HYPOPITUITARISM: causes, main symptoms, therapy.

Lhypopituitarism is a medical condition characterized by the reduction or complete absence of the production of pituitary hormones, that is, the substances produced by the pituitary gland. The panpipopituitarism it is the most severe form of pituitary deficiency, as it manifests itself with the complete absence of secretion of pituitary hormones.


What is hypopituitarism? Hypopituitarism it is a syndrome characterized by the reduced or absent secretion of one or more pituitary hormones, with consequent dysfunction of the peripheral glands on which these hormones normally have action, such as the thyroid gland, the adrenals, the ovaries. The deficiency of all pituitary hormones sets up the picture of panhypopituitarism, while the deficiency of two or more hormones is called partial hypopituitarism, and the deficiency of only one hormone is called selective hypopituitarism.

Hypopituitarism: is it a frequent problem?

Panhypopituitarism is a very rare condition, as opposed to partial hypopituitarism, especially the iatrogenic one, which is more frequent. The 10% of patients undergoing surgery in the hypothalamic-pituitary region may in fact present hypopituitarism; of patients undergoing radiotherapy for the treatment of intracranial tumors, after 10 years, almost half (45% to be precise) have a secretion deficit of gonadotropins, the 30% a deficit of ACTH (adrenocorticotropic hormone), the 10% a deficiency of TSH (thyrotropin). It mainly affects subjects between the ages of 25 and 45 and is more frequent in women.

What causes hypopituitarism?

What are the causes of hypopituitarism? Hypopituitarism can be secondary to the destruction of pituitary cells, taking the form of primary hypopituitarism, or caused by a reduced secretion of particular hypothalamic hormones (Releasing Hormones), giving rise to a secondary hypopituitarism.Hypopituitarism can be congenital (rare) or acquired, organic (with damage to the thyroid gland) or functional (i.e. in the absence of organic damage). Hypopituitarism occurs clinically when at least 70% of the gland is destroyed, while total loss of pituitary hormone secretion occurs when at least 90% of the pituitary tissue has been damaged.

Causes of hypopituitarism

The possible causes of hypopituitarism are many: We see in the following list the main causes of hypopituitarism:Organic causes of hypopituitarism

  • Acquired hypopituitarism:
    • Tumors: the main neoplasms that can give rise to pituitary dysfunction are hypothalamic tumors or pituitary neoplasms, craniopharyngoma, glioma, meningioma, or the presence of metastases
    • latrogenic: it means a pituitary damage secondary to surgical, radiotherapy, chemotherapy therapies
    • Discontinuation of hormone replacement therapy
    • Autoimmune
    • Vascular: Vascular damage resulting in hemorrhagic or ischemic necrosis of the pituitary gland occurs in pituitary apoplexy or Sheehan's syndrome
    • Infections such as meningitis or encephalitis
    • Infiltrative disorders: the most common are sarcoidosis, histiocytes X, hemochromatosis
    • Trauma
    • Internal carotid aneurysm
    • Idiopathic causes
  • Congenital causes of hypopituitarism:
    • Agenesis or hypoplasia of the pituitary: caused by an impaired embryonic development of the Rathke's pouch
    • Primary empty sella syndrome: due to incomplete or total absence of the sellar diaphragm
    • Kallmann syndrome: hereditary syndrome characterized by gonadotropin deficiency with hypo or anosmia (inability to recognize odors).
    • Isolated GH deficiency
    • Trauma following childbirth

Functional causes of hypopituitarism

  • Nervous anorexia
  • Malnutrition
  • Dwarfism

Now let's see some of these causes in more detail:

As for theacquired hypopituitarism, the main causes are neoplasms that somehow involve the pituitary gland, vascular, autoimmune and iatrogenic causes.

The neoplasms: the most frequent cause of pituitary dysfunction in adults is Lpituitary adenoma, both of the secreting and non-secreting types. The adenomatous nodule can in fact compress the adjacent surrounding pituitary tissue, causing damage to the functioning pituitary cells and consequently a reduced secretion of pituitary hormones. Hormone deficiency is progressive, first affecting the gonadotropins (FSH and LH) and GH and then TSH and ACTH. Prolactin may be reduced, but more often it is increased due to the loss of dopamine inhibition, especially if the tumor is of the type that compresses the pituitary stalk.In children, however, the most frequent cause of hypopituitarism is the craniopharyngioma. Hypothalamic tumors, CNS tumors or metastases of other neoplasms can also induce hypopituitarism both due to direct compromise of the hypothalamic nuclei and by producing compression at the level of the pituitary stalk.

Iatrogenic damage. Surgery in the sellar and parasellar region, especially transcranial, and radiation therapy in the neck or head region are relatively frequent causes of hypopituitarism. Permanent hypopituitarism can also develop following radiotherapy, which persists years after exposure.

