Adrenal hypoplasia congenita: Delayed presentation of a rare cause of primary adrenal insufficiency

Case Report A developmentally normal 11 year old boy was referred from a peripheral hospital where he was admitted for recurrent episodes of vomiting, dehydration, abdominal pain, malaise, anorexia, growth retardation and increasing pigmentation over body for past 3-4 years. He had severe dehydration with shock requiring inotropic support. There were two similar episodes in the past year requiring hospitalization. Patient had distinct craving for salty diet. He was asymptomatic in the neonatal period and early childhood. One younger male sibling had died at the age of one year due to some neurological disorder (developmental delay with seizures). He was investigated at the All India Institute of Medical Science, New Delhi but parents could not recall the diagnosis and records were not available. There are two elder sisters who are apparently normal. There was no history of abortion, consanguinity or any significant family history.


Introduction
Majority of cases of primary adrenal insufficiency are due to congenital adrenal hyperplasia (CAH), adrenal hypoplasia congenita (AHC) being a rarer cause 1 .
Here, we report a patient with AHC who presented in pre-adolescent phase with recurrent episodes of dehydration, shock and severe hyperpigmentation.

Case Report
A developmentally normal 11 year old boy was referred from a peripheral hospital where he was admitted for recurrent episodes of vomiting, dehydration, abdominal pain, malaise, anorexia, growth retardation and increasing pigmentation over body for past 3-4 years. He had severe dehydration with shock requiring inotropic support. There were two similar episodes in the past year requiring hospitalization. Patient had distinct craving for salty diet. He was asymptomatic in the neonatal period and early childhood. One younger male sibling had died at the age of one year due to some neurological disorder (developmental delay with seizures). He was investigated at the All India Institute of Medical Science, New Delhi but parents could not recall the diagnosis and records were not available. There are two elder sisters who are apparently normal. There was no history of abortion, consanguinity or any significant family history.
On examination, he was wasted and stunted with weight for age (17.5 kg) and height for age (121 cm) below 3 SD as per World Health Organization ___________________________________________ 1  Inheritance of AHC is commonly X-linked due to mutation or deletion of the DAX-1 gene and this form presents in early infancy 2 . In this form, hypogonadotropic hypogonadism and progressive high frequency deafness commonly occur in adolescence 6,7 . The rarer autosomal recessive type of AHC, which too is associated with hypogonadotropic hypogonadism, is due to a mutation or deletion of the gene encoding steroidogenic factor 1 on chromosome 9q33. Hypogonadotropic hypogonadism is clinically detected as pubertal delay and these patients may benefit from testosterone replacement 5,6 . Index patient presented in SMR stage I and there was no pubertal growth in 2 years of follow up. LH and FSH were also in the pre-pubertal range suggesting hypogonadotropic hypogonadism. However, we will have to wait till 15 years before labelling it as hypogonadism. In our case there was no hearing deficit at presentation and during 2 year follow up.
A small number of patients with AHC, usually the autosomal recessive form, may present between 2-9 years of age 8 , when acquired causes of adrenal failure such as autoimmune/infections should be ruled out, as in our case where ANA, HIV and total blood count were all normal. DAX-1 mutations also occur in glycerol kinase deficiency and Duchenne muscular dystrophy 9,10 which were excluded, as serum creatinine kinase and triglyceride levels were normal.
Anatomically, in the X-linked type there is hypoplasia of the adrenal cortex with preservation of the fetal zone. In the autosomal recessive type there is absence of the fetal zone and severe hypoplasia of the definitive adult adrenal zone 1,4,5 . Rudimentary adrenal glands revealed on abdominal MRI, absence of hearing loss in the 2 year follow up and delayed presentation indicates autosomal recessive form of AHC, but death of a male sibling and healthy female siblings suggest X linked form. The mutations and deletions associated with AHC could not be detected, Karyotyping was normal and FISH analysis could not be done 11 .
The possibility of AHC should be considered in cases of adrenal insufficiency, not only in early infancy but also in the pre-adolescent age group as early recognition and treatment will improve the clinical outcome significantly. Long term monitoring of this patient is essential especially for hypogonadotropic hypogonadism and hearing deficits.