Pituitary News, Issue 20 - Summer 2001.

As in any branch of medicine, there is plenty of small print when it comes to pituitary disease. Much of it, of course, is only of direct relevance to those of you who have, or know somebody with, the conditions in question. However, I hope that what follows will be of general interest. If nothing else you will hopefully learn a few exotic medical terms with which to impress your friends!

A

Aneurysm

Arteries are elastic-walled blood vessels that carry blood under pressure from the heart to the rest of the body. If a weakness develops in the wall of an artery, a localised 'blow out', or aneurysm, can occur, a bit like the first swelling to develop when blowing up a long thin balloon. If this occurs in one of the blood vessels near the pituitary, such as a carotid artery, it can compress the pituitary or nearby structures. This may mimic a Pituitary tumour, but it is very important to distinguish between the two conditions (as the treatment is very different); this can usually be achieved by CT or MRI scanning. If an aneurysm is getting bigger or causing symptoms, it may need to be clipped (requiring an 'open' operation) or blocked (in an operation carried out within the blood vessel) to prevent further problems.

Apoplexy

Pituitary apoplexy is a rare but serious condition that usually results from problems with the blood supply to, or within, a pituitary tumour. If this occurs, part or all of the tumour may be damaged through lack of oxygen (pituitary infarction) and there may be associated bleeding into the gland. This can result in rapid expansion of the pituitary, causing severe headache, visual problems, hypopituitarism and even reduced consciousness. The condition can be difficult to recognise, especially in people not already known to have a pituitary tumour - the features may mimic other conditions such as meningitis or a burst blood vessel elsewhere within the head. Sometimes the condition settles down with just supportive treatment (including replacing pituitary hormone deficiencies) but surgery may be needed to 'decompress' the pituitary tumour and thus decrease pressure on surrounding structures. This is particularly important if there are visual problems.

B

Bacterial Infection

Infections of the pituitary are fortunately very rare. Bacteria may reach the gland either through the blood stream from an infection elsewhere, or by direct extension from adjacent structures such as the sinuses. A pituitary abscess may result and surgical drainage may be needed to allow the infection to resolve.

C

Chordoma

A rare, slow growing tumour which arises from a line of cells (the notochord) which, at an early stage in the developing embryo, defines the midline axis (the line of symmetry down the midline of the body). The tumours are therefore always in the midline and can be near the pituitary. Chordomas rarely occur before the age of 30. They can grow quite aggressively and occasionally spread to distant parts of the body (i.e. metastasise). Effects include compression of the pituitary and nearby structures, and pain is often a prominent symptom. Treatment is difficult and usually consists of surgery and Radiotherapy.

Cyst

A cyst is a closed cavity which contains fluid or semi-solid material. Many different types of cyst can occur in and around the pituitary. These include arachnoid cysts, dermoid cysts and epidermoid cysts, and Rathke's cleft cysts. These arise from different structures but may be difficult to distinguish without examination of the cyst wall microscopically. Arachnoid cysts arise from one of the thin membranes which envelop the brain, while Rathke's cleft cysts are thought to originate from Rathke's pouch which is the precursor of the anterior pituitary in the developing fetus. Small Rathke's cleft cysts have been found in up to a fifth of pituitaries examined at post mortem - so obviously the vast majority never cause any symptoms. Occasionally, if a cyst enlarges, it may have effects very similar to a pituitary tumour, in which case surgery may be necessary. Recurrence is unusual. In addition to 'true' cysts, pituitary tumours can undergo 'cystic change', meaning that part of the tumour, instead of being solid, becomes liquified. This is one reason why a Prolactinoma, for example, may fail to shrink on treatment with a dopamine agonist drug such as cabergoline - the solid bits, made up of living cells, get smaller, but the liquid parts remain unaffected.

