Neonatal Cushing Syndrome: A Rare but Potentially Devastating Disease.

Neonatal Cushing syndrome (CS) is most commonly caused by exogenous administration of glucocorticoids and rarely by endogenous hypercortisolemia. CS owing to adrenal lesions is the most common cause of endogenous CS in neonates and infants, and adrenocortical tumors (ACTs) represent most cases. Many ACTs develop in the context of a TP53 gene mutation, which causes Li-Fraumeni syndrome. More rarely, neonatal CS presents as part of other syndromes such as McCune-Albright syndrome or Beckwith-Wiedemann syndrome. Management usually includes resection of the primary tumor with or without additional medical treatment, but manifestations may persist after resolution of hypercortisolemia.

Prenatal Cushing's syndrome secondary to nodular adrenocortical hyperplasia with unsuppressed plasma ACTH levels.

We report a newborn girl (36th week of gestation, birth weight 1,054 g) with Cushing's syndrome secondary to nodular adrenocortical hyperplasia with normal plasma ACTH levels. From birth she was hypertensive, hyperglycaemic and slightly hirsuit. Hypercortisolaemia (>1,380 nmol/l) was accompanied by normal plasma ACTH levels (8.64-23.9 pg/ml). A 48-h dexamethasone suppression test decreased plasma cortisol by 35%, indicating some degree of ACTH dependency. However, there was no ACTH rise on CRF test. MRI showed enlarged adrenal glands with a possible cyst on the right; the pituitary gland was normal. At the age of 6 weeks she underwent bilateral adrenalectomy. Histology showed enlarged adrenals with multiple non-pigmented nodules (up to 5 mm) in both glands. However, over the next few weeks she developed liver failure and sepsis. She died at the age of 3 months. Post mortem examination confirmed the diagnosis. Nodular adrenocortical hyperplasia may present at birth with severe Cushing's syndrome and unsuppressed ACTH levels, indicating some degree of ACTH dependency in this condition.

A case of neonatal McCune-Albright syndrome with Cushing syndrome and hyperthyroidism.

We describe a female newborn infant with McCune-Albright syndrome. In addition to the cutaneous pigmentation, she had apparent manifestations of hyperthyroidism and Cushing syndrome since birth. X-ray examinations showed many scattered lucencies in multiple bones. Endocrinological findings were as follows: serum T 4 276 nmol/l; free T 4 125 pmol/l; TSH less than 1 mU/l; serum cortisol greater than 2210 nmol/l; plasma ACTH less than 10 pg/ml; urinary free cortisol 865 nmol/day; estradiol 0.36 nmol/l. Regardless of treatment with antithyroid drugs and an inhibitor of 3 beta-hydroxysteroid dehydrogenase, the patient died of cardiac failure at the age of 4 months. Autopsy findings included a follicle cyst in the right ovary and multinodular hyperplasia in the thyroid and both adrenals. To our knowledge such a severe neonatal form of McCune-Albright syndrome has not been described in the literature.

Adrenocortical carcinoma in a child with congenital hemihypertrophy.

We describe a very rare case of adrenocortical carcinoma (ACC) presenting with Cushing's virilising syndrome in a female child with congenital hemihypertrophy (CHh). CHh was of more value for early detection of ACC than Cushing's virilisation.

Familial congenital Cushing's syndrome due to bilateral nodular adrenal hyperplasia.

Two siblings with congenital Cushing's syndrome due to bilateral nodular adrenal hyperplasia are described. The older, a boy, presented with severe hypertension and died soon after subtotal adrenalectomy. His sister, who had clitoral enlargement and showed persistent hyponatraemia, had a two-stage total adrenalectomy and is still alive. Investigations in the second case showed grossly elevated urinary cortisol metabolites, 17-oxosteroids and 3 beta-hydroxy-5-ene-steroids. These were not suppressed by dexamethasone, and plasma ACTH was undetectable, indicating that the disorder was not due to excessive ACTH secretion. Cell culture studies on the resected adrenals failed to demonstrate an abnormal pattern of steroid synthesis in vitro, and normal trophic responses were obtained with 1-24 ACTH and monobutyryl cyclic AMP. No stimulation of steroid synthesis was obtained with a range of polypeptide hormones, and the cause of the adrenal hyperplasia remains unknown.