ACTH Deficiency - National Organization for Rare Disorders (2023)

Saber

NORD thanks Andrew A. Bremer, MD, PhD, Department of Pediatrics, Division of Endocrinology, Vanderbilt University School of Medicine, for his assistance in preparing this report.

Synonym

  • adrenocorticotropic hormone deficiency, isolated

general illnesses

ACTH deficiency results from reduced or absent production of adrenocorticotropic hormone (ACTH) by the pituitary gland. A drop in ACTH levels in the blood leads to reduced secretion of adrenal hormones, resulting in adrenal insufficiency (hypoadrenalism). Adrenal insufficiency causes weight loss, loss of appetite (anorexia), weakness, nausea, vomiting, and low blood pressure (hypotension). Because these symptoms are so common, the diagnosis is sometimes delayed or missed altogether. Because of this, some doctors believe the disorder is more common than previously thought.

Signs and symptoms

ACTH deficiency can be congenital or acquired, and its manifestations are clinically indistinguishable from those of glucocorticoid deficiency. Symptoms include weight loss, loss of appetite (anorexia), muscle weakness, nausea and vomiting, and low blood pressure (hypotension). Low blood sugar levels and dilutional hyponatremia (low blood sodium levels) may occur; however, blood potassium levels are typically normal because affected patients are deficient in glucocorticoids rather than mineralocorticoids due to their intact renin-angiotensin-aldosterone system. The pituitary hormone ACTH may not be detected in blood tests, and levels of the adrenal hormone cortisol are abnormally low. Urinary levels of 17-hydroxycorticosteroids and 17-ketosteroids produced by the adrenal cortex are also abnormally low. Some depressed adrenal hormones are precursors of male sex hormones and are also known as "pre-androgens".

While men with this disorder usually have a normal pattern of hair, women may have very little pubic and underarm hair. In contrast to Addison's disease, skin pigmentation usually remains normal. Emotional symptoms can range from depression to psychosis.

causes

The exact cause(s) of ACTH deficiency are still unknown. A defect in the brain's hypothalamus or pituitary gland can cause the deficiency. There is also a congenital (present at birth) form of ACTH deficiency due to mutations in T-box 19 (TBX19) gene (also known as TPIT) on the long arm of chromosome one (1q23-q24) and the corticotropin-releasing hormone (CRH) on the long arm of chromosome eight (8q13). The inheritance pattern is believed to be autosomal recessive.

The chromosomes, present in the nucleus of human cells, carry the genetic information of each individual. Cells in the human body normally have 46 chromosomes. Pairs of human chromosomes are numbered 1 through 22 and the sex chromosomes are labeled X and Y. Males have an X and a Y chromosome, and females have two X chromosomes. Each chromosome has a short arm called a "p" and a long arm called "q". Chromosomes are divided into many bands which are numbered. For example, chromosome 1q23-q24 refers to a region on the long arm of chromosome 1 between bands 23 and 24. Likewise, chromosome 8q13 refers to band number 13 on the long arm of chromosome 8. The bands The numbered lines indicate the position of the thousands of genes present on each chromosome.

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

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If a person gets both a normal gene and a gene for the disease, he or she is a carrier of the disease but usually has no symptoms.

The risk of two carrier parents passing on the defective gene and therefore having an affected child is 25% with each pregnancy. The risk of having a carrier child like the parents is 50% with each pregnancy. There is a 25% chance that a child will receive normal genes from both parents and be genetically normal for that particular trait. The risk is the same for men and women.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (blood relatives) are more likely than unrelated parents to both be carriers of the same abnormal gene, increasing the risk of having children with a recessive genetic disorder.

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

(Video) What is a Rare Disease?

