The pituitary is a small endocrine gland (that is, one that produces hormones) located at the base of the brain near the root of the nose. It consists of two parts: the anterior pituitary, or adenohypophysis, and posterior pituitary, or neurohypophysis.

By producing specific hormones, the adenohypophysis regulates the function of other endocrine glands, including the thyroid, adrenal glands, testes and ovaries. The adenohypophysis also produces growth hormone (GH) and prolactin.

The neurohypophysis is really part of the brain. Its main job is to produce antidiuretic hormone, which is necessary for maintaining the correct water balance in the body.

The pituitary gland is connected to the hypothalamus (a region of the brain) through the pituitary stalk. It is through this pedicle that the brain regulates the function of the pituitary. In close proximity to the pituitary gland are the optic chiasm (where the nerves of the eyes intersect), the oculomotor nerves (which make our eyes move), and the carotid arteries, in their cerebral part.

The adenohypophysis produces the following hormones:

  • Growth hormone (GH): regulates growth during childhood until sexual development is complete; it also plays a significant role in regulating protein and fat metabolism
  • Adrenocorticotropic hormone (ACTH): regulates cortisol production (the cortisone produced in our body) by the adrenal glands; cortisol regulation is vital for survival; cortisol plays a very important role in brain function, our response to infections, and in overcoming diseases.
  • Thyroid-stimulating hormone (TSH): regulates thyroid function; the hormones produced by the thyroid regulate the speed at which all bodily functions occur.
  • Follicle-stimulating hormone (FSH): regulates the function of the ovary and testis
  • Luteinising hormone (LH): regulates the function of the ovary and testis
  • Prolactin (PRL): responsible for the manufacture of breast milk

The neurohypophysis produces the following hormones

  • Antidiuretic hormone (ADH): regulates reabsorption of water by the kidney, thus saving water, which is an essential substance for our body.
  • Oxytocin: responsible for uterine contractions

There are various types of diseases of the pituitary gland. They range from alterations in function (ie, excessive production of a hormone or defective production of one or more hormones), to inflammation (for example, autoimmune hypophysitis), and tumours (pituitary adenoma); the latter can sometimes cause alteration in pituitary function, producing excess hormone; at other times, the pituitary adenoma does not produce an excess of hormone, but, if large enough, it can affect the normal pituitary mechanically, by reducing the production of one or more hormones (hypopituitarism), or sometimes, due to a compression effect, it can impair vision (pressure on the optic chiasm), or result in diplopia (split vision, due to compression on the oculomotor nerves, which make the eyes move). It can also cause headaches or, albeit rarely, the discharge of cerebrospinal fluid (the liquid that envelops the brain) from the nose.

The disorders linked to pituitary disease are highly variable (SEE section dedicated to the manifestations of pituitary diseases) and can occur in isolated or associated form; people with pituitary disease do not necessarily have all the symptoms at the same time and more commonly have only some of them. Moreover, many manifestations of pituitary diseases are common to other general or endocrinological conditions, which can delay correct identification of the disease.

Once pituitary disease is suspected, it is definitely advisable not to delay, but to contact an endocrinologist with specialist skills who can establish the most appropriate diagnostic and therapeutic pathway.

Diseases of the pituitary gland can occur as a result of excessive production of a pituitary hormone, which in turn causes excessive production of the peripheral endocrine gland under its regulation; for example under normal conditions, the TSH produced by the pituitary regulates the production of thyroid hormones (T4 and T3) by the thyroid; excessive TSH production (due to the rare presence of a TSH-secreting pituitary adenoma) leads to excessive production of T4 and T3 by the thyroid and the condition of hyperthyroidism (central); people with this rare condition will have manifestations of hyperthyroidism. By contrast, conditions can occur in which the pituitary does not produce sufficient TSH (for example, non-functioning hypophyseal adenoma, which will compress the normal pituitary gland, external radiotherapy, etc.), to be able to stimulate the thyroid to produce enough T4 and T3; in this situation, patients will have hypothyroidism disorders (due to lack of thyroid hormones).

On the other hand, diseases of the pituitary gland can emerge not so much because of an excess or a hormonal defect, as because of the onset of disorders relating to the visual or neurological sphere; these disorders (visual field defects, double vision, headaches) are due to effects of a growth that is, compression by part, in general, of a non-functioning hypophyseal macroadenoma, or by another “growth” that develops in the pituitary gland.

