SERIO is a registry for adverse events of immunotherapies (immune-related adverse events, irAE).
In particular, we aim to collect cases of rare, complex and therapy-refractory adverse events as well as adverse events in special patient groups (i.e. patients with autoimmune diseases or patients with a solid organ transplant). Immunotherapies include checkpoint-inhibitors, cellular therapies, e.g. CAR T cells, and bispecific antibodies.
Our goal is to improve side effect management, gain insights into the pathogenesis of irAE, and be able to make predictions about irAE.




Who we are
SERIO is based at the Department of Dermatooncology at the University Hospital of Munich (LMU). The SERIO online register is operated in cooperation with the Paul Ehrlich Institute. Over the past 13 years, we have collected more than 1832 cases of rare, complex or very severe side effects from 27 centres in 6 countries. We cooperate with side effect specialists from all over the world.
SERIO was first initiated in 2011 by dermatooncologists from the University Hospital of Erlangen. The first documented case of SERIO dates back to 2009. A close collaboration with endocrinologists, cardiologists and gastroenterologists soon developed, which led to the initiation of our interdisciplinary Tox Board. Our cooperation with the Working Group Dermatooncolgy (ADO) includes the implementation of joint projects and the exchange of experiences.
SERIO aims to help physicians manage side effects and gain better knowledge of side effects induced by immunotherapy.
What we do
- Collect and analyze cases of rare, complex, severe and therapy-refractory adverse reactions induced by immunotherapy
- Provide physicians with recommendations for the management of irAE
- Conduct research and assist others conducting research related to irAE
Case of the Month
56-year old male patient with ipilimumab/ nivolumab-induced adrenalitis
05/22 melanoma of unknown primary (MUP)
Manifestation: Lymph node metastasis right axilla
TxN3M1b (1), (AJCC 2017)
Staging cMRT and CT-thorax/abdomen: Pulmonary lymph node metastases
06-08/22 – 4 cycles of combined immunotherapy with ipilimumab 3mg/kg + nivolumab 1mg/kg
Since 08/22 – monotherapy with nivolumab (paused 11-12/22)
10 weeks after initiation of combined immunotherapy with ipilimumab and nivolumab, the patient presented with nausea, fatigue and impaired vision. First, immune-related hypophysitis was suspected (irHypophysitis) and subsequently hydrocortisone treatment was initiated. Later on the patient developed increasing hyponatraemia and impaired renal function. The hydrocortisone therapy was continued.
The endocrinological examination showed low cortisol (0,5 µg/dl; reference range: 6,2-18,0 µg/dl), and increased adrenocorticotropic hormone (ACTH) levels (570 pg/ml; reference range: 4-61 pg/ml)). As the ACTH provocation test was negative (low cortisol (0,6 µg/dl) 30min after administration of ACTH, irHypophysitis was ruled out and irAdrenalitis was diagnosed with primary adrenocortical insufficiency.
As hydrocortisone therapy improved symptoms, nivolumab was re-initiated without any further complications. Sodium, glomerular filtration rate (GFR) and creatinine returned to levels within the normal range.
We initiated systemic therapy with hydrocortisone with a dose of 30mg/day (20-10-0mg, later 20-5-5mg). Importantly, individual dose adjustments of hydrocortisone may be necessary (e.g. illness, infection, operation, stress, hyperthyreodism, etc.). Mineralocorticoids were replaced by fludrocortisone (Astotin H 0,05mg/day). Based on individual symptoms like decreased well-being or low libido, some patients also take dehydroepiandrosterone.
Nivolumab monotherapy was temporarily paused until symptoms subsided. In combination with the administration of hydrocortisone and fludrocortisone, Nivolumab was re-initiated without complications.
Endocrine adverse events occur in approximately 10% of patients treated with combined immunotherapy (Hattersley et al., ClinMed, 2021), thyroiditis (10-16%) and hypophysitis (17%) being the most common (Husebye et al., European Journal of Endocrinology, 2023). Adrenalitis with primary adrenal insufficiency (1%), diabetes mellitus and diabetes insipidus (0,9-2%) are rare however critical to diagnose (Husebye et al., European Journal of Endocrinology, 2022). Most endocrinopathies present with non-specific symptoms like fatigue, nausea, headache and arthralgia and can thus be missed (Braun GS et al., Nephrologe, 2020; Heinzerling et al., Dtsch Arztebl Int, 2019; Hattersley et al., ClinMed, 2021). Immunotherapy may be paused temporarily during endocrinological assessments.
Decreased fasting cortisol (morning) < 5 μg/dl and a change of less than 9 µg/dl after administration of 250µg of ACTH provide diagnostic clues for primary adrenal insufficiency (PAI) caused by i.e. irAdrenalitis. The classic short corticotropin test with ACTH is considered as the gold standard method to confirm the PAI. The electrolytes should also be checked as hyponatraemia and hyperpotassaemia can occur.
In the differential diagnosis of adrenal insufficiency, irHypophysitis has to be considered initially. IrHypophysitis occur in approximately 17% of patients receiving combined ICI therapy. If hypophysitis is suspected, checks for clinical signs like new severe headaches or complaints of vision changes, biochemical assessment of the hypothalamic-pituitary axis and MRI scan of pituitary are recommended (Husebye et al., European Journal of Endocrinology, 2022). Neurological examination should be performed once to rule out any other neurological causes. The pituitary hormones (GH, prolactin, LH, FSH, TSH, and ACTH) as well as target hormones should be measured. The corticotropic axis is most commonly affected. Low fasting cortisol (morning) 7-16 µg/dl and serum ACTH value not higher than normal (reference range 4-61 pg/ml) establish the diagnosis of secondary adrenal insufficiency caused by i.e. hypophysitis (Hattersley et al., ClinMed, 2021, Wolters Kluwer et al., UpToDate, 2023).
Treatment usually involves lifelong hormone replacement therapy (corticosteroid and mineralocorticoid). Due to the risk of acute adrenal crisis, patients will need to be educated to increase the dose in stress situations (infections, trauma etc.) and should carry an emergency card with them at all times.
Adrenalitis is a rare side effect of immune checkpoint inhibitors. Prompt diagnosis and treatment with hydrocortisone as well as patient education is essential.