Endocrine Abstracts

Background: The Endocrine Society Guidelines recommend screening for hypercortisolism especially in patients with specific features that best discriminate Cushing’s Syndrome (CS): easy bruising, facial plethora, proximal myopathy and striae. Clinical experience suggests that these features, though suggestive of hypercortisolism, are not enough sensitive. Indeed, patients with hypercortisolism frequently manifest primarily less discriminatory cortisol-related features, such as arterial hypertension, diabetes mellitus, weight gain, osteoporosis, defining a hidden form of CS, also defined as “non classic hypercortisolism” (nCH). We conducted a study to retrospectively compare the biochemical and clinical data of patients with hypercortisolism, in CS and nCH forms at their first presentation.

Methods: Fifty-eight adult patients (age 47.7±16.7 years, female/male 50/8) with proven biochemical hypercortisolism referred to our hospital from 2008 to 2021 were included. In all patients we evaluated the clinical features present at their first presentation to our outpatient clinic. The subjects were divided into two groups according to the presence or absence of classic and highly specific presenting symptoms, CS and nCH groups respectively. In all patients we assessed 24-hour urinary free cortisol (UFC), cortisol after 1mg-overnight-dexamethasone (F-1mgDST), the delay between estimated clinical onset and diagnosis, the therapy undertaken, the recovery and/or persistence/recurrence of the disease.

Results: In the whole sample, hypertension was the most frequent feature present at presentation (18.2% of all presenting symptoms), followed by weight gain (15.6%) and facial plethora (13%). Classic signs of CS accounted for only 25.2% among all presenting symptoms. Twenty-eight patients were classified with CS (48.3%) and 30 with nCH (51.7%). Hypertension and weight gain were the most common features (48% and 41.4%, respectively) without difference between CS and nCH. UFC and F-1mgDST levels were higher in CS patients (625.9±496.3 μg/24h, 18.2±13.5 μg/dl, respectively) than in nCH patients (272.1±261.6 μg/24h, 9.6±7.3 μg/dl respectively, P<0.05 for all comparisons). Notably, hypertension was the most frequent sign in patients with nCH (56.7%) and the second most frequent in CS (39.3%), second only to weight gain (50.0%) in the latter group. Importantly, in all hypertensive patients hypertension was non controlled or resistant or with early onset. Diagnostic delay was three-fold longer for nCH than for CS (5.4±5.6 vs 1.9±1.7 years, P=0.003).

Conclusions: Specific signs of CS are frequently absent at clinical onset of hypercortisolism, most common finding being hypertension. It is crucial for the clinician to recognize potential non-classical features of hypercortisolism which, although non-specific, may present peculiar features and allow a correct diagnosis.