CASE REPORT

A 66 year old man presented with visual field loss in his left eye, headaches, decreased sexual drive, and erectile dysfunction. He was on no medications. He had no classical symptoms of hyperthyroidism or adrenal insufficiency. There was no known family history of pituitary or thyroid disease. A left inferior temporal visual field defect was confirmed by perimetry. He had normal secondary sexual characteristics, and was clinically euthyroid with no palpable goitre. Magnetic resonance imaging (MRI) revealed a 2.5 cm diameter lesion in the pituitary (fig 1). The referring physician found total thyroxine 152 nmol/l (58–155), total triiodothyronine 3.39 nmol/l (1.3–3.0), and TSH 3.3 mIU/l (0.06–5.0). At our clinic the serum prolactin was 475 pmol/l (182–817), 1500 h cortisol 0.1 μmol/l (0.14–0.7), testosterone 0.8 nmol/l (9.45–37.45), follicle stimulating hormone (FSH) 6.6 mIU/ml (1.3–19.3), and luteinising hormone <3.0 mIU/ml (1.2–8.6). Serum alpha subunit was not measured.

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Figure 1

MRI scan (A, coronal; B, sagittal) demonstrating a pituitary lesion with suprasellar extension, impinging on the optic chiasm.

He underwent transsphenoidal surgery to remove the pituitary adenoma, and had a prompt improvement in his visual field. Immunoreactive staining of the tumour showed scattered TSH-secreting and FSH-secreting cells, but was negative for adrenocorticotrophic hormone, growth hormone, luteinising hormone, and prolactin.

Mild elevation of total thyroxine (213–241 nmol/l) and total triiodothyronine (2.0–5.51 nmol/l), with “inappropriately normal” TSH (1.72–2.01 mIU/l), persisted for 14 months after surgery. Because of concern that he may have “subclinical” TSH-dependent hyperthyroidism, he was treated with octreotide for two months, up to a dosage of 100 μg twice a day, with little change in his thyroid function tests. At that stage, review of his record revealed that triiodothyronine uptake, an indirect measure of serum thyroid binding capacity, had been persistently raised (>2.0, normal range 0.72–1.24) since before he underwent pituitary surgery. TBG, free thyroxine, and free triiodothyronine were all measured for the first time some 16 months after he presented with his original symptoms. Serum free thyroxine was 10.3 pmol/l (10.3–34.8) and free triiodothyronine was 5.36 pmol/l (3.23–6.78). Serum TBG (Quest Diagnostics Inc, San Juan Capistrano, CA 92675) was considerably raised at 71 mg/l (normal range 17–36). These tests established the diagnosis of TBG excess, with otherwise normal thyroid function. He has remained symptomatically and clinically euthyroid. He initially declined testosterone replacement therapy despite persistently low serum testosterone levels, but started using testosterone gel with good clinical effect approximately two years after his pituitary surgery because of totally absent libido and diminished energy. Serum TBG remained raised at 57 mg/l during testosterone gel treatment.

DISCUSSION

It is not uncommon for patients with either a TSH-secreting pituitary adenoma or TBG excess to undergo treatment directed primarily at the thyroid, because of misattribution of the raised total thyroxine and triiodothyronine levels to primary hyperthyroidism, before the correct diagnosis is established.^3,4 The case history we describe illustrates some instructive variations on this theme of misdiagnosis.

Despite the absence of hyperthyroid symptoms, we believe the concern about a TSH-secreting adenoma was understandable. Just as one sometimes sees patients with primary hyperthyroidism with minimal or no hyperthyroid symptoms, the reasoning was that this patient may have had asymptomatic central hyperthyroidism. The presence of scattered TSH-secreting, as well as FSH-secreting, cells reinforced this concern. However, it is clear, in retrospect, that he did not have central hyperthyroidism, and that the pituitary tumour was non-functioning. Measurement of serum alpha subunit may have led to this conclusion at an earlier stage. Focus on the triiodothyronine uptake test from the outset would also certainly have led to earlier diagnosis of TBG excess.

We believe the degree of TBG excess in this case is characteristic of a primary (familial) aetiology, though we don’t know if any other family members have raised TBG levels and we have not investigated whether this raised TBG was the normal rather than the abnormal variant. Also we are not aware of any medical literature that relates TBG excess to pituitary tumorigenesis. Treatment with testosterone can be associated with a decrease in TBG levels, but we know of no evidence that the inverse is true. This patient’s TBG level fell during testosterone gel treatment, but remained significantly increased.

The superiority of free, rather than total, thyroid hormone measurement to define true thyroid status is established beyond doubt.⁶ The present case is a further illustration of this. We support the view that routine measurement of total thyroid hormones and indirect indices of thyroid binding capacity should be abandoned entirely in favour of free thyroid hormone assays.⁷

Finally, we believe this is the first report of TBG excess occurring in conjunction with a pituitary macroadenoma containing TSH-producing cells.