Jyothis T George Department of Endocrinology, York Hospital, York, UK , Jonathan C Thow Department of Endocrinology, York Hospital, York, UK , Bruce Matthews Department of Neurosurgery, Hull Royal Infirmary, Hull, UK , Maurice P Pye Department of Cardiology, York Hospital, York, UK , Vijay Jayagopal Department of Endocrinology, York Hospital, York, UK

Discussion

TSH producing tumours of the pituitary are usually large tumours and they usually cause enlargement of the thyroid gland. Despite this however, overt thyrotoxicosis is uncommon, possibly due to a reduction in the biological activity of the secreted TSH. This case illustrates that although uncommon and thought to present with insidious symptoms, TSH secreting pituitary tumours (TSHomas) can occasionally present with acute manifestations like rapid atrial fibrillation and cardiac decompensation.

The majority of TSHomas (72%) secrete TSH alone, but 16% also secrete growth hormone (GH), 11% secrete prolactin (PRL), and 1% secretes LH or FSH [6]. The elevation in serum testosterone levels in our patient was secondary to co-secretion of LH and FSH by the adenoma. This illustrates the need to systematically assess complete pituitary function in such patients especially as some pituitary adenomas express positive histological staining for hormones without corresponding biochemical hyper-secretion [7].

Thyroid hormone concentrations can influence the metabolic rates of proteins and thus can alter the amount of vitamin K-dependent clotting factors, which in turn can alter the sensitivity to warfarin [8, 9]. This may lead to changes in anticoagulation, increasing the risk of thromboembolic or hemorrhagic events. The volatile response to warfarin treatment in our patient stabilised with correction of his hyperthyroidism. Patients with AF associated with hyperthyroidism therefore need close monitoring of their anticoagulation profile. It is critical to distinguish central hyperthyroidism from the more common types of primary hyperthyroidism. Measuring TSH alone as a ‘screening test’ may result in misdiagnosis of patients with TSHomas. Elevated Free T4 and/or T3 levels with a normal (non-suppressed) TSH should trigger investigations looking for a pituitary cause as inadvertent thyroid ablation resulting from such misdiagnosis can result in enlargement of these tumours [4]. Assays cross reactivity, presence of heterophilic antibodies and pituitary resistance to thyroid hormones are the three important alternatives to be considered. Assessment of TSH alpha subunit and TRH stimulation tests can help in differentiating TSHomas from pituitary and peripheral resistance to thyroid hormones. These tests were considered in our case but not performed as the diagnosis was adequately established from the available biochemistry and radiological appearance. We feel that further testing would not have contributed further in the evaluation of our patient but accept that it often can be useful in the diagnostic work up of such cases.

Conclusions

Elevated Free T4 and/or T3 levels with a normal (non-suppressed) TSH should trigger a thorough investigation process looking for a pituitary cause of hyperthyroidism. In pituitary hyperthyroidism, complete pituitary function tests help identify pituitary adenomas that co- secrete other hormones along with TSH. Early diagnosis and treatment of TSH-secreting adenomas is critical in avoiding the neurological and endocrine complications that can result especially when misdiagnosed as primary hyperthyroidism and treated with radioiodine ablation.

This case also highlights the need to evaluate thyroid function in all patients presenting with atrial fibrillation. Presentation of TSH-secreting pituitary adenomas with acute cardiac decompensation is uncommon, but prompt management of the underlying hyperthyroidism is critical to a successful outcome.