D

Dermoid Cyst

See cyst

DIDMOAD

See Wolfram Syndrome

E

Empty Sella

The 'sella' is the bony cup in which the Pituitary gland sits. It may be described as 'empty' (or, in most cases 'partially empty') when filled largely with Cerebrospinal fluid (the liquid which bathes the brain) rather than pituitary tissue, which may be compressed to a thin rim. Some cases occur for no apparent reason and are known as 'primary empty sella'. This is commonest in middle aged women, and is usually found by chance on X-rays or scans carried out for other reasons. Usually, the pituitary functions normally despite being a bit squashed, but some patients have a raised Prolactin level or partial hormone deficiencies.

'Secondary empty sella' occurs when the pituitary or a pituitary tumour shrinks, leaving a fluid-filled space. This can occur, for example, after treatment of a pituitary tumour, or following apoplexy (see above), Sheehan's syndrome or Hypophysitis (see below). Occasionally, as a result of scarring, structures above the pituitary, such as the optic nerves, may be drawn downwards, causing visual problems. Pituitary function may be disturbed as a result of the underlying condition. Usually no treatment is needed for the empty sella itself.

F

Feedback Tumour

Not really a tumour at all, but reversible enlargement of the pituitary as a result of thyroid failure. Lack of feedback from the thyroid results in the thyroid-stimulating hormone (TSH)-producing cells enlarging and becoming more numerous. The whole pituitary can become enlarged, sometimes sufficient to mimic a pituitary tumour.

G

Germ Cell Tumours

Rare tumours which derive their name from their origin in 'germ cells' (nothing to do with 'germs' or 'bugs' but the term given to a type of 'young' or 'immature' cell with the potential to develop into many different mature cell types or tissues). Several different types are recognised, including germinomas and teratomas, which behave slightly differently. They are commonest in teenagers, usually arise in the midline and can occur above the pituitary gland ('suprasellar'). The tumours typically enlarge slowly causing Diabetes Insipidus, visual disturbance and hypopituitarism. The diagnosis of a germ cell tumour relies on the clinical picture together with blood tests (for 'tumour markers'), scans, sometimes a lumbar puncture and occasionally a biopsy. Germ cell tumours are best treated by radiotherapy: the outlook is rather better for germinomas than teratomas, up to 90% of germinoma patients surviving for 10 years or more after diagnosis.

Glioma

Gliomas are tumours of the supporting cells of the nervous system. They can affect the pituitary when they arise from the optic nerves or Hypothalamus (the part of the brain that lies above the pituitary and controls its function). They are commoner in children, particularly in those with the inherited condition, neurofibromatosis. Their effects include hormonal disturbances, including diabetes insipidus, and visual problems. Treatment is controversial; surgery or radiotherapy may be helpful, depending on the position of the tumour.

H

Haemochromatosis

A condition in which the body becomes overloaded with iron, either because of an inherited abnormality or multiple blood transfusions (necessary in some blood disorders such as thalassaemia). Iron is deposited in many parts of the body including the pituitary. This typically results in gonadal failure (caused by lack of the pituitary hormones, LH and FSH, which control the testes and ovaries). The high iron content of the pituitary may give it a characteristic appearance on MRI scan.

Hamartoma

Hypothalamic hamartomas are congenital (i.e. present from birth) abnormalities which consist of a benign clump of disorganised brain cells. Although rare, they can cause unusual endocrine abnormalities by producing hypothalamic hormones that act on the pituitary. This can result in precocious (early) puberty or, very rarely, Acromegaly or Cushing's syndrome. Another curious feature of hypothalamic hamartomas is their association with 'gelastic' seizures, fits of laughter. Treatment is usually surgical.

Histiocytosis

A rare and diverse group of diseases, commonest in childhood. 'Granulomas', tiny clumps of inflammatory cells develop in many different parts of the body including the skin, liver and bones. Granulomas in the hypothalamus or posterior pituitary can cause diabetes insipidus. Although the condition tends to wax and wane over some years, the diabetes insipidus, if present, tends to persist.

I

Infarction

See apoplexy

Isolated Pituitary Hormone Deficiencies

Rarely, children are born with a defect in their pituitary gland or hypothalamus which makes them unable to produce one of the pituitary hormones. Sometimes this is caused by an abnormality in the gene for these hormones. The effects are predictable - for example, Growth hormone deficiency results in Short stature while TSH deficiency causes Hypothyroidism from birth, which can have profound effects on growth and mental development.

