ACTH is a hormone released by your pituitary gland. It signals your adrenal glands to make and release Cortisol (the ‘tress Hormone’) and Androgens (a group of sex hormones).
ACTH deficiency occurs when the pituitary gland does not produce enough Adrenocorticotropic hormone (ACTH). This causes less ACTH in your blood than usual, which leads to your adrenal glands making fewer hormones. Eventually, this can result in adrenal insufficiency, where you might experience weight loss, no appetite, weakness, nausea, vomiting, and low blood pressure.1,4
Since these symptoms are common for many issues, diagnosing ACTH deficiency may be delayed or overlooked.
ACTH is a hormone made in the front part of the pituitary gland.1,2 It is made from larger molecules which are controlled by signals from our brain.5 ACTH helps the body handle stress and has effects on different parts of the adrenal glands.1,2
When ACTH is released into the bloodstream, it signals the adrenal glands to produce cortisol, which is important while dealing with stressful situations. As a signalling hormone, it also causes an increase in the size of the adrenal glands to make and release larger amounts of Cortisol over time. However, higher levels of ACTH over prolonged periods of time can cause the adrenal glands to become too big, and inversely, too little ACTH, again over prolonged periods of time, can shrink the adrenal glands.1-5
ACTH also has a role in signalling the production of other hormones called Androgens, which are important for day-to-day functioning, for example, regulation of hair growth, appetite, weight regulation, etc.6 Hence, some of the symptoms of ACTH deficiency may be as non-specific as insufficient hair growth or unexplained weight loss.2,6
ACTH deficiency is a serious condition that can be potentially fatal if not diagnosed in time.1,7 It may be a generalised problem with your pituitary gland or an isolated condition.7 Solated ACTH deficiency is uncommon without a cause, with one of the most common causes being a side effect of certain medications. In both cases, delays in diagnosing and treating it due to the non-specific nature of signs and symptoms are noted frequently.1,7
Causes of ACTH deficiency
The exact cause of ACTH deficiency is yet to be known. However, based on current knowledge, it is speculated that ACTH deficiency can be caused by abnormalities/defects in the brain's hypothalamus or pituitary glands.
In the congenital variants of ACTH deficiency, the cause has been found to be related to mutations in specific genes (TBX19 and the CRH genes).
Given that this disorder might be inherited or passed on from parents to offspring discussing the inheritance pattern of this condition is important. The known inheritance pattern of ACTH deficiency is autosomal recessive (which means if one parent has the condition there is a 50% likelihood that it may passed on to the offprings).1-8
Genetic conditions are decided by the mix of genes from both parents. Recessive conditions happen when someone gets two similar (in this case, genes that can cause ACTH deficiency) copies of a gene for a trait, one from each parent.8 If they get one normal gene and one gene for the condition, they might not show symptoms but can pass it on to their children.8
Parents who are related have a higher chance of both carrying the same abnormal gene, which increases the risk of having children with a recessive condition.8
Signs and symptoms of ACTH deficiency
ACTH deficiency may be present since birth (congenital) or can be acquired later in life (side effect of certain medications).1-7 Most of the signs and symptoms are quite non-specific.3,4 Some common signs and symptoms of ACTH deficiency are (NORD):
- Weight loss
- Diminished appetite or desire to eat (anorexia)
- Muscular weakness
- Nausea and vomiting
- Low blood pressure
- Low blood sugar and sodium levels.
Blood tests might not show enough ACTH, and cortisol levels might be too low. Also, 17-hydroxycorticosteroids and 17-ketosteroids also released from similar areas of the adrenal glands might be lower than usual in their urinary concentration. The androgens secreted by adrenal glands are pre-cursors of sex hormones in males assigned at birth and are hence also commonly known as pre-androgens.1-7 In males assigned at birth, hair pattern is commonly normal or without any abnormality while in females assigned at birth, hair growth might be insufficient in the axillary (armpits) and the pubic regions.
In contrast to Addison's disease, skin colour typically stays the same in individuals with ACTH deficiency. ACTH deficiency may lead to emotional/mental health symptoms, which may range from psychosis to depression.
May make you lose weight, feel weak, and can cause stomach issues. Blood tests may be helpful in establishing a diagnosis of ACTH deficiency.3,4 It is important to remember that symptoms of ACTH deficiency may be highly non-specific and may also include mental health problems. Thus in case you or someone you may know might be experiencing any of the above signs or symptoms, it might be helpful to contact and book an appointment with your local GP surgery at the earliest.
