hypopituitarism

Generality

Hypopituitarism is a condition characterized by the reduced or absent secretion of one or more hormones by the pituitary gland (a small gland located at the base of the brain). The clinical picture that follows can be clinically evident or latent.

The symptoms of hypopituitarism depend on which is the missing hormone and can include fatigue, infertility, absence of milk secretion, cold intolerance and short stature. The deficiency or absence of one, many or all of the pituitary hormones can lead to major changes in the body (except for oxytocin and prolactin).

Hypopituitarism recognizes numerous causes, including inflammatory disorders, pituitary tumors or insufficient blood supply to the gland.

The diagnosis requires the performance of neuroradiological examinations and the dosage of pituitary hormones, in basal conditions and after various types of stimulus tests. These investigations aim to determine which hormones are deficient and whether they need to be replaced pharmacologically.

Treatment is aimed at the underlying cause of hypopituitarism and usually includes hormone replacement therapy.

What's this

Hypopituitarism is the syndrome that results from the partial or complete loss of function of the anterior pituitary lobe (or adenohypophysis).

This results in a hormonal deficit :

• Global (panipopituitarism) : the secretion of all pituitary hormones is compromised;
• Selective (unitropic or partial hypopituitarism) : the deficiency involves only one or some hormones.

A further classification of hypopituitarism is carried out according to the clinic:

• Obvious hypopituitarism : it is defined when the hormonal deficit is clinically evident;
• Latent hypopituitarism : it occurs only in certain clinical conditions (eg stress, pregnancy, etc.) or is detected only through some specific hormonal tests.

The pituitary gland produces several hormones:

1. ACTH (adrenocorticotropic hormone) : stimulates the adrenal glands to produce cortisol.
2. TSH (thyroid-stimulating or thyrotropic hormone) : regulates the production of hormones by the thyroid gland.
3. LH (luteinizing hormone) and FSH (follicle stimulating hormone) : they control fertility in both sexes (ovulation in women, production of sperm in men) and stimulate the secretion of sex hormones from ovaries and testicles (estrogen and progesterone in women; testosterone in women). 'man).
4. GH (growth hormone or somatotrope) : it is necessary for development in children (bones and muscle mass); has effects on the whole body during life.
5. PRL (prolactin or lactotropic hormone) : responsible for milk production by mothers after childbirth.
6. Oxytocin : hormone necessary for labor, delivery (stimulates contractions) and breastfeeding.
7. ADH (antidiuretic hormone or vasopressin) : helps maintain a normal water balance.

Causes

The causes of hypopituitarism are numerous.

• In most cases, this dysfunction depends on a pituitary adenoma . This tumor is almost always benign, but when it increases its size it can exert excessive pressure on the normal portion of the gland. Consequently, the adenoma causes a limitation or destruction of healthy pituitary tissue, making it unable to produce hormones properly. It should also be pointed out that pituitary adenoma can be associated with overproduction of some hormones, making at the same time those produced by the remaining healthy portion of the gland.
• Hypopituitarism can also result from the treatment of the same tumor . In fact, radiotherapy or surgery to remove adenoma can damage a part of the normal pituitary gland or the vessels and nerves that belong to it. Precisely for this reason, before and after a therapeutic intervention, it is recommended to perform the dosage of all pituitary hormones.
• In addition to the adenoma, other neoplastic processes (such as craniopharyngioma and Rathke cysts) that develop near the pituitary gland can cause hypopituitarism, as well as metastases of tumors originating in other parts of the body.
• Hypopituitarism is caused by inflammatory processes, as can happen in the case of meningitis, hypophysitis, sarcoidosis, histiocytosis and tuberculosis.
• The impairment of pituitary hormone production may also depend on direct radiotherapy to the pituitary or brain; this side effect can also be late, even after several months or years of treatment.
• Another pathological event capable of triggering a rapid pituitary insufficiency is the apoplexy of the gland, secondary to a sudden hemorrhage . This represents a medical emergency and can be recognized by the typically associated symptoms (severe headache, neck stiffness, fever, visual field defects and abnormal eye movements). Insufficient blood supply to the pituitary gland can also be caused by blood clots, anemia or other vascular conditions.
• Finally, hypopituitarism can be caused by severe cranial trauma, usually accompanied by coma or other neurological problems.

The reduced functionality of the target glands includes both forms of pituitary insufficiency (secondary hypopituitarism) and those of hypothalamic origin (tertiary hypopituitarism).

