SciELO - Scientific Electronic Library Online

vol.45 issue3Differential diagnosis of distal ileal obstruction in young women What is the role of magnetic resonance enterography?Doege-Potter syndrome author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand




Related links

  • On index processCited by Google
  • Have no similar articlesSimilars in SciELO
  • On index processSimilars in Google


Acta Medica Colombiana

Print version ISSN 0120-2448

Acta Med Colomb vol.45 no.3 Bogotá July/Sept. 2020  Epub June 06, 2021 

Cases presentation

Exogenous Cushing's syndrome with a difficult diagnosis

Luis Felipe Fierro-Mayaa 

Angélica María González-Clavijob  * 

Miguel Ángel Álvarez-Lozanoc 

Gonzalo Alejandro Moreno-Solerc 

Sebastián Rodríguez-Pazc 

Daniela Tarquino-Rincónc 

a Instituto Nacional de Cancerología, Unidad de Endocrinología Oncológica; Bogotá, D.C. (Colombia)

b Instituto Nacional de Cancerología, Unidad de Endocrinología Oncológica. Universidad Nacional de Colombia, Facultad de Medicina, Departamento de Ciencias Fisiológicas, Unidad de Bioquímica; Bogotá, D.C. (Colombia)

c Universidad Nacional de Colombia, Facultad de Medicina, Departamento de Ciencias Fisiológicas, Unidad de Bioquímica. Bogotá, D.C. (Colombia).



Cushing's syndrome (CS) is a group of signs and symptoms caused by chronic exposure to excessive glucocorticoids. The use of medications containing glucocorticoids is the most common cause, but they may be hidden in some products sold as nutritional supplements or naturopathic medications, which makes the diagnostic approach more difficult.

Case presentation:

this was a 40-year-old patient with typical clinical signs of Cushing's syndrome and discordant results of diagnostic tests to identify its origin. It was ultimately determined that the patient had been chronically taking a "naturopathic" product known as artrin®, which was analyzed in the institution's lab and found to contain cortisol.


chronic exposure to exogenous glucocorticoids, whether surreptitious, unknown or prescribed, causes CS and should be promptly distinguished from endogenous forms to avoid inappropriate diagnostic tests and treatments.(Acta Med Colomb 2020; 45. DOI:

Key words: syndrome; exogenous glucocorticoids; herbal supplements



el síndrome de Cushing (SC) es un grupo de signos y síntomas causados por la exposición crónica al exceso de glucocorticoides. El uso de fármacos con glucocorticoides es la causa más frecuente, pero algunos productos vendidos como suplementos nutricionales o medicamentos naturistas para el control de los dolores articulares pueden contenerlos de forma oculta, lo cual dificulta el enfoque diagnóstico

Presentación del caso:

paciente de 40 años con signos clínico típicos de síndrome de Cushing con resultados discordantes en las pruebas diagnósticas para identificar su origen. Finalmente se logra establecer que el paciente consumía de forma crónica un producto "naturista" conocido como artrin®, el cual fue analizado en el laboratorio de la institución con resultados positivos para cortisol.


la exposición crónica a glucocorticoides exógenos, ya sea subrepticia, desconocida o prescrita, causa SC y debe distinguirse tempranamente de las formas endógenas para evitar la realización de pruebas diagnósticas y tratamientos inadecuados.(Acta Med Colomb 2020; 45. DOI:

Palabras clave: de Cushing; glucocorticoides exógenos; suplementos herboles


Cushing's syndrome (CS) is a rare disease with an in cidence of two to three cases per million people per year, but with a high morbidity and mortality 1. It is caused by prolonged and inappropriate exposure to excessive glucocorticoids. The presence of physical signs such as moon face, truncal obesity, purple striae, hirsutism and acne, as well as related metabolic complications like diabetes, arterial hypertension and osteoporosis, should raise a suspicion of hypercortisolism. However, the diagnosis is almost always a clinical challenge.

There are two types of Cushing's syndrome: endogenous and exogenous. Endogenous Cushing's syndrome may be ACTH dependent, constituting 80-85% of cases, arising in most cases from an ACTH-secreting pituitary adenoma, or caused by ectopic secretion of ACTH or of corticotropin-releasing hormone (CRH) in certain pulmonary or pancreatic neuroendocrine tumors. ACTH-independent Cushing's syndrome makes up 15-20% of endogenous hypercortisolism cases and is a result of adrenal adenomas or carcinomas 2-4.

