Pituitary Tumour

PITUITARY TUMOUR

Clinical Presentation

The presetting features are due to:

The size of the tumour
Endocrine disturbance

Headache occurs principally in patients with acromegaly and is uncommon in other type of pituitary tumour.

Visual failure

Careful assessment of the visual fields, the visual acuity and the optic fundi are essential. Suprasellar extension of the pituitary tumour causes compression of the optic chiasm resulting in a bitemporal hemianopia. The bitemporal hemianopia initially involves the upper quadrants, before extending to the lower quadrants of the visual field. If the chiasm is prefixed, that is place more anteriorly than usual, a homonymous hemianopia may occur due to compression of the optic tract. Bilateral central scotomas result from the tumour pressing on the posterior part of the chiasm where the macular fibres decussate. Primary optic atrophy will be evident in patients with long standing compression of the chiasm.

Ocular palsies occur in about 10% of patients and are due to invasion of the cavernous sinus. The 3rd nerve is the most frequently affected, followed by the 6th and 4th cranial nerves. Facial pain results from compression of the trigeminal nerve, usually the ophthalmic division, as a result of cavernous sinus invasion.

Endocrine abnormalities

Endocrine disturbance is due either to hypopituitism or excess secretion of a particular pituitary hormone.

Hypopituitarism

Hypopituitarism result from failure of the hormones secreted by the adenohypophysis and it gives rise to clinical features first described by Simmonds in 1914. Pituitary gland failure does not occur if the tumour is a microadenoma, but may be clinically evident in the large tumours. The endocrine secretions are not equally depressed but there is selective failure and the order of susceptibility is as follows: growth hormone, gonadotrophin, corticotrophin, thyroid stimulating hormone.

Gonadotrophic deficiency prior to puberty retards the development of secondary sex characteristics, adult men have poor beard growth, women suffer from amenorrhoea and both sexes have loss of libido and deficient public and axillary hair. The biochemical abnormality is manifest by a low oestrogen and androgen production with reduced urinary 17-keto steroids.

Hypopituitarism initially results in vague symptoms, including lack of energy, undue fatiguability, muscle weakness and anorexia and, when prolonged and severe, it will cause low blood pressure. Clinical hypothyroidism is manifest by physical and mental sluggishness and a preference for warmth. When the hypopituitism is severe, episodic confusion occurs and the patient will become drowsy. It is essential to recognize the features of severe pituitary insufficiency as an endocrine crisis can be precipitated by minor stressful events occurring during hospital investigation or as a result of an intercurrent infection.

Pituitary apoplexy results from spontaneous hemorrhage into a pituitary tumour. It is characterised by sudden, severe headache followed by transient or more prolonged loss of consciousness with features of neck stiffness, vomiting and photophobia. The condition is similar to subarachnoid haemorrhage resulting from a ruptured aneurysm, but is often associated with paralysis of one or more of the ocular muscles (usually bilateral) and acute visual deterioration. An acute endocrine crisis may be precipitated by the apoplexy.

Prolactinoma

The prolactin secreting tumour may be a microadenoma or macroadenoma within the pituitary fossa. The patients are usually women, who present with infertility associated with amenorrhoea and galactorrhoea, although the tumour may occasionally cause infertility in men. Large prolactinomas occur in the elderly and in males, and these can cause endocrine disturbance associated with hypopituitism and visual failure.

Acromegaly

Acromegaly results from a growth hormone secreting pituitary adenoma which, as described previously, consists of cells that stain either as acidophils, chromophobes or both. The onset of acromegaly is slow and insidious, usually during the third and fourth decades of life, with both sexes being affected equally. The clinical features include bone and soft tissue changes that are evident as an enlarged supraciliary ridge, enlarged frontal sinuses and increased mandibular size, which will cause the chin to project (prognathism). The hands and feet enlarge, the skin becomes coarse and greasy and sweats profusely. The voice becomes hoarse and gruff and thoracic kyphosis occurs as a result of osteoporosis.

Other problem associated with acromegaly includes hypertension, cardiac hypertrophy and diabetes. Headache is often severe in patients with pituitary tumours causing acromegaly and patients complain of lack of energy, physical weakness and lassitude.

Suprasellar extension of the tumour occurs in about 15% if cases and may result in compression of the optic pathways.

A pituitary adenoma with excessive growth hormone secretion occasionally presents in childhood and result in giantism.

Cushing’s disease

Cushing’s disease is due to ACTH producing pituitary adenomas. Over 80% of the tumours are microadenomas and the remainder are either macroadenomas involving the whole of the sella or with extrasellar extension.

