Exogenous glucocorticoid therapy can be classified as “ACTH-independent” since, On the other hand, GRs are activated when cortisol levels are higher, as at. ACTH (adrenocorticotropic hormone) blood tests are used, usually in conjunction with cortisol tests, to help detect, diagnose, and monitor. Cortisol levels can be too low (from dysfunction of the adrenal cortex), hence creating very high levels of ACTH, which is primarily manifested in the disease.
In this article, we will briefly review normal control where appropriate because this information is necessary for understanding the pathophysiology of the HPA axis. The control of cortisol secretion is one of the classic examples of a hypothalamic-pituitary-target gland axis Fig. Basal and stress-inputs to the hypothalamic parvocellular nuclei lead to an increase in the neurocrine factor corticotrophin-releasing hormone CRH release into the hypophysical-portal veins.
From the point of view of patho-physiology, the most important basal input to CRH secretion is from the circadian rhythm generator in the hypothalamic suprachiasmatic nucleus, In individuals with established nocturnal sleep and daytime wakefulness, circulating cortisol concentrations peak between and h and have a nadir between and h.
From a metabolic point of view, the increase in cortisol that starts at about h helps to maintain plasma glucose via increases in hepatic gluconeogenesis until awakening when the overnight fast can be broken Interestingly, there is also a cortisol awakening response. Like cortisol, levels of adrenocorticotropic hormone are generally high in the morning when we wake up and fall throughout the day. This is called a diurnal rhythm. It also increases production of the chemical compounds that trigger an increase in other hormones such as adrenaline and noradrenaline.
How is adrenocorticotropic hormone controlled?
Secretion of adrenocorticotropic hormone is controlled by three inter-communicating regions of the body, the hypothalamus, the pituitary gland and the adrenal glands. This is called the hypothalamic—pituitary—adrenal axis. When adrenocorticotropic hormone levels in the blood are low, a group of cells in the hypothalamus release a hormone called corticotrophin-releasing hormone which stimulates the pituitary gland to secrete adrenocorticotropic hormone into the bloodstream.
High levels of adrenocorticotropic hormone are detected by the adrenal glands which stimulate the secretion of cortisol, causing blood levels of cortisol to rise. As the cortisol levels rise, they start to slow down the release of corticotrophin-releasing hormone from the hypothalamus and adrenocorticotropic hormone from the pituitary gland.
As a result, the adrenocorticotropic hormone levels start to fall.
This is called a negative feedback loop. Given the seriousness of adrenal crisis, caregiver education on the signs of adrenal insufficiency is critical.
Greater vigilance may be indicated in patients receiving both types of hormone therapy in tandem. Although a routine post-hormone laboratory assessment of adrenal function may not be feasible in all patients, replacement or stress dose hydrocortisone is necessary for all patients with suspected adrenal insufficiency.
You and Your Hormones
Early and successful treatment of infantile spasms and the associated epileptic encephalopathy can improve developmental and seizure outcomes 12.
Some infantile spasms patients who do not respond to ACTH will respond to oral corticosteroids, and vice versa 4. Thus, some clinicians switch to the alternative hormone therapy after a patient fails to respond to the first hormone therapy. The risk of secondary adrenal insufficiency due to the suppression of the hypothalamic—pituitary—adrenal HPA axis following long-duration high-dose corticosteroids is well known 9. Suppression of the HPA axis may be partial or total, as a result of adrenal gland atrophy, with great individual variability Even short-duration corticosteroid therapy e.
Adrenocorticotropic hormone | You and Your Hormones from the Society for Endocrinology
When steroid therapy is withdrawn in patients with suppressed adrenal function, acute adrenal insufficiency or Addisonian crisis may occur, which is a serious and potentially life-threatening condition.
Signs of mild adrenal insufficiency are non-specific, but can include nausea, tiredness, poor feeding, and lethargy in young children.
Signs of severe acute adrenal insufficiency can include vomiting, diarrhea, fever or hypothermia, hypotension, hypoglycemia, shock, and coma. No study has assessed adrenal function or the incidence of clinical adrenal insufficiency following the treatment of infantile spasms with modern regimens of high-dose corticosteroid therapy.
Exogenous ACTH stimulates the adrenal gland, resulting in hypercortisolism, as evidenced in ACTH-treated infants who develop Cushingoid appearance as a result of this effect. The mechanism of decreased pituitary reserve following exogenous ACTH therapy has been postulated to result from hypercortisolemia, which suppresses pituitary ACTH secretion; this causes rapid involution of the adrenal cortex after stopping ACTH treatment and reduced responsiveness to ACTH stimulation There is very limited data available on the risk of suppression of the HPA axis following modern regimens of ACTH therapy for infantile spasms.
There have been three small infantile spasms studies totaling 24 patients treated with ACTH who had a post-treatment assessment of adrenal function 13 — In these three studies, adrenal function was assessed either soon after stopping ACTH or up to 2 weeks later; these studies did not assess the occurrence of clinical adrenal insufficiency in the months following treatment.
Although two large series of infantile spasms patients treated with synthetic or natural ACTH did not report any cases of clinical adrenal insufficiency following treatment with ACTH, these studies did not assess adrenal function 16 It is important to note that symptoms of clinical adrenal insufficiency in patients with a suppressed HPA axis may not be clinically evident without stress e.
It is also unknown if the risk of adrenal insufficiency is increased, if the alternative hormone therapy is used after the first hormone therapy, either when one is used immediately after the other i. Given the uncertainty of adrenal insufficiency following hormone therapy for infantile spasms, and a personal experience of clinical adrenal insufficiency following corticosteroid therapy in a patient with infantile spasms 18our guideline initially included a post-hormone endocrinologist-guided laboratory evaluation of adrenal function.
Here, we report our experience with monitoring of adrenal function following hormone therapy for infantile spasms as well as the occurrence of clinical adrenal insufficiency.