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Hidden hypercortisolism: a too frequently neglected clinical condition

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Abstract

Purpose

Classic Cushing’s syndrome (CS) is a severe disease characterized by central obesity, hypertension, easy bruising, striae rubrae, buffalo hump, proximal myopathy and hypertricosis. However, several CS cases have also been reported with unusual or camouflaged manifestations. In recent years, several authors investigated the prevalence of “hidden hypercortisolism” (HidHyCo) among subjects affected with bone fragility, hypertension and type 2 diabetes mellitus (DM2). The prevalence of the HidHyCo is estimated to be much higher than that of classic CS. However, similarly to classic CS, HidHyCo is known to increase the risk of fractures, cardiovascular disease and mortality.

Methods

We reviewed all published cases of unusual presentations of hypercortisolism and studies specifically assessing the HidHyCo prevalence in diabetic, osteoporotic and hypertensive patients.

Results

We found 49 HidHyCo cases, in whom bone fragility, hypertension and diabetes were the presenting manifestations of an otherwise silent hypercortisolism. Amongst these cases, 34.7%, 32.7%, 6.1% and 19.0%, respectively, had bone fragility, hypertension, DM2 or hypertension plus DM2 as the sole clinical manifestations of HidHyCo. Overall, 25% of HidHyCo cases were of pituitary origin, and bone fragility was the very prevalent first manifestation among them. In population studies, it is possible to estimate that 1–4% of patients with apparent primary osteoporosis has a HidHyCo and the prevalence of this condition among diabetics ranges between 3.4 and 10%.

Conclusion

These data indicate that patients with resistant or suddenly worsening hypertension or DM2 or unexplainable bone fragility should be screened for HidHyCo using the most recently approved sensitive cut-offs.

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Authors and Affiliations

  1. Unit for Bone Metabolism Diseases and Diabetes and Lab of Endocrine and Metabolic Research, Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano, IRCCS, Via Magnasco 2, 20149, Milan, Italy

    L. Giovanelli, C. Aresta, V. Favero, M. Bonomi, B. Cangiano, A. Falchetti, L. Persani & I. Chiodini

  2. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

    L. Giovanelli, C. Aresta, V. Favero, M. Bonomi, B. Cangiano, L. Persani & I. Chiodini

  3. Unit of Endocrinology, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy

    C. Eller-Vainicher, G. Grassi & V. Morelli

  4. Unit of Endocrinology and Diabetology “Casa Sollievo della Sofferenza” Hospital, IRCCS, San Giovanni Rotondo, FG, Italy

    F. Pugliese & A. Scillitani

  5. Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy

    L. Gennari

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All authors declare no support from any organization for the submitted work. Luca Giovanelli, Vittoria Favero, Marco Bonomi, Biagio Cangiano, Cristina Eller-Vainicher, Giorgia Grassi, Valentina Morelli, Flavia Pugliese, Alberto Falchetti, Luigi Gennari, Alfredo Scillitani and Luca Persani, have no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years and no other relationships or activities that could appear to have influenced the submitted work. Iacopo Chiodini, Carmen Aresta and Valentina Morelli are investigators in studies on relacorilant (Corcept Therapeutics) in patients with hypercortisolism. Iacopo Chiodini received consulting fees from Corcept Therapeutics and HRA Pharma.

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40618_2020_1484_MOESM1_ESM.tif

Supplementary Figure 1 Pituitary Magnetic Resonance Imaging in patient #1. Right image: coronal section. Left image: sagittal section. The images are obtained after gadolinium. A 7 mm area of reduced signal in the left-sided gland suggestive for pituitary adenoma is indicated by arrows (TIFF 584 kb)

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Giovanelli, L., Aresta, C., Favero, V. et al. Hidden hypercortisolism: a too frequently neglected clinical condition. J Endocrinol Invest 44, 1581–1596 (2021). https://doi.org/10.1007/s40618-020-01484-2

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