Hypofunction of anterior pituitary

The endocrine system

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The endocrine system affects all aspects of body function, including growth and development, energy metabolism, muscle and adipose tissue distribution, sexual development, fluid and electrolyte balance, inflammation and immune responses.

There are two types of organization of the endocrine system: cerebropituitary type and pituitary-independent type.

Cerebropituitary type includes the brain cortex, hypothalamus, anterior pituitary, peripheral endocrine gland, and the target cells. The brain cortex exerts neurogenic influence on the hypothalamus which produces liberins or statins. The hypothalamic hormones are secreted into the pituitary portal system and affect trophocytes producing tropins (e.g. ACTH, gonadotropins). The latter are secreted into general circulation and reach the peripheral endocrine glands where they exert stimulating or inhibitory effect.

In pituitary-independent system the pituitary stage is omitted. For example, parathyroid gland or beta-cells of the pancreas are not regulated by pituitary trophins.

Endocrinopathy can result from hormone deficiency (hypofunction), hormone excess (hyperfunction), resistance to hormone action, or constitutive mutations, that activate hormone response systems in the absence of ligand.

Primary, Secondary, and Tertiary Disorders

Endocrine disorders in general can be divided into primary,

secondary, and tertiary groups.

Primary defects in endocrine function originate in the target gland responsible for producing the hormone.

In secondary disorders of endocrine function, the target gland is essentially normal, but its function is altered by defective levels of stimulating hormones from the pituitary system. For example, adrenalectomy produces a primary deficiency of adrenal corticosteroid hormones.

Removal or destruction of the pituitary gland eliminates ACTH stimulation of the adrenal cortex and brings about

a secondary deficiency.

A tertiary disorder results from hypothalamic dysfunction (as may occur with craniopharyngiomas or cerebral irradiation); thus, both the pituitary and target organ are understimulated.

Causes of hypofunction of an endocrine gland

Congenital defects can result in the absence or impaired development of the gland or the absence of an enzyme needed for hormone synthesis.

The gland may be destroyed by a disruption in blood flow, infection, inflammation, autoimmune responses, or neoplastic growth.

There may be a decline in function with aging, or the gland may atrophy as the result of drug therapy or for unknown reasons.

Some endocrine-deficient states are associated with receptor defects (Peripheral (non-glandular) mechanism of hormone activity disturbance: blockade of hormonal receptors, hormone receptors may be absent, the receptor binding of hormones may be defective, or the cellular response to the hormone may be impaired.

In some cases a gland may produce a biologically inactive hormone or that an active hormone may be destroyed by circulating antibodies before it can exert its action.

Hyperfunction usually is associated with excessive hormone production. This can result from excessive stimulation and hyperplasia of the endocrine gland or from a hormoneproducing tumor of the gland. An ectopic tumor can produce hormones; for example, certain bronchogenic tumors produce hormones such as antidiuretic hormone (ADH) and adrenocorticotropic hormone (ACTH).

The pituitary gland and hypothalamus

The pituitary gland and hypothalamus are so closely interlinked that diseases of the pituitary gland involve the hypothalamus, and the hypothalamus dysfunctions cause secondary changes in the pituitary.

Functionally diseases of the pituitary can be classified as 

i) Hypopituitarism.

 ii) Hyperpituitarism;

Causes of hypopituitarism

- Tumors and mass lesions—pituitary adenomas, cysts, metastatic cancer, and other lesions

- Pituitary surgery or radiation

- Infiltrative lesions and infections—hemochromatosis, lymphocytic hypophysitis

- Pituitary infarction—infarction of the pituitary gland after substantial blood loss during childbirth (Sheehan’s syndrome)

- Pituitary apoplexy—sudden hemorrhage into the pituitary gland

- Genetic diseases—rare congenital defects of one or more pituitary hormones

- Empty sella syndrome—an enlarged sella turcica that is not entirely filled with pituitary tissue

- Hypothalamic disorders—tumors and mass lesions

(e.g., craniopharyngiomas and metastatic malignancies),

hypothalamic radiation, infiltrative lesions (e.g., sarcoidosis),

trauma, infections.

Hypopituitarism is associated with increased morbidity and

mortality.

Hypofunction of anterior pituitary

Adenohypophyseal hypofunction is developed due to destruction of the anterior lobe of more than 75% because the anterior pituitary has a large functional reserve. Two important syndromes are: 1)panhypopituitarism and 2)dwarfism.

