Glucocorticoid-remediable aldosteronism in a large kindred: clinical spectrum and diagnosis using a characteristic biochemical phenotype.
OBJECTIVE
To define the clinical spectrum of glucocorticoid-remediable aldosteronism (GRA) in a large kindred.


METHODS
Screening all at-risk relatives of a proband for GRA using a specific biochemical phenotype and collecting of medical histories of kindred members from five generations.


METHODS
Outpatient General Clinical Research Centers and patients' homes.


METHODS
Screening was done while patients were on a self-selected diet and included blood pressure determinations; serum potassium and plasma renin activity and aldosterone measurements; and 24-hour urinary tetrahydroaldosterone, 18-oxotetrahydrocortisol, and 18-hydroxycortisol measurements.


RESULTS
Diagnosis of GRA was established on the basis of a previously described specific biochemical abnormality, overproduction of the cortisol C-18 oxidation products (18-oxotetrahydrocortisol and 18-hydroxycortisol) in urine and their ratio relative to tetrahydroaldosterone. Glucocorticoid-remediable aldosteronism was diagnosed in 11 additional patients spanning three generations; this group included the youngest patient (3 months old) ever diagnosed with GRA. Complete penetrance of the biochemical abnormality is likely, with 11 of 18 at-risk patients displaying the phenotype. All patients with GRA had elevated blood pressure. Affected adult patients had been diagnosed as hypertensive before reaching 21 years of age (n = 7 mean, 16.1 +/- 3.4 years). All affected patients were normokalemic (4.3 +/- 0.3 mmol/L).


CONCLUSIONS
Hypertension is a characteristic feature of GRA. Elevated blood pressure in this kindred developed at an early age and often was severe. Because a normal potassium level does not exclude the diagnosis of GRA, the disorder may be underdiagnosed. The value of a specific cortisol C-18 oxidation phenotype in the diagnosis of GRA has been confirmed.
Rich
G M
GM
Brigham and Women's Hospital, Boston, Massachusetts.
Ulick
S
S
Cook
S
S
Wang
J Z
JZ
Lifton
R P
RP
Dluhy
R G
RG
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D006929:Hyperaldosteronism / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D006973:Hypertension / Q000235:genetics; D007223:Infant; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D011446:Prospective Studies; D012083:Renin / Q000097:blood; D012680:Sensitivity and Specificity
D003907:Dexamethasone; D012083:Renin; D006854:Hydrocortisone