National Organization for Rare Disorders, Inc.

ACTH Deficiency

It is possible that the main title of the report ACTH Deficiency is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • Adrenocorticotropic Hormone Deficiency, Isolated

Disorder Subdivisions

  • None

Related Disorders List

Information on the following diseases can be found in the Related Disorders section of this report:

  • Addison's Disease
  • Adrenal Hyperplasia, Congenital
  • Adrenal Insufficiency, Secondary

General Discussion

ACTH deficiency arises as a result of decreased or absent production of adrenocorticotropic
hormone (ACTH) by the pituitary gland. A decline in the concentration of ACTH in the blood
leads to a reduction in the secretion of adrenal hormones, resulting in adrenal
insufficiency (hypoadrenalism). Adrenal insufficiency leads to weight loss, lack of
appetite (anorexia), weakness, nausea, vomiting, and low blood pressure (hypotension).
Because these symptoms are so general, the diagnosis is sometimes delayed or missed
entirely. For that reason, some clinicians believe the disorder to be more common than
previously thought.


ACTH deficiency is a disorder that usually starts during adulthood, although a few cases
have begun during childhood. Symptoms include weight loss, lack of appetite (anorexia),
muscle weakness, nausea and vomiting, and low blood pressure (hypotension). Low blood levels of sugar and dilutional hyponatremia (low blood sodium levels) may occur; however, blood potassium levels are typically normal as affected patients are deficient in glucocorticoids and not mineralocorticoids due to their intact renin-angiotensin-aldosterone system. The pituitary hormone ACTH may be undetectable in blood tests, and the level of the adrenal hormone cortisol is abnormally low. Concentration of the adrenal cortex hormones 17-hydroxy- and 17-ketosteroid, are also abnormally low in the urine. Some adrenal hormones that are decreased are precursors of male sex hormones and are
also known as "pre-androgens".

Although males with this disorder usually have a normal hair pattern, females have very little pubic and underarm (axillary) hair. In contrast to Addison's disease, skin
pigmentation usually remains normal. Emotional symptoms may range from depression to


The exact cause(s) of ACTH deficiency remain unknown. A defect in the brain's hypothalamus or in the pituitary gland may cause the deficiency. Also, there is a congenital (present at birth) form of ACTH deficiency that has been tracked to mutations of the T-box 19 (TBX19) gene (also referred to as TPIT) on the long arm of chromosome one (1q23-q24) and the corticotropin releasing hormone (CRH) gene on the long arm of chromosome eight (8q13). The inheritance pattern is thought to be autosomal recessive.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, chromosome 1q23-q24 refers to a region on the long arm of chromosome 1 between bands 23 and 24. Similarly chromosome 8q13
refers to the band numbered 13 on the long arm of chromosome 8. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are
on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms.

The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Affected Populations

Symptoms of ACTH deficiency most often occur in adults, but the disorder may also be diagnosed in infancy. The disorder affects males and females in equal numbers.

Related Disorders

Symptoms of the following disorders may be similar to those of ACTH Deficiency. Comparisons may be useful for a differential diagnosis:

Congenital Adrenal Hyperplasia (CAH) is a group of disorders resulting from defective synthesis of the corticosteroid hormones of the adrenal gland. The adrenal gland becomes
enlarged. The adrenal gland produces "male" sex hormones ("pre-androgens") in both males and females because these are overproduced in certain forms of CAH. The external genitals of some females with this disorder become masculinized to various degrees. Lack of glucocorticoids, especially cortisol, causes various metabolic problems. Lack of mineralocorticoids, primarily aldosterone, causes salt and water imbalances which may be life threatening. (For more information on this disorder, choose "Adrenal Hyperplasia" as your search term in the Rare Disease Database.)

Addison's Disease (primary adrenal insufficiency) usually develops later in life. It is
characterized by chronic diminished adrenocortical function. The resulting deficiencies of
glucocorticoids and mineralocorticoids cause weakness, low resistance to physiological
stress, metabolic abnormalities, and circulatory insufficiency. Many Addison's patients
have sufficient levels of these corticosteroids to permit adequate functioning under normal
circumstances. Even mild physiologic stress, however, can precipitate an Addisonian crisis consisting of circulatory collapse and, if untreated, death. With replacement of the
essential adrenal hormones, Addison's patients can lead a normal life. (For more
information on this disorder, choose "Addison" as your search term in the Rare Disease

Secondary Adrenal Insufficiency results from insufficient production or release of the
pituitary hormone ACTH. It may be caused by prolonged corticosteroid therapy. ACTH
production doesn't return to normal for several months after completion of the therapy. Central nervous system tumors affecting the pituitary gland, granulomatous disease, and death (necrosis) of the pituitary gland after a pregnancy (Sheehan's syndrome) also may cause adrenal insufficiency.

Standard Therapies

When ACTH deficiency is suspected, blood samples are taken for analysis, especially of the level of cortisol in the blood. Cortisol is the name of one of the hormones produced by the outer portion (cortex) of the adrenal glands. If the concentration of cortisol is low, it typically indicates a low concentration of ACTH. On occasion, an ACTH stimulation test may be administered.

Hormone replacement therapy with cortisol is the treatment of choice for this disorder. With such therapy, patients can lead a normal life.

Investigational Therapies

Information on current clinical trials is posted on the Internet at All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010

For information about clinical trials sponsored by private sources, contact:


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NIH/National Institute of Diabetes, Digestive & Kidney Diseases
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Genetic and Rare Diseases (GARD) Information Center
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Tel: (301)251-4925
Fax: (301)251-4911
Tel: (888)205-2311
TDD: (888)205-3223

The information provided in this report is not intended for diagnostic purposes. It is provided for informational purposes only. NORD recommends that affected individuals seek the advice or counsel of their own personal physicians.

It is possible that the title of this topic is not the name you selected. Please check the Synonyms listing to find the alternate name(s) and Disorder Subdivision(s) covered by this report

This disease entry is based upon medical information available through the date at the end of the topic. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder.

For additional information and assistance about rare disorders, please contact the National Organization for Rare Disorders at P.O. Box 1968, Danbury, CT 06813-1968; phone (203) 744-0100; web site or email

Last Updated:  3/5/2009
Copyright  1988, 1989, 2004, 2009 National Organization for Rare Disorders, Inc.

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Topic Contents
 Disorder Subdivisions
 Related Disorders List
 General Discussion
 Affected Populations
 Related Disorders
 Standard Therapies
 Investigational Therapies