Growth Hormone deficiency

Clinical features

In children:

Produces growth delay

In adults:

Produces vague symptoms with metabolic syndrome (decreased lean body mass, centripetal obesity, reduced exercise tolerance, impaired sense of well-being)
Hypogonadism: amenorrhea (women), loss of libido, infertility
Increased fat mass (especially central adiposity)
Decreased lean body mass
Decreased muscle strength
Decreased exercise performance
Decreased cardiac capacity
Decreased bone mineral density and increased risk of fracture
Atherogenic lipid profile
Thin, dry skin
Psychosocial problems and decreased quality of life

Fatigue
Depression
Anxiety
Impaired sleep
Social isolation

Qol-Aghda score McKenna et al., 1999

This is to check for adult GH deficiency.

The QoL-AGHDA score is interpreted as a symptom-burden measure:

more “Yes” answers mean worse disease-specific quality of life in adult growth hormone deficiency.

Score is calculated

The questionnaire has 25 items with yes/no responses.
Each “Yes” (problem present) scores 1 point; each “No” scores 0.
Total score = sum of “Yes” answers, giving a range from 0 to 25.

Interpretation

Low scores (closer to 0) indicate fewer problems and better quality of life.
High scores (closer to 25) indicate many symptoms and markedly impaired quality of life.
In population data from England and Wales, mean scores were about 6–7 in the general population vs 14–16 in untreated GHD patients, illustrating the degree of impairment in typical clinical cohorts.

Using the score in practice

Many services consider QoL-AGHDA alongside biochemistry when deciding on GH replacement; higher baseline scores are associated with a greater chance of meaningful improvement.
Guidance used by some regulators recommends reassessing about 9 months after starting GH and expecting at least a 7‑point reduction; if improvement is <7 points, continuation of treatment may not be justified.
Use the baseline score to document initial QoL impairment, then repeat periodically to track change over time.
A decrease in score over follow‑up represents improvement; an increase indicates deterioration or emerging problems that may warrant review of GH dosing, comorbidities, or psychosocial factors.

Item	Statement	Yes	No
1	I have to struggle to finish jobs	ㅤ	ㅤ
2	I feel a strong need to sleep during the day	ㅤ	ㅤ
3	I often feel lonely even when I am with other people	ㅤ	ㅤ
4	I have to read things several times before they sink in	ㅤ	ㅤ
5	It is difficult for me to make friends	ㅤ	ㅤ
6	It takes a lot of effort for me to do simple tasks	ㅤ	ㅤ
7	I have difficulty controlling my emotions	ㅤ	ㅤ
8	I often lose track of what I want to say	ㅤ	ㅤ
9	I lack confidence	ㅤ	ㅤ
10	I have to push myself to do things	ㅤ	ㅤ
11	I often feel very tense	ㅤ	ㅤ
12	I feel as if I let people down	ㅤ	ㅤ
13	I find it hard to mix with people	ㅤ	ㅤ
14	I feel worn out even when I’ve not done anything	ㅤ	ㅤ
15	There are times when I feel very low	ㅤ	ㅤ
16	I avoid responsibility if possible	ㅤ	ㅤ
17	I avoid mixing with people I don’t know well	ㅤ	ㅤ
18	I feel as if I am a burden to people	ㅤ	ㅤ
19	I often forget what people have said to me	ㅤ	ㅤ
20	I find it difficult to plan ahead	ㅤ	ㅤ
21	I am easily irritated by other people	ㅤ	ㅤ
22	I often feel too tired to do the things I ought to do	ㅤ	ㅤ
23	I have to force myself to do all the things that need doing	ㅤ	ㅤ
24	I often have to force myself to stay awake	ㅤ	ㅤ
25	My memory lets me down	ㅤ	ㅤ

Diagnosis

IGF-1 (somatomedin-C) level

An excellent integrative marker of average GH secretion because

It is not secreted in pulses like GH
IGF-I has a long half-life
Mediates most growth hormone actions

To assess for

High GH levels (acromegaly)

The recommended initial test (testing for elevated IGF-1 is extremely sensitive for acromegaly)

Low GH levels

Good test at post op to test for remission:

