Hypopituitarism

Hypopituitarism: Overview

Hypopituitarism is a general term that refers to any under-performance of the pituitary gland.  This is a clinical definition used by endocrinologists and is interpreted to mean that one or more functions of the pituitary are deficient.  The term may refer to both anterior and posterior pituitary gland failure.

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Below is a list of the hormones secreted by the pituitary and their functions:

  • growth hormone (stimulates cell division and bone growth)
  • thyroid stimulating hormone (stimulates the thyroid gland to secrete hormones that affect body metabolism)
  • adrenocorticotropic hormone (stimulates the adrenal gland to secrete hormones that affect metabolism)
  • prolactin (stimulates female breast development and milk production)
  • luteinizing hormone (controls sexual function in males and females)
  • follicle stimulating hormone (controls sexual function in males and females)
  • melanocyte stimulating hormone (controls pigmentation of the skin)
  • antidiuretic hormone (controls water loss by the kidneys)
  • oxytocin, (stimulates contraction of the uterus during labor and milk release from the breasts).

Growth hormone is necessary in children for growth, but also appears necessary in adults to maintain normal body composition (muscle and bone mass).  It may also be helpful for maintaining an adequate energy level, optimal cardiovascular status and some mental functions.

Incidence; Causes and Development; Contributing Risk Factors

The incidence is 1 out of 10,000 people.

In cases of hypopituitarism, single or multiple hormone deficiencies are present.  The deficiencies affect the target organ activity or secretion (the thyroid; the adrenals; or the gonads, which includes both female and male sexual development and function).  Causes of hypopituitarism are tumors or lesions of various origins, congenital defects, trauma, radiation, surgery, encephalitis, hemochromatosis, and stroke.  In children, the condition results in slowed growth and development and is known as dwarfism.  The cause may also be unknown.

Deficient pituitary gland function can result from damage to either the pituitary or the area just above the pituitary, namely the hypothalamus.  The hypothalamus contains releasing and inhibitory hormones that control the pituitary.  Since these hormones are necessary for normal pituitary function, damage to the hypothalamus can also result in deficient pituitary gland function.  Injury to the pituitary can occur from a variety of insults, including damage from an enlarging pituitary tumor, irradiation of the pituitary gland, limited blood supply (as experienced in a stroke), trauma or abnormal iron storage (hemochromatosis).  There appears to be a predictable loss of hormonal function with increasing damage.  The progression from most vulnerable to least vulnerable is usually as follows:

  • Growth hormone (GH)
  • Gonadotropins (LH and FSH which control sexual/reproductive function)
  • TSH (which control thyroid hormone release)
  • ACTH (which controls adrenal function)

Risk factors are related to the cause and may include previous history of diabetes insipidus, previous history of adrenal insufficiency, previous history of a pituitary tumor, cessation of menses in a premenopausal woman, and short stature.

Signs and Symptoms

Symptoms of growth hormone deficiency in adults include:

  • fatigue
  • poor exercise performance
  • social isolation
  • weakness
  • sensitivity to cold
  • decreased appetite
  • weight loss
  • abdominal pain
  • low blood pressure
  • headache
  • visual disturbances
  • short stature (< 5 feet) if onset is during a growth period
  • loss of armpit or pubic hair
  • in women: cessation of menses, infertility, or failure to lactate
  • in men: decreased sexual interest, loss of body or facial hair
  • in children: slowed growth and sexual development

Note: Symptoms may develop slowly and may vary greatly depending upon the severity of the disorder and the number of deficient hormones and their target organs.

Additional symptoms that may be associated with this disease:

  • weight gain (unintentional)
  • joint stiffness
  • hoarseness or changing voice
  • hair loss
  • facial swelling

Gonadotropin Deficiency
Women develop ovarian suppression with irregular periods or absence of periods (amenorrhea), infertility, decreased libido, decreased vaginal secretions, breast atrophy, and osteoporosis.  Blood levels of estradiol are low.  Estrogen should be replaced along with progesterone.  Annual pap smears and mammograms are mandatory.

Men develop testicular suppression with decreased libido, impotence, decreased ejaculate volume, loss of body and facial hair, weakness, fatigue and often anemia.  On testing, blood levels of testosterone are low and should be replaced.  In the United States, testosterone may be given as a biweekly intramuscular injection, in a patch form or as a gel or cream preparation.  In some countries, oral preparations of testosterone are available.