Hypopituitarism is not a common pathology, but the incidence is constantly increasing in correlation with post-traumatic forms.

Symptoms, signs and complications

The clinical manifestations of hypopituitarism may vary depending on the missing or deficient hormone.

Usually, the onset of symptoms is gradual and the condition can go unnoticed for a long time. Only in certain cases, the disorders associated with hypopituitarism appear suddenly and dramatically.

Sometimes, the pituitary gland reduces the production of a single pituitary hormone; more often, the levels of more hormones decrease simultaneously (panipopituitarismo).

Adrenocorticotropic deficiency

ACTH deficiency results in cortisol deficiency due to hypoactivity of the adrenal glands.

This involves symptoms such as:

• Low levels of sugar (glucose) in the blood;
• Weakness and reduced tolerance to effort;
• Weight loss;
• Abdominal pain;
• Decrease in blood pressure values;
• Reduction of plasma sodium levels.

This is the most serious pituitary hormone deficiency, as it can lead to the patient's death.

Thyrostimulant hormone deficiency

The lack or deficiency of the thyroid stimulating hormone affects the thyroid activity (in particular, on the production of T3 and T4), resulting in hypothyroidism.

Symptoms associated with TSH deficiency include:

• Fatigue;
• Generalized swelling;
• Weight increase;
• Cold intolerance;
• Constipation;
• Dry skin;
• Difficulty concentrating;
• Pallor;
• Drowsiness;
• High cholesterol levels;
• Liver problems.

Follicle stimulating and luteinizing hormone deficiency

In pre-menopausal women, the lack of LH and FSH can cause:

• Decreased regularity of menstrual cycles;
• Infertility;
• Vaginal dryness;
• Osteoporosis.

In men, however, this hormonal deficit manifests itself with:

• Decreased libido (interest in sexual activity);
• Difficulty in having and maintaining an erection (impotence, erectile dysfunction);
• Quantitative and qualitative alteration of sperm.

In children, LH and FSH deficiency leads to delayed puberty.

Growth hormone deficiency

In children, GH deficiency is responsible for a poor and slow overall development. Furthermore, this deficiency causes an increase in fat mass and a short stature.

In adults, growth hormone deficiency can determine:

• Lack of physical energy;
• Changes in body composition (increase in fat and decrease in muscle mass);
• Increased cardiovascular risk.

Prolactin deficiency

Prolactin deficiency is associated with the reduction or total absence of milk production after delivery.

Antidiuretic hormone deficiency

The lack of antidiuretic hormone (or vasopressin) affects the kidneys and can result in diabetes insipidus. This condition typically occurs with excessive thirst, diluted urine and frequent urination (polyuria), particularly during the night.

Diagnosis

The diagnosis of hypopituitarism is formulated on the basis of the symptoms presented by the patient and on the outcome of laboratory tests (hormonal dosages) and diagnostic tests for images performed on the pituitary gland.

More in detail, the investigations necessary to establish the presence of the condition include:

• Hormonal dosages : they are performed on blood and, sometimes, on urine, to measure the levels of hormones secreted by the pituitary gland and their target organs (free thyroxine, TSH, prolactin, LH, FSH and testosterone in men or estradiol in women). In some cases, a stimulation test is required to assess cortisol or GH deficiency.
• Neuroradiological examinations : to exclude structural anomalies, such as the presence of pituitary adenomas, patients suspected of having hypopituitarism are subjected to neuroradiological investigations, such as a high resolution computed tomography (CT) or magnetic resonance (RM) with contrast medium . Cerebral angiography is indicated only when other radiological techniques suggest the presence of vascular abnormalities or aneurysms.

Therapy

Although there is no definitive cure for hypopituitarism, it is treatable with the replacement of deficient hormones with synthetic compounds, at a level as physiologically correct as possible. The goal is to minimize the symptoms (ie the patient should not feel the consequences of the hormonal deficiency) and allow the conduction a normal life.

Hormone replacement therapy is adapted to each individual case of hypopituitarism. For this reason, the patient must be regularly monitored by his doctor after starting treatment. This makes it possible to verify the effects of the therapeutic protocol and, if necessary, modify it.

Usually, once the optimal dose of hormone replacement therapy has been established, it remains adequate for a long time, except for the onset of conditions that affect the plasma levels of hormones (for example, GH may require an increase in the daily dose of cortisol ).

Sometimes, the treatment of hypopituitarism involves the surgical removal or irradiation of any pituitary tumors.