Affected Populations

Symptoms of ACTH deficiency are more common in adults, but the disorder can also be diagnosed in childhood. The disease affects men and women in equal numbers.

related diseases

The symptoms of the following disorders can resemble those of ACTH deficiency. Comparisons can be useful for a differential diagnosis:

Congenital adrenal hyperplasia (CAH) is a group of disorders resulting from defective synthesis of adrenal corticosteroid hormones. The adrenal gland is enlarged. In certain forms of CAH, the adrenal gland produces excessive amounts of "male" sex hormones ("pre-androgens") in both men and women. The external genitalia of some women with this disorder become masculinized to varying degrees. The lack of glucocorticoids, especially cortisol, causes various metabolic problems. Deficiencies in mineralocorticoids, especially aldosterone, cause salt and water imbalances that can be fatal. (For more information on this condition, select "Congenital Adrenal Hyperplasia" as a search term in the Rare Disease Database.)

Addison's disease (primary adrenal insufficiency) usually develops later in life. It is characterized by chronically reduced function of the adrenal cortex. The resulting lack of glucocorticoids and mineralocorticoids causes weakness, low resistance to physiological stress, metabolic abnormalities, and circulatory failure. Many Addison's patients have adequate levels of these corticosteroids to allow adequate functioning under normal circumstances. However, even mild physiological stress can trigger an Addisonian crisis, which consists of circulatory collapse and death if left untreated. With the replacement of essential adrenal hormones, Addison's patients can lead normal lives. (For more information on this condition, select "Addison" as a search term in the Rare Disease Database.)

Secondary adrenal insufficiency results from insufficient production or release of the pituitary hormone ACTH. May be caused by prolonged corticosteroid therapy. ACTH production does not return to normal for several months after therapy ends. Central nervous system tumors that affect the pituitary gland, granulomatous disease, and death (necrosis) of the pituitary gland after pregnancy (Sheehan syndrome) can also cause secondary adrenal insufficiency.

To diagnose

If ACTH deficiency is suspected, blood samples are taken for analysis, particularly of blood cortisol levels. Cortisol is the name of one of the hormones produced by the outer part (cortex) of the adrenal glands. When the cortisol level is low, it usually indicates low ACTH levels. Occasionally, an ACTH stimulation test may be done.

standard therapy

Treatment

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

investigative therapies

Information about ongoing clinical trials can be found on the Internet atwww.clinicaltrials.gov. All studies funded by the US government, and some supported by private industry, are published on this government website.

For information about clinical trials conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll Free: (800) 411-1222
TTY: (866) 411-1010
E-mail:[Email protected]

For information on privately-sponsored clinical trials, please contact:www.centerwatch.com

(Video) Natural History Studies for Rare Diseases

For information on clinical trials conducted in Europe, contact:https://www.clinicaltrialsregister.eu/

Contact for more information about ACTH deficiency:
Andrew A. Bremer, MD, PhD
Department of Pediatrics
Department of Endocrinology
Vanderbilt University School of Medicine
11134-A DOT 9170
2200 children's path
Nashville, TN 37232-9170
Tel: 615.936.1874
Fax: 615.875.7633
E-mail:[Email protected]

references

TEXT BOOKS
Berkow R., Hrsg. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:956-58.

Biere MH, Berkow R, editores The Merck Handbook, 17ª edição Whitehouse Station, NJ: Merck Research Laboratories; 1999:104-05.

Bennett JC, Plum F, editors Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co.; 1996:1215–1

Wilson JD, Foster DW, editors, Textbook of Endocrinology. 8th ed. Philadelphia, PA: W.B. Saunders Company; 1992:249.

NEWSPAPER ARTICLE
Agha A, Rogers B, Sherlock M et al. Anterior pituitary dysfunction in survivors of traumatic brain injury. J Clin Endocrinol Metab. 2004;89:4929-36.

N. Chikada, T. Imaki, M. Hotta et al. An assessment of bone mineral density in patients with Addison's disease; Isolated ACTH deficiency treated with glucocorticoid. Endocr J.2004;51:355-60.

Agha A, Liew A, Finucane F et al. Conventional glucocorticoid replacement therapies overtreat adult patients with partial ACTH deficiency. Clin Endocrinol (Oxf). 2004;60:688-93.

Selva KA, LaFranchi SH, Boston B. A new presentation of familial glucocorticoid deficiency (FGD) and recent literature review. J Pediatric Endocrinol Metab. 2004;17:85-92.