K

Kallmann's Syndrome

A condition in which the area of the brain responsible for the sense of smell and the hypothalamic cells which produce GnRH (gonadotrophin-releasing hormone) fail to develop properly. This results in reduced or absent sense of smell ('hyposmia' or 'anosmia') in association with reduced activity of the ovaries or testes (Hypogonadism, caused by lack of LH and FSH secretion by the pituitary). The condition is about four times commoner in boys than girls and can be inherited or 'sporadic' (occurring without any family history). The condition usually comes to light when the normal changes associated with puberty fail to materialise during the teenage years. The gene responsible for Kallmann's syndrome has been identified and studied in detail. It appears to be responsible for the normal migration of certain brain cells in the developing foetus.

Further details may be obtained in the book Kallmann's Syndrome - Your Questions Answered, available from The Pituitary Foundation.

L

Lymphocytic Hypophysitis

A rare disorder, which is much commoner in women than in men. Most cases occur in late pregnancy and during the first year after childbirth. The condition appears to be caused by the body's immune system attacking the pituitary, resulting in gradual damage and loss of function. In the early stages, the gland may be enlarged, mimicking a pituitary tumour, but later, as the inflammation subsides, it becomes scarred and shrunken, sometimes causing a partial empty sella (see above). In the early stages, symptoms relate to 'space occupying effects', such as headache, and hypopituitarism, which may be partial (ACTH deficiency with consequent adrenal gland failure is particularly common, while gonadal function is often preserved). Diabetes insipidus may also develop. Recovery of pituitary function is unusual. Steroids have been used to suppress the inflammation of hypophysitis, but there is no convincing evidence of its effectiveness.

M

Meningioma

A (usually) Benign tumour of the meninges, the membranes which surround the brain and spinal cord. Meningiomas are quite common, being found in up to 2% of patients at post mortem, but the large majority are small and have little or no effect. They are much commoner in women, and are most frequently found in middle age. Meningiomas arising near the pituitary may cause visual problems, headaches, diabetes insipidus and hypopituitarism and may be difficult to distinguish from a non-functioning pituitary tumour. Treatment is usually surgical.

Metastases

A metastasis is a 'secondary' deposit from a malignant tumour elsewhere in the body. Metastases in the pituitary are quite rare, but occasionally occur in patients with cancer of the lung, breast, kidney or bowel. Usually, the patients are already unwell with extensive disease, although occasionally the pituitary metastasis is the first sign of the illness. Effects include hypopituitarism and 'space occupying symptoms', such as headache.

Multiple Endocrine Neoplasia Type 1 (MEN1)

MEN-1 is an inherited condition in which affected individuals tend to develop tumours of the pituitary, parathyroid glands (causing an increase in blood calcium level), and the endocrine part of the pancreas. Children of an affected parent have a 50% chance of inheriting the condition. Pituitary tumours occur in more than half MEN-1 patients and most commonly produce prolactin, growth hormone or ACTH. The gene responsible for MEN-1 has now been identified and DNA testing may be successful in detecting affected family members: those with the abnormal MEN-1 gene then require screening for calcium, pituitary and pancreatic problems while those without do not require further testing.

N

Nelson's Syndrome

Occasionally, in patients with pituitary-dependent Cushing's (i.e. caused by an ACTH-producing pituitary adenoma), the only way to control the condition satisfactorily is to remove the Adrenal glands. Following this operation, particularly if pituitary radiotherapy has not been given, Nelson's syndrome may develop. This consists of an enlarging ACTH-producing pituitary tumour together with increasing skin pigmentation (an effect of very high ACTH levels), and is thought to result from reduced steroid feedback on the pituitary adenoma (even though replacement steroids are always given after Adrenalectomy). The pituitary adenomas can be difficult to cure and both surgery and radiotherapy may be required.

