Endocrine Abstracts

Case History: A 39 year old female who was trying to conceive was referred with a raised T4 and non-suppressed TSH, on a background of a miscarriage after embryo transfer one month earlier. She reported no symptoms, however, on specific questioning she had palpitations, a mild tremor and later showed mild tachycardia on holter monitoring. There were no childhood features of Resistance to Thyroid Hormone β (RTHb). There was a family history of primary hypothyroidism only.

Investigations: Centaur TSH 5.89 mU/l (RR 0.35-5.5), FT4 30.9 pmol/l (10.5-21), FT3 11.3 pmol/l (3.5-6.5). Detailed biochemical analyses excluded assay interference testing. Additional results were conflicting: some were consistent with an underlying diagnosis of RTHb (SHBG 158 nmol/l, RR 10-180 nmol/l; MRI pituitary with contrast reported as normal), however, others were in keeping with thyrotropinoma (a subunit, aSU, 1.52 mU/l, RR <1 mU/l; two fold increase in TSH following TRH stimulation: 0 min TSH 5.12 mU/l, 30 mins TSH 10.28 mU/l; absence of THRB mutation on sequencing). Response to somatostatin receptor ligand (SRL) therapy (autogel lanreotide 90 mg every 28/7) showed a fall in TSH (4.01 to 1.4 mU/l) and both FT4 (41.8 to 17 pmol/l) and FT3 (9.3 to 3.69 pmol/l).

Results and Treatment: Following analysis of SRL response, images from the MRI pituitary were re-examined and a 5 mm left sided pituitary mass, typical of an adenoma, was identified. Trans-sphenoidal surgery was performed, and histology was consistent with a thyrotropinoma. Post-operative TSH suppression ensued, with associated mild transient central hypothyroidism, with later restoration of normal TSH, FT4, FT3 levels. Menses continued as expected and post-operative short synachten testing was normal.

Conclusion and Points for Discussion: This case highlights the (i) clinical challenges in diagnosing microthyrotropinomas and (ii) management of microthyrotropinomas prior to planned conception. (i) Tests to differentiate RTHb from thyrotropinomas are less sensitive and specific in patients with small tumours (10% RTHb have pituitary incidentalomas/negative THRB sequencing/no affected family members, small tumours may not lead to aSU or SHBG rise). Analysis of biochemical response to SRL therapy can be a very helpful diagnostic and therapeutic manoeuvre. (ii) Untreated thyrotropinoma presents potential risks in pregnancy (due to thyroxicosis and presence of pituitary adenoma). Ongoing SRL therapy is an option, but is not licensed in pregnancy and there are risks (tachyphylaxis, development of SRL resistance, tumour growth). Surgery is the ideal treatment, given a high rate of cure in experienced hands (~90%) and low rate of complications.