Exogenous Cushing's, which is the main cause of hy percortisolism, is a consequence of prolonged exposure to medications with a glucocorticoid effect. Generally, it is transient and resolves when exposure is discontinued. However, when products with hidden glucocorticoids are used, it may become a chronic disease which is difficult to diagnose 5.

Clinical case

A 40-year-old patient with a history of psoriatic arthritis from the age of 30, who developed physical changes with central obesity, purple abdominal striae and a moon face a year prior to this consult, associated with brittle diabetes mellitus and severe arterial hypertension. He was studied in his usual place of residence, with a finding of hypercortisolism. The patient repeatedly denied taking glucocorticoid drugs.

He was referred to the Instituto Nacional de Cancerología with a diagnosis of ACTH-dependent Cushing's syndrome, with pituitary imaging negative for adenomas. The bio chemical tests were repeated on the initial exam (Table 1), as their results were not congruent. The institutional lab results are also shown in Table 1, with findings indicative of ACTH-independent Cushing's syndrome. A tomography of the suprarenal glands was normal.

Table 1 Patient's clinical laboratory tests. 

Month Cortisol A.M ACTH A.M LDDST Cortisol 24-hour urine cortisol (ug/24 h)
August 2008 (external) 9.0 82 3.9 308 (RV 32-243)
November 2008 (INC) 8.07 Less than 1 10.9 ND
March 2009 (INC) 3.4 ND ND ND
ND: No data LDDST: Low-dose dexamethasone suppression test.

Subsequently, on a second visit, the patient's basal cortisol was suppressed, which led to a suspicion of surreptitious ingestion of glucocorticoids. The patient reported taking a "naturopathic" product sold as artrin® intermittently for more than 12 months, with three to four-month periods of constant use, and periods of up to two weeks with no use. Artrin® is a product sold in Colombia without an INVIMA [Translator's note: drug and food regulation agency] license 6. However, the label does not mention glucocorticoids as one of its ingredients, as shown in Figure 1. Due to the time coincidence between artrin® consumption and the clinical picture and the lack of information regarding its contents in official sources (INVIMA), we conducted a cortisol measurement test on a tablet of artrin®. For this test, one tablet was dissolved in 5 cc of normal saline solution and an aliquot was taken, which was processed in our institution's clinical laboratory using the first generation Elecsys cortisol assay (Roche® Diagnostics) with a result greater than 1,352 nmol/L (chemiluminescence, range <5-1,352 nmol/L).

Figure 1 Packaging and label of the artrin ® product. 

The patient was instructed to discontinue use of the «naturopathic» product and, to avoid adrenal insufficiency due to axis suppression, the patient received oral prednisolone replacement at 5 mg/day, with gradual dose reduction until it was completely withdrawn at six weeks. The pa tient experienced progressive improvement of the physical characteristics of Cushing's and complete correction of the hyperglycemia, although arterial hypertension persisted.


Cushing's syndrome (CS) is a group of signs and symptoms caused by chronic exposure to excessive glucocorticoids. In the initial diagnostic approach to any patient with clinical signs of hypercortisolism, it is imperative to rule out the use of glucocorticoid-containing medications. These drugs are commonly prescribed for oral, parenteral, topical, rectal or inhaled use. Patients receiving pain-control injections may not be aware that they have received a potent glucocorticoid. Glucocorticoids may also be present in a variety of over-the-counter medications. Recently, the use of skin whitening creams and their association with Cushing's syndrome has been reported 7.

Some products sold without a prescription mention con taining plant extracts with analgesic and anti-inflammatory properties. While bromelia extracts containing flavonoid glycosides may have anti-inflammatory properties 8, as may Boswellia serrata extracts 9, in the case of the ar trin® product used by the patient, we inferred that it was a fraudulent product, since the label had an incorrect list of the plant extracts it claimed to contain, and especially since glucocorticoid content was proven by cortisol detection on the clinical laboratory test.

When a patient who uses this type of product devel ops Cushing's syndrome characteristics, measurement of synthetic steroids in blood or urine is recommended 10. However, lab tests to determine the concentrations of these synthetic steroids are not available in our setting. Thus, we depend on synthetic glucocorticoids such as prednisolone, prednisone and methylprednisolone cross-reacting with the plasma and urine cortisol test using immunoassay methods as shown in Table 2. By contrast, dexamethasone causes little or no cross-reaction with cortisol in analytical assays, which justifies its use as the diagnostic screening test for Cushing's syndrome known as the low-dose dexamethasone suppression test 11.