Neurosarcoidosis

Sarcoidosis is a mysterious condition in which granulomas (see histiocytosis) can develop in many different parts of the body including the lungs, skin, eyes, liver and bones. In neurosarcoidosis, involvement of the hypothalamus (or occasionally the pituitary) can result in diabetes insipidus and hypopituitarism. Other hypothalamic effects include weight gain, disturbed regulation of body temperature and sleep disorder. Treatment with steroids may suppress the development of the granulomas, but neurosarcoidosis responds less well than the disease in other parts of the body.

O

Optic Nerve Glioma

See glioma

P

Postpartum Pituitary Necrosis

Also known as Sheehan's syndrome. During pregnancy, the pituitary gland gradually enlarges (mainly because of an increase in the size of prolactin-producing cells in preparation for lactation) and becomes increasingly dependent on an increased blood supply. If serious bleeding occurs during or after delivery, the resulting reduction in blood pressure can lead to pituitary damage through insufficient blood flow. The usual symptoms, in addition to the history of serious problems during delivery, are inability to lactate (prolactin deficiency) and failure of normal periods to return (LH and FSH deficiency). There may also be deficiencies of other pituitary hormones, and occasionally partial diabetes insipidus can be demonstrated. Scarring and shrinkage of the pituitary may lead to a partial empty sella (see above). Sheehan's syndrome is very rare in the UK and other developed countries, but is a relatively common cause of hypopituitarism worldwide.

R

Rathke's Cleft Cyst

See cyst

S

Sheehan's Syndrome

See postpartum pituitary necrosis

Septo-Optic Dysplasia (SOD)

A condition in which a number of structures normally found in the midline of the brain are absent or underdeveloped. This typically involves the optic nerves (the nerves of sight), optic chiasm (where the optic nerves partially cross over in the midline, near the pituitary) and the hypothalamus. Other structures in the midline may also be affected, and occasionally there are associated abnormalities such as cleft lip or palate. The hypothalamic abnormality can result in hypopituitarism which usually manifests as lack of growth in childhood. Other effects include delayed (or, rarely, early) puberty, diabetes insipidus, thyroid and adrenal failure. Involvement of the optic nerves causes visual impairment that typically results in abnormal side-to-side or rotational eye movements (nystagmus).

T

Teratoma

See germ cell tumours

Tuberculosis

Tuberculosis of the pituitary is rare. The bacteria can reach the gland either through the blood stream or by direct extension from nearby structures, for example in TB meningitis. Pituitary damage leads to hypopituitarism which, despite treatment with antibiotics, is unlikely to recover.

Thyrotrophinoma or TSHoma

Less than 1% of pituitary adenomas arise from TSH (Thyroid stimulating hormone or Thyrotrophin) producing cells. These tumours overproduce TSH, resulting in overactivity of the Thyroid Gland (thyrotoxicosis), and are an exceedingly rare cause of thyrotoxicosis. A TSHoma can easily be differentiated from other causes of thyroid overactivity by its characteristic biochemical picture (with raised TSH levels in the blood, in contrast to the low levels usually seen in thyrotoxicosis). In about a third of cases, the tumour also produces excess growth hormone resulting in mild acromegaly. As with other pituitary tumour types, depending on the size of the tumour, there may be 'space-occupying' effects including hypopituitarism, headache and visual disturbance.

W

Wolfram Syndrome (Acronym: DIDMOAD)

A rare inherited condition comprising diabetes insipidus (DI), diabetes mellitus (DM or 'sugar diabetes'), optic atrophy (OA, degeneration of the nerves of sight) and deafness (D). There is progressive damage to certain parts of the brain and gradual destruction of the insulin-producing cells of the pancreas. Diabetes mellitus is usually the first manifestation of the condition, developing in childhood. Optic atrophy is present in almost all cases and is associated with gradually deteriorating vision. The other features are more variable, diabetes insipidus, for example, being present in only about a third of cases.

Y

Yolk Sac Tumour

A particularly aggressive type of germ cell tumour with a poor prognosis.

Z

Zymurgy

The art of brewing. Nothing to do with the pituitary, but if you've read this far you deserve a drink!