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

Abstract

Introduction: Hyperthyroidism is a well established cause of atrial fibrillation (AF). Thyroid Stimulating Hormone-secreting pituitary tumours are rare causes of pituitary hyperthyroidism. Whilst pituitary causes of hyperthyroidism are much less common than primary thyroid pathology, establishing a clear aetiology is critical in minimising complications and providing appropriate treatment. Measuring Thyroid Stimulating Hormone (TSH) alone to screen for hyperthyroidism may be insufficient to appropriately evaluate the thyroid status in such cases.

Case presentation: A 63-year-old Caucasian man, previously fit and well, presented with a five-day history of shortness of breath associated with wheeze and dry cough. He denied symptoms of hyperthyroidism and his family, social and past history were unremarkable. Initial investigation was in keeping with a diagnosis of atrial fibrillation (AF) with fast ventricular response leading to cardiac decompensation.

TSH 6.2 (Normal Range = 0.40 –4.00 mU/L), Free T3 of 12.5 (4.00 – 6.8 pmol/L) and Free T4 51(10-30 pmol/L). Heterophilic antibodies were ruled out. Testosterone was elevated at 43.10 (Normal range: 10.00 –31.00 nmol/L) with an elevated FSH, 18.1 (1.0-7.0 U/L) and elevated LH, 12.4 (1.0-8.0 U/L). Growth Hormone, IGF-1 and prolactin were normal. MRI showed a 2.4 cm pituitary macroadenoma. Visual field tests showed a right inferotemporal defect. While awaiting neurosurgical removal of the tumour, the patient was commenced on antithyroid medication (carbimazole) and maintained on this until successful trans-sphenoidal excision of the macroadenoma had been performed. AF persisted post-operatively, but was electrically cardioverted subsequently and he remains in sinus rhythm at twelve months follow-up off all treatment.

Conclusions: This case reiterates the need to evaluate thyroid function in all patients presenting with atrial fibrillation. TSH-secreting pituitary adenomas must be considered when evaluating the cause of hyperthyroidism. Early diagnosis and treatment of such adenomas is critical in reducing neurological and endocrine complications.

 

Introduction

Atrial fibrillation (AF) is a common arrhythmia associated with increased morbidity and mortality [1] and its association with hyperthyroidism is well documented [2]. Thyroid function tests to exclude hyperthyroidism are part of the clinical assessment of patients presenting with AF [1]. However, the optimum method to assess thyroid function is not clearly defined. Measurement of Thyroid Stimulating Hormone (TSH) alone as a ‘screening test’ may result in the misdiagnosis of patients with pituitary causes of hyperthyroidism [3].

TSH-secreting pituitary tumours (TSHomas) are rare causes of hyperthyroidism where there is stimulation of the thyroid gland by TSH resulting in thyroid over-activity [4]. Failure to diagnose these correctly and inadvertent thyroid ablation in the case of TSHomas can result in tumour enlargement with neurological and endocrine complications [4]. Clinical features of hyperthyroidism are usually present at diagnosis; sometimes these are milder than expected given the level of thyroid hormones and also perhaps due to the longstanding duration of the hyperthyroidism. Acute presentation is uncommon [5].

Case presentation

A 63-year-old Caucasian man, previously fit and well, presented with a five-day history of shortness of breath associated with wheeze and dry cough. His symptoms had progressively become worse, limiting his exercise tolerance. He denied symptoms of hyperthyroidism such as heat intolerance or weight loss and reported no palpitations or chest pain. His past history was unremarkable with no history of ischaemic heart disease or diabetes and he was taking no regular medications. He lived independently at home with his wife, working six days a week and had stopped smoking 30 years ago. His systemic enquiry and family history were unremarkable.

Clinical examination

The patient had tachycardia, irregularly irregular, at 122/min with a raised jugular venous pressure (JVP) and a respiratory rate of 24/minute. He had no peripheral oedema or cyanosis. Cardiovascular auscultation revealed a soft mitral murmur. Baseline full blood count, electrolytes and renal function were normal. Chest X-ray showed cardiomegaly, pulmonary congestion and a small right pleural effusion.

Initial diagnosis

A diagnosis of Atrial Fibrillation (AF) with fast ventricular response was made and the patient was given intravenous diuretics and digoxin and anticoagulation was commenced with Low Molecular Weight Heparin. Despite 48 hours of treatment, the tachycardia persisted and the JVP remained elevated. Echocardiogram, though limited by tachycardia, showed no impairment of ventricular function.

Investigations

Thyroid Function Tests showed TSH 6.2 (Normal Range = 0.40 –4.00 mU/L), Free T3 of 12.5 (4.00 – 6.8 pmol/L) and Free T4 51(10-30 pmol/L). Repeat Thyroid Function Tests showed TSH 6.6, Free T4 57 and Free T3 19.4 confirming a pituitary cause for hyperthyroidism. Retesting at a second laboratory corroborated these values. Heterophilic antibodies, which can interact with immunoassays, were ruled out. Pituitary function tests showed testosterone levels were elevated at 43.10 (Normal range: 10.00 –31.00 nmol/L) along with elevated FSH, 18.1 (Normal range: 18.1 U/L) and elevated LH at 12.4 (1.0-8.0 U/L). Growth Hormone (GH), IGF-1 and prolactin were normal.

An MRI of the brain showed a pituitary macroadenoma, 2.4 cm in diameter, abutting the optic chiasm, deviating the pituitary infundibulum and internal carotid artery. Visual field tests showed a defect in the right inferotemporal field with a normal field on the left. (Figure 1) The patient was commenced on warfarin, but his International Normalised Ratio (INR) estimating his control on warfarin was markedly elevated with loading doses of warfarin and required reversal of anticoagulation with Vitamin K and introduction of low molecular weight heparin.

Treatment and management

The patient was diagnosed as having a TSHoma and a decision was made to attempt neurosurgical removal. He was commenced on antithyroid medication (carbimazole) in the interim. Attempts to wean down his carbimazole resulted in an escalation of his symptoms and he was therefore maintained on this until successful trans-sphenoidal excision of his pituitary macroadenoma had been performed. His AF persisted post-operatively, but was electrically cardioverted and he remains in sinus rhythm at twelve months follow-up off all treatment.

Outcome

Post-operative MRI showed near total removal of the pituitary adenoma. (Figure 2) Histology showed positive staining for GH, Prolactin and TSH. His TSH and T4 levels have remained normal post-operatively and glucagon stimulation test demonstrated adequate cortisol and GH response. His testosterone levels have also normalised after a transient fall post-operatively. GH, Prolactin and IGF-1 levels remained normal. FSH is persistently slightly raised at 9.1 U/L (1.0-7.0). The patient is asymptomatic, needing no treatment and back at full time employment. Arrangements are in place for a follow-up pituitary MRI.