Table 2 Cross-reactivity in immunoassays for cortisol. 

Based on the test results, we suspected that artrin® con tained one of the three synthetic steroids mentioned. How ever, for INVIMA, artrin® is a product whose legitimate composition is unknown 6.

The discrepancy between the serum cortisol and ACTH tests seen in this patient was explained by the intermittent use of artrin® and the use of different analytical methods for the various measurements.


Chronic exposure to exogenous glucocorticoids should be ruled out early in any patient suspected of having Cushing's syndrome, and "naturopathic medications" should be considered, especially those with "anti-inflammatory and analgesic properties," since they may contain hidden synthetic steroids.


1. Hagen C, Jorgensen J, Kosteljanetz M, Kristensen L, Laurberg P, Schmidt K, Weeke J. 2001 Incidence and late prognosis of Cushing 's syndrome: a population-based study.J Clin Endocrinol Metab86:117-123 [PubMed] [Google Scholar] [ Links ]

2. Pivonello R, De Martino MC, De Leo M, Lombardi G, Colao A.Cushing's síndrome Endocrinol Metab Clin North Am .2008 Mar;37(1):135-49, ix. doi: 10.1016/j.ecl.2007.10.010. [ Links ]

3. Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Cushing's síndrome. Lancet. 2015 Aug 29;386(9996):913-27. doi: 10.1016/S0140-6736(14)61375-1. Epub 2015 May 21. [ Links ]

4. G. Arnaldi, A. Angeli, A. B. Atkinson, X. Bertagna, F. Cavagnini, G. P. Chrousos, G. A. Fava, J. W. Findling, R. C. Gaillard, A. B. Grossman, B. Kola, A. Lacroix, T. Mancini, F. Mantero, J. Newell-Price, L. K. Nieman, N. Sonino, M. L. Vance, A. Giustina, M. Boscaro, Diagnosis and Complications of Cushing's Syndrome: A Consensus Statement,The Journal of Clinical Endocrinology & Metabolism ,Volume 88, Issue 12, 1 December 2003, Pages 5593-5602, ]

5. Wei L, MacDonald TM, Walker BR. 2004 Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med 141:764-770 [PubMed] [Google Scholar] [ Links ]


7. Z, Smith P, et al. Combinations of potent topical steroids, mercury and hydroquinone are common in internationally manufactured skin-lightening products: a spectroscopic study. Clin Exp Dermatol 2016;41:196-201 [ Links ]

8. Da Silva Balin, P. et al. Toxicological evaluation and anti-inflammatory potential of an ethanolic extract from Bromelia balansae (Bromeliaceae) fruit. Journal of ethnopharmacology, 2018; 79-86. [ Links ]

9. Kumar R, et al. Effect of Boswellia Serrata Extract on Acute Inflammatoiy Parameters and Tumor Necrosis Factor-a in Complete Freund's Adjuvant-Induced Animal Model of Rheumatoid Arthritis. Int J Appl Basic Med Res. 2019; 9(2):100-106. [ Links ]

10. Nieman LK. Recent Updates on the Diagnosis and Management of Cushing's Syndrome.Endocrinol Metab (Seoul). 2018 Jun;33(2):139-146. doi: 10.3803/EnM.2018.33.2.139. PMID: 29947171; PMCID: PMC6021313 [ Links ]

11. Reimondo G, Pia A, Bovio S, Allasino B, Daffara F, Angeli A, Terzolo M. Laboratory differentiation of Cushing's síndrome.Clinica Chimica Acta; International Journal of Clinical Chemistry. 2007, 388(1-2):5-14] DOI: 10.1016/j.cca.2007.10.036 [ Links ]

12. UCSF. Clinical Labs-Chemistry, 1-12; tomado de: ]

13. Krasowski, M. D., et al. Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction.BMC clinical pathology ,2014;14: 33. [ Links ]

Received: July 31, 2019; Accepted: April 13, 2020

* Correspondencia: Dra. Angélica María González-Clavijo. Bogotá, D.C. (Colombia). E-mail:

Creative Commons License This is an open-access article distributed under the terms of the Creative Commons Attribution License