Pituitary Tumours: Recommendations for Service Provision and Guidelines for Management of Patients

 

## Prescribing for patients with pituitary disease
GPs may be asked to prescribe appropriate drugs for these patients in the community, provided adequate shared care treatment plans have been agreed locally with both clinicians and purchasing authorities. Experimental treatments should usually remain under specialist prescription. Provision of routine medication may be expected through the GP, once the patient's condition and therapeutic regimen have been optimised.
Objectives of treatment are broadly defined as:

## ?
Restoration of a feeling of well-being.

## Follow-up
Visual field assessment: regular visual assessment (acuity and fields) is required. Radiological: early imaging to detect residual tumour, usually 2-3 months post-operatively. In some circumstances, an immediate post-operative scan may be required. Follow-up to detect tumour regrowth is required, a suggested schedule being 6-12 months, then at 1-5 year intervals.
Endocrinological: early assessment of Cortisol requirement may be performed before discharge. In many patients glucocorticoid cover is maintained until first post-operative assessment, usually 6-12 weeks after surgery. Improvement or normalisation of deficiencies may occur and requires assessment. If deficiency persists at 12 weeks, this is likely to be permanent.

## External irradiation
Post-operative Practice varies from routine use post-operatively to withholding external irradiation until recurrence is apparent. The possibility of external irradiation should be considered for surgically treated cases if tumour removal is incomplete. Further data are required to identify patients with a high risk of recurrence to enable post-operative external irradiation to be confined to this high-risk group.

## Follow-up
Visual assessment: as for surgery alone.
Radiological: the frequency of scans is currently uncertain; late recurrence can occur, and clinical circumstances should dictate frequency of scans. Endocrinological: the effects of external irradiation are most marked in the first 2 years and slowly progressive thereafter. Lifelong hormonal follow-up is required, optimal intervals are unknown but suggested at 6 months, 1 year, 2 years, then bi/triennially. helps diagnose hypogonadism as these may be inappropriately low.
Growth hormone (GH)
Children: children suspected of GH deficiency require dynamic tests in a specialist paediatric endocrine centre. Recommended dynamic tests include the insulin hypoglycaemia test, which is not recommended for children under 10 years. Alternatives are glucagon and arginine stimulation. Sex hormone priming is necessary in hypogonadal and pre-or peri-pubertal patients. Adults: GH reserve may be assessed during insulin hypoglycaemia or the glucagon test. Other tests (eg insulin-like growth factor (IGF)-l or the binding protein (BP) IGFBP-3) may be of value.

## Vasopressin (adh)
If the 24-hour urine volume is less than 3 litres and plasma sodium is normal, diabetes insipidus is unlikely. A water deprivation test, followed by desmopressin administration is usually necessary to confirm ADH deficiency. Adequate glucocorticoid replacement must be provided to avoid spurious results.
Therapeutic options ACTH Hydrocortisone is the preferred glucocorticoid replacement. Prednisolone is acceptable, but not recommended for children. Dosage is adjusted individually on clinical and biochemical grounds. Patients must be educated to increase oral glucocorticoids (2-4 fold) with illness and to seek medical advice for systemic therapy if necessary. Self-administered parenteral hydrocortisone may be useful for travel abroad.
MedicAlert or SOS bracelets/pendants are recommended in addition to carrying a steroid card. TSH L-thyroxine is the treatment of choice, the dosage being monitored clinically and by serum thyroid hormone levels.

