Acromegaly

Should be done by specialists

The objective of treatment in acromegaly is not only to alleviate symptoms, improve quality of life, and prevent complications but also to reverse the increased (two to threefold) mortality from vascular and respiratory disease and colon cancer. That this can be achieved if "target" basal growth hormone concentrations of [is less than] 5 mU/l (2.5 ng/ml) are reached has been shown,[1 2] with the proviso that serum insulin-like growth factor 1 (IGF-1) values may need to be reduced to the normal age-related reference range.[3] Transsphenoidal adenomectomy is the most rapid means of reducing serum growth hormone and IGF-1 in acromegaly. The question then arises of how effective surgery is at achieving the target growth hormone and IGF-1 values. Subsidiary issues are: (a) what determines the outcome of surgery? (b) what is the relapse rate? (c) what is the complication rate? and (d) what is the most cost effective service provision?

Surgical outcomes in terms of safe target growth hormone concentrations have recently been reported in over 1000 patients[3-11] All these series show that large tumour size, together with the degree of extrasellar extension (particularly lateral), and high preoperative serum growth hormone concentrations are major determinants of initial surgical failure. Thus, in 1999 a patient with a microadenoma ([is less than] 1 cm in diameter) or mesoadenoma ([is greater than] 1 cm but confined to the sella turcica) should have upwards of 80% chance of successful adenomectomy. However, the surgical outcome for those with a macroadenoma ([is greater than] 1 cm with extension outside the sella) is by no means so successful, with at best 60% achieving the safe target growth hormone concentration. However, even for macro-adenomas it is important to reduce the serum growth hormone level as much as possible, since the outcome of adjuvant treatment with somatostatin analogues, dopamine agonists, or radiotherapy is directly related to the pretreatment growth hormone concentration.[8]

What is new in the recent reports is the demonstration that the outcome of surgical treatment for acromegaly is related to the experience of the operator. In the study from Manchester,[8] where 73 patients were operated on by any of nine surgeons, fewer than 20% of patients achieved a growth hormone [is less than] 5 mU/l, an outcome the authors attribute to the few cases operated on by any one surgeon. Likewise, the success rate in Birmingham was also low at 33%,[5] where eight surgeons were involved. However, in Oxford, Newcastle, or St Bartholomew's Hospital, London (each of which had only one surgeon performing pituitary surgery), a patient had a chance of a successful adenomectomy of 42-56%.[4 6 10] Interestingly, Yamada et al in Japan report a doubling of the success rate when a single surgeon started operating on their patients with acromegaly (from 37% to 81%).[7] Similarly, the proportion of patients achieving the target basal growth hormone concentration of [is less than] 5 mU/l in Birmingham doubled (from 33% to 64%) when a single surgeon took over all operations.[11] The Oxford authors also report improvement in results of a single surgeon as his experience grew over 20 years.[10]

The relapse rate 5-10 years after successful initial surgery is low, at 0-7%, and major complication rates (leaks of cerebrospinal fluid, meningitis, permanent diabetes insipidus, new pituitary hypofunction) are also low, at less than 10%. Thus, in experienced centres adenomectomy for small adenomas secreting growth hormone is effective and safe and has low relapse and complication rates. However, even in the best hands some 15-20% of microadenomas and 40-50% of macroadenomas will not achieve safe growth hormone concentrations after initial surgery and will require additional long term adjunctive treatment (radiotherapy or medical treatment). Since adjunctive treatment is expensive, and may be required for many years, it is dearly in everyone's interests for people with acromegaly to be operated on by experienced pituitary surgeons. It is difficult to measure cost of treatment, but the cost of the most effective medical treatment, somatostatin analogues, alone is around 12 000 [pounds sterling] per patient per year.

Endocrinologists are normally responsible for advising patients with acromegaly. Since this is usually pituitary surgery first they should choose the "best" surgeon, even if this means referring outside their immediate local service. Not only will this be best for the patient but it will also result in the most effective use of NHS resources since fewer patients will require adjuvant treatment. Pressure must be exerted to put in place a system whereby many fewer centres and surgeons in the United Kingdom operate on patients with acromegaly and other pituitary tumours. Where this has happened, in Japan[7] and in Birmingham,[11] the effect has been dramatic.

How many centres should there be? Our own view is that the minimum population that should be served is 5 000 000, which would produce 20-30 new cases of acromegaly a year. With two surgeons per centre this would mean no more than 10 centres in the UK.

[1] Bates AS, van't Hoff W, Jones JM, Clayton RN. An audit of outcome of treatment in acromegaly. Quart J Med 1993;86:293-9.

[2] Orme SM, McNally RJQ Cartwright RA, Belchetz PE. Mortality and cancer incidence in acromegaly: a retrospective cohort study. J Clin Endocrinol Metab 1998;83:2730-4.

[3] Swearingen B, Barker FG, Katznelson L, Biller BMK, Grinspoon S, Klibanski A, et al. Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 1998;83: 3419-26.

[4] Osman IA, James RA, Chatterjee S, Mathias D, Kendall-Taylor P. Factors determining the long-term outcome of surgery for acromegaly. Quart J Med 1994;87:617-23.

[5] Jenkins S, O'Brien I, Johnson A, Shakespear R, Sheppard MC, Stewart PM. The Birmingham pituitary database: auditing the outcome of the treatment of acromegaly. Clin Endocrinol 1995;43:517-22.

[6] Sheaves R, Jenkins P, Blackburn P, Huneidi AH, Afshar F, Medbak S, et al. Outcome of transsphenoidal surgery for acromegaly using strict criteria for surgical cure. Clin Endocrinol 1996;45:407-13.

[7] Yamada S, Aiba T, Takada K, Ozawa Y, Shimizu T, Sawano S, Shishiba Y, Sano T. Retrospective analysis of long-term surgical results in acromegaly: preoperative and postoperative factors predicting outcome. Clin Endocrinol 1996;45:291-8.

[8] Lissett CA, Peacey SR, Laing I, Tetlow L, Davis JRE, Shalet SM. The outcome of surgery for acromegaly: the need for a specialist pituitary surgeon for all types of growth hormone secreting adenomas. Clin Endocrinol 1998;49:653-7.

[9] Abosch A, Tyrell JB, Lamborn KR, Hannegan LT, Applebury CB, Wilson CB. Trans sphenoidal microsurgery for growth hormone secreting pituitary adenomas: initial outcome and long-term results. J Clin Endocrinol Metab 1998;83:3411-18.

[10] Ahmed S, Elsheikh M, Page RCL, Adams CBT, Wass JAH. Outcome of transphenoidal surgery for acromegaly and its relationship to surgical experience. Clin Endocrinol 1999;50:561-7.

[11] Gittoes NJL, Johnson AP, Sheppard MC, Stewart PM. Outcome of surgery for acromegaly: the experience of a single surgeon. Quart J Med (in press).

R N Clayton professor of medicine

Keele University and North Staffordshire Hospital, Stoke on Trent ST4 7QB

P M Stewart professor of medicine

Queen Elizabeth Hospital, Birmingham B15 2TH

S M Shalet professor of endocrinology

Christie Hospital, Manchester M20 4BX

J A H Wass professor of endocrinology

Radcliffe Infirmary, Oxford OX2 6HE

COPYRIGHT 1999 British Medical Association
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