The onset is insidious and the disease may affect children or adults. Severe obesity occurs, the skin is tense and painful and purple striae appear around the trunk. Fat is deposited, particularly on the face (moon face), neck, cervicodorsal junction (buffalo hump) and trunk. He skin becomes a purple colour due to vasodilatation and stasis. Spontaneous bruising is common. The skin is greasy, acne is common and facial hair excessive.

Glucose tolerance is impaired, the serum potassium is low and vascular hypertension occurs. If untreated, 50% of cases are fatal in 5 years.

Cushing’s syndrome, that is an excessive cortisol production, is due to an ACTH producing pituitary adenoma (Cushing’s diseases) in 90% of cases, other causes of Cushing’s syndrome are an adrenal or carcinoma of the lung or aberrant adrenocortical tissue occurring outside the adrenal gland.

Nelson-Salassa syndrome

This consists of an ACTH producing pituitary adenoma in a patient who has undergone bilateral or subtotal adrenalectomy. Before the development of CT scanning and transphenoidal microsurgery, patients with Cushing’s disease often underwent total adrenalectomy when pneumoencephalography had failed to reveal a pituitary tumour. However, accelerated growth of an existing adenoma is induced by the loss of normal corticosteroid feedback. Unlike the adenomas of Cushing’s diseases, about half the patients with Nelson’s syndrome have macroadenomas. Patients have marked cutaneous hyperpigmentation due to secretion of either beta melanocyte stimulating hormone and/or beta lipotropin.

Treatment

The objectives of treatment of patients with pituitary tumours depends on whether the patient has presented with features of endocrine disturbance or problem related to compression of adjacent neural structures. The methods of treatment used are:

Operative procedures
transphenodial excision
transcranial excision
Radiotherapy
Medical treatment with antisecretory drugs

Surgical excision

This will be used as the primary method of treatment for:
Large tumours causing compression of adjacent neural structures, particularly the visual pathways

Growth hormone secreting tumours causing acromegaly
ACTH secreting tumours causing Cushing’s disease
The occasional treatment of a prolactin secreting adenoma, either microadenoma or macroadenoma confined within the sella, when the medical treatment using bromocriptine is not tolerated.

Most tumours can be excised via the transphenoidal approach to the pituitary fossa. The development of the surgical microscope and fluoroscopic radiography has made this a safe procedure. The sphenoid sinus is usually entered using a trans-septal approach, with the incision either in the nasal mucosa or sublabially. The mucosa is reflected from the nasal spectrum and floor and the sphenoid is opened. The anterior wall of the sella is removed and the pituitary fossa entered. Microadenomas (tumours less than 10mm diameter) may be evident on the surface of the gland of may become evident only once the gland is incised.

These tumours can be completely excised, preserving pituitary function. The suprasellar extension of the tumour can be gently coaxed down into the pituitary fossa by slightly raising the intracranial pressure or by the anaesthetist injecting small increments of nitrous oxide and oxygen mixture into the lumbar theca until field. This will also have the additional benefit that the intracranial gas will provide a pneumoencephalogram, outlining the remaining suprasellar extension of tumour.

Occasionally, a transcranial operation is necessary, particularly where there is a subfrontal or retroclival extension of the tumour.

Postoperative management requires careful attention to the fluid balance and hormonal status. Endocrine deficiency in the immediate postoperative period will require replacement with parenteral hydrocortisone and possibly the use of vasopressin for the treatment of transient diabetes insipidus, which commonly occurs after the excision of a large pituitary. In the early postoperative period aqueous vasopressin (Pitressin®) should be given by intramuscular or subcutaneous injection and, if the diabetes insipidus persists, by the intranasal route. Other long-term hormonal replace may include cortisone acetate (12.5-25 mg twice daily), thyroxin and testosterone.

Radiotherapy

Postoperative radiotherapy is used if there has been a subtotal excision of the tumours.
The postoperative endocrine studies demonstrate residual excessive hormone secretion.

Medical Treatment

Treatment of patients with by replacement of the pituitary hormone itself or by replacement of the hormone of pituitary gland. This will be a necessary preoperative procedure in patients with evidence of hypopituitism and will frequently be necessary after the surgical excision of a macroadenoma.
The treatment of prolactin secreting pituitary tumours by bromocriptine, a dopamine agonist. This is the preferred treatment for a symptomatic prolactin secreting microadenoma and may be used as either the definitive treatment of larger prolactin tumours or in conjunction with surgery. Some patients show poor tolerance to postural hypotension, and these patients will required surgical treatment of the tumour.