pain - B vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Bodily pain - B vs C was 76.5 points	MD 6 points higher (14.43 lower to 26.43 higher)
SF36 - General health - A vs B Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^d	-	The mean SF36 - General health - A vs B was 61.8 points	MD 1 points higher (13.06 lower to 15.06 higher)
SF36 - General health - A vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^d	-	The mean SF36 - General health - A vs C was 59.8 points	MD 3 points higher (11.81 lower to 17.81 higher)
SF36 - General health - B vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^d	-	The mean SF36 - General health - B vs C was 59.8 points	MD 2 points higher (10.3 lower to 14.3 higher)
SF36 - Vitality - A vs B Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^d	-	The mean SF36 - Vitality - A vs B was 47.5 points	MD 15 points higher (6.14 lower to 36.14 higher)
SF36 - Vitality - A vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^d	-	The mean SF36 - Vitality - A vs C was 44 points	MD 18.5 points higher (3.15 lower to 40.15 higher)
SF36 - Vitality - B vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^d	-	The mean SF36 - Vitality - B vs C was 44 points	MD 3.5 points higher (17.46 lower to 24.46 higher)
SF36 - Social functioning - A vs B Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Social functioning - A vs B was 92.5 points	MD 2.5 points lower (16.11 lower to 11.11 higher)
SF36 - Social functioning - A vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Social functioning - A vs C was 85 points	MD 7.5 points higher (6.61 lower to 21.61 higher)
SF36 - Social functioning - B vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Social functioning - B vs C was 85 points	MD 7.5 points higher (6.61 lower to 21.61 higher)
SF36 - Role emotional - A vs B Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^e	-	The mean SF36 - Role emotional - A vs B was 66.6 points	MD 16.7 points higher (17.35 lower to 50.75 higher)
SF36 - Role emotional - A vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^e	-	The mean SF36 - Role emotional - A vs C was 73.3 points	MD 10 points higher (23.77 lower to 43.77 higher)
SF36 - Role emotional - B vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^e	-	The mean SF36 - Role emotional - B vs C was 73.3 points	MD 6.7 points lower (42.81 lower to 29.41 higher)
SF36 - Mental health - A vs B Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Mental health - A vs B was 80 points	MD 0.4 points lower (16.49 lower to 15.69 higher)
SF36 - Mental health - A vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Mental health - A vs C was 80 points	MD 0.4 points lower (15.83 lower to 15.03 higher)
SF36 - Mental health - B vs C Scale from: 0 to 100 follow-up: 6 weeks (higher is better)	10 (1 RCT)	⨁◯◯◯ Very low^a^,^b^,^c	-	The mean SF36 - Mental health - B vs C was 80 points	MD 0 points (15.92 lower to 15.92 higher)

Outcomes

№ of participants (studies) Follow-up

Certainty of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with comparator

Risk difference with intervention

SF36 - Physical functioning - A vs B

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Physical functioning - A vs B was 79.5 points

MD 9 points higher

(9.74 lower to 27.74 higher)

SF36 - Physical functioning - A vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Physical functioning - A vs C was 80.5 points

MD 8 points higher

(10.99 lower to 26.99 higher)

SF36 - Physical functioning - B vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Physical functioning - B vs C was 80.5 points

MD 1 points lower

(22.26 lower to 20.26 higher)

SF36 - Role Physical – A vs B

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Role Physical - A vs B was 62.5 points

MD 15 points higher

(17.36 lower to 47.36 higher)

SF36 - Role Physical - A vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Role Physical - A vs C was 55 points

MD 22.5 points higher

(14.15 lower to 59.15 higher)

SF36 - Role Physical - B vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Role Physical - B vs C was 55 points

MD 7.5 points higher

(28.29 lower to 43.29 higher)

SF36 - Bodily pain - A vs B

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Bodily pain - A vs B was 82.5 points

MD 2.6 points higher

(16.67 lower to 21.87 higher)

