The ACTH stimulation test may be ordered when you have a low result on a cortisol test and a combination of signs and symptoms that suggest low cortisol or adrenal insufficiency, such as:
- Weight loss
- Muscle weakness
- Fatigue
- Low blood pressure
- Abdominal pain
- Dark patches of skin (this occurs in Addison disease but not secondary adrenal insufficiency)
- Low blood sugar (hypoglycemia, especially in children)
The ACTH stimulation test, despite its name, doesn't directly measure the adrenocorticotropic hormone (ACTH). Instead, it evaluates cortisol production and assists in diagnosing adrenal insufficiency.
Cortisol is a hormone produced by the adrenal glands, two small glands located on top of the kidneys. It is essential in metabolizing proteins, fats, and carbohydrates. Cortisol influences blood sugar levels, aids in maintaining blood pressure, and is integral to the immune system's regulation. Under typical conditions, cortisol levels in the blood follow a predictable daily pattern, peaking after waking up and decreasing to a minimum by bedtime.
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The adrenal glands' cortisol production is maintained by a feedback loop involving the hypothalamus in the brain and the pituitary gland situated beneath the brain. In a healthy individual:
- A drop in cortisol prompts the hypothalamus to release corticotropin-releasing hormone (CRH).
- CRH then instructs the pituitary gland to produce ACTH.
- ACTH triggers the adrenal glands to produce and release cortisol.
- As cortisol levels increase, the hypothalamus cuts back on CRH production, leading the pituitary gland to decrease ACTH, which in turn reduces cortisol production by the adrenal glands.
For optimal cortisol production, the hypothalamus, pituitary, and adrenal glands must all be functioning and coordinating seamlessly.
Cortisol levels might decline due to:
- Inactive or damaged adrenal glands leading to limited cortisol production, termed as primary adrenal insufficiency or Addison's disease.
- A malfunctioning pituitary gland or its tumor preventing ACTH production, referred to as secondary adrenal insufficiency.
- The intake of glucocorticoids like dexamethasone and prednisone.
If a cortisol test indicates low levels, healthcare professionals often recommend the ACTH stimulation test to verify the results and pinpoint the underlying cause.
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If your adrenal glands are functioning normally, then your cortisol level will rise in response to the ACTH you are given. (The cortisol level in the second sample drawn should be elevated above a certain level and to a certain degree when compared to the baseline sample.) This result rules out primary adrenal insufficiency (Addison disease).
If your adrenal glands are damaged or not functioning properly, then your cortisol level will not increase after you are given ACTH. You may be diagnosed with adrenal insufficiency. Additional testing may be necessary to identify the cause.
The ACTH stimulation test is not a definitive test for adrenal insufficiency due to pituitary damage. If injury to the pituitary occurred only in the previous few weeks, a falsely normal response to ACTH injection may be observed. A repeat ACTH stimulation test 6 to 8 weeks later might then reveal secondary adrenal insufficiency. Other tests may also be considered.
Rarely, there is a problem with the hypothalamus and the production of corticotropin-releasing hormone (CRH). The ACTH stimulation test does not distinguish this problem from other causes of adrenal insufficiency.
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The ACTH (adrenocorticotropic hormone) stimulation test, also known as the Cortrosyn test, is used to diagnose adrenal insufficiency and to assess the function of the adrenal glands. During the test, synthetic ACTH (Cortrosyn) is injected, and cortisol levels are measured before and after the injection to see how the adrenal glands respond to the stimulation.
What is the normal response?
The normal response is for blood cortisol levels to rise after the administration of synthetic ACTH. The specifics can vary based on the laboratory and the methods used, but generally, a normal response is as follows:
1. The baseline cortisol level is measured before the ACTH is administered.
2. Synthetic ACTH (Cortrosyn) is injected.
3. Cortisol levels are measured again at 30 minutes and 60 minutes after the injection.
A normal response is typically an increase in blood cortisol to a certain level above the baseline. In many cases, the cortisol level should double from its baseline or reach a minimum of 18-20 micrograms per deciliter (mcg/dL) or 500-550 nanomoles per liter (nmol/L) at 30 or 60 minutes after the ACTH is given. However, this can vary, so it's important to refer to the reference range provided by the specific laboratory that processes the test.
Elevated cortisol levels in response to ACTH stimulation can signify different things depending on the context and the baseline cortisol levels:
→ Adrenal Hyperplasia or Overactivity: If cortisol levels rise much higher than expected, it may suggest that the adrenal glands are overactive, which could be due to conditions such as congenital adrenal hyperplasia or other disorders causing hypercortisolism.
