Polycythemia in a patient
with 21-hydroxylase deficiency
M. Mercè Albareda, José
Rodríguez-Espinosa, Angel Remacha, Narcís Prat,
Susan M. Webb.
Depts of Endocrinology, Biochemistry and Hematology, Hospital de
Sant Pau, Autonomous University of Barcelona. Barcelona, Hospital
de Figueres, Spain.
Correspondence: M. Mercè Albareda, Depts of Endocrinology,
Biochemistry and Hematology, Hospital de Sant Pau, Autonomous
University of Barcelona. Barcelona, Hospital de Figueres,
Spain.
Twenty-one hydroxylase deficiency (21OHD) is the most frequent
cause of congenital adrenal hyperplasia (CAH), which may present
in different clinical forms: salt losing, simple virilizing and
non-classical or attenuated, depending on the severity of enzyme
deficiency. We present a man with 21OHD who surprisingly was not
diagnosed until the age of 38 years during the study of
polycythemia.
A 38 year-old male, who was an occasional smoker and alcohol
drinker, presented with a 1 year history of hypertension, treated
with atenolol, and polycythemia and was referred to our hospital
after finding bilateral adrenal gland enlargement on a CT scan.
performed in the investigation of polycythemia. He had presented
precocious puberty and a growth spurt at the age of 5 years, with
no family history of growth disorders or hirsutism. On examination
there was no liver or spleen enlargement, blood pressure was
140/100 mm Hg (without treatment), height 1.49 m, his skin was
hyperpigmented, testicular volume 10/12 ml and his body hair was
increased. Analytically he had polycythemia with undetectable
erythropoietin (epo) and an otherwise normal blood count, with
increased ACTH, adrenal androgens and 17OH-progesterone
(Table
1). An ACTH stimulation
test with 250 mg confirmed CAH (cortisol &endash;212 and 253
nmol/L- and 17OH-progesterone &endash;1190 and 1680 nmol/L-
basally and 30 min after ACTH; normal response: cortisol >600
nmol/L, 17OH-progesterone <15 nmol/L). After beginning
hydrocortisone treatment there was a fall in androgens and
normalization of the red cell count and epo (Table
1). This patient had CAH
due to 21OHD in its simple virilizing form, associated with
polycythemia. Even though one case of polycythemia associated to
CAH was described in 1959 in a 3 month-old boy,1
clinical descriptions of this entity do not mention this
association, and in a series of 21 children with CAH, no
abnormalities in the red cell series was observed.2 The
most probable cause of polycythemia is hyperandrogenism. Androgens
exert a direct effect on hemopoietic precursors, as well as a
stimulatory effect on epo production.3 It is suggested
that a direct androgen effect on the production of red blood cells
induced this patient's polycythemia, which by negative feedback
inhibited epo production. After treatment, both red blood cell
counts and epo levels returned to reference values. In
concordance, Dickerman et al. have described in healthy subjects
an elevation of hemoglobin after androgen treatment, together with
epo at or below the normal lower limit.4 In contrast to
other cases of CAH diagnosed and treated earlier in life,
polycythemia in this patient is probably due to the very long
standing chronic hyperandrogenism, and contributes to explain the
role of androgens on hematopoiesis.
