This depends on the type and size of tumour and is discussed in more detail in the relevant sections (acromegaly, prolactinoma). In general therapy has three aims:
1 Removal/control of tumour
(a) Surgery-usually via the trans-sphenoidal route is the treatment of choice. Large tumours are removed via the open transfrontal route. Radiotherapy is given if the tumour is incompletely removed.
(b) Radiotherapy-external three-beam technique, or occasionally via implant of yttrium needles. Used when surgery is impracticable as it rarely abolishes tumour mass.
(c) Medical-octreotide or bromocriptine sometimes shrinks specific types of tumour.
2 Reduction of excess hormone secretion. Usually obtained by surgical removal but sometimes by medical treatment, e.g. bromocriptine or octreotide alone. Prolactinomas respond with significant tumour shrinkage to bromocriptine. Acromegaly, however, responds less well. ACTH secretion usually cannot be controlled by medical means.
3 Replacement of hormone deficiencies.
Small turn ours producing no significant symptoms, pressure or endocrine effects may be observed with regular clinical, visual field, imaging and endocrine assessments.
Deficiency of hypothalamic releasing hormones or of pituitary trophic hormones may be either selective or multiple. There are, for example, rare congenital isolated deficiencies of LH/FSH and ACTH, some of which may be autoimmune in nature.
Multiple deficiencies usually result from tumour growth or other destructive lesions. With the latter there is generally a progressive loss of anterior pituitary function in the order shown from left to right in Fig. 16.6. GH and gonadotrophins, LH before FSH, are usually first affected. Rather than prolactin deficiency, hyperprolactinaemia occurs relatively early because of loss of tonic inhibitory control by dopamine. TSH and ACTH are usually last to be affected. Panhypopituitarism refers to deficiency of all anterior pituitary hormones; it is most commonly caused by pituitary turn ours, surgery or radiotherapy. Vasopressin and oxytocin secretion will only be significantly affected if the hypothalamus is involved, either by a hypothalamic tumour or by major suprasellar extension of a pituitary lesion.
Disorders causing hypopituitarism; pituitary and hypothalamic tumours are the commonest.
Symptoms and signs depend upon the extent of hypothalamicand/or pituitary deficiencies. Loss of libido, amenorrhoea and impotence are symptoms of gonadotrophin and thus gonadal deficiencies, while hyperprolactinaemia may cause galactorrhoea and hypogonadism. GH deficiency is clinically ‘silent’ except in children, though new evidence suggests markedly impaired wellbeing in adults. Secondary hypothyroidism and adrenal failure lead to tiredness, slowness of thought and action, and mild hypotension. Long-standing panhypopituitarism may give the classical picture of pallor with hairlessness (‘alabaster skin’).
Particular syndromes related to hypopituitarism include:
KALLMANN’S SYNDROME (isolated gonadotrophin deficiency, which leads to hypogonadism);
One sex-linked form has been shown to be due to abnormality of a cell adhesion molecule.
SHEEHAN’S SYNDROME. This situation, now rare, is pituitary infarction following postpartum haem orrhage.
PITUITARY APOPLEXY. A pituitary tumour may infarct or haemorrhage into itself. This may produce severe headache sometimes followed by acute lifethreatening hypopituitarism.
THE ‘EMPTY SELLA’ SYNDROME. This is sometimes due to a defect in the diaphragma and extension of the subarachnoid space (cisternal herniation) or may follow spontaneous infarction of a tumour. All or most of the sella turcica may be devoid of apparent pituitary tissue, but, despite this, pituitary function is usually normal, the pituitary being eccentrically placed and flattened against the floor or roof of the fossa.
Each axis of the hypothalamic-pituitary system may require separate investigation. The presence of normal gonadal function (ovulatory/menstruation or normal libido/erections) suggests that multiple defects of anterior pituitary function are unlikely.
Tests range from the simple basal levels, e.g. T. for the thyroid axis, to stimulatory tests for the pituitary, and tests of feedback for the hypothalamus. The insulin tolerance test is now less widely used, as basal 0900 h cortisol levels above 500 nmol litre'” reliably indicate an adequate reserve and levels below 100 nrnol litre'” predict an inadequate response. The intravenous Synacthen test, though indirect, has proved to be an adequate indicator of hypothalamic-pituitary adrenal status.
Steroid and thyroid hormones are essential for life. Both may be given as oral replacement drugs, aiming to restore the patient to clinical and biochemical normality. Sex hormone production may be replaced with androgens and oestrogens for symptomatic control; if necessary, human chorionic gonadotrophin (HCG, mainly LH) and metrotrophin (Pergonal) or urofollitrophin (Metrodin, mainly FSH) can be given if fertility is desired. Pulsatile GnRH (luteinizing hormone releasing hormone, LHRH) therapy is sometimes used where there is residual pituitary function but is expensive and timeconsuming. GH therapy may be given if necessary in the growing child and also produces substantial changes in body composition, work capacity and psychological well-being in acquired GH deficiency in the adult; long-term safety is not yet established and therapy may cost £4000-10000 per annum-at present it is only used in clinical trials. Two important warnings are necessary: Thyroid replacement should not commence until normal glucocorticoid function has been demonstrated or replacement steroid therapy initiated.
2 Glucocorticoid deficiency may mask impaired urine concentrating ability, diabetes insipidus only becoming apparent after steroid replacement.
Weight, exercise and stress
These are important factors in hypothalamic-pituitary function. Anorexia nervosa, the ‘slimming disease’ commonly affecting young females, is associated with major functional hypopituitarism. This often presents as amenorrhoea, without which the diagnosis is extremely unlikely. Anorexia is an extreme example, but more marginal degrees of underweight are a cause of secondary amenorrhoea and oligomenorrhoea, and are often unrecognized as a cause of sub fertility. Similar effects are seen in female athletes undergoing heavy training with menstrual irregularity that invariably reverts to normal when training stops. Stress, though difficult to define, also affects endocrine function, especially menstruation. Emotional deprivation in childhood is an important cause of growth retardation and may be mediated by reduced GH secretion.