What is congenital adrenal hyperplasia?
Congenital adrenal hyperplasia (CAH) is a family of inherited disorders affecting the adrenal glands, which are small organs located on top of each kidney. The condition results from defects in enzymes required for the synthesis of cortisol, a crucial hormone for regulating metabolism, immune response, and stress. The most common enzyme deficiency in CAH is 21-hydroxylase, accounting for approximately 90-95% of cases. Due to the impaired production of cortisol, the body's feedback system increases the production of adrenocorticotropic hormone (ACTH) to stimulate the adrenal glands, leading to an overproduction of androgenic hormones. This hormonal imbalance can result in a range of symptoms, from ambiguous genitalia in newborn females to precocious puberty in both genders, and can affect growth and development. Management of CAH often includes lifelong hormone replacement therapy and monitoring to maintain proper hormone levels and mitigate complications. Genetic counseling may be recommended as CAH is an autosomal recessive trait, meaning that it can be passed on to children when both parents are carriers of the gene mutation.
→ Adrenal Tumors or Adenomas: In some cases, if there is an adrenal tumor or adenoma, the cortisol levels may rise higher than normal, but this would typically be investigated further with additional tests and imaging.
→ Cushing's Syndrome: Blood cortisol levels above the expected range following ACTH stimulation may be consistent with Cushing’s syndrome. Further testing is required to confirm this diagnosis. If a patient has Cushing's syndrome, their cortisol levels might be elevated at baseline and may not show a normal rise after ACTH stimulation. However, the ACTH stimulation test is not the primary test for diagnosing Cushing's syndrome; rather, tests like the dexamethasone suppression test would be used.
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If an ACTH stimulation test results in elevated cortisol levels, it is important to interpret the results in the context of the individual's clinical presentation and history. The treatment would depend on the underlying cause of the elevated cortisol. Here are some potential scenarios and their respective treatments:
→ Primary Adrenal Hyperplasia or Tumors: If the cause of the elevated cortisol is due to a benign adrenal tumor or hyperplasia, surgical removal of the tumor or affected adrenal gland may be considered. In cases of bilateral hyperplasia, medical therapy to control cortisol production may be preferred.
→ Cushing's Syndrome: If the patient is diagnosed with Cushing's syndrome, the treatment depends on the cause:
→ Medication Effects: Certain medications can increase cortisol levels, so a review of the patient's medication regimen is necessary. Adjusting or discontinuing the causative medication may be required.
→ Stress or Illness: Elevated cortisol can also be a response to physical or emotional stress, or illness. In these cases, no specific treatment for the cortisol elevation may be necessary, and it may resolve once the stressor or illness is managed.
In all cases, it is critical to have a thorough evaluation by an endocrinologist or a healthcare provider specializing in hormonal disorders to determine the exact cause of the elevated cortisol levels and to develop an appropriate treatment plan. This plan should be personalized, considering the patient's overall health, the severity of the cortisol elevation, the cause of the hormonal imbalance, and any other existing health conditions. Regular follow-up and monitoring of cortisol levels are also important to ensure the effectiveness of treatment and make any necessary adjustments.
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If cortisol levels do not adequately increase after ACTH administration, it may suggest adrenal insufficiency. Conversely, if the levels increase normally, it generally indicates that the adrenal glands are functioning correctly.
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17-Hydroxypregnenolone, MS (female), 17-OH Progesterone, ACTH, Plasma, ADH, Aldos/Renin Ratio, Aldosterone, Aldosterone/Plasma Renin Activity Ratio, Anti-Mullerian Hormone (AMH), Calcitonin, Serum, Cortisol - ACTH (Cortrosyn) Stimulation Test, Cortisol - AM (Serum), Cortisol, Serum, Cortisol-Binding Globulin (CBG), DHEA, Unconjugated, DHEA-S : Cortisol Ratio, DHEAS (Serum), Estradiol, Estradiol (male), Estradiol, Ultrasensitive, LC/MS, Estriol, Serum, Estrogens, Total (female), Estrogens, Total (male), Estrone, Serum (Female), Estrone, Serum (Male), Free Cortisol, Serum, Free Estradiol, Percent, Free Estradiol, Serum, Glucagon, Growth Hormone, Human Chorionic Gonadotropin (hCG), Total, IA-2 Autoantibodies, IGF Binding Protein 1 (IGFBP 1), IGF Binding Protein 3 (IGFBP 3), Leptin, Luteinizing Hormone, Human (hLH), Pregnenolone (male), Progesterone (male), Progesterone (Serum), Prolactin, Renin Activity, Plasma, Total Testosterone (Female/ng/mL)