1. Panhypopituitarism. Three most common causes of panhypopituitarism are:

1. Non-secretory (chromophobe) adenoma, 2. Sheehan's syndrome and Simmond's disease, and 3) empty-sella syndrome.

Sheehan's syndrome it is pituitary insufficiency occurring due to postpartum pituitary necrosis. The main pathogenetic mechanism underlying Sheehan's necrosis is the enlargement of the pituitary occurring during pregnancy which may be damaged by hypotensive shock, DIC following delivery, traumatic injury to vessels, and excessive haemorrhage. The first clinical manifestation of Sheehan's syndrome is failure of lactation following delivery which is due to deficiency of prolactin.

The causes of Simmond's disease may be pituitary adenomas, pituitary surgery or radiation, ischemic necrosis, syphilis, tuberculosis, metastatic carcinoma, trauma ect.

The common signs of Sheehan's syndrome and Simmond's disease include loss of body (axillary and pubic) hair, amenorrhoea, sterility and loss of libido, premature aging, progressive emaciation, low blood pressure, fatigue, hyponatreamia. The sign of melanocyte-stimulating hormone loss is pallor. Concomitant deficiency of TSH and ACTH may result in hypothyroidism and adrenocortical insufficiency.

Empty-sella syndrome. Most commonly, it results from defect in diaphragma sella that allows the arachnoidea mater and cerebrospinal fluid to penetrate into the sella resulting compression of the pituitary Other less common causes are: Sheehan's syndrome, infarction and scarring, irradiation damage, or surgical removal of the gland.

       2) Pituitary dwarfism. Most commonly, isolated GH deficiency is the result of an inherited autosomal recessive disorder. Less often it may be due to a pituitary adenoma or craniopharyngioma, infarction and trauma to the pituitary. The clinical features of inherited cases appear after one year of age. These include proportionate retardation in growth of bones, normal mental state for age, poorly-developed genitalia, delayed puberty and episodes of hypoglycaemia.

       Hypofunction of posterior pituitary and hypothalamus is rare.

Deficient secretion of ADH causes diabetes insipidus. It can result from: inflammatory and neoplastic lesions of the hypothalamo-hypophyseal axis, destruction of neuro-hypophysis due to surgery, radiation, traumas of head. The main features are excretion of large volume of dilute urine of low specific gravity (below 1.010); serum sodium and osmolality are increased owing to excessive renal loss of free water resulting polyuria and polydipsia. May develop life-threatening dehydration.

Hyperpituitarism

Hyperpituitarism is characterised by oversecretion of one or more of the pituitary hormones.

Three common syndromes of adenohypophyseal hyperfunction are: gigantism and acromegaly, hyperprolactinaemia and Cushing's disease.

1. Gigantism and acromegaly. Both these clinical syndromes result from excess of growth hormone (GH), most commonly by somatotroph adenoma.

Gigantism is produced when GH excess occurs in prepubertal period. The main clinical feature in gigantism is the excessive and proportionate growth of the child. There is enlargement and thickening of the bones resulting in considerable increase in height and enlarged thoracic cage.

Acromegaly results when there is overproduction of GH in adults following cessation of bone growth and is more common than gigantism. The term 'acromegaly' means increased growth of extremities. There is enlargement of hands and feet, coarseness of facial features with increase in soft tissues, prominent supraorbital ridges and prognathism (a more prominent lower jaw and protrusion of the lower teeth in front of upper teeth). Other features include enlargement of the tongue and lips, thickening of the skin and kyphosis. Sometimes, may be thyrotoxicosis, and gonadotropin insufficiency causing amenorrhoea in the females and impotence in the male, generalized muscle weakness, hypertension, arthritis, congestive heart failure.

2. Hyperprolactinaemia is the excessive production of prolactin (PRL), most commonly by prolactinoma. Several classes of drugs can cause hyperprolactinaemia, including dopamine receptor antagonists such as neuroleptic drugs (phenothiazines, haloperidol) and antihypertensive drugs such as reserpine, which inhibit dopamine storage. Other causes of hyperprolactinaemia include estrogens, renal failure, and hypothyroidism. In the female, hyperprolactinaemia causes amenorrhoea-galactorrhoea syndrome characterized clinically by infertility and expression of milk from breast, not related to pregnancy or puerperium. In the male, it may cause impotence or reduced libido.

       3. Cushing's Disease or pituitary-dependent hypercortisolism (about 60-70% cases of hypercortisolism) results from АСTН excess. Most frequently, it is caused by corticotroph adenoma. The adrenal glands in patients with Cushing's disease are characterized by of nodular cortical hyperplasia caused by elevated levels of ACTH.