Endocrine Abstracts

Case history: A 53-year-old male with melanoma who had a previous surgical excision of his skin lesion in December 2018 was being treated with adjuvant pembrolizumab. In June 2019 his treatment changed to combination immune checkpoint inhibitor therapy (ICPi) with ipilimumab and nivolumab due to radiological recurrence.

Investigations: There were no pre-ICPi endocrine investigations available. In July 2019, thyroid function tests (TFTs) showed thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels of 0.2 mu/l (0.55–4.78) and 20.3 pmol/l (10–22) respectively leading to a diagnosis of ICPi-mediated thyroiditis. A mid-afternoon cortisol was measured as 352 nmol/l. In August 2019, TFTs showed primary hypothyroidism (TSH 49.93 mu/l; fT4 2.2 pmol/l). A random mid-afternoon cortisol was 140 nmol/l and consequently a short synacthen test (SST) was performed. This showed cortisol measurements of 331, 707 and 836 nmol/l at 0, 30 and 60 min (post-tetracosactide) respectively and a serum adrenocorticotrophic hormone (ACTH) of 30 ng/l (0–46) at baseline. The remainder of his pituitary function was normal. A subsequent CT scan of the thorax, abdomen and pelvis showed a reduction in tumour volume.

Results and treatment: The patient was started on levothyroxine replacement. In September 2019 he presented with weight-loss, dizziness, headaches and a reduction in appetite. A repeat SST showed cortisol values of 187, 556 and 706 nmol/l at 0, 30 and 60 min respectively. Due to the reduction in the baseline cortisol, the patient was advised to contact endocrinology if symptoms progressed. After 20 days, he complained of progressive fatigue and muscle aches; his 0900 h cortisol was undetectable with a corresponding ACTH of 27 ng/l. Hydrocortisone replacement therapy was commenced and led to symptom resolution. His pituitary magnetic resonance imaging (MRI) scan was normal.

Conclusions and points for discussion: 1. Important to consider endocrine consequences of immunotherapy, including isolated ACTH-deficiency. It is not uncommon for multiple gland pathology (in this case thyroid and pituitary).

2. The SST may lack sensitivity in the early phases of ACTH deficiency, as in patients with recent pituitary surgery, considering it may reflect residual adrenal reserve.

3. An SST may have a role (depending on random/morning cortisol) in the diagnosis of ICPi-mediated ACTH deficiency (based on existing national guidelines). It is important though to recognise the need for re-assessment if clinical suspicion persists despite an initial satisfactory SST.

4. A normal MRI pituitary scan does not reliably rule out hypophysitis, especially when the manifestation is isolated ACTH-deficiency.