Endocrine Abstracts

Case history: A previously healthy 39 year-old male presented to his optometrist with visual disturbance. Visual field perimetry confirmed bitemporal hemianopia, prompting referral to endocrinology. On questioning, he reported an increase in hand and shoe size, but no headache or diaphoresis. Examination revealed classical acromegaloid features including prognathism, spatulate hands and prominent orbital margins, as well as marked bilateral macro-orchidism.

Investigations: Clinical investigations included conventional biochemical evaluation of anterior pituitary function, MRI pituitary and testicular ultrasound.

Results and treatment: Biochemical findings were in keeping with acromegaly, with IGF1 64.4 nmol/l (9.5–45.0), basal GH 1.5 mcg/l and GH nadir of 1.2 mcg/l after a 75 g oral glucose challenge. FSH was elevated (107 U/l (1.0–10.1)) with normal LH (1.2 U/l (1.5–6.3)) and testosterone (9.3 nmol/l (8.0–29.0)). Anterior pituitary function was otherwise intact. MRI demonstrated a large pituitary macroadenoma with suprasellar expansion, displacing the chiasm and extending into the left cavernous sinus. Ultrasound revealed testicular volumes of 46 and 50 ml on the left and right respectively, without features of neoplasia. Transsphenoidal resection of the pituitary lesion resulted in normalisation of visual fields and partial reduction in testicular volumes. Postoperatively, IGF1 remained elevated (55 nmol/l), however the GH nadir improved to 0.48 mcg/l after oral glucose challenge. FSH reduced to 26.3 U/l. Testosterone, FT₄ and cortisol were all below the normal range, so hormone replacement was commenced. MRI showed an intrasellar remnant with minimal suprasellar extension, no longer impacting on the optic chiasm. Histological analysis of the excised lesion confirmed a pituitary adenoma with predominant FSH staining, sparse LH staining, but no staining for GH. The possibility of coexistent ectopic GH or GHRH secretion was considered, however CT chest, abdomen and pelvis did not reveal an ectopic source, and no circulating GHRH was detectable by immunoassay. Serial follow up confirmed persistent mild elevation in IGF1 (1.1-1.4x ULN), GH nadir >0.6 mcg/l, and FSH between 30–40 U/l. MRI showed a slowly enlarging remnant in the pituitary fossa. Treatment with a somatostatin analogue was commenced, however there was no improvement in IGF1 or GH levels after 6 months. Repeat surgery is therefore planned.

Conclusions and points for discussion: This case (a) represents a functioning gonadotrophinoma in a male; (b) demonstrates clinical and biochemical evidence of GH excess without a somatotroph adenoma or hyperplasia, and without evidence for ectopic secretion; and (c) was refractory to somatostatin analogue therapy. Two further, similar cases have since been identified.