{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:13:46Z","timestamp":1783660426620,"version":"3.55.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The adrenal gland plays a pivotal role in the stress response via the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis and the sympatho\u2013adrenomedullary system (SAMS). Congenital adrenal hyperplasia (CAH) results from pathogenic variants in genes encoding adrenal steroidogenic enzymes. The most common form, 21-hydroxylase deficiency, impairs cortisol biosynthesis, leading to compensatory overproduction of adrenocorticotropic hormone (ACTH) and chronic adrenal hyperplasia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A 40-year-old man was referred for incidentally detected bilateral adrenal lesions on abdominal computed tomography (CT). CT revealed marked bilateral adrenal enlargement with clear contours. One month before admission, he had an acute upper respiratory tract infection and recovered after treatment with a cephalosporin. On admission, physical examination showed hyperpigmentation of the nipples region, lips, gums, and buccal mucosa. Superficial lymph nodes were palpable. He reported a history of infertility and suspected precocious puberty. Endocrinology markers demonstrated an elevated ACTH level (180 ng\/L; reference range 5.0\u201378.0 ng\/L) with a cortisol level of 174 nmol\/L (reference range 133.0\u2013537.0 nmol\/L). Luteinizing hormone and follicle-stimulating hormone levels were both low, whereas dehydroepiandrosterone sulfate was elevated. Markedly elevated 17\u03b1-hydroxyprogesterone levels and a blunted cortisol response were observed under ACTH-stimulated conditions. Based on the clinical phenotype and biochemical findings, CAH due to 21-hydroxylase deficiency was diagnosed and considered consistent with the simple virilizing form, which was subsequently genetically supported by the CYP21A2 I172N homozygous mutation in exon 4. Remarkably, without any specific treatment, adrenal volume decreased substantially within one month, from 61.06 cm\n                      <jats:sup>3<\/jats:sup>\n                      to 33.47 cm\n                      <jats:sup>3<\/jats:sup>\n                      , corresponding to an approximately 1.8-fold reduction, although the adrenal glands remained enlarged compared with normal reference values. After excluding adrenal-related tumors, hemorrhage, infections and autoimmune diseases, we postulated that the transient morphological changes reflected stress-induced compensatory hypertrophy and\/or hyperplasia of the adrenal cortex following the respiratory infection, aimed at augmenting cortisol production to modulate inflammation and maintain homeostasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with 21-OHD and residual enzymatic activity, infectious stress may trigger transient enlargement of pre-existing adrenal hyperplasia, potentially as a compensatory response to increased cortisol demand, followed by partial regression after stress resolution.<\/jats:p>\n                  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