Underactive Pituitary Gland (Hypopituitarism), Hormone Deficiency

The pituitary gland is the small pea-sized gland located at the base of the skull. It produces many trophic hormones – these are hormones which act on other endocrine glands in order to stimulate or suppress hormonal activity. Its effect on multiple systems and almost all the other endocrine glands in the body has earned it the title of ‘master gland‘. It can essentially regulate any humoral process in the body. The actions of the pituitary gland are largely regulated by the hypothalamus, a neighboring site which is sensitive to different signals from other parts of the body. Essentially it is the hypothalamus that coordinates most of the pituitary activity and should always be considered in pituitary diseases as hypothalamic disorders may be the primary condition.

Pituitary Hormones

The pituitary gland has an anterior and posterior lobe which secrete different hormones. It is the anterior pituitary that is the most active and secretes majority of the trophic hormones. This includes :

• adrenocorticotropin hormone (ACTH)
• follicle stimulating hormone (FSH)
• growth hormone (GH)
• luteinizing hormone (LH)
• prolactin
• thyroid stimulating hormone (TSH)

The posterior pituitary only secretes two hormones – antidiuretic hormone (ADH) and oxytocin.

Pituitary disease either causes an overactivity or underactivity. An overactive pituitary gland is known as hyperpituitarism while an underactive pituitary gland is known as hypopituitarism.

What is hyperpituitarism?

Hypopituitarism is a deficiency of pituitary (trophic) hormones associated with underactivity of the pituitary gland. Despite the rather small size of the pituitary gland, hormone deficiency only arises when there is damage or destruction to significant amounts of pituitary tissue. In hypopituitarism is is primarily the anterior pituitary that is compromised thereby leading to a deficiency of one or more hormones. Rarely this can involve all the anterior pituitary hormones and this is known as panhypopituitarism. Posterior pituitary underactivity leads to a deficiency of ADH.

Hypopituitarism is not always a total deficiency – often there is only lower than normal levels of the specific trophic hormone which do not increase despite stimulus from the  hypothalamus and other feedback mechanisms. Being the master gland, a deficiency of a trophic hormone leads to an underactivity of the target gland. The presentation of hypopituitarism can differ drastically from person to person and depends entirely on the portion of the pituitary gland that is compromised.

Causes of an Underactive Pituitary Gland

The causes of hypopituitarism may include any disease or disorder that occurs in the pituitary gland itself (primary), surrounding tissue which then impacts on the pituitary gland or in the hypothalamus which regulates the pituitary (secondary).

Tumors and Growths

A pituitary adenoma is a well known cause of hyperpituitarism (overactivity of the pituitary gland) but large lesions can exert pressure on the pituitary gland thereby leading to underactivity. An adenoma is a benign tumor and this can sometimes cause overactity followed by underactivity of the pituitary gland. Metastatic lesions (cancer) are more likely to cause hypopituitarism which is progressive and eventually leads to panhypopituitarism. Carcinoma of the pituitary is very rare. Cysts may also be responsible for hypopituitarism.

Other growths (benign and malignant) and cysts of surrounding tissue may also be responsible for hypopituitarism. This includes a craniopharyngioma, meningioma, leukemia, lymphoma, chordoma, germinoma (pinealoma) and an arachnoid cyst.  Of these growths, a pituitary adenoma, craniopharyngioma and meningioma are the most common.

Trauma

Injury to the pituitary gland may be a due to :

• Head injury
• Surgery to the pituitary gland or sella (the groove where the pituitary gland sits in the skull).
• Radiation to the head and cranium specifically.

Inflammatory and Infiltrative Lesions

Inflammation of the pituitary gland may occur  either due to infectious or non-infectious causes. Infections include tuberculosis, syphilis, encephalitis, meningitis and a pituitary abscess. Non-infectious causes includes radiation therapy (injury), sarcoidosis (autoimmune), lymphocytic hypophysitis (granulomatous) and hemochromatosis (blood disorders).

Ischemia and Hemorrhage

A partial or complete loss of blood supply or oxygen availability may lead to ischemia of the pituitary tissue. This eventually leads to necrosis (cell death).

One of the important causes of pituitary ischemia is a condition known as Sheehan syndrome (post-partum necrosis). The anterior pituitary enlarges during pregnancy but is not accompanied by a simultaneous increase in blood supply. If there is any significant blood loss during delivery, the already limited blood supply to the anterior pituitary is further compromised.

Other causes of ischemic necrosis includes raised intracranial pressure, sickle cell disease, head trauma, hypovolemic shock (for any other reason) and disseminated intravascular coagulation (DIC). Pituitary apoplexy is a condition where there is sudden and often severe bleeding in the pituitary gland often associated with a pituitary adenoma. This condition is a medical emergency.

Genetic

Most genetic causes of hypopituitarism are due to a congenital deficiency of one or more releasing hormones from the hypothalamus. This includes GnRH gonadotrophin-releasing hormone (GnRH) /Kallmann syndrome, growth hormone-releasing hormone (GHRH), thyrotrophin-releasing hormone (TRH) and corticotrophin-releasing hormone (CRH). These hormones act on the anterior pituitary to stimulate the secretion of the respective trophic hormone.

Signs and Symptoms

The clinical presentation depends on the trophic hormone deficiency.

• Anterior pituitary
  • ACTH – adrenal insufficiency (underactive adrenal cortex)
  • FSH and LH – hypogonadism (underactive gonads)
  • GH – failure to thrive (FTT)
  • TSH – hypothyroidism (underactive thyroid gland)
• Posterior pituitary
  • ADH – diabetes insipidus

Certain causes, namely progressive lesions like cancer, will cause destruction of the tissue over time and this may first be seen a marked deficiency of one trophic hormone only to be followed by another. This continues to contribute to the overall clinical presentation and can be confusing. A characteristic sequence of events may present in the following order :

• Growth hormone deficiency is the first to be seen – fatigue, weight loss and muscle weakness
• LH and FSH deficiency then follows – loss of libido, menstrual irregularity (women), gynecomastia and low sperm count (men)
• ACTH deficiency and therefore low cortisol levels are seen – hypoglycemia, hypotension, dehydration, weight loss and fatigue