Dr Steve Ball
Royal Victoria Infirmary, Newcastle

Hypopituitarism is a complex state, occurring in different patterns in different individuals. All hormones need to be replaced properly and Growth hormone (GH) can't be looked at in isolation. All patients are different, but common characteristics of adults needing GH replacement are: the presence of central fatty mass; an adverse lipid profile (high low-density lipoprotein cholesterol (LDLc), low high-density lipoprotein cholesterol (HDLc) and high fibrinogen) and insulin resistance. These three increase cardiovascular risk. Additional characteristics include reduced muscle strength, reduced bone mass, fatigue and poor concentration.

Treatment with GH:

• Reduces body fat;
• Decreases coronary heart disease risk factors. In short-term (1-10 years) studies there have been improvements in body composition, lipid profile, insulin resistance, fibrinolytic in thrombotic cascade in some but not all patients;
• Increases bone mass after 18-24 months; and
• Improves sense of well-being. Patients say they feel better but measuring improvement is difficult.

What indicates GH deficiency (GHD)?

The indications are the signs and symptoms of GHD with a measured peak GH of <9 mU/l, measured either by an insulin tolerance test (ITT) or glucagons tolerance test, or an Arg-GRF test. Children (under 16 years) can be treated when only GH is deficient. GHD acquired in adulthood is indicated by at least one other hormone deficiency (not including Prolactin). Contraindications include active malignancies and pregnancy.

GH replacement therapy is self-administered via a daily Subcutaneous injection. Natural GH levels vary throughout life and reduce with age. The correct dose is calculated by a dose titration method, which mimics the natural process. Children's doses can be measured by their growth. In adults, blood tests measure Insulin-like Growth Factor-1 (IGF-1) levels, which indicate how much GH the body is receiving. Initially, blood samples are taken every 2-6 weeks to correct the dose to the required level. Dosage is adjusted to reflect normal populations' maximum/minimum IGF-1 levels at different ages. A standard deviation (SD) score is used where 0 = normal. Doses are adjusted on an individual basis and over-treatment avoided. It takes time to get the dose right, but it will be constant for a long time after. The average dose is 0.2-0.4 mg.

In Newcastle, patients are selected for treatment if their signs and symptoms match the criteria. A pre-assessment stage checks that there is optimum replacement of all other hormones. Other possible causes of symptoms such as tiredness and weight gain are assessed. GHD is confirmed via ITT or Arg-GRF tests and if a GH level of less than 9 mU/l is shown then initial treatment begins. The introductory phase involves questionnaires, blood tests and dose titration. After 6 months the results are reviewed and treatment is continued if improvement is shown and the patient wants to continue.

There are some negative public perceptions of GH treatment. If you are travelling abroad with GH consider carrying an authenticated letter explaining the need for treatment.

Comments arising from the audience's questions included:

• There is no evidence that GH makes you lose weight.
• Currently, the ends of the ranges of IGF-1 levels are known, and the 'middle of the goal' is often aimed for. Time will ratify precisely what the correct target is/should be.
• Dr Ball recommended patients avoid purchasing supplies from the Web.
  (NB: The Pituitary Foundation has complained to the Medicines Control Agency and the Advertising Standards Agency about one of these, known as Orangeburst.)
• Patients may be taken off oral HRT as high dose oestrogens can affect how GH works.
• The current average cost of GH treatment is £2000-£4000 per annum, depending on dosage.
• There is an increased risk of tumour growth (cancer risk) for people with IGF-1 values at the top of the reference range. Current evidence indicates GH therapy to be safe and effective when administered responsibly.
• If your health authority won't fund GH, continue to lobby, contact your MP and support The Pituitary Foundation's work with NICE - there is no easy answer.