SF36 - Bodily pain - A vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Bodily pain - A vs C was 76.5 points

MD 8.6 points higher

(10.2 lower to 27.4 higher)

SF36 - Bodily pain - B vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Bodily pain - B vs C was 76.5 points

MD 6 points higher

(14.43 lower to 26.43 higher)

SF36 - General health - A vs B

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^d

The mean SF36 - General health - A vs B was 61.8 points

MD 1 points higher

(13.06 lower to 15.06 higher)

SF36 - General health - A vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^d

The mean SF36 - General health - A vs C was 59.8 points

MD 3 points higher

(11.81 lower to 17.81 higher)

SF36 - General health - B vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^d

The mean SF36 - General health - B vs C was 59.8 points

MD 2 points higher

(10.3 lower to 14.3 higher)

SF36 - Vitality - A vs B

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^d

The mean SF36 - Vitality - A vs B was 47.5 points

MD 15 points higher

(6.14 lower to 36.14 higher)

SF36 - Vitality - A vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^d

The mean SF36 - Vitality - A vs C was 44 points

MD 18.5 points higher

(3.15 lower to 40.15 higher)

SF36 - Vitality - B vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^d

The mean SF36 - Vitality - B vs C was 44 points

MD 3.5 points higher

(17.46 lower to 24.46 higher)

SF36 - Social functioning - A vs B

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Social functioning - A vs B was 92.5 points

MD 2.5 points lower

(16.11 lower to 11.11 higher)

SF36 - Social functioning - A vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Social functioning - A vs C was 85 points

MD 7.5 points higher

(6.61 lower to 21.61 higher)

SF36 - Social functioning - B vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Social functioning - B vs C was 85 points

MD 7.5 points higher

(6.61 lower to 21.61 higher)

SF36 - Role emotional - A vs B

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^e

The mean SF36 - Role emotional - A vs B was 66.6 points

MD 16.7 points higher

(17.35 lower to 50.75 higher)

SF36 - Role emotional - A vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^e

The mean SF36 - Role emotional - A vs C was 73.3 points

MD 10 points higher

(23.77 lower to 43.77 higher)

SF36 - Role emotional - B vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^e

The mean SF36 - Role emotional - B vs C was 73.3 points

MD 6.7 points lower

(42.81 lower to 29.41 higher)

SF36 - Mental health - A vs B

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Mental health - A vs B was 80 points

MD 0.4 points lower

(16.49 lower to 15.69 higher)

SF36 - Mental health - A vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Mental health - A vs C was 80 points

MD 0.4 points lower

(15.83 lower to 15.03 higher)

SF36 - Mental health - B vs C

Scale from: 0 to 100

follow-up: 6 weeks (higher is better)

(1 RCT)

⨁◯◯◯

Very low^a^,^b^,^c

The mean SF36 - Mental health - B vs C was 80 points

MD 0 points

(15.92 lower to 15.92 higher)

: Explanations
a: Downgraded by 2 increments due to very serious risk of bias: Study authors do not provide necessary details around recruitment and randomisation so outcomes are at very high risk of selection bias..
b: Downgraded by 1 increment as population includes males only [Female subjects were excluded because of the potential effect of oestrogen status on corticosteroid-binding globulin (CBG) levels]
c: Downgraded by 2 increments as confidence interval crossed both MIDs (+/− 3)
d: Downgraded by 2 increments as confidence interval crossed both MIDs (+/− 2)
e: Downgraded by 2 increments as confidence interval crossed both MIDs (+/− 4)

From: Routine pharmacological management of secondary and tertiary adrenal insufficiency

Cover of Routine pharmacological management of secondary and tertiary adrenal insufficiency

Routine pharmacological management of secondary and tertiary adrenal insufficiency: Adrenal insufficiency: identification and management: Evidence review G.

NICE Guideline, No. 243.

London: National Institute for Health and Care Excellence (NICE); 2024 Aug.

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