Silent, isolated ACTH deficiency in malignant melanoma patients treated with immune checkpoint inhibitors.

Silent, isolated ACTH deficiency in malignant melanoma patients treated with immune checkpoint inhibitors.

Publication date: May 27, 2021

Treatment with immune checkpoint inhibitors (ICI) has drastically improved the prognosis for melanoma patients, but immune-mediated adverse events can occur in any organ, including the pituitary. In ICI-induced hypophysitis, lymphocytic infiltration and hypersensitivity reactions cause headache and pituitary deficiency. Most cases with ICI-induced hypophysitis develop central adrenal insufficiency. Here, we describe three patients treated with anticytotoxic T-lymphocyte-associated protein 4 (ipilimumab) for metastatic malignant melanoma: case 1 was asymptomatic when hypocortisolism was suspected; case 2 had symptoms of hypocortisolism and suspected severe systemic infection; case 3 had unspecific fatigue. In all cases, routine cortisol measurements and clinical suspicion (cases 2 and 3) led to the diagnosis of adrenocortical hormone (ACTH) deficiency and thereby central adrenal insufficiency. Undiagnosed and untreated, central adrenal insufficiency results in adrenal crisis. In patients treated with ICI, particularly, ipilimumab, hypophysitis and ACTH deficiency must be considered if morning cortisol is low or unspecific clinical symptoms of hypocortisolism are present.

Concepts Keywords
Anticytotoxic Unspecific fatigue
Clinical Malignant melanoma
Hypocortisolism Severe systemic infection
Lymphocyte Prognosis melanoma
Lymphocytic Adrenal gland disorders
Organ Organ systems
Prognosis Endocrine diseases
Clinical medicine
Adrenal insufficiency
Adrenal crisis
Adrenocorticotropic hormone
Checkpoint inhibitor
Endocrine system


Type Source Name
drug DRUGBANK Corticotropin
disease MESH malignant melanoma
pathway KEGG Melanoma
disease MESH hypophysitis lymphocytic
disease MESH hypersensitivity
disease MESH hypophysitis
disease MESH adrenal insufficiency
drug DRUGBANK Ipilimumab
disease MESH infection
drug DRUGBANK Hydrocortisone
disease MESH diagnosis
disease MESH cancer
disease MESH pituitary disorders
disease MESH skin cancer

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