Hiroi N, Ichijo T, Tsuchida Y, et al. A trial of intranasal administration of ACTH (1-24) in a patient with isolated ACTH deficiency. With SciMonet. 2004;10:CS9-13.

Connery LE, Coursin DB. Diagnosis and therapy of selected endocrine disorders. Anesthesiol Clin North America. 2004;22:93-123.

Gonc EN, Kandemir N, Kinik ST. Role of low-dose and standard-dose ACTH testing versus overnight metyrapone testing in the diagnosis of childhood adrenal insufficiency. Horm Res. 2003;60:191-97.

(Video) Life After Gene Therapy

[PubMed] Joffe RT, Brasch JS, MacQueen GM. Psychiatric aspects of endocrine disorders in women. Psychiatric Clinic North America. 2003;26:683-91.

Packham EA, Brook JD. T-box genes in human diseases. Hummol Genet. 2003;12 Specification No. 1:R37-44.

Mody S, Brown MR, Parks JS. The spectrum of hypopituitarism caused by PROP1 mutations. Best Practice Res Clin Endocrinol Metab. 2002;16:421-31.

From Louis DA, Aller R, Rosemary E. Isolated ACTH deficiency. Horm Res. 1998:247-49.

INTERNET
Online Mendelian inheritance in humans (OMIM). The Johns Hopkins University. ACTH deficiency, isolated; IAD. Entry number: 201400. Last edited September 23, 2011. Available at:https://omim.org/entry/201400. Accessed January 27, 2017.

Programs and resources

  • public utility services
  • patient organizations
  • Register

rare care®public utility services

NORD is striving to open new grant programs as funding allows. If we don't have a program for you now, please continue to contact us.

Additional Utilities

MedicAlert Utility

NORD and the MedicAlert Foundation have partnered on a new program to protect patients with rare diseases in emergency situations.

To know more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

Rare Disease Education Support Program

It is an integral part of NORD's mission to ensure that patients and caregivers are equipped with the tools they need to live their best lives while managing their rare condition.

(Video) Gene Therapy Yesterday, Today and Tomorrow

To know more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Retirement program for rare caregivers

This unique support program is for caregivers of children or adults diagnosed with a rare disease.

To know more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

Learn more about Patient Assistance Programs >

patient organizations

No patient organizations related to this disease state were found.

To cry®patient record

Backed by NORD, the IAMRARE registration platform®is driving transformative change in rare disease research. With contributions from physicians, researchers, and the U.S. Food & Drug Administration, NORD created IAMRARE to facilitate patient-centered natural history studies to shape the study and treatment of rare diseases. The ultimate goal of IAMRARE is to unite patients and research communities to improve care and drug development.

Learn more >

FAQs

Can ACTH deficiency be cured? ›

ACTH deficiency can be treated with either hydrocortisone or prednisolone, which is a synthetic corticosteroid drug [3]. In patients with hypopituitarism whose aldosterone levels are approximately normal, there is no need to replace mineralocorticoids [3].

How can I increase my ACTH naturally? ›

Natural Remedies
  1. Adjust Your Diet. ...
  2. Reduce Stress. ...
  3. Make Getting Good Sleep a Priority. ...
  4. Consider Changing Your Exercise Routine. ...
  5. Try Beneficial Supplements.
Apr 16, 2018

What is ACTH deficiency disorder? ›

Isolated ACTH deficiency (IAD) is a rare disorder, characterized by secondary adrenal insufficiency (AI) with low or absent cortisol production, normal secretion of pituitary hormones other than ACTH and the absence of structural pituitary defects.

What is the treatment for ACTH deficiency? ›

Medications. Hormone replacement medications may include: Corticosteroids. These drugs, such as hydrocortisone (Cortef) or prednisone (Rayos), replace the adrenal hormones that aren't being produced because of an adrenocorticotropic hormone (ACTH) deficiency.

What does low ACTH feel like? ›

Symptoms include weight loss, lack of appetite (anorexia), muscle weakness, nausea and vomiting, and low blood pressure (hypotension).

