Pain Perception in Adrenal Insufficiency Not Affected by Hydrocortisone Dose

Cross section of kidney and adrenal gland.
Cross section of kidney and adrenal gland.
Mechanical pain perception and somatosensory function in secondary adrenal insufficiency were examined.

Dose of oral hydrocortisone (HC) therapy does not alter mechanical pain perception or somatosensory functioning in people with secondary adrenal insufficiency (SAI), according to research published in PLoS One.1 These findings contradict previous research demonstrating that lower-dose HC resulted in an increase in subjective pain perception in patients with SAI.2

Forty-six patients with SAI were randomly assigned to receive either low-dose HC (total daily dose: 0.2-0.3 mg/kg body weight) for 10 weeks followed by high-dose HC (total daily dose: 0.4-0.6 mg/kg body weight) HC or high-dose HC followed by low-dose HC for the same duration. Doses were administered before breakfast, lunch, and dinner, with the highest dose administered first.

Blood samples were obtained and somatosensory function was evaluated by assessing mechanical detection threshold, mechanical pain threshold, mechanical pain sensitivity, and pain pressure threshold. 

One hour after HC administration, significantly increased plasma cortisol levels were noted in patients taking high-dose HC compared with those taking low-dose HC (median 741 nmol/L; interquartile range [IQR]: 669-870 vs median 499 nmol/L; IQR: 363-605; P <.001). Similar differences were noted 5 hours after the morning HC dose (median: 235 nmol/L; IQR: 170-314 and median: 112 nmol/L; IQR: 75-199; for higher and lower doses, respectively; P <.001). However, no z-score differences were recorded in any somatosensory functioning measures, and rates of sensory abnormality did not differ between patients taking lower or higher doses of HC (27%; 95% CI, 14%-40% vs 29%; 95% CI, 16%-24%, respectively).

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“Despite the previously observed difference in subjective pain reports…comparing both doses of HC, sensory changes supportive for HC induced alteration of mechanical function could not be established,” the researchers concluded, emphasizing that HC dose has no impact on mechanical pain perception in patients with SAI.


  1. Buning JW, Konopka K-H, Brummelman P, et al. Somatosensory function in patients with secondary adrenal insufficiency treated with two different doses of hydrocortisone — results from a randomized controlled trial [published online July 7, 2017]. PLoS One. doi: 10. 1371/journal.pone/0180326
  2. Werumeus Buning J, Brummelman P, Koerts J, et al. The effects of two different doses of hydrocortisone on cognition in patients with secondary adrenal insufficiency—results from a randomized controlled trial. Psychoneuroendocrinology. 2015;55:36-47.