described in a pediatric patient by hung and migeon in 1968 , it can present during the first year of life as result of a specific genetic mutation , such as a pro - opiomelanocortin ( pomc ) or t - box transcription factor ( tpit ) mutation     [ 25 ] , or later in childhood due to unknown factors     [ 1 , 610 ] . we report a new case of this unusual condition and summarize data in children published in the literature . a 7-year - old girl was admitted to the hospital due to episode of unconsciousness following a fall from a scooter . it turned out that six months earlier she had seizures and blood glucose 21  mg / dl during a febrile illness treated in intensive care unit . fatigue , decreased appetite , and increased irritability were noted by parents since age 4 years . height was 123.1  cm ( 50 < p < 75% ) , weight 22.6  kg ( 25 < p < 50% ) , and bmi 14.9  kg / m   ( 25 < p < 50% ) . mu / l , free t4 1.67  ng / dl , t3 1.42  ng / ml , prolactin 10.2  ng / ml , acth < 5  pg / ml , cortisol 0.0  ug / dl , dheas < 15  ug / dl , igf-1 296  ng / ml , plasma renin activity 2.60  ng / ml / hr , and normal serum electrolytes . repeat morning acth was < 5  pg / ml , and cortisol 0.0  ug / dl . acth 124 stimulation test showed cortisol 0.0  ug / dl at 45 min after cortrosyn 0.250  mg injection . crh stimulation test demonstrated plasma acth < 5  pg / ml at 15  min , 30  min , 45  min , and 60  min after acthrel 1  mcg / kg intravenous injection . head mri scan without and with contrast using pituitary protocol demonstrated a tiny 2 - 3  mm cyst localized in the midline at the posterior margin of the anterior pituitary ( figure 1 ) . detailed evaluation of adrenal function and pituitary function demonstrated that the child had isolated acth deficiency . genetic cause for this disorder in treatment with hydrocortisone 16  mg / m / day divided in three doses given by mouth resulted in resolution of all symptoms and normalization of blood glucose . the patient remained symptoms free and had normal igf-1 , tsh , and free t4 on clinic followup one year after the diagnosis . our patient had undetectable cortisol levels before and after cortrosyn stimulation , which indicated that her hypoglycemia was due to glucocorticoid deficiency . very low acth despite undetectable cortisol showed that glucocorticoid deficiency was secondary to acth deficiency . lack of hyperpigmentation and absence of electrolyte abnormalities , such as hyperkalemia and hyponatremia , normal blood pressure , and plasma renin activity provided evidence that acth - independent mineralocorticoid function was preserved , which further supported diagnosis of secondary adrenal insufficiency . growth hormone secretion was sufficient to maintain normal height and igf-1 , and other pituitary hormones were normal , in particular , tsh and prolactin , which was consistent with isolated acth deficiency . absent acth response to crh stimulation indicated that defect in acth production was localized in the pituitary and was not due to hypothalamic dysfunction .   to our knowledge , this is the first time that isolated acth deficiency was associated with a tiny cyst in the midline of the pituitary . in contrast to somatotroph , lactotroph , and thyrotroph cells scattered throughout the anterior pituitary , corticotroph cells are mainly located in its central region . the tiny cyst close to that region might be due to an unknown genetic factor that caused isolated acth deficiency or could be an incidental finding [ 12 , 13 ] .   in comparison with isolated deficiencies of other pituitary hormones , such as idiopathic gh deficiency , gonadotropin deficiency , and central hypothyroidism , isolated acth deficiency is uncommon , except for acth suppression after treatment with exogenous glucocorticoids . acth deficiency usually occurs in combination with other pituitary hormone deficiencies as part of hypopituitarism . a possibility of lymphocytic hypophysitis should be considered particularly if there is pituitary enlargement , a mass , or thickening of the pituitary stalk [ 15 , 16 ] . isolated acth deficiency during the first year of life was reported in thirty - three children . five of them had pomc mutations , eighteen had tpit mutations , and ten patients had unknown genetic defect     [ 25 ] . among twenty - two families of children with isolated acth deficiency , where detailed history was obtained , six families ( > 25% of cases ) suffered an unexpected neonatal death of the patient 's sibling     [ 4 , 5 ] . pomc and tpit mutations were inherited as autosomal recessive traits     [ 2 , 4 ] . loss - of - function mutations of the pomc gene resulted in a complete loss of pomc - derived acth , a - msh and b - endorphin , and caused secondary hypocortisolism , red hair , pale skin and early - onset severe obesity . among five children with this syndrome , four presented with hypoglycemic seizures during the first weeks of life , and the fifth patient at age 12 months [ 2 , 3 ] . inactivating tpit mutations disrupted terminal differentiation of corticotroph cells specialized in pomc gene expression and presented with severe hypoglycemia , seizures , and failure to thrive in neonatal period in all cases , although the diagnosis was occasionally delayed until age 2 years . among eighteen patients with isolated acth deficiency due to a tpit mutation fifteen out of twenty - five patients with this syndrome had subnormal acth response on metyrapone test , indicative of isolated acth deficiency . these striking findings unveiled a potential reason for very high annual death rate in children with prader - willi syndrome ( 3% ) , who are at risk for unexpected fatal outcomes during mild - to - moderate respiratory tract infections , fatal apnea , and bathtub drowning . treatment with hydrocortisone during stress was recommended unless central adrenal insufficiency was ruled out by metyrapone test [ 9 , 17 ] . further study of hypothalamic - pituitary - adrenal axis in prader - willi syndrome is needed . there were only six such cases between ages 2 and 9 years published in the literature     [ 1 , 68 , 10 ] . all children presented with severe hypoglycemia . in four out of six cases , hypoglycemic seizures or loss of consciousness occurred during stress of febrile illness     [ 1 , 7 , 8 , 10 ] . there were singular reports of isolated acth deficiency in association with kabuki syndrome and multiple congenital malformations [ 19 , 20 ] . we conclude that isolated acth deficiency is an unusual diagnosis and its prevalence could be underestimated , in particular in the neonatal period and in children with prader - willi syndrome . clinicians should be aware that this rare condition occurs in older children as well as in neonates .
isolated acth deficiency causes life - threatening severe hypoglycemia . a 7-year - old girl with hypoglycemia due to this rare disorder 
 is described . 
 our patient had undetectable plasma acth repeatedly and cortisol 0  mcg / dl before and after acth 1 - 24 stimulation . 
 there was no evidence of other pituitary hormone deficiency . 
 glucocorticoid replacement therapy resulted in resolution of all symptoms and normalization of blood glucose . 
 previously published data on isolated acth deficiency in children is summarized . 
 review of the literature showed that the prevalence of this condition could be underestimated in the neonatal period and in prader - willi syndrome . 
 isolated acth deficiency occurs in older children as well as in neonates .