IGF-1 levels measured 6 weeks postoperatively can be used in most patients to assess remission
Although patients with mildly elevated IGF-I may yet normalize by 3–6 months

Normal levels depend on

Age (peaking during puberty) /2

Normal IGF-1 by age

Age (yrs)	Level (ng/ml)
1-5	49-327
6-8	52-345
9-11	74-551
12-15	143-996
16-20	141-903
21-39	109-358
40-54	87-267
>54	55-225

Gender

Oestrogen may suppress IGF-1 levels

Pubertal stage
Lab

Typical fasting levels by age are shown in

GGC normal values: 97-502 microG/L
A low IGF-1 in the presence of 3 or more other anterior pituitary hormone deficiencies in an otherwise healthy individual is a strong predictor of GH deficiency

Treatment should be considered without dynamic testing.

A low IGF-1 level may be present in 30% % of patients without GH deficiency → will need further dynamic tests of GH secretion.

Be aware

Assays may produce spurious or misleading results in patients with severe liver disease, uncontrolled diabetes, malnutrition, or those taking combined oral contraceptives

Dynamic/provocative testing

Is still warranted in that nearly 58.5% of severely GHD patient have total IGF-I levels within age-related normal range

Test	Protocol	GH diagnostic cutoff	Advantages	Additional comments
Insulin-induced hypoglycemia (ITT)	Regular insulin 0.1 units/kg IV. Measure glucose, GH, and cortisol at baseline and every 30 min for 3 h	5 ng/mL	Gold standard test. Simultaneously assesses HPA axis	Risk of serious side effects. Significant contraindications. Resource intensive
GHRH-Arg	GHRH 1 μg/kg. Arginine 0.5 g/kg over 30 min. Measure GH at baseline and every 30 min for 3 h	BMI <25: 11 ng/mL BMI 25–30: 8 ng/mL BMI >30: 4 ng/mL	Low risk of side effects	GHRH not commercially available in US. Low sensitivity for GH diagnosis in patients with hypothalamic etiologies of GHD
Glucagon stimulation test (GST)	Glucagon 1 mg i.m. or s.c. (1.5 mg for patients >90 kg), not i.v. Measure glucose and GH (and cortisol if desired) at baseline and every 30 min for 4 h	3 ng/mL	Glucagon readily available	Side effects (nausea, vomiting, headache)
GH secretagogues (ghrelin and ghrelin mimetics)	1 mcg/kg IV. Measure GH response every 15 min for 120 min	BMI <25: 7.3 ng/mL BMI 25–30: 2.9 BMI >30: 0.6	GH peak in 60 min	Oral formulation; side effect – bad taste (macimorelin)

Note: growth hormone stimulation test is more sensitive and specific for GH deficiency than measuring basal GH levels

Considered the “gold standard” diagnostic test for GHD
Also used in testing cortisol reserve
Results:

Insulin administration should

Dec. IGF1
Inc. in GH

Severe GH deficiency: peak level < 10 mU/L or < 3 μg/L

CI (Due to hypoglycemia inducing)

Coronary artery disease
Seizures
Elderly

False positive with

Obesity

GNRH-arginine stimulation and glucagon stimulation test which have a higher sensitivity than IGFBP-3 levels.

Treatment

GH replacement therapy

CI in patient with active cancer (other than pituitary tumour) (theoretical risk)
NICE 2003: Recombinant human growth hormone (somatropin) treatment

To be used if it fulfil following criteria:

Severe GH deficiency, defined as a

Peak GH response of less than 9 mU/litre (3 ng/ml) during an insulin tolerance test or
Cross-validated GH threshold in an equivalent test.

Impairment of quality of life (QoL), as demonstrated by a reported score of at least 11 in the disease-specific 'Quality of life assessment of growth hormone deficiency in adults' (QoL-AGHDA) questionnaire.
They are already receiving treatment for any other pituitary hormone deficiencies as required.

Reassessment

QoL status of people who are given GH treatment should be re-assessed 9 months after the initiation of therapy

GH treatment should be discontinued for those people who demonstrate a QoL improvement of less than 7 points in QoL-AGHDA score

Reference

Reed 2013