Can you live without ACTH? ›

Adrenal crisis is a serious condition that can cause death in people who lack the pituitary hormone ACTH. ACTH is responsible for regulating the adrenal gland. Often, people are unaware that they lack this hormone and therefore do not know about their risk of adrenal crisis.

Does caffeine increase ACTH? ›

Caffeine in dietary doses increases both adrenocorticotropin (ACTH) and cortisol secretion in humans (15). Caffeine's effect on glucocorticoid regulation therefore has the potential to alter circadian rhythms and to interact with stress reactions.

Does exercise increase ACTH? ›

In normal subjects, exercise induced a significant increase in plasma ACTH and serum cortisol levels, with peak levels at 20 minutes for ACTH (84% higher than baseline) and at 30 minutes for cortisol (70% higher than baseline).

What stimulates ACTH increase? ›

Corticotropin-releasing hormone (CRH) is released from the hypothalamus, which stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH then acts on its target organ, the adrenal cortex.

How does ACTH make you feel? ›

The injection into the shoulder may cause moderate pain or stinging. Some people feel flushed, nervous, or nauseated after the injection of ACTH.

What happens if your ACTH is low? ›

A lower-than-normal level of ACTH may indicate: Glucocorticoid medicines are suppressing ACTH production (most common) Pituitary gland not producing enough hormones, such as ACTH (hypopituitarism) Tumor of the adrenal gland that produces too much cortisol.

Does ACTH affect behavior? ›

Indeed, ACTH IgG were significantly associated with antisocial behavior and the HPA axis response in stressed adolescents. As such, higher plasma levels of ACTH IgG were present in boys with increased antisocial behavior.

Does low ACTH cause fatigue? ›

Secondary adrenal insufficiency occurs when the pituitary gland doesn't make enough of the hormone ACTH. The adrenal glands then don't make enough cortisol. Mild symptoms may be seen only when a person is under physical stress. Other symptoms may include weakness, fatigue, and weight loss.

What are the long term side effects of ACTH? ›

Associated with long-term therapy: Bone loss, cataracts, indigestion, muscle weakness, back pain, bruising, acne, hyperpigmentation, menstrual irregularities, oral candidiasis. (See Warnings/Precautions under Cautions.)

Can you have Cushings with low ACTH? ›

Most forms of glucocorticoids, including inhaled and topical forms, can cause Cushing's syndrome. Less common causes of Cushing's syndrome that occur with low ACTH levels include benign or malignant (cancerous) tumors of the adrenal gland, which produce excess cortisol.

Does stress affect ACTH? ›

Stress also stimulates adrenocorticotropic hormone production and the resulting increase in cortisol levels. If there are any issues with your hypothalamus, pituitary gland or adrenal glands, it can affect the balance of hormones involved in this process, including ACTH.

What are 3 diseases that affect the adrenal glands? ›

Some of the most common include:
  • Addison's disease, also called adrenal insufficiency. In this disorder, you don't produce enough cortisol and/or aldosterone.
  • Cushing's syndrome. ...
  • Congenital adrenal hyperplasia. ...
  • Adrenal gland suppression. ...
  • Hyperaldosteronism. ...
  • Virilization.
Jun 7, 2021

Where do you feel adrenal pain? ›

Symptoms caused by a large adrenal cancer pressing on nearby organs. As an adrenal cancer grows, it presses on nearby organs and tissues. This may cause pain near the tumor, a feeling of fullness in the abdomen, or trouble eating because of a feeling of filling up easily.

Does ACTH affect body weight? ›

ACTH caused a significant percentile weight increase in the liver, kidney, heart, and pituitary, but growth hormone did not.

Does sleep affect ACTH? ›

Sleep restriction was associated with a 19% increase in overall ACTH levels (P < . 03) that was correlated with the individual amount of sleep loss (rSp = 0.63, P < .

Can you live a long life with adrenal insufficiency? ›

Treatment is tailored to the underlying cause and, in most cases, lifelong treatment is necessary. With appropriate treatment and a few added precautions, people with adrenal insufficiency can lead active lives and have a normal life expectancy.

