Abstract
We present a boy with a genetically proven congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. While massively elevated 17-hydroxyprogesterone (17-OHP) concentrations after birth led to the diagnosis, 17-OHP concentrations became immeasurable starting with the second year of life even though the dose of hydrocortisone was continuously decreased to ∼7 mg/m2/day. Furthermore, 17-OHP levels were immeasurable during the ACTH test and after withdrawing hydrocortisone medication. In contrast, ACTH levels increased after cessation of hydrocortisone treatment suggesting complete primary adrenal cortex failure. We discuss this case based on the differential diagnosis of complete adrenal cortex failure including other genetic causes in addition to CAH, prednisolone treatment, autoimmune adrenalitis, adrenoleukodystrophy, CMV infection, and adrenal hemorrhage infarction. The most likely disease in our boy is autoimmune adrenalitis, which is difficult to prove years after the onset of the disease. Treatment of CAH had masked the classical symptoms of complete adrenal cortex insufficiency leading to delayed diagnosis in this case.
References
1.
New
MI
, Abraham
M
, Gonzalez
B
, Dumic
M
, Razzaghy-Azar
M
, Chitayat
D
, et al. Genotype-phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency
. Proc Natl Acad Sci USA
. 2013
Feb
;110
(7
):2611
–6
.
[PubMed]
0027-84242.
Kulle
AE
, Riepe
FG
, Melchior
D
, Hiort
O
, Holterhus
PM
. A novel ultrapressure liquid chromatography tandem mass spectrometry method for the simultaneous determination of androstenedione, testosterone, and dihydrotestosterone in pediatric blood samples: age- and sex-specific reference data
. J Clin Endocrinol Metab
. 2010
May
;95
(5
):2399
–409
.
[PubMed]
0021-972X3.
Kulle
AE
, Reinehr
T
, Simic-Schleicher
G
, Hornig
NC
, Holterhus
PM
. Determination of 17OHPreg and DHEAS by LCMSMS: Impact of Age, Sex, Pubertal Stage and BMI on the Delta5-steroid-pathway
. J Clin Endocrinol Metab
. 2016
Nov
;•••
:jc20162849
. 0021-972X4.
Wudy
SA
, Schuler
G
, Sánchez-Guijo
A
, Hartmann
MF
. The art of measuring steroids: principles and practice of current hormonal steroid analysis
. J Steroid Biochem Mol Biol
. 2017
Sep
;S0960-0760(17)30250-9
.
[PubMed]
1879-12205.
Liddell
BS
, Oberlin
JM
, Hsu
DP
. Inhaled corticosteroid related adrenal suppression detected by poor growth and reversed with ciclesonide
. J Asthma
. 2017
Jan
;54
(1
):99
–104
.
[PubMed]
0277-09036.
Park
J
, Didi
M
, Blair
J
. The diagnosis and treatment of adrenal insufficiency during childhood and adolescence
. Arch Dis Child
. 2016
Sep
;101
(9
):860
–5
.
[PubMed]
0003-98887.
Di Dalmazi
G
, Berr
CM
, Fassnacht
M
, Beuschlein
F
, Reincke
M
. Adrenal function after adrenalectomy for subclinical hypercortisolism and Cushing’s syndrome: a systematic review of the literature
. J Clin Endocrinol Metab
. 2014
Aug
;99
(8
):2637
–45
.
[PubMed]
0021-972X8.
Prete
A
, Paragliola
RM
, Bottiglieri
F
, Rota
CA
, Pontecorvi
A
, Salvatori
R
, et al. Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing disease and nonmalignant primary adrenal Cushing syndrome
. Endocrine
. 2017
Mar
;55
(3
):969
–80
.
[PubMed]
1355-008X9.
Yates
G
, Bass
C
. The perpetrators of medical child abuse (Munchausen Syndrome by Proxy) - A systematic review of 796 cases
. Child Abuse Negl
. 2017
Oct
;72
:45
–53
.
[PubMed]
0145-213410.
Akin
L
, Kurtoglu
S
, Kendirci
M
, Akin
MA
, Kardas
F
. Primary adrenal failure due to viral infection in an infant
. Eur J Pediatr
. 2010
Jul
;169
(7
):887
–9
.
[PubMed]
0340-619911.
Lynnhtun
K
, Achan
A
, Lam
V
. IgG4 related pseudotumour (calcifying fibrous tumour) of adrenal gland
. Pathology
. 2013
Aug
;45
(5
):519
–21
.
[PubMed]
0031-302512.
Ramon
I
, Mathian
A
, Bachelot
A
, Hervier
B
, Haroche
J
, Boutin-Le Thi Huong
D
, et al. Primary adrenal insufficiency due to bilateral adrenal hemorrhage-adrenal infarction in the antiphospholipid syndrome: long-term outcome of 16 patients
. J Clin Endocrinol Metab
. 2013
Aug
;98
(8
):3179
–89
.
[PubMed]
0021-972X13.
Michels
A
, Michels
N
. Addison disease: early detection and treatment principles
. Am Fam Physician
. 2014
Apr
;89
(7
):563
–8
.
[PubMed]
1532-065014.
15.
Betterle
C
, Scalici
C
, Pedini
B
, Mantero
F
. [Addison’s disease: principal clinical associations and description of natural history of the disease]
. Ann Ital Med Int
. 1989
Jul-Sep
;4
(3
):195
–206
.
[PubMed]
0393-934016.
Leisti
S
, Ahonen
P
, Perheentupa
J
. The diagnosis and staging of hypocortisolism in progressing autoimmune adrenalitis
. Pediatr Res
. 1983
Nov
;17
(11
):861
–7
.
[PubMed]
0031-399817.
Betterle
C
, Scarpa
R
, Garelli
S
, Morlin
L
, Lazzarotto
F
, Presotto
F
, et al. Addison’s disease: a survey on 633 patients in Padova
. Eur J Endocrinol
. 2013
Oct
;169
(6
):773
–84
.
[PubMed]
0804-464318.
Dahlqvist
P
, Isaksson
M
, Bensing
S
. Is Adrenal Insufficiency a Rare Disease?
Front Horm Res
. 2016
;46
:106
–14
.
[PubMed]
0301-307319.
Eason
RJ
, Croxson
MS
, Perry
MC
, Somerfield
SD
. Addison’s disease, adrenal autoantibodies and computerised adrenal tomography
. N Z Med J
. 1982
Aug
;95
(714
):569
–73
.
[PubMed]
0028-844620.
Marthinsen
LM
, Scott
H
, Ejderhamn
J
. Autoimmune enteropathy in Swedish children, 1985-2002: a call for strict diagnostic criteria
. Scand J Gastroenterol
. 2008
;43
(9
):1102
–7
.
[PubMed]
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2018
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