Indian Journal of Endocrinology and Metabolism

LETTERS TO THE EDITOR
Year
: 2020  |  Volume : 24  |  Issue : 2  |  Page : 220--222

Paradoxical cortisol response to dexamethasone in corticotroph microadenoma: A useful feature of underlying cyclic hormonogenesis


Rahin Mahata, Partha Pratim Chakraborty, Anirban Sinha, Animesh Maiti 
 Department of Endocrinology and Metabolism, Medical College, Kolkata, 88 College Street, Kolkata 73, West Bengal, India

Correspondence Address:
Partha Pratim Chakraborty
Department of Endocrinology and Metabolism, Super Specialty Block (SSB), 4th Floor, Medical College, 88 College Street, Kolkata 73, Kolkata, West Bengal
India




How to cite this article:
Mahata R, Chakraborty PP, Sinha A, Maiti A. Paradoxical cortisol response to dexamethasone in corticotroph microadenoma: A useful feature of underlying cyclic hormonogenesis.Indian J Endocr Metab 2020;24:220-222


How to cite this URL:
Mahata R, Chakraborty PP, Sinha A, Maiti A. Paradoxical cortisol response to dexamethasone in corticotroph microadenoma: A useful feature of underlying cyclic hormonogenesis. Indian J Endocr Metab [serial online] 2020 [cited 2021 Sep 25 ];24:220-222
Available from: https://www.ijem.in/text.asp?2020/24/2/220/283570


Full Text



Sir,

Endogenous Cushing's syndrome (CS) was diagnosed in a 22-year-old lady with new-onset diabetes mellitus and oligomenorrhea according to the clinical practice guideline of the Endocrine Society [Table 1]. She declined bilateral inferior petrosal sinus sampling (BIPSS). Hormonal parameters at her subsequent follow-up (FU) visits have been summarized in [Table 1]. Owing to her minimal symptoms, she refused both surgery and ketoconazole therapy. No endogenous hypercortisolemia could be documented during her last visit in December, 2019.{Table 1}

In CD, the setpoint of feedback inhibition of glucocorticoid (GC) on adrenocorticotropic hormone (ACTH) release from corticotrophs is elevated and more than 50% suppression of serum cortisol following high-dose dexamethasone suppression test (HDDST) is seen in 90% of microadenomas and 50% of macroadenomas. Primary pigmented nodular adrenocortical disease (PPNAD) is characterized by paradoxical rise of endogenous cortisol secretion following dexamethasone administration in about 69-75% of cases. Such paradoxical response may also be seen in about 20% cases of adrenal adenoma and very rarely in CD, particularly in corticotroph macroadenoma, and has never been reported in microadenoma.[1],[2] We noticed progressive rise of dexamethasone suppression test (DST) cortisol with an increasing dose of dexamethasone, from 1 mg-overnight DST (ONDST) to low dose DST to HDDST during her initial visit, which prompted us to perform the Liddle's test. Paradoxical rise of ACTH following GC administration in CD was demonstrated long back and a number of postulations like periodic hormonogenesis (with purely fortuitous post-dexamethasone response), GC receptor overexpression on pituitary corticotrophs and, dual feedback mechanisms were put forward.[1],[3] Cyclic CS is an unusual form of CS, wherein periodic endogenous excess cortisol synthesis is interspersed by episodes of normal/suppressed cortisol secretion. Endogenous hypercortisolemia was documented at the initial and second FU visits, but not at first and third FU visits, suggesting cyclic CS in this lady. Endogenous hypercortisolemia subsided spontaneously during the first and third FU visits. An intriguing feature we noticed, was paradoxical cortisol response with dexamethasone during her initial presentation and second FU visit (i.e., during periods of relapse), but adequately suppressed high dose DST cortisol at her first and third FU visits (i.e., during periods of remission). This could be explained by two possibilities:First, the DST tests were performed during the ascending arm of cyclic hormonogenesis and falsely interpreted as positive Liddle's test. Second, the paradoxical cortisol response is seen only during endogenous hypercortisolemia. The presence of a GC positive feedback loop on corticotrophs and simultaneous endogenous hypercortisolemia has been suggested as the underlying cause of such paradoxical response.[4] A period of low endogenous cortisol, as seen during the trough of cyclic CD, probably changes the character of pituitary corticotroph adenoma, that eventually develops a positive feedback response to GC only during subsequent hypercortisolemia in the peak phase of cyclic CS. Exogenous GC administration thus results in paradoxical ACTH-dependent rise in cortisol secretion only during endogenous hypercortisolemia (as noticed during initial visit and second FU visit) and preceding episode of hypocortisolemia is an essential prerequisite to trigger ACTH hypersecretion through a positive feedback loop. Progressive rise in DST-cortisol values with incremental doses of dexamethasone during the evaluation of CS may thus point towards cyclical hormonogenesis in ACTH-producing corticotroph microadenoma.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Checchi S, Brilli L, Guarino E, Ciuoli C, Di Cairano G, Mazzucato P, et al. Cyclic cushing's disease with paradoxical response to dexamethasone. J Endocrinol Invest 2005;28:741-5.
2Lila AR, Sarathi V, Bandgar TR, Shah NS. Paradoxical response to dexamethasone and spontaneous hypocortisolism in Cushing's disease. BMJ Case Rep 2013;2013:bcr2012008035.
3Fehm HL, Voight KH, Lang RE. Paradoxical ACTH response to glucocorticoids in Cushing's disease. N Engl J Med 1977;297:904-7.
4Seki Y, Morimoto S, Saito F, Takano N, Kimura S, Yamashita K, et al. ACTH-dependent cyclic cushing syndrome triggered by glucocorticoid excess through a positive-feedback mechanism. J Clin Endocrinol Metab 2019;104:1788-91.