Endocrine Abstracts

Case history: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant disorder caused by heterozygous pathogenic variants in the FLCN gene encoding folliculin on chromosome 17p11, first described clinically in 1975. It is a ‘hamartomatous’ disorder usually manifesting with pulmonary cysts, benign cutaneous tumours and conferring a high risk of renal malignancy. A 43 year old man had a 34 x 22 mm right adrenal nodule discovered incidentally on a CT CAP. Relative percentage washout was reassuring at 77%. Relevant past medical history included a recent hemithyroidectomy with histology diagnostic of a follicular adenoma. A diagnosis of multiple sclerosis was made at the age of 22 following episodes of retrobulbar neuritis, on the basis of an MRI showing multiple areas of high signal in the periventricular area. In terms of family history; the patient’s mother also had a diagnosis of multiple sclerosis in addition to a spontaneous pneumothorax requiring drainage and a sublingual lipoma. The patient’s maternal grandparents had multiple (poorly characterised) malignancies. Clinical examination showed an absence of BHDS-related skin lesions. Blood pressure was 144/90.

Investigations: There was no evidence of endocrine functionality. 24-hour urinary free cortisols (228 and 118 nmol) (50–300), 24-hour urinary normetadrenaline (0.2 umol x 2) (0.0–3.8), 24-hour urinary metadrenaline (0.1 umol x2) (0.0–2.2), plasma renin 6.0 mU/l (5.4–60) and aldosterone 127 pmol/l (90–720). Interval imaging showed the adrenal nodule had grown to 51 x 40 mm prompting a laparoscopic right adrenalectomy.

Results and treatment: Histologically the morphological and immunohistochemical findings were felt to be somewhat ambiguous. Given the positivity with markers for CD56 and synaptophysin and the negative SF1 immunohistochemistry a diagnosis of oncocytic pheochromocytoma was made. PASS score 7/20. A PET CT showed bilateral multiple pulmonary cysts in a predominantly basal distribution. Sequencing of the FLCN gene showed the patient to be heterozygous for a pathogenic variant c.1285dupC, p.(His429ProfsTer27) confirming BHDS.

Conclusions: Oncocytic variant pheochromocytoma is very rare histological subtype where the tumour cells have an eosinophilic granular cytoplasm. Only 6 cases have been reported in the literature. Only one other case of an adrenal oncocytic tumour has been reported in a patient with BHDS; this was also non-secretory. We present the first reported case of BHDS associated with multiple non-functioning endocrine tumours. Under current ESE guidance the initial adrenal nodule is classified as radiologically benign despite the histological diagnosis.