Some of the disorders that can form part of the presentation of various pituitary diseases are shown below; the disorders reflect both excess diseases and hormone defects such as the manifestations due to the effect of a growth:

  • Loss of sexual appetite
  • Difficulties in procreating (male or female)
  • Changes in menstruation
  • Weight changes (gain or loss)
  • Alterations of the skin (variations in colour, red stretch marks, development of body hair, hair loss)
  • Fragile capillaries, easily bruised
  • Mood changes (depression or anxiety)
  • Changes in metabolism
  • Unexplained tiredness
  • Sleep disturbances
  • Arterial hypertension (high blood pressure)
  • Arterial hypotension (low blood pressure)
  • Diabetes mellitus
  • Hypoglycaemia
  • Disturbed vision
  • Headaches
  • Split vision

Diseases of the pituitary gland can have an extremely varied presentation that depends on the convergence of several factors: the excess or defect of one or more hormones and the mechanical effect that can be exerted by a growth or tumour in the pituitary gland. Furthermore, the speed of onset of the disease plays an important part; many diseases of the pituitary gland are slow and progressive, so that the signs are not immediately noticed by the patient, nor are they readily recognised by doctors.

Many pituitary adenomas produce a large amount of one or, more rarely, more hormones, and the most common symptoms associated with these depend on an excessive production of hormones. The symptoms may be a direct consequence of excess pituitary hormone (eg prolactin, see below), or due to excessive stimulation of the peripheral endocrine gland which is controlled by the pituitary gland (for example, excessive ACTH production by the pituitary gland leads to excessive cortisol production by the adrenal cortex: the clinical signs are linked to excess cortisol in the body, leading to Cushing’s syndrome).

An excess of prolactin can be responsible for discontinued menstrual flow (amenorrhea), or loss of rhythm (oligomenorrhea), which may or may not be associated with milk production outside pregnancy (galactorrhoea).

An excess of growth hormone can lead to excessive statural growth or change in appearance (gigantism or acromegaly); diabetes mellitus, raised blood pressure and many other manifestations relating to the effects of excessive amounts of growth hormone or its effector, IGF-1 can also develop.

An excess of cortisol (in cases of pituitary diseases due to a hypophyseal adenoma that produces excess ACTH) can lead to a redistribution of fat, which is concentrated mainly in the abdomen, and is combined with a reduction of muscle mass, especially in the thighs and arms; moreover, red stretch marks, arterial hypertension, diabetes mellitus, fragility of the skin and frequent infections often occur; unexplained osteoporosis can also be due to excess cortisol.

In some patients, the manifestations due to excessive production of hormones may be accompanied by headaches, changes in vision, and changes in sleep and eating habits.

The onset of tiredness, very low blood pressure, especially when standing, low spirits or true depression, reduction in ability to carry out physical activities, dryness of the skin, social isolation, difficulties with motherhood or fatherhood, thinning of the beard or changes in sexual response, increased cholesterol, or even repeated episodes of hypoglycaemia, may be signs of defective pituitary function.

Sometimes, changes in thirst or the discharge of large quantities of urine (diabetes insipidus) are signs of pituitary disease.

In other cases, when the underlying pituitary disease is caused by a non-functioning pituitary adenoma, the clinical signs are related to the mechanical effect of these tumours on the healthy pituitary (eg, fatigue and loss of energy, linked to hypopituitarism) and nearby structures (eg, headaches and impaired vision).

All diseases of the pituitary gland are treated at the centre:

  • Non-secreting pituitary adenomas
  • Acromegaly and gigantism
  • Cushing’s disease
  • hyperprolactinaemia
  • Diabetes insipidus
  • Autoimmune hypophysitis
  • Pituitary tumours
  • Hypopituitarism (hypophyseal function defect)
  • Central hypothyroidism
  • Central hypoadrenalism
  • Growth hormone deficiency

A suitable diagnostic and therapeutic pathway for complex pituitary diseases is based on the collaboration of a dedicated team with specific experience in the field of pituitary disease, such as the one working at the San Rossore Healthcare Facility. The skills of the team in relation to pituitary diseases have also led to the publication of articles in leading international scientific journals.

The specialist skills in the diagnosis and treatment of pituitary diseases are:

  • Endocrinology
  • Neurosurgery
  • Otolaryngology
  • Pathological anatomy (Laboratory Medicine)
  • Anaesthesiology, intensive care and resuscitation
  • Radiotherapy
  • Neuroradiology

This is a chronic, debilitating disease that significantly compromises the patient’s quality of life. Its symptoms include enlargement of the feet and hands (acral enlargement), the tongue and facial bones, and all internal organs (heart, liver, thyroid, intestine, kidney etc.). In almost all cases, Acromegaly is due to a pituitary adenoma that produces excessive, uncontrolled amounts of growth hormone (GH); the clinical signs are due to excess GH and its peripheral effector IGF-1 (insulin like growth factor 1).

The disease has an insidious, extremely slow development, which is the main reason why diagnosis can be delayed for several years; in our experience, the average time between the (presumed) onset of the disease and its diagnosis has gone from 10 years in the 80s and 90s to 5 years in the 2000s, as a consequence of early diagnosis.