Discontinuation of corticosteroid therapy: a very frequent cause of selective hypopituitarism and the sudden withdrawal of long-term glucocorticoid therapy for non-endocrine diseases. Prolonged treatment with corticosteroids in fact causes a hypofunction of the pituitary-adrenal axis, as it exerts a negative feedback on the secretion of ACTH, causing secondary hypotrophy at the adrenal level; consequently the sudden interruption of the administration of exogenous corticosteroids is not followed by the immediate resumption of the secretion of ACTH and cortisol, precisely because of the "sluggish" adrenal gynadola, no longer used to work. In these patients, it is therefore necessary to gradually reduce (taper) the cortisone dose to allow the progressive functional recovery of the pituitary-adrenal axis.

Autoimmunity: lymphocytic hypophysitis is an autoimmune process involving the adenohypophysis and which in 50% of cases is associated with other endocrinopathies of autoimmune origin (especially it is accompanied by Hashimoto's thyroiditis). It mainly affects women and in 60% of cases it appears after pregnancy. In these patients the presence of autoantibodies directed against one or more types of pituitary cells was found.

Vascular causes: pituitary apoplexy is caused, in most cases, by a spontaneous hemorrhagic infarction of a pituitary tumor which involves the sudden destruction of the hypophysis. In some cases the pituitary apoplexy completely destroys the tumor so that, once the acute event has been overcome, paradoxically you can have the remission of the symptoms and complete recovery of the pituitary function. Another cause of hypopituitarism, now quite rare, is Sheehan's syndrome, in which ischemic necrosis of hypolysis occurs during or immediately after childbirth. During pregnancy, the pituitary gland increases in size and therefore also increases its metabolism; therefore, the bleeding that can occur at the time of delivery can lead to a critical reduction in the blood supply to the gland. Other conditions, fortunately rare, which can alter the blood flow level pituitary are diabetes mellitus, sickle cell anemia, head trauma, anticoagulant therapy or congenital and acquired defects of coagulation.

Signs and symptoms of hypopituitarism

What are the main symptoms of impaired pituitary function? The clinical manifestations of hypopituitarism depend on the type of hormone deficient, the degree of insufficiency and age of onset. For example, in the developmental age idiopathic or congenital forms prevail, essentially manifesting as growth retardation due to GH deficiency, delayed puberty due to a deficiency of gonadotropins, and absence of adrenarch (i.e. that phase of the developmental age that precedes and merges with actual puberty, in which the definitive maturation of the adrenal cortex takes place (due to a deficiency of ACTH), while the lack of secretion of other pituitary hormones causes milder clinical signs. TSH deficiency induces different clinical pictures depending on the age at which it occurs: the congenital deficiency (very rare) can cause lethargy, difficulty in sucking, prolonged jaundice, hypotonia, hypothermia and mental retardation which occur later. The appearance of deficits during the childhood period causes growth retardation and absent or delayed pubertal development, but is usually accompanied by a normal development of the intellectual sphere.

In the'adulthood the acquired forms prevail. first of all the pituitary macroadenoma, in which the process of gradual destruction of the pituitary gland compromises first the gonadotropins, then the GH, the TSH and finally the ACTH. Evolution is often devoid of major symptoms, and natural history is progressive, except in cases of trauma, Sheehan's syndrome, and pituitary apoplexy. Clinical signs and symptoms, from mild to very evident, are similar to those of the corresponding primitive forms, but are usually characterized by lesser severity, as a residual function of the target glands of the pituitary hormones often remains, even in the absence of the latter. Here is a list of the main signs and symptoms of hypopituitarism, classified according to the type of hormonal deficiency from which they derive:

Symptoms of hypopitoitis:

Deficit of FSH and LH in women:

  • oligo-amenorrhea (little or no menstruation),
  • decreased libido (decreased sexual desire),
  • dyspareunia (pain during sexual intercourse),
  • hot flashes,
  • thinning of pubic and axillary hair
  • vaginal dryness,
  • atrophy of the vaginal mucosa,

Deficit of FSH and LH in humans:

  • reduction in testicular size,
  • decreased libido (decreased sexual desire),
  • impotence,
  • sterility,
  • rarefaction of the beard of hair on pubis and armpits
  • gynecomastia (breast enlargement)

Deficit of FSH and LH in the child:

  • delayed puberty

GH deficiency in adults

  • increased increase in body fat, dyslipldemia (hypertriglyceridaemia and hypoercolesterolemia),
  • reduction in muscle mass
  • decreased muscle strength,
  • rarefaction of bone tissue,
  • alterations of the cardiovascular system with an increase in cardiovascular risk

GH deficiency in the child:

