Diagnosis and Treatment > Medication
Search for other papers by Carlos Tavares Bello in
Google Scholar
PubMed
Search for other papers by Emma van der Poest Clement in
Google Scholar
PubMed
Search for other papers by Richard Feelders in
Google Scholar
PubMed
Summary
Cushing’s syndrome is a rare disease that results from prolonged exposure to supraphysiological levels of glucocorticoids. Severe and rapidly progressive cases are often, but not exclusively, attributable to ectopic ACTH secretion. Extreme hypercortisolism usually has florid metabolic consequences and is associated with an increased infectious and thrombotic risk. The authors report on a case of a 51-year-old male that presented with severe Cushing’s syndrome secondary to an ACTH-secreting pituitary macroadenoma, whose diagnostic workup was affected by concurrent subclinical multifocal pulmonary infectious nodules. The case is noteworthy for the atypically severe presentation of Cushing’s disease, and it should remind the clinician of the possible infectious and thrombotic complications associated with Cushing’s syndrome.
Learning points:
-
Severe Cushing’s syndrome is not always caused by ectopic ACTH secretion.
-
Hypercortisolism is a state of immunosuppression, being associated with an increased risk for opportunistic infections.
-
Infectious pulmonary infiltrates may lead to imaging diagnostic dilemmas when investigating a suspected ectopic ACTH secretion.
-
Cushing’s syndrome carries an increased thromboembolic risk that may even persist after successful surgical management.
-
Antibiotic and venous thromboembolism prophylaxis should be considered in every patient with severe Cushing’s syndrome.
Search for other papers by Judith Gerards in
Google Scholar
PubMed
Search for other papers by Michael M Ritter in
Google Scholar
PubMed
Search for other papers by Elke Kaminsky in
Google Scholar
PubMed
Search for other papers by Andreas Gal in
Google Scholar
PubMed
Search for other papers by Wolfgang Hoeppner in
Google Scholar
PubMed
Search for other papers by Marcus Quinkler in
Google Scholar
PubMed
Summary
DAX1 (NR0B1) is an orphan nuclear receptor, which plays an important role in development and function of the adrenal glands and gonads. Mutations in DAX1 cause X-linked adrenal hypoplasia congenita (X-linked AHC), which is characterized by adrenal insufficiency (AI) and hypogonadotropic hypogonadism (HHG). Affected boys present with adrenal failure usually in childhood and, later in life, with delayed puberty. However, patients with a late-onset form of X-linked AHC have also been described in the past years. We report a male patient who presented with symptoms of an adrenal crisis at the age of 38 years and was later diagnosed with HHG. Family history was positive with several male relatives diagnosed with AI and compatible with the assumed X-chromosomal inheritance of the trait. Direct sequencing of DAX1 of the patient revealed a hemizygous cytosine-to-thymine substitution at nucleotide 64 in exon 1, which creates a novel nonsense mutation (p.(Gln22*)). In order to compare the clinical presentation of the patient to that of other patients with X-linked AHC, we searched the electronic database MEDLINE (PubMed) and found reports of nine other cases with delayed onset of X-linked AHC. In certain cases, genotype–phenotype correlation could be assumed.
Learning points:
-
X-linked AHC is a rare disease characterized by primary AI and hypogonadotropic hypogonadism (HHG). The full-blown clinical picture is seen usually only in males with a typical onset in childhood.
-
Patients with a late-onset form of X-linked AHC have also been described recently. Being aware of this late-onset form might help to reach an early diagnosis and prevent life-threatening adrenal crises.
-
Adult men with primary AI of unknown etiology should be investigated for HHG. Detecting a DAX1 mutation may confirm the clinical diagnosis of late-onset X-linked AHC.
-
In relatives of patients with genetically confirmed X-linked AHC, targeted mutation analysis may help to identify family members at risk and asymptomatic carriers, and discuss conscious family planning.