The main treatment for acromegaly is the neurosurgical intervention of adenomectomy via the trans-nasal-sphenoid using an endoscope (a thin tube with micro-scalpels, which is introduced into the nose to access the floor of the sella turcica at the base of the brain, where the pituitary gland is located).

If the intervention is not conclusive, or if for various reasons it is not practicable, various medical devices are available. These include slow release somatostatin analogues (both traditional, LAR ocherotide and LAR lanreotide, and more recent options, panececeptorial, pasireotide analogues), and the growth hormone receptor antagonist (pegvisomant).

External radiotherapy, although available in various forms (conventional radiotherapy, gamma-knife, cyberknife, hadrontherapy) is only used in selected cases.

The modern approach to patients suffering from acromegaly is not limited to the treatment of excess growth hormone and pituitary adenoma, but is aimed at studying and treating the manifestations of excess growth hormone over the whole body; it is for this reason that the heart, intestine, metabolism, thyroid, etc. must be investigated.

Cushing’s disease is caused by an ACTH-secreting pituitary adenoma (ie, one that produces high, unregulated quantities of ACTH). Under normal conditions ACTH stimulates the adrenal glands to produce cortisol. Excessive stimulation of the adrenal cortex by ACTH leads to over production of cortisol, which is ultimately responsible for the outward signs of this syndrome: full moon facies, excessive hair growth (in women), thinning of the hair, outbreak of red stretch marks on the abdomen, central obesity (abdominal) marked by a reduction in muscle mass; changes in menstruation and the onset of arterial hypertension and diabetes mellitus also occur. Excess cortisol is also responsible for coagulation changes that increase the risk of thrombosis (thrombo-embolic disease), and an increase in infections; furthermore, capillary fragility and bruising often occur even after very minor trauma.

In some cases excess cortisol is manifested by bone disease characterised by increased fragility and high-grade osteoporosis with multiple fractures. In some patients the main signs are concerned with the psychic and behavioural sphere.

The preferred treatment is the surgical removal of the ACTH-secreting hypophyseal adenoma; however, the adenoma is often small and sometimes cannot be viewed using magnetic resonance; it follows that medical treatment is commonly required after the neurosurgical intervention. Fortunately, in the past few years a somatostatin analogue with pan-receptor activity (pasireotide) has been made available. This is effective in a high percentage of patients; further drugs are also available, such as cabergoline and ketoconazole; a new drug (osilodrostat) with a powerful blocking effect on cortisol synthesis by the adrenal glands is in its experimental phase. It is not uncommon for patients with Cushing’s disease, who are not cured by adenomectomy surgery, to resort to complex pharmacological combinations and, sometimes, bilateral adrenal surgery. External radiotherapy can also play a part, albeit limited.

An increase in circulating prolactin can have various causes, including pituitary adenoma.

Prolactin-secreting adenomas, unlike the GH or ACTH secreting ones, are a common pituitary disease; they are more often found in women of childbearing age, while in men they are more common in the fourth and fifth decade of life; about half are microadenomas. In men, however, macroadenomas are more common. In women, high levels of prolactin cause the absence of menstruation (amenorrhea) and the inappropriate production of milk outside the pregnancy (galactorrhoea); in men the most significant symptoms are reduction in sexual desire (decreased libido) and an erectile dysfunction. Dysfunction of the gonads (ovary or testis) can lead to osteoporosis and increased cardiovascular risk in the long term.

The main treatment for prolactin-secreting pituitary adenoma generally involves drugs similar to dopamine, the neurotransmitter which, under normal conditions, acts as an inhibitory brake on prolactin secretion; the available dopamine-agonistic drugs are cabergoline and bromocriptine. Surgical adenomectomy is indicated for invasive tumours or in the event of failure to respond to medical treatment.

Diabetes insipidus is due to insufficient production of, or dysfunction of, the antidiuretic hormone (ADH) produced by the neurohypophysis; ADH produced by specific neurons (nerve cells) of the hypothalamus (a part of the brain) arrives in the posterior pituitary (or neurohypophysis), from where it is released into the circulation; it travels through the blood to the kidneys where, by binding to a specific receptor, it enables water to be reabsorbed.

Central diabetes insipidus is due to the lack of ADH, while nephrogenic diabetes insipidus is due to the lack of any effect of ADH in the kidneys (due, in most cases, to failure of the renal receptor for ADH).

The clinical signs are related to the lack of recovery of the water filtered by the kidney; it follows that large volumes of water are lost through the urine (4-8 litres per day) (polyuria) with consequent stimulation of thirst and intake of large volumes of liquid (polydipsia).

The treatment of insipid diabetes due to pituitary disease (central diabetes insipidus) is based on the administration of synthetic antidiuretic hormone, generally orally.

For more information, or to book a medical examination, please contact the Healthcare Facility at the following address:

Tel: +39 050 586425
Monday to Friday: 9.00-13.00 – 15.00-19.00