An eight month old boy brought by parents in clinic with complaint of increased genital pigmentation. Initial investigations showed low serum cortisol with an ACTH level 1250 pg/ml (6–48 pg/ml). He was started on steroid replacement of hydrocortisone and fludrocortisones with the diagnosis of primary adrenal insufficiency. He was doing well and repeated laboratory results revealed ACTH level of 7 pg/ml and 14.7 pg/ml on two occasions after steroid replacement. Later the diagnosis of primary adrenal insufficiency was re-visited based on laboratory results, when off fludrocortisone and hydrocortisone his serum cortisol decreased with highly elevated ACTH level but normal electrolytes and plasma rennin activity. His diagnosis was changed to isolated glucocorticoid deficiency.
At age of two and half years he developed generalized body swelling and facial puffiness. His baseline labs showed a serum creatinine of 0.5 mg/dl, serum sodium of 139 meq/L and a serum potassium of 4.0 meq/L. Endocrine workup revealed a ACTH level of 1179 pg/ml, cortisol of 6.15 μg/dl (2.8 to 23 μg/dL) and plasma renin activity of 3.35 ng/ml/hr (2.35 to 37 ng/mL/hour). The question was raised about compliance to medicine. Further labs were done for possible nephrotic syndrome based on his clinical presentation which showed a 24 hour urinary protein result of 3679 mg/24 hour with serum total protein of 3.6 g/dl, albumin of 0.9 gm/dl and a globulin level of 2.7 gm/dl. Steroid dose was increased but proteinuria did not respond and later immunosuppressive therapy was added.
Renal biopsy was undertaken and histopathology showed single core of renal tissue with up to 12 glommeruli. Of these four were totally sclerosed with reactive epithelial proliferation. Three showed segmental sclerosis, while five of them showed minor changes. There was no vasculopathy but tiny patches of mild tubular atrophy and interstitial sclerosis were seen. Immunoflorescense done on frozen tissue showed granular membrane and mesangial positivity of IgM, weak positivity of C3 andC1q in the same distribution as IgM while IgG and IgA were negative. In conclusion, light microscopy and IMF features were suggestive of focal segmental glomerulosclerosis.
Renal functions rapidly deteriorated and his serum creatinine reached a level of 4.9 mg/dl. He progressed to end stage renal disease (ESRD) within a year of diagnosis and was started on renal replacement therapy. He was on hemodialysis for one year and later received living related (uncle was donor) renal transplant at the age of five years. He is doing well after transplant and his ACTH level is 1.4pmol/L now on steroid replacement.
The patient’s elder brother had the same presentation of increased genital pigmentation. He was diagnosed to have primary adrenal insufficiency initially. Hydrocortisone and fludrocortisone was started which he took for around 7–8 years. His diagnosis was reviewed later in view of low serum cortisol, high ACTH level with normal plasma rennin activity and electrolytes when he was off medicines. The diagnosis was changed to isolated glucocorticoid deficiency. Currently he is on hydrocortisone replacement for the last 8 years without any problem with recent ACTH level within normal range. His kidney functions test and urine detail report are normal.
His younger brother also had same problem of isolated glucocorticoid deficiency, and he was on steroid replacement. He also later developed nephrotic syndrome with biopsy proven focal segmental glomerulosclerosis. He ultimately received renal replacement therapy but died at the age of four years, before he could undergo renal transplantation.
Patient’s mother also noticed same increased pigmentation on genitals of her nephew; his lab workup was consistent with isolated glucocorticoid deficiency and was started on steroid replacement. He is now 3 years of age with no evidence of nephrotic syndrome so far.
Patient’s family is not recalling any such type of illness history in their predecessors, although there is strong history of consanguineous marriages in the family (Figure 1).
In view of patient and siblings clinical presentation with low serum cortisol and high ACTH level with normal plasma renin activity, biopsy proven FSGS in both of them and consanguineous marriages, diagnosis of familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis has been made.