Endocrine Abstracts

Case history: A 20-year-old man was referred to the metabolic bone clinic following a left sided neck of femur fracture (sustained after a simple fall whilst roller skating). He was otherwise well with no past medical history; systemic enquiry was unremarkable. A DEXA scan revealed osteoporosis (Z scores: total hip −2.97; lumbar spine −3.1), and bone turnover markers were significantly raised. Unexpectedly, the patient was found to have an elevated serum testosterone level (37.4 nmol/l (8–29)). Serum TSH was also mildly raised (8.41 mU/l (0.35–5.5)). He was therefore referred for endocrine review.

Investigations: Although serum total testosterone was again raised (31.0 nmol/l), SHBG was markedly increased (145 nmol/l (10–57)) yielding a calculated free testosterone of just 0.22 nmol/l, with LH 9.3 U/l (1.5–6.3) and FSH 5.6 U/l (1.0–10.1). Further investigations included:

- serum prolactin 42 mU/l (45–375).

- serum TSH 8.41 mU/l, free T4 (fT4) 52.7 pmol/l (10–19.8), free T3 (fT3) 29.5 pmol/l (3.5–6.5); assay interference was excluded.

- TRH test: TSH (mU/l): 0 minutes, 6.46; 30 minutes, 11.19; 60 minutes, 7.81.

- Alpha subunit: 5.9 IU/l (<1.0).

- Octreotide (100 mcg s.c.) suppression test: 74% reduction in serum TSH at 300 minutes.

- Pituitary MRI: 35x29x13 mm macroadenoma, compressing the optic chiasm.

Results and treatment: The patient was commenced on Lanreotide ATG 120 mg s.c. every 28 days. After three injections, his TFTs had improved but remained abnormal. In preparation for surgery, subcutaneous octreotide (200 mcg tds) and propylthiouracil (200 mg tds) were substituted, with resultant normalisation of serum fT3. An endoscopic endonasal approach revealed a vascular tumour, which precluded safe transsphenoidal resection. Subsequent angiography demonstrated a ‘tumour blush’ but no prominent intratumoural arteries. At craniotomy a gross total resection was achieved. Immuno-histochemical staining was strongly positive for TSH and negative for all other pituitary hormones (MIB-1 3.6%). Following surgery, the patient developed central hypothyroidism and continues on levothyroxine replacement. He is otherwise eupituitary. Postoperative imaging demonstrated no evidence of residual or recurrent tumour.

Conclusion and points for discussion: This case illustrates several challenges that may be encountered in the investigation and management of TSH-secreting pituitary adenomas:

1. Paucity of symptoms despite markedly raised serum fT4 and fT3 with target organ damage.

2. Masking of hypogonadism in the presence of dramatically elevated SHBG levels.

3. Limitation of octreotide suppression test in predicting depot SRL responsiveness.

4. Requirement for multimodal medical therapy to control thyrotoxicosis prior to surgery.

5. Surgical challenge presented by prominent tumoural vascularity.