Prevalence and outcome of secondary hypogonadism in male patients with Cushing's syndrome and mild autonomous cortisol secretion

Author:

Nowak Elisabeth1ORCID,Vogel Frederick1ORCID,Braun Leah1ORCID,Zopp Stephanie1,Rubinstein German1ORCID,Schilbach Katharina12ORCID,Bidlingmaier Martin1ORCID,Zimmermann Petra3,Thorsteinsdottir Jun4ORCID,R O L Schweizer Júnia1ORCID,Ritzel Katrin1ORCID,Beuschlein Felix156ORCID,Reincke Martin1ORCID

Affiliation:

1. Department of Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich , Germany

2. Deggendorf Institute of Technology , 94469 Deggendorf , Germany

3. Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich , 80336 Munich , Germany

4. Department of Neurosurgery, LMU University Hospital, LMU Munich , 80336 Munich , Germany

5. Department of Endocrinology, Diabetology, and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH) , 8091 Zurich , Switzerland

6. The LOOP Zurich—Medical Research Center , 8044 Zurich , Switzerland

Abstract

Abstract Background Secondary hypogonadism (SH) is common in men with Cushing's syndrome (CS), but its impact on comorbidities is largely unknown and longitudinal data are scarce. If SH also affects men with mild autonomous cortisol secretion (MACS) is unknown. Methods We included 30 treatment-naïve adult men with CS and 17 men with MACS diagnosed since 2012. Hypogonadism was diagnosed based on total testosterone (TT) concentrations < 10.4 nmol/L and age-specific cut-offs. Outcomes were compared to age- and BMI-matched controls. In 20 men in remission of CS, a longitudinal analysis was conducted at 6, 12, and 24 months. Results Men with CS had significantly lower concentrations of TT, bioavailable T, and free T compared to controls (P < .0001) with lowest concentrations in ectopic CS. Likewise, TT was lower in men with MACS compared to controls. At baseline, 93% of men with CS and 59% of men with MACS had SH. Testosterone correlated negatively with late night salivary cortisol and serum cortisol pre- and post-1 mg dexamethasone suppression test. Following successful surgery, TT increased significantly (P = .001), normalising within 6 months. Despite normalisation, several RBC parameters remained lower in men with CS even 2 years after successful surgery. Conclusions Secondary hypogonadism is common in men with CS and MACS but usually reversible after successful surgery. The persisting changes observed in RBC parameters need to be further investigated in larger cohorts and longer follow-up durations.

Funder

German Cushing’s Registry CUSTODES

Else Kröner-Fresenius-Stiftung

Deutsche Forschungsgemeinschaft

Clinician Scientist Program RISE

Eva Luise und Horst Köhler Stiftung

Munich Clinician Scientist Program

LMU Hospital Munich

Publisher

Oxford University Press (OUP)

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