  • growth retardation or arrest

TSH deficiency in adults:

  • reduced tolerance to cold and hypothermia
  • asthenia (tiredness),
  • drowsiness,
  • constipation
  • dry and pale scalp, dry hair,
  • slowing of mental activity,
  • depression,
  • bradycardia (slow heart rate)
  • hypotension (low blood pressure)

TSH deficiency in childhood and adolescence:

  • growth retardation,
  • delayed puberty
  • impaired dentition (delayed tooth development)

TSH deficiency in the newborn:

  • lethargy,
  • difficulty in sucking the nipple,
  • jaundice (yellowing of the skin),
  • muscle hypotonia (poor muscle tone),
  • hypothermia,
  • mental delay

ACTH deficiency in adults:

  • perennial fatigue (asthenia),
  • weight loss (weight loss)
  • arterial hypotension,
  • nausea and / or vomiting,
  • hypoglycemia (reduced blood glucose levels),
  • skin hypopigmentation

ACTH deficiency in the child:

  • absence of adrenarca

The prolactin deficiency instead it involves the difficulty or actual impossibility of breastfeeding after childbirth.NB: in addition to the signs and symptoms of reduced secretion of pituitary hormones, the clinical manifestations of the pathology that caused hypopituitarism often overlap. Let's see what are the symptoms of two of the most frequent conditions favoring hypopituitarism:

  1. Pituitary adenomas. If the tumor is secreting, the patient has the clinical characteristics of the hormone secreted in excess; the most frequent are prolactinoma (galactorrhea, oligo-amenorrhea, impotence) and GH-secreting adenoma that causes acromegaly. There are also symptoms caused by the compression of the tumor on nearby structures for which the patient complains of painkiller resistant headache and / or visual disturbances due to compression of the nerve tract of the optic chiasm.
  2. Pituitary apoplexy. It is an acute event; the patient complains of severe headache in the frontal region with nausea and vomiting, visual disturbances, ophthalmoplegia due to compression of the III, IV and VI cranial nerve, sensory clouding that can progress to coma; hypopituitarism sets in within two weeks of the event.

Hypopituitarism Diagnosis

To diagnose pituitary insufficiency, it is necessary to test all hormones produced by the pituitary and those produced by the target glands these hormones are aimed at. To test for a possible gonadotropin deficiency, LH, FSH, testosterone (in men) and estradiol (in women) should be measured first, and eventually prolactin, GnRH (gonadotropin-releasing hormone) in a second step and, in men, perform a spermiogram.To evaluate a possible thyroid hormone deficiency, the TSH and the thyroid hormones fT3 and fT4, and possibly the TRH (thyrotropin releasing hormone, or thyrotropin releasing hormone), should be measured. basal adrenocorticotropic hormone (ACTH) dosage and after stimulation and basal cortisolemia dosage at 8 am and after night suppression test with 8 mg of dexamethasone Growth hormone deficiency (GH) is tested by performing the insulin stimulus test and GHRH (GH-releasing hormone) stimulation tests with arginine (GHRH + arginine) or with pyridostigmine (GHRH + pyridostigmine)The execution of CT of the skull and sella turcica or of MRI (magnetic resonance imaging) are also fundamental in radiological diagnostics.

Hypopituitarism therapy

The therapy of pituitary gland insufficiency is linked to the type and extent of pituitary secretion deficiency, and aims to make up for specific hormonal deficiencies pharmacologically. Specifically, the deficiency of ACTH secretion, and therefore the adrenocortical insufficiency that consequently, it is compensated with corticosteroid therapy, usually one of the following:

  • cortisone acetate (cortone acetate) at the starting dosage of 25 mg in the morning + 12.5 mg in the evening
  • prednisone (deltacortene) at a dosage of 5 mg in the morning + 2.5 mg in the evening

The deficiency of TSH, and therefore of thyroid hormones, is compensated with the replacement therapy with levothyroxine (Eutirox or Tirosint the most common trade names) at the initial dosage of 1.2-1.5 µg / kg every day. it is compensated in women with estrogen-progestogen therapy, and in men with testosterone therapy or with testosterone esters administered intramuscularly or transdermally. Growth hormone deficiency is treated with recombinant hGH.

Hypopituitarism Prognosis

People with hypopituitarism treated correctly they can make eyesight fairly similar to that of people with normal pituitary function. Nevertheless, the reduced tolerance to stress and the presence of frequent comorbidities, that is, concomitant diseases, are factors that can somehow justify the reduction in the average life expectancy that characterizes people with pituitary insufficiency. The fundamental thing to do in any degree of hypipotuitism is to rely on a valid endocrinologist who follows the course of the disease over time and who can recommend the most appropriate diagnostic and therapeutic procedure.


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