C7 (Clinical Case) ACTH-dependent Cushing’s in an 8-Year-Old: A Diagnostic Challenge
Authors: Hudson Summer , Lissinna Brittany , Thorpe Marian , Yang Ashlee , Thawer Zoyah 
Published: September 2023

Introduction/Background

Cushing’s syndrome (CS) is rare, with 2-5 cases per million annually, and only 10% of these occurring in children. Cushing’s disease (CD) (excessive adrenocorticotropic hormone [ACTH] secretion by a pituitary source leading to hypercortisolism) is the most common organic etiology of CS in children (75-90%). Ectopic ACTH syndrome (EAS), in contrast, accounts for less than 1%.

Case Description

An 8-year-old male presented with extensive vertebral compression fractures, rapid weight gain, and headaches. He was found to have hypertensive urgency (blood pressure 170/110 mmHg, &gt; 99.9 percentile) and Cushingoid features. Investigations revealed hypokalemia (2.0 mmol/L), elevated serum cortisol (1654 nmol/L, ref 85-620) and elevated 24-hour urine cortisol (27244 nmol/day, ref &lt; 25). An elevated ACTH (35pmol/L, ref 1.6-13.9) confirmed ACTH-dependent CS. Although non-invasive dynamic testing (high dose dexamethasone suppression and desmopressin stimulation tests) suggested an ectopic source, inferior petrosal sinus sampling (IPSS) suggested a pituitary source. Unfortunately, anatomical (3T MRI Sella) and functional imaging (18 F-DOPA and Gallium-68 dotatate PET/CT scans) have not identified a causative lesion to date. On 18 F-DOPA PET/CT imaging, a 1cm focus of avidity was found in the small bowel, concerning for neuroendocrine tumour. However, excisional biopsy identified the mass as a Meckel’s diverticulum with cortisol and ACTH persistently elevated post-operatively. As such, he has been started on ketoconazole to control the hypercortisolemia and reduce morbidity. This has been mainly effective, with 24-hour urine cortisol reduced to 70 nmol/day. He will undergo serial imaging and continue medical therapy as long as tolerated. Exploratory pituitary surgery may be considered if medical therapy proves ineffective or overly burdensome over time.

Discussion

We present a diagnostically challenging case of ACTH-dependent Cushing’s syndrome, suspected Cushing’s disease. Non-invasive dynamic tests have limited sensitivity and specificity when used in isolation. As a result, source localization in ACTH-dependent Cushing’s can be challenging. Ultimately, IPSS was suggestive of a pituitary source. However, a causative lesion has not been identified despite multiple modalities of anatomic and functional imaging. Medical therapy can be a useful temporizing measure while pursuing further workup, but can have problematic side effects and requires frequent laboratory monitoring. This patient’s story highlights the difficulty in diagnosis and in choosing a management strategy for a patient without an identified source of excess ACTH, as all options carry risk of morbidity.

Conclusion

CS is rare in paediatrics but should be considered in a patient with suggestive exam findings and refractory hypertension. Diagnostic workup should proceed in sequential order to confirm hypercortisolemia, distinguish between central vs peripheral origin, and localize the responsible lesion. In cases with inconclusive investigations, IPSS remains necessary for localization.