## Gonadotrophins (lh and fsh)
In women, cyclical oestrogen and progestogen, or lower-dose sequential hormone replacement therapy should be given until at least age 50, assuming there is no contraindication. Treatment of women with infertility and pubertal induction in both girls and boys should be performed in centres with appropriate expertise.
Testosterone replacement therapy in men can be given orally, by intramuscular injection, patches, or implant. Stimulation of spermatogenesis will require input from specialist centres.
Journal of the Royal College of Physicians of London Vol. 31 No. 6 November/December 1997 R N Clayton and J A H Wass GH Children: biosynthetic GH is given under supervision from centres with specialist auxological and endocrine expertise. Regionally agreed, shared care protocols should be in place to facilitate primary care involvement.
Adults: GH has potential beneficial actions after growth has ceased; long-term efficacy of GH therapy in adult GH deficiency is currently being evaluated. ADH Desmopressin is the treatment of choice, given intranasally or orally in divided doses. Parenteral therapy is also available.
Peri-operative management Patients should be managed jointly by the surgeon and endocrinologist. Systemic glucocorticoid therapy is usually required. The hydrocortisone dose should be reduced over several days to a maintenance regimen, until post-operative pituitary endocrine evaluation. Antibiotic prophylaxis against meningitis is advisable with transsphenoidal surgery.
Post-operative diabetes insipidus is common, but often transient. It may be managed by fluid replacement, but desmopressin should be given if it is prolonged (>2 days).
Long-term care and follow-up Once replacement therapy has been optimised, patients should receive long-term specialist follow-up at 6-12 monthly intervals. Testing for additional pituitary hormone deficiency should be performed at regular intervals (annually) in patients receiving radiotherapy since hormone deficiencies may develop years later.

## Management of craniopharyngiomas and peripituitary tumours

# Introduction
The incidence of craniopharyngioma is approximately 9% of all intracranial tumours in childhood. Poor prognostic features are a young age, presentation with hydrocephalus, and hypothalamic involvement. First presentation may be in adult life.

## Presentation
Acute presentation is usually with raised intracranial pressure, one-third of patients requiring urgent surgical decompression. Visual impairment is common, and usually severe before it is recognised; squints, which may be non-paretic, may also occur.
Presentation with growth failure due to an endocrine deficiency occurs in 20-30% of cases.

## Diagnostic tests
When possible, the child should be assessed by an ophthalmologist, psychologist, neurologist and endocrinologist. Pre-operative endocrine assessment of thyroid status, adrenal reserve, and posterior pituitary function is required, and a pre-operative MRI scan is mandatory.
Therapeutic options plus outcomes Acutely raised intracranial pressure will require urgent surgery. The most effective form of therapy is an attempt at complete excision, usually by craniotomy. Recurrence after initial surgical procedure is common. Morbidity figures are similar for complete resection and subtotal excision followed by elective radiotherapy. Preservation of hypothalamic function should be one of the most important aims of treatment.
Radiotherapy may prevent or slow down the rate of growth following partial surgical resection, but should not usually be given to children younger than 6-7 years.
The treatment of recurrent cysts is by surgical drainage, installation of local chemotherapy or intracavitary radiation using yttrium.

## Long-term care and follow-up
Follow-up is usually coordinated by an endocrinologist, with input from specialists in neurology, psychology and ophthalmology. Transfer to an adult endocrinologist will be required as lifelong specialist follow-up is essential. Gynaecological advice should be sought early.
Endocrine follow-up will include the management of hypothalamic obesity, the re-establishment of normal statural growth with growth hormone replacement treatment as well as the establishment of puberty and maintenance of sexual maturation.
Hypothalamic syndrome, particularly diabetes insipidus in combination with absent thirst, requires careful monitoring. Fluid balance crises may be associated with intercurrent illness.
Psychological and educational difficulties caused by partial sightedness, blindness and neurological impairment require specialised resources. Specialist long-term follow-up is indicated in all patients, with regular measurement of urinary free and/or plasma Cortisol day profiles.

## Follow-up
Patients with Cushing's syndrome of all causes require regular follow-up in a specialist endocrine clinic at least until complete recovery of the normal hypothalamo-pituitary-adrenal axis. Patients who have had adrenal adenomas removed might be discharged to GP care at this stage but all other causes require lifelong follow-up to detect recurrence, development of Nelson's syndrome, and to monitor steroid replacement therapy Tests of other pituitary function (see section on functional testing and replacement therapy).

## Objectives of treatment
Restoration of GH secretion to currently acceptable safe values (mean value <5 mu/1), normalisation of IGF-1 and to retain normal pituitary function.