Thyroid Stimulation Hormone (TSH) Deficiency
Deficiency of thyroid hormone causes a syndrome consisting of decreased energy, increased need to sleep, intolerance of cold (inability to stay warm), dry skin, constipation, muscle aching and decreased mental functions.  This variety of symptoms is very uncomfortable and is often the symptom complex that drives patients with pituitary disease to seek medical attention.  Replacement therapy consists of a either T4 (thyroxine) and/or T3 (triiodothyronine).  The correct dose is determined through experimentation and blood tests.

Adrenal Hormone Deficiency
Deficiency of ACTH resulting in cortisol deficiency is the most dangerous and life-threatening of the hormonal deficiency syndromes.  With gradual onset of deficiency over days or weeks, symptoms are often vague and may include weight loss, fatigue, weakness, depression, apathy, nausea, vomiting, anorexia and hyperpigmentation.  As the deficiency becomes more serious or has a more rapid onset (Addison crisis), symptoms of confusion, stupor, psychosis, abnormal electrolytes (low serum sodium, elevated serum potassium), and vascular collapse (low blood pressure and shock) can occur.  Treatment consists of cortisol administration or another similar steroid (like prednisone).  For patients with acute adrenal insufficiency, rapid intravenous administration of high dose steroids is essential to reverse the crisis.

Posterior Pituitary – Antidiuretic Hormone (ADH) Deficiency
Replacement of antidiuretic hormone resolves the symptoms of increased thirst and urination seen in diabetes insipidus.  Antidiuretic hormone (ADH) is currently replaced by administration of a synthetic type of ADH either by subcutaneous injection, intranasal spray, or by tablet, usually once or twice a day.

Diagnosis and Tests

Diagnosis of hypopituitarism must confirm hormonal deficiency due to abnormality of the pituitary gland, and rule out disease of the target organ.

  • Cranial CT scan, revealing a mass (aggregation of cells) consistent with pituitary tumor
  • Cranial MRI, revealing a pituitary mass
  • Serum luteinizing hormone, decreased
  • Serum follicle stimulating hormone, decreased
  • Serum testosterone level, decreased
  • Serum estradiol, decreased
  • Serum cortisol, decreased
  • Serum sodium, reduced
  • Serum highly-sensitive ACTH, decreased
  • T4, decreased
  • Serum thyroid stimulating hormone, decreased
  • Serum thyroid stimulating hormone response to thyroid-releasing hormone, decreased

This disease may also alter the results of the following tests:

  • Growth hormone
  • Glucose test
  • Estriol – urine
  • 17-ketosteroids
  • 17-hydroxycorticosteroids

Treatment and Prevention

If the hypopituitarism is caused by a lesion or tumor, removal of the tumor or radiation or both are treatment options.  Hormone replacement therapy may be required permanently after such a procedure.

Endocrine substitution therapy is indicated for replacement of hormones for the affected organs.  These include corticosteroids, thyroid hormone, sex hormones (testosterone for men and estrogen for women), and growth hormone.  Drugs are available to treat associated infertility in men and women.

Growth hormone is only available in injectable form and is usually given 6-7 times per week.  Homeopathic GH or IGF has been proven to provide benefits in blinded trials.

In most cases, the disorder is not preventable.  Awareness of risk may allow early diagnosis and treatment.

Prognosis; Complications; Seek medical attention if...

Hypopituitarism is usually permanent and requires life-long treatment; however, a normal life span can be expected.

Side-effects of drug therapy can develop.

Call your health care provider if symptoms of hypopituitarism develop.

Signs, symptoms & indicators of Hypopituitarism:

Lab Values - Hormones

Having low-normal/having low TT4 level

When TSH and Total T4 are both low, a poorly-functioning pituitary gland is suspected.

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Hypopituitarism could instead be:

Autoimmune

Recommendations for Hypopituitarism:

Hormone

DHEA

Six months of treatment with DHEA (at 30mg per day if over 45 years of age and 20mg per day if under 45 years of age) induced androgen effects on skin and axillary and pubic hair in a study of 38 women with androgen deficiency due to hypopituitarism.  Improved alertness, stamina and initiative was also reported.  [J Clin Endocrinol Metab 2002;87(5): pp.2046-2052]

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