S P E C I A L
I m a g e
i n
F E A T U R E
E n d o c r i n o l o g y
131I-Noriodocholesterol Uptake by Testicular
Adrenal Rest Tumors in a Patient With Classical
21-Hydroxylase Deficiency
Valérie Bernard, Cécile N. Chougnet, Florence Tenenbaum, and Jacques Young
Université Paris-Sud, Faculté de Médecine Paris-Sud (V.B., J.Y.), 94270 Le Kremlin Bicêtre, France;
Assistance Publique-Hôpitaux de Paris (V.B., J.Y.), Reproductive Endocrine Department, Hôpital de
Bicêtre, 94275 Le Kremlin-Bicêtre, France; Nuclear Medecine Department (C.N.C.), St-Louis Hospital,
75016 Paris, France; Nuclear Medecine Department (F.T.), Cochin Hospital, 75679 Paris, France; and
INSERM U693 (V.B., J.Y.), 94270 Le Kremlin-Bicêtre, France
esticular adrenal rest tumors (TARTs) are a complication responsible for infertility in men born with a
classical form of 21-hydroxylase deficiency (21OHD) (1).
A 17-year-old man was referred to us for bilateral testicular tumors. 21OHD with salt loss had been diagnosed at birth and was confirmed after puberty by a very
high basal serum 17-hydroxyprogesterone level (703
nmol/L; normal, ⬍3.03). His final height was 1.67 m, for
a target height of 1.78 m. Molecular analysis of the patient
and his parents showed that he carried two severe recurrent mutations of CYP21A2 in the compound heterozygous state, namely a large deletion on one allele and
p.Gly110ValfsX21 on the other allele (2). The patient was
prescribed hydrocortisone (30 mg/d) and 9␣-fludrocortisone (100 ␮g/d) but was nonadherent. Physical examination showed two palpable masses with a stony consistency
suggestive of intratesticular adrenal inclusions. Two testicular tumors were visible on magnetic resonance imaging
(MRI), measuring 65 and 48 mL on the right and left,
respectively (Figure 1A), and occupying virtually the
whole intratesticular space (3). 131I-Noriodocholesterol
scintigraphy (131I-N) showed significant bilateral scrotal
uptake on days 3 and 7 (Figure 1B) but no significant
adrenal uptake (Supplemental Figure 1). Fusion images of
the testicular computed tomography (CT) and 131I-N
functional images showed that the uptake in the right and
left testes corresponded to the two gonadal masses (Figure
1, C and D). 18F-Fluorodeoxyglucose (FDG)-positron
emission tomography (PET)/CT functional imaging
showed no testicular or adrenal FDG uptake in this pa-
tient, contrary to what we had found in a 20-year-old man
with classical salt-wasting 21OHD, whose TARTs
showed significant FDG uptake on FDG-PET/CT (Figure
2) (4).
At the request of the patient and his parents, the two
tumors were resected. Serum levels of cortisol, 21-deoxycortisol, and 11-hydroxyandrostendione were measured
by HPLC/tandem mass spectrometry, as previously described (5, 6) with minor modifications, in left and right
testicular venous effluent blood drawn preoperatively and
were compared to peripheral serum levels. The very high
levels in both spermatic veins of these 11-hydroxylated
steroid hormones produced exclusively by the adrenal
glands demonstrated that both testicular masses were of
adrenal origin (Table 1) (7). Histological examination
showed a typical aspect of steroidogenic tissue compatible
with TART (3).
This first report of nordiodocholesterol uptake by
TART indicates that this ectopic adrenal tissue possesses
active cholesterol uptake and steroidogenic activity. The
possible therapeutic value of this radiotracer uptake, as
well as its possible deleterious impact on spermatogenesis
(8) in patients with these hard-to-treat tumors remains to
be determined (3). The reason some TARTs take up FDG
whereas others do not also remains to be determined.
ISSN Print 0021-972X ISSN Online 1945-7197
Printed in U.S.A.
Copyright © 2014 by the Endocrine Society
Received April 29, 2014. Accepted August 5, 2014.
First Published Online August 14, 2014
Abbreviations: CT, computed tomography; FDG, 18F-fluorodeoxyglucose; 131I-N, 131Inoriodocholesterol scintigraphy; MRI, magnetic resonance imaging; 21OHD, 21-hydroxylase deficiency; PET, positron emission tomography; TART, testicular adrenal rest tumor.
T
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jcem.endojournals.org
Acknowledgments
Address all correspondence and requests for reprints to: Prof.
Jacques Young, MD, PhD, Service d’Endocrinologie et des Mal-
J Clin Endocrinol Metab, November 2014, 99(11):3956 –3957
doi: 10.1210/jc.2014-2195
doi: 10.1210/jc.2014-2195
jcem.endojournals.org
3957
Figure 1. MRI and functional imaging of bilateral TARTs in a patient with classical 21-OHD. A, Testicular axial MRI. B, 131I-noriodocholesterol
uptake by TART in the scrotal region. C and D, Fused axial 131I-N/CT images showing noriodocholesterol uptake by the TARTs in the same patient.
Serum ACTH levels at the time of 131I-N were between 123 and 246 pg/mL (normal, ⬍62).
adies de la Reproduction, Hôpital Bicêtre, 78 rue du General
Leclerc, F-94275, Kremlin-Bicêtre, France. E-mail: jacques.
[email protected].
2.
This work was supported by the French Association of Patients with Adrenal Diseases.
Disclosure Summary: The authors have no conflicts of interest to declare.
3.
References
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Table 1. Serum Steroids in the Spermatic Vein
Effluents Compared to Peripheral Vein in the Patient
Figure 2. FDG-PET/CT functional imaging showing increased
testicular and adrenal FDG uptake in a 20-year-old man with classical
21OHD (carrying the homozygous severe recurrent c.290 –13C/A⬎G
mutation) (2) and TARTs. A, Whole-body scintigraphy (blue arrows and
red arrows show adrenal and TART FDG focal uptake, respectively). B,
Axial FDG view, red arrows show TARTs focal FDG uptake. C, Axial CT
view showing the bilateral TARTs (yellow arrows). D, Merged FDG-PET/
CT, TARTs uptake is indicated by yellow arrows. Serum ACTH and 17hydroxyprogesterone levels (range) at the time of FDG-PET/CT
scintigraphy were 98 –157 pg/mL and 523– 618 nmol/L, respectively
(normal, ⬍62 pg/mL for ACTH and ⬍3.03 nmol/L for
17-hydroxyprogesterone).
Steroid
Patient SV
Patient PV
Cortisol
21-DF
11-OHAdione
17-OHP
Adione
143/122 (298 –389)a
1383/1244 (0.39 – 0.47)a
887/981 (35.0 –137)a
3356/2998 (165–232)a
588/653 (106 –142)a
61 (239 – 612)b
128 (0.1– 0.46)b
39 (2.2–9.8)b
874 (2.4 – 4.9)b
31 (2.2–5.3)b
Abbreviations: SV, spermatic vein; PV, peripheral vein; 21DF,
21-deoxycortisol; 11-OHAdione, 11-␤hydroxy-⌬4-androstenedione;
17OHP, 17-hydroxyprogesterone; Adione, ⌬4-androstenedione.
Results are expressed in nanomoles/liter.
a
Spermatic blood samples obtained during surgery for varicocele in
two adult subjects without endocrinopathy. For comparison, SV steroid
levels in two men without 21OHD are indicated in parentheses.
b
Normal range in four men.