Response to sirolimus in a case of diffuse congenital hyperinsulinaemic hypoglycaemia due to homozygous KCNJ11 mutation.

We present a case of a male neonate with refractory and persistent neonatal hypoglycaemia not responding to octreotide. On evaluation for hypoglycaemia, his cortisol was within the reference range while the serum insulin concentrations were high. Gallium-68 dotatate scan (GA-68 DOTA) showed diffuse pancreatic involvement. Genetic diagnosis of congenital hyperinsulinaemic hypoglycaemia due to KCNJ11 mutation was made. He was started on tablet sirolimus, after which the child was off all other medication and was euglycaemic. However, he developed bilateral pneumonia leading to acute respiratory distress syndrome with refractory shock. Our case highlights the response to sirolimus in a case of congenital hyperinsulinaemia (CHI) due to KCNJ11 mutation and severe adverse event thereafter.

Primary pigmented nodular adrenal disease presenting as hypertensive crisis.

We present a case of a young girl who presented with hypertensive crisis and recent onset weight gain with hirsutism. On evaluation for Cushing syndrome (CS), her cortisol concentration was high, showed a paradoxical cortisol rise on dexamethasone suppression and the adrenocorticotropic hormone (ACTH) was low. Adrenal imaging showed normal adrenal morphology. Genetic diagnosis of primary pigmented nodular adrenal disease (PPNAD) was made. She was operated for bilateral adrenalectomy and histopathology confirmed the diagnosis of PPNAD. Our case highlights the rare aetiology of PPNAD as a cause of CS resulting in a hypertensive crisis. To the best of our knowledge, this is the youngest case of ACTH independent CS presenting as hypertensive encephalopathy.

Variable presentations of GCK gene mutation in a family.

We describe siblings born from non-consanguineous parents, with older sibling having asymptomatic hyperglycaemia while younger sibling presented with low birth weight and persistent hyperglycaemia from first month of life. Our case, the older sibling was heterozygous for paternally inherited GCK pathogenic variant resulting in diabetes of maturity-onset in the young (MODY) manifested as mild fasting hyperglycaemia. GCK gene sequencing revealed that the younger sibling was compound heterozygous for missense mutations (two) combined in a novel GCK-permanent neonatal diabetes mellitus (PNDM) genotype. Thus, heterozygous inactivating GCK mutations are likely to lead to maturity-onset diabetes of the young type 2 (MODY 2) and the homozygous inactivating or compound heterozygous GCK mutations are a cause of PNDM.

Rare case of renal Ewing sarcoma presenting as ectopic Cushing syndrome in a 12-year-old girl.

We present a 12-year-old girl with recent onset weight gain and purple striae over the abdomen. Examination revealed her to be hypertensive. On evaluation for Cushing syndrome (CS), her cortisol and adrenocorticotropic hormone (ACTH) were found to be high. MRI brain showed a suspicious lesion (thought to be pituitary microadenoma). Inferior petrosal sinus sampling was not conclusive of pituitary source of ACTH. High dose dexamethasone suppression test confirmed an ectopic source of ACTH secretion and CT scan revealed a mass in the right kidney which was laparoscopically excised. Histopathology and immunohistochemistry confirmed Ewing sarcoma. Our case highlights the rare presentation of renal Ewing sarcoma (RES) as CS. To the best of our knowledge, this is only the second case report of RES/primitive neuroectodermal tumour of the kidney presenting as CS in paediatric age group and first with a concomitant pituitary incidentaloma.