Management and treatment
ACTH deficiency can be managed using medications like hydrocortisone or prednisolone, which are synthetic corticosteroids. If an individual’s aldosterone levels are nearly normal, they might not need extra mineralocorticoids. But in most cases, ACTH deficiency is partial, which means it's not clear if lifelong treatment is needed or treatment may only be needed during stressful times.3,7
Certain blood tests may be helpful to plan the treatment for an individual with ACTH deficiency. If a stimulation test shows blood cortisol levels above 10 µg/dL and specific deficiency symptoms are absent, there might be a partial deficiency. In this case, monitoring the patient without medication or smaller dose treatment with hydrocortisone (10 mg) or prednisolone (2.5 mg) followed by observing the individual in the long term may suffice. If any significant differences are noted prior to and after the onset of treatment with corticosteroid medication, then treatment might be stopped. If improvement is observed in the overall health of the individual, the treating clinician might decide, based on their evaluation, whether to continue with the same dose or titrate it to 12.5 to 15.0 mg of hydrocortisone or 3.75 mg of prednisolone. Treatment is generally indicated with either prednisolone or hydrocortisone; the choice for your treatment relies on the treating clinician.3,8 For further questions around this, Klarity recommends that you ask your treating clinician since they may be more helpful.
During pregnancy, hydrocortisone is usually preferred over prednisolone to avoid passing through the placenta.3,7 The dose might need to be adjusted during pregnancy due to changes in hormone levels.3,7
During times of stress, the treatment might need to be titrated to increase the dosage,, and adjustments might be necessary if certain liver enzymes are involved. Patients need to be educated/counselled appropriately about adrenal crises and may need to be advised to carry hydrocortisone with them at all times.3.7 Pregnant women and those receiving estrogen therapy might need specific dose adjustments.3,7 Although some studies suggest that replacing a hormone called dehydroepiandrosterone (DHEA) can improve sexual desire, it's not a standard treatment yet.3,7 Patients should also learn how to self-inject hydrocortisone.3,7
Measuring ACTH levels in the blood is a way to find, understand, and keep an eye on health problems linked to too much or too little cortisol in the body.3,7
A stimulation test is needed only when a clear diagnosis is necessary. For diagnosing ACTH deficiency, ACTH and/or cortisol levels can be measured using metyrapone, ACTH, or CRH or with an insulin-induced hypoglycemia test (insulin tolerance test). However, it can be safely done with careful supervision by a doctor to effectively check growth hormone (GH) secretion levels and the presence of ACTH deficiency.3,7
In a medical setting, the quick ACTH stimulation test is preferred if a patient is at risk of experiencing low blood sugar (hypoglycemia). This test measures cortisol levels after giving ACTH to help with diagnosis. In fact, several studies have found that the low-dose 1 µg ACTH stimulation test is more effective in spotting adrenal gland problems (like central or secondary adrenal insufficiency) caused by ACTH deficiency, compared to the usual 250 µg dose used in the quick ACTH test. 3,7
ACTH deficiency is a condition where the body lacks enough adrenocorticotropic hormone, impacting stress response and hormone production. Symptoms include weight loss, weakness, low blood pressure, and disrupted electrolyte levels. Diagnosis involves blood tests and stimulation tests. Treatment includes hormone replacement with medications like hydrocortisone and prednisolone that may require adjustment in doses based on individual needs. Those individuals with ACTH deficiency need to be vigilant about adrenal crises and carry medication for timely intervention if needed.ACTH deficiency can be a significant health problem in pregnant individuals and requires special care.
Can ACTH deficiency be prevented?
ACTH deficiency may be inherited or acquired later in life. In the case of a genetic cause, prevention is not possible; however, if it is acquired due to an external factor such as medication that may cause decreased ACTH secretion, addressing the underlying cause may prevent ACTH deficiency.1,7
Can ACTH deficiency be life-threatening?
Although not life-threatening by itself, it can create a serious health problem, i.e., adrenal crises that may be potentially fatal.1,8
- Kannan CR. Isolated ACTH deficiency. In: The Pituitary Gland [Internet]. Boston, MA: Springer US; 1987 [cited 2023 Nov 9]. p. 295–307. Available from: http://link.springer.com/10.1007/978-1-4613-1849-1_10
- Allen MJ, Sharma S. Physiology, adrenocorticotropic hormone(Acth). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Nov 9]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK500031/
- Kim SY. Diagnosis and treatment of hypopituitarism. Endocrinol Metab (Seoul). 2015 Dec;30(4):443–55.
- Cooper MS, Stewart PM. Diagnosis and treatment of ACTH deficiency. Rev Endocr Metab Disord [Internet]. 2005 Jan [cited 2023 Nov 9];6(1):47–54. Available from: http://link.springer.com/10.1007/s11154-005-5224-0
- Rhodes ME. Adrenocorticotropic hormone. In: Stress: Neuroendocrinology and Neurobiology [Internet]. Elsevier; 2017 [cited 2023 Nov 9]. p. 109–16. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9780128021750000103
- Dutt M, Wehrle CJ, Jialal I. Physiology, adrenal gland. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Nov 9]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK537260/
- Andrioli M, Giraldi FP, Cavagnini F. Isolated corticotrophin deficiency. Pituitary [Internet]. 2006 Dec [cited 2023 Nov 9];9(4):289–95. Available from: http://link.springer.com/10.1007/s11102-006-0408-5
- Gulani A, Weiler T. Genetics, autosomal recessive. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Nov 9]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK546620/