Delhi doctors report rare cases of ACTH resistance syndrome

Delhi doctors reported cases of ACTH resistance syndrome that have appeared in the Indian Journal of Endocrinology and Metabolism.Authors Dr Alpesh Goyal at Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India and cooleagues from other Delhi hospitals have reported three cases with ACTH resistance syndrome, highlighting the approach to diagnosis and management in such patients.

The term adrenocorticotropin (ACTH) resistance syndrome is used for a group of rare inherited disorders, which present with primary adrenal insufficiency during childhood. The syndrome includes two disorders inherited in an autosomal recessive fashion – familial glucocorticoid deficiency and triple A syndrome.Inherited adrenocorticotropin (ACTH) insensitivity syndromes comprise a group of rare diseases in which resistance to ACTH is either the sole feature or associated with other symptoms.

Cases 1 and 2
A 3½-year-old male child was brought to the outpatient department with complaints of diffuse hyperpigmentation of the body, noticed by the parents for the past 6 months. Hyperpigmentation initially started in face, hands, and thighs, and later on involved gums, tongue, and buccal mucosa. Eventually, he had diffuse hyperpigmentation all over the body. Plasma ACTH level was found to be markedly elevated at 3320 pg/mL (normal range: 7.2-63.3 pg/mL) and he was referred to endocrinology services with provisional diagnosis of hypoadrenalism.

A younger sister of the index case (age 12 months) showed normal 8 am serum cortisol (9.6 μg/dL) and high plasma ACTH (260 pg/mL). The parents denied any history suggestive of hyperpigmentation or hypoadrenalism in the child. They did not agree for further investigations of the child but agreed to observe her closely for any hyperpigmentation. Her 8 am serum cortisol level was 5.2 μg/dL, with corresponding plasma ACTH level of 470 pg/mL. In view of similar illness in her elder brother, diagnosis of FGD (familial glucocorticoid deficiency) was considered and she too was started on treatment (oral prednisolone 2.5 mg/day).

Case 3
A 9-year-old male was brought with complaints of progressive darkening of complexion, noted by the parents since the past 6 months. There was a history of decreased appetite along with poor height and weight gain for the same duration. He had generalized hyperpigmentation involving the knuckles, palmar crease, nail bed, extensor aspects of extremities, and mucosa of the tongue.