Paediatric and adolescent ectopic Cushing's syndrome: systematic review.

OBJECTIVE: The data on clinical, biochemical, radiological characteristics, and outcomes in paediatric ectopic adrenocorticotropic hormone syndrome (EAS) are limited owing to rarity of the condition. We report three new cases and perform a systematic review of paediatric EAS. DESIGN AND METHOD: Case records of paediatric and adolescent EAS patient's ≤20 years presenting at our centre between 1997 and 2021 were retrospectively reviewed, and a systematic review of the literature published between January 1970 and December 2022 was performed. RESULTS: A total of 161 patients including 3 new patients from our centre were identified. Bronchial neuroendocrine tumours (NET) (28.5%), thymic NET (22.9%), primitive cell-derived tumours (18.6%), and gastro-entero-pancreatic-NET (13.7%) were the common causes. Primitive cell-derived tumours were the most common in the first decade (24/45, 53.4%) and were the largest (82 [60-100] mm), whereas bronchial NETs predominated during the second decade (42/116, 36.2%) and were the smallest (15 [10-25] mm). Computed tomography localized 92.9% (118/127) of paediatric EAS patients. Immediate postoperative remission was attained in 77.9% (88/113) patients, whereas 30.4% (24/79) relapsed over a median (IQR) period of 13 (8-36) months. Over a median (IQR) follow-up of 2 (0.6-4.6) years, 31.4% of patients died. The median survival was higher in bronchial NET than in other tumour groups. Distant metastasis and tumour size were independent negative predictors of survival. CONCLUSIONS: Aetiological profile of paediatric and adolescent EAS is distinct from that of adults. Bronchial NETs have the best long-term survival, whereas distant metastasis and tumour size predict poor survival.

Pediatric Ectopic Cushing Syndrome Caused by Hepatic Neoplasms: A Case Report and Systematic Review.

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is rare in children, and localizing the source of EAS is often challenging. Here, we report EAS in an adolescent boy who presented with Cushingoid features and had endogenous ACTH-dependent hypercortisolism on hormonal evaluation. Abdominal ultrasound and CT revealed a hepatic lesion with characteristics suggestive of hemangioma, whereas the lesion was tracer non-avid on 68Ga-DOTANOC positron emission tomography/CT. A regional sampling of ACTH was done to confirm the hepatic lesion as the source of EAS, and a definitive ACTH gradient was observed between the hepatic vein and the right internal jugular vein. Further, a preoperative biopsy of the lesion revealed a small round cell tumor with positive immunostaining for ACTH and synaptophysin, suggestive of a neuroendocrine tumor. The patient was managed with partial hepatectomy, resulting in hormonal and clinical remission of Cushing syndrome. In a systematic review of pediatric EAS due to primary hepatic tumors (n = 11), calcifying nested stromal epithelial cell tumors were the most common. EAS-associated hepatic tumors were larger (≥10 cm) except benign primary hepatic neuroendocrine tumors (PHNET). The latter were misdiagnosed as hemangioma in two cases by anatomical imaging but correctly diagnosed by somatostatin receptor scintigraphy. Hepatic tumors causing EAS in children required extensive resection, except benign PHNET. Nevertheless, all benign tumors with an uncomplicated perioperative course demonstrated disease-free survival over a median follow-up period of two years.

A mysterious case of recurrent fracture: Tumour-induced osteomalacia.

We report a case of tumour-induced osteomalacia in a 59-year-old man who presented with a long-standing history of myalgia, bone pain and pathological fracture of the bilateral femur at different intervals in the past 4 years. A biochemical evaluation revealed hypophosphatemia secondary to phosphaturia. Localization study by Ga-68 DOTANOC PET-CT for adult-onset hypophosphatemic osteomalacia revealed a tumour in the right femoral head. Resection of the tumour resulted in clinical improvement as well as normalization of biochemical parameters.

Neonatal thyrotoxicosis with maternal hypothyroidism.

Neonatal Graves' is uncommon, but a potentially fatal condition caused by transplacental transfer of thyroid stimulating immunoglobulin (TSI). It is seen in 1%-5% of infants born to a mother with Graves' disease. Here, we report a unique case of transient neonatal thyrotoxicosis with positive TSI in a premature neonate born to the mother with primary hypothyroidism. A short course of antithyroid drug treatment leads to significant clinical and biochemical improvement followed by complete recovery.

Quadriplegia and rhabdomyolysis as a presenting feature of Conn's syndrome.

Conn's syndrome is an important endocrine cause for secondary hypertension. Hypokalaemia paralysis and rhabdomyolysis with accelerated hypertension may be the presenting symptoms of Conn's syndrome. Here, we present one such case of a 38-year-old woman presenting with accelerated hypertension and acute onset quadriplegia. On biochemical evaluation, she was found to have severe hypokalaemia, metabolic alkalosis and elevated creatinine phosphokinase. Further evaluation revealed an elevated aldosterone renin ratio suggestive of primary hyperaldosteronism which was localised to left adrenal adenoma on contrast-enhanced CT. Patient's blood pressure and serum potassium levels normalised after resection of the adrenal adenoma.

Insulin autoimmune syndrome: a rare cause of spontaneous hypoglycaemia in non-diabetic individuals.

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycaemia, characterised by recurrent hypoglycaemic episodes secondary to insulin autoantibodies in individuals who are not exposed to exogenous insulin. We are reporting a case of IAS in a 64-year-old gentleman, who presented with predominant postprandial hypoglycaemic episodes. On biochemical evaluation, he was found to have hyperinsulinemic hypoglycaemia. Localisation studies with MRI abdomen and endoscopic ultrasound (EUS) were negative for pancreatic tumour. Tests sent for insulin antibody levels were elevated. The patient was treated with frequent meals, acarbose and glucocorticoids. Patient condition improved and did not experience hypoglycaemia on follow-up.