## Therapeutic options plus outcome
No active treatment only when long-term sequelae unlikely to modify prognosis.

## Transsphenoidal adetiomectomy
Treatment of choice for most cases is transsphenoidal adenomectomy. Serum GH levels to aim for are basal mean value <5 mu/1, suppressing to <2 mu/1 after glucose loading. Assess 6-12 weeks post-surgery. If surgery leaves some residual tumour, options include repeat surgery, pituitary radiotherapy, medical treatment or all three.

## Medical treatment
If long-term medical treatment required, first consider bromocriptine up to 20 mg/day. Efficacy of bromocriptine can be determined within 3 months (only effective in 10-20%); if ineffective, use somatostatin analogue. Somatostatin analogue: indicated in bromocriptine non-responders, those in whom surgery is contraindicated or unsuccessful, and while awaiting the effects of pituitary radiotherapy. It is effective in 40-60% of cases. Watch for gallstone development. months, then annually with monitoring of prolactin levels. Repeat MRI at 3-6 months, then annually until prolactin normalised and/or evidence of maximal tumour shrinkage. Most patients will require long-term treatment, but continue reducing and possibly stopping every 3-5 years to check for the small number who maintain normal prolactin levels.
Treat hypogonadism, hypoadrenalism and hypothyroidism, but check need for long-term replacement when prolactin normalised and/or tumour shrinkage, usually by 6-9 months.
Consider surgery and/or radiotherapy if patient intolerant of drugs, or if prolactin levels/tumour size continue to increase despite maximal dopamine agonist therapy. Consider surgery in those presenting with visual or cranial nerve problems if no improvement occurs within 7 days of initiation of dopamine agonist treatment.

## Outcomes
Dopamine agonist treatment Normoprolactinaemia and ovulatory cycles are restored in over 80% of women with idiopathic hyperprolactinaemia or microprolactinomas within 6 months, and up to 90% within one year of starting therapy. Most (up to 90%) prolactinomas show significant reduction in size, often maximal by 6 months but more slowly in a significant number. Visual field improvement occurs in 80-90%.

## Surgery
Different series report 'cure' rates after surgery with preservation of normal pituitary function in 40-90% of cases if the pre-operative prolactin level is <10,000 mu/1. In patients whose prolactin has retnrned to normal after surgery, a recurrence rate of 10-40% has been reported at 5 years (usually in the first year). Surgery for macroprolactinomas is less often (30-60%) associated with normalisation of prolactin, and there is a higher incidence of hypopituitarism and recurrence.

## Pregnancy
Women on bromocriptine or quinagolide should generally stop therapy and obtain a pregnancy test if a period is missed. Consider continuation if macroprolactinoma present. There are no adverse effects of bromocriptine on mother or fetus when used before or during pregnancy. Clinically significant expansion occurs in only 1-5% of microprolactinomas and up to 10% of macroprolactinomas during pregnancy. Patients should be checked every two months throughout pregnancy for signs or symptoms of tumour expansion. If they occur, use dopamine agonists. Surgery is an option for those who are intolerant, fail to respond, or prefer this approach. Breast feeding: women with macroprolactinomas should be advised that there may be a risk of enlargement of the adenoma if they breast feed.
[table] 3: At the specialist centre, which may be located across several sites, management plans should be agreed jointly by endocrinologists, pituitary surgeons and radiotherapists. Options include joint clinics or case discussion sessions. Neuroscience units should have formal links with an endocrinologist. Joint surgical/endocrinological review is desirable at least within the first 12 months after diagnosis and treatment. 4 Adequate facilities for visual field and acuity testing must be available. These can be managed by [/table]
[table] ?: Relief of pressure symptoms. Treatment of hormone excess symptoms.Restoration of or substitution for specific system deficits.Prevention of tumour regrowth.Lowering of increased long-term mortality.Formal test of visual acuity and fields. MRI scan to delineate size and anatomical relations of tumour is important for determining the surgical approach. [/table]