Cushing’s syndrome encompasses the full range of clinical manifestations caused by chronic exposure to excess glucocorticoids, which can result from a variety of causes [1].

It is considered rare, with an annual incidence of approximately one to six cases per million people per year [1][2]. Cushing’s syndrome can be iatrogenic in origin, resulting from long-term use of glucocorticoids or the administration of a treatment combining a glucocorticoid with medications that alter its pharmacokinetics. Its diagnosis requires both clinical and laboratory evidence. Clinical suspicion is based on the presence of signs of protein hypercatabolism, namely muscle and skin atrophy, vascular and bone fragility, and stretch marks; and a facial-trunk redistribution of fat manifested by android obesity, a moon-shaped, erythematous face, and a “bison hump” appearance. The diagnosis is confirmed by laboratory tests showing excessive cortisol secretion—as evidenced by urinary free cortisol levels more than 3 or even 4 times the normal range—or by evidence of disruption of the circadian rhythm of cortisol secretion, as indicated by a midnight serum cortisol level exceeding 3.6 μg/dl (100 nmol/l) or elevated midnight salivary cortisol levels [2][3].

A chronological link between corticosteroid administration and the onset of specific signs, as well as discrepancies between the clinical presentation and hormonal testing, are arguments supporting an iatrogenic cause [4][5].

Cushing’s syndrome is associated with a reduced quality of life and excess mortality, primarily of cardiovascular origin; hence, the need for early diagnosis and treatment, along with long-term follow-up of patients.

The aim of this study was to present the consequences of the inappropriate use of high-dose, continuous corticosteroids, which led to the development of Cushing’s syndrome in a 49-year-old patient. This is intended to help raise awareness among healthcare professionals and patients regarding the need to adhere to the indications and dosages for corticosteroids.

The inability to perform certain tests and our patient’s limited financial resources posed limitations. Additionally, the inability to measure cardiac biomarkers and perform an autopsy presented constraints in our clinical case.

This case report highlights certain therapeutic errors that can occur during the prescription process, particularly when prescriptions are issued by personnel not qualified to do so and without regard for the indications and contraindications of the prescribed medications. Given our limited resources, we diagnosed hyperosmolar decompensation based on the following criteria: the absence of Kusmaul’s dyspnea and acetone-like breath odor, traces of ketonuria, plasma osmolarity greater than 300 mOsm/L, and plasma bicarbonate levels greater than 18 mmol/L. A ketonuria of 2 crosses or higher would have led us to include a ketotic decompensation in the diagnosis. This is not the case here.

From an epidemiological perspective, Cushing’s syndrome—considered a relatively rare but potentially fatal disease—has an annual incidence of approximately one to six cases per million inhabitants per year and is more common in women, according to several authors [4][6]. This corroborates our data, as we diagnosed two cases of iatrogenic Cushing’s syndrome over a two-year period in a region with a population of 1,939,300 in 2022 [7]. Iatrogenic Cushing’s syndrome is rarely described in the literature. Inappropriate use of corticosteroids can lead to this condition [2]. This was the case for our patient, who received high-dose corticosteroid therapy for 9 months to treat limb cramps. The maximum dose was exceeded because the medication was taken as needed, and the patient and his caregivers stated that the medication was sometimes administered 5 or 6 times a day as soon as he felt the cramps. This amounts to an administration of 24 mg of betamethasone. However, the maximum dose for our patient should have been no more than 16 mg per day. The duration of treatment was very long, and discontinuation was abrupt. All of this is contrary to the precautions for the use of corticosteroids.

Clinically, there were specific signs and less specific signs. In our case, there were numerous specific signs, namely weight gain, stretch marks, bruising, and a “buffalo hump”. Several authors have noted the same specific signs [8]-[10]. However, bone fragility was not objectively observed in our patient.

The classic side effects of corticosteroid therapy—namely, depigmentation, skin fragility, gastric lesions, and diabetic decompensation—were observed in our patient.

The patient’s caregivers reported prolonged administration of high-dose corticosteroids, a finding confirmed by the patient himself. Biochemically, the blood electrolyte panel revealed hypokalemia and hypocalcemia, as described in the literature. This hypokalemia is thought to be related to the mineralocorticoid action of cortisol. The suppression of the adrenocorticotropic axis due to exogenous glucocorticoids explains why the patient presented with signs of adrenal insufficiency (notably severe asthenia), which was confirmed by low serum cortisol levels. Additional endocrine tests were not performed because they were not available at our hospital or within a 180-km radius.

The cramps experienced by the patient, which necessitated the prescription of corticosteroids, could be adverse effects of metformin. A thorough understanding of the side effects of antidiabetic medications and adherence to the indications and contraindications for corticosteroids would have allowed us to avoid this situation. The occurrence of iatrogenic Cushing’s syndrome in the context of metabolic disorders (diabetes, dyslipidemia) has also been described by Behidj S. in Algeria [10].

From a therapeutic standpoint, betamethasone was discontinued and urgently replaced with injectable hydrocortisone, as the patient was considered to have acute adrenal insufficiency [11]. This hydrocortisone supplementation is recommended in the literature [11][12].

Blood glucose control was achieved with high doses of insulin, which highlights the hyperglycemic effect of corticosteroids [11]. Prophylactic anticoagulant therapy was initiated because the patient was bedridden and obese, to reduce the risk of thromboembolic events. This treatment consisted of subcutaneous enoxaparin injections.

The prognosis could have been favorable if diagnosis and treatment had been initiated early. This was not the case for our patient, in whom the diagnosis was made very late. Cushing’s syndrome is rare and is usually associated with severe morbidity and excess mortality, particularly of cardiovascular origin. The cardiovascular complications of Cushing’s syndrome account for its severity, with a mortality rate four times higher in these patients compared to healthy individuals. These complications are primarily due to a high prevalence of cardiovascular risk factors, namely hypertension, abdominal obesity, diabetes,dyslipidemia, and abnormalities in blood viscosity. This was the case with our patient, whose course was unfavorable, as it was marked by cardiovascular complications such as acute pulmonary edema [2][4]. Our patient died on the 16th day of hospitalization with symptoms of acute pulmonary edema (APE). According to the literature, APE can occur in the context of Cushing’s syndrome and is often exacerbated by chronic heart failure [2].

Iatrogenic Cushing’s syndrome is a rare but serious condition that can lead to the development of cardiovascular complications. The presence of specific clinical signs, along with low serum cortisol levels in the context of prolonged administration of high-dose betamethasone, allowed us to establish the diagnosis. Healthcare professionals must be fully knowledgeable about the adverse effects of corticosteroids, as well as the adjunctive treatment and the pre-treatment assessment for corticosteroid therapy. Corticosteroid therapy should not be prescribed by paramedical staff. Strict adherence to the indications and dosages of corticosteroids is essential to prevent the onset of this condition.