How long does ACTH take to come back? ›

1-3 days. May take longer based on weather, holiday or lab delays.

Can adrenal insufficiency be reversed? ›

Although there's no cure, primary adrenal insufficiency can be managed effectively by taking cortisol and aldosterone replacement hormones, with the goal of stabilizing hormone levels and relieving signs and symptoms.

What can increase ACTH? ›

Cushing's disease: This is the most common cause of increased ACTH levels. A benign (non-cancerous) tumor (adenoma) in your pituitary gland that produces excess amounts of ACTH, which then elevates cortisol levels, causes ACTH. It's important to note the difference between Cushing's disease and Cushing's syndrome.

What vitamins help adrenal insufficiency? ›

Specifically, vitamins such as magnesium, B and C can help prevent adrenal fatigue. Magnesium aids in calming and supporting the nervous system, improving your quality of sleep, reducing stress levels, and boosting energy production.

What drugs cause adrenal insufficiency? ›

Glucocorticoids such as prednisone, hydrocortisone, and dexamethasone are similar to natural hormones produced by the adrenal glands.
...
Other drugs that may cause adrenal insufficiency include the following:
  • Megestrol.
  • Ketoconazole.
  • Metyrapone.
  • Aminoglutethimide.
  • Mitotane.

What organ is responsible for ACTH? ›

ACTH is a hormone made by the pituitary gland, a small gland at the base of the brain. ACTH controls the production of another hormone called cortisol. Cortisol is made by the adrenal glands, two small glands located above the kidneys.

What organs does ACTH target? ›

Endocrine gland/ source of hormoneHormoneTarget organ or tissue
Anterior pituitary (adenohypophysis)ACTH (adrenocorticotrophic hormone)Adrenal cortex
FSH (follicle stimulating hormone)Ovaries / testes (tubules)
LH (luteinizing hormone)Ovaries / testes (Leydig cells)
GH (growth hormone)All tissues
27 more rows

How does ACTH affect the immune system? ›

Corticotropin (ACTH) was one of the first neuropeptides shown to bind to receptors on leukocytes and modulate immune responses. Generally ACTH inhibits immune responses, but certain functions can be enhanced.

Why is my ACTH so low? ›

A lower-than-normal level of ACTH may indicate: Glucocorticoid medicines are suppressing ACTH production (most common) Pituitary gland not producing enough hormones, such as ACTH ( hypopituitarism ) Tumor of the adrenal gland that produces too much cortisol.

What does ACTH do in females? ›

The main function of ACTH is to regulate the glucocorticoid (steroid) hormone cortisol. Cortisol is released by the adrenal gland. It regulates blood pressure, blood sugar, the immune system, and the response to stress.

Videos

1. Rare Disease Special
(The Balancing Act)
2. Rare and Undiagnosed Disease Program: Mayo Clinic Radio
(Mayo Clinic)
3. Rare Disease Film Festival: Pyruvate Kinase Deficiency Advocacy
(Informa Connect Life Sciences)
4. Treating Short Stature: Pediatric Endocrinologist on Growth Hormone Deficiency, Achondroplasia &More
(MediFind)
5. Grand Rounds: Developing Gene Therapies for Ultra-rare Diseases in the Academic Setting
(MassGeneralHospital)
6. Medical Mysteries and Rare Diseases: William Gahl at TEDxCMU 2011
(TEDx Talks)
Top Articles
Latest Posts
Article information

Author: Prof. Nancy Dach

Last Updated: 03/03/2023

Views: 5733

Rating: 4.7 / 5 (77 voted)

Reviews: 92% of readers found this page helpful

Author information

Name: Prof. Nancy Dach

Birthday: 1993-08-23

Address: 569 Waelchi Ports, South Blainebury, LA 11589

Phone: +9958996486049

Job: Sales Manager

Hobby: Web surfing, Scuba diving, Mountaineering, Writing, Sailing, Dance, Blacksmithing

Introduction: My name is Prof. Nancy Dach, I am a lively, joyous, courageous, lovely, tender, charming, open person who loves writing and wants to share my knowledge and understanding with you.