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HPA Axis Suppression

John Montgomery4 min read

HPA Axis Suppression

Hypothalamic-pituitary-adrenal (HPA) axis suppression happens when enough steroid is absorbed through the skin that the body turns down its own cortisol production. The Australasian consensus (Mooney 2015) separates two states. Physiological suppression is a cortisol level below normal that recovers promptly. Pathological suppression means true adrenal insufficiency, adrenal crisis, or lab suppression that does not recover. After weeks to months of heavy exposure the adrenal glands can atrophy. A sudden stop or a stress such as illness can then trigger an adrenal crisis. Features of Iatrogenic Cushing Syndrome can appear alongside. High- and ultra-high-potency steroids carry most of the risk (AFP 2009).

Topical Corticosteroids [causes] HPA Axis Suppression HPA Axis Suppression [precedes] Iatrogenic Cushing Syndrome

Paediatric evidence. The Axon umbrella review (BMJ Open 2021) pooled 11 uncontrolled observational studies of 522 children using TCS of any potency. 3.8% (95% CI 2.4–5.8%) had biochemical adrenal suppression, and it reversed when treatment stopped. Two RCTs of once-daily very potent or moderate TCS for up to 2 weeks (n=129) found none. One RCT of potent Weekend Therapy found suppression in 2 of 44 children. There was no evidence of growth suppression, though long-term data were thin and 34 of 38 reviews were low quality. Mooney 2015 counts 25 paediatric case reports in the literature. Most involved superpotent Clobetasol Propionate applied for 1–17 months to nappy-area eczema, where the nappy acts as occlusion. There were also two infant deaths from sepsis linked to marked TCS overuse. The panel knew of no pathological suppression when TCS was stopped once eczema resolved.

Weekend Therapy [relates] HPA Axis Suppression Clobetasol Propionate [causes] HPA Axis Suppression Nappy Rash [relates] HPA Axis Suppression

Clinical significance. For a toddler using mild or moderate TCS in courses dosed by Fingertip Unit, suppression is usually a lab finding with no symptoms, and it resolves on stopping. DermNet says Cushing-type effects need very large long-term quantities: more than about 50 g of clobetasol, or more than 500 g of Hydrocortisone, per week. In practice such cases mostly follow inappropriate prescribing or OTC/unregulated sales. Risk factors are potent or very potent steroid, large body area, occlusion (wet wraps, nappies), long continuous use, and combining TCS with inhaled or oral steroids. This is why NICE CG57 limits whole-body Wet Wrap Therapy with steroid to 7–14 days.

Wet Wrap Therapy [worsens] HPA Axis Suppression Fingertip Unit [prevents] HPA Axis Suppression

Conflict: [Eumovate Rx PIL, emc 3807, n.d.] warns that prolonged daily TCS in children “can affect their growth”. [Axon et al., BMJ Open 2021] found no evidence of growth suppression, and [Mooney et al., 2015] found pathological suppression only with misuse. Unresolved — add to open_questions.

Undeclared steroids. Some of the most serious infant cases come from potent steroid hidden in Adulterated Herbal Creams. Hidden clobetasol has caused infant Cushing’s (Razzaghy Azar 2015). In these cases nobody plans a taper, so stopping abruptly can unmask adrenal insufficiency. The MHRA (2024) also warns that stopping TCS suddenly is dangerous if adrenal suppression is present, which is relevant to Topical Steroid Withdrawal advice to stop “cold turkey”.

Adulterated Herbal Creams [causes] HPA Axis Suppression Topical Steroid Withdrawal [relates] HPA Axis Suppression

Hidden potent steroid in "herbal" creams

Infant Cushing’s syndrome and adrenal suppression have been reported after months of an unlabelled “natural” cream that contained clobetasol. If such a cream has been used heavily, do not stop abruptly without medical advice.

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