It is generally accepted that a minority of patients with CS demonstrate cyclic hypersecretion of cortisol. Although approximately half of cases of cyclic CS are attributable to an ACTH-producing pituitary adenoma (Cushing's disease), other pathologic causes, including ectopic ACTH syndrome and adrenal CS (adenoma or primary pigmented nodular adrenocortical disease), have been recognized.[2,7,8]
In this case, the CRH stimulation test indicated a meaningful rise in ACTH secretion (Figure 4). Moreover, an FDG-PET/CT scan revealed no evidence of lesions other than the known pituitary tumor. Therefore, hypersecretion of ACTH was thought to be caused by a pituitary tumor (Cushing's disease) rather than ectopic ACTH syndrome.
Although no endocrine investigations had been performed previously, this patient is likely to have had periodic secretion of ACTH and cortisol for several years, given his report of transient sensations of whole-body swelling and improvement of the skin lesions. Indeed, he experienced sensations of whole-body swelling and a concomitant marked decrease in urinary sodium excretion and progressive hypokalemia when there was a rise in his cortisol secretion during the hospital stay (Figure 2), indicating water retention as a result of the mineralocorticoid effect of a marked increase in serum cortisol. This observation lent credibility to his unusual story.
Although Cushing's disease is usually associated with pituitary microadenoma, our case presented as pituitary macroadenoma. However, there are no reports suggesting a difference in the frequency of cyclic Cushing's disease between macroadenoma and microadenoma.
Our patient is currently being treated with topical glucocorticoids, namely, dexamethasone (class 2, potent) or clobetasol (class 1, superpotent) for psoriasis vulgaris that first developed 20 years ago. Although a paradoxical increase in urinary free cortisol in response to a dexamethasone suppression test has been reported in patients with primary pigmented nodular adrenal disease, a paradoxical increase in ACTH and cortisol levels may also occur after administration of dexamethasone in cyclic Cushing's disease. However, in our case, it was unclear how the topical glucocorticoids were previously involved in cyclic secretion of ACTH. The topical glucocorticoid was discontinued after admission to avoid an effect on the hypothalamic-pituitary-adrenal axis. On hospital days 1 and 2, the cortisol levels were almost normal (Figure 2). The morning serum cortisol level was high (19.6 μg/dL) on day 3 after oral administration of dexamethasone 1 mg at 11:00 PM on day 2. This finding raised the possibility that the paradoxical response was caused by dexamethasone. Nevertheless, a higher (8 mg) dose of dexamethasone was administered at 11:00 PM on day 12, and the serum cortisol levels continued to decline thereafter. Therefore, transient ACTH and cortisol hypersecretion may have occurred regardless of administration of dexamethasone.
Several mechanisms have been put forward to explain the cyclicity of Cushing's disease, including episodic hemorrhage or fluctuations in the hypothalamic-pituitary-adrenal axis feedback; however, the pathophysiology remains to be elucidated. Although the postoperative pathology specimen showed no necrosis in this case, there were small patchy hypointense areas suggestive of tumor necrosis in the pituitary magnetic resonance imaging. Therefore, we believe that spontaneous episodic hemorrhage might cause cyclicity of ACTH secretion.
Psoriasis is an immune-mediated inflammatory disease that is treated by immunosuppressive or immunomodulatory agents. It is also known that autoimmune-related diseases, such as Graves' disease, rheumatoid arthritis, and psoriasis, may occur after resolution of hypercortisolemia due to CS.[3–5] However, to the best of our knowledge, there have been no reports of improvement in an autoimmune-related disease during a period of cortisol hypersecretion in cyclic CS.
We have encountered a very rare case of cyclic pituitary CS in which we observed dramatic improvement of psoriasis vulgaris due to transient hypersecretion of cortisol during a short hospital stay.
We thank the patient for allowing us to share his story with the medical community. We are grateful to our secretary, Saori Beppu, for her help in preparing this paper.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
J Endo Soc. 2021;5(7) © 2021 Endocrine Society