Reversible impairment of the processing of proopiomelanocortin into ACTH in pituitary enlargement suspected of lymphocytic hypophysitis

Akatsuka, Hiroshi

doi:10.1507/endocrj.ej12-0161

Cited by 5 publications

(5 citation statements)

References 21 publications

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“…Akahori [17] also reported that biologically inactive ACTH was detected during the course of lymphocytic hypophysitis, endorsing the existence of biologically inactive ACTH in our case.…”

Section: Discussionsupporting

confidence: 85%

Nivolumab-induced hypophysitis causing secondary adrenal insufficiency after transient ACTH elevation

et al. 2019

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A 62-year-old man was referred to our department for elevation of plasma ACTH and cortisol levels during nivolumab administration for renal cell carcinoma. Although his ACTH and cortisol levels had been maintained within their reference ranges, they were elevated to 232.7 pg/mL and 21.9 μg/dL, respectively, after eight courses of nivolumab without any subjective symptoms or Cushing's sign. He was hospitalized for endocrinological investigation. ACTH and cortisol returned to their normal ranges (29.18 pg/mL and 11.4 μg/dL, respectively) in the early morning on day 1, but fell down sharply to 3.7 pg/mL and 1.6 μg/dL, respectively, in the early morning on day 2 without subjective symptoms or vital sign changes. Brain magnetic resonance imaging showed no abnormality in his pituitary gland. ACTH response to CRH was apparently normal, but cortisol did not respond to increased ACTH. A rapid ACTH stimulation test showed slightly reduced response of cortisol to exogenous ACTH (1-24). These findings and his clinical course suggested secondary adrenal insufficiency arising from nivolumab-induced hypophysitis. In previous reports, most cases of immune checkpoint inhibitor (ICI)-induced hypophysitis were diagnosed based on adrenal insufficiency symptoms or hyponatremia with low ACTH and cortisol. The ACTH elevation observed in the present case may reflect destruction of the pituitary gland, suggesting that this finding may be important for early detection of ICI-induced hypophysitis. Our case underlines the necessity of close monitoring for subsequent onset of adrenal insufficiency when ACTH elevation is observed during ICI administration.

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“…Akahori [17] also reported that biologically inactive ACTH was detected during the course of lymphocytic hypophysitis, endorsing the existence of biologically inactive ACTH in our case.…”

Section: Discussionsupporting

confidence: 85%

Nivolumab-induced hypophysitis causing secondary adrenal insufficiency after transient ACTH elevation

et al. 2019

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“…The authors explain these findings by the possibility of elevated ACTH as a result of the destruction of pituitary glands on the early stage or excretion of the biological inactive "big" ACTH [56]. Inactive ACTH excretion in lymphocytic hypophysitis was reported previously by other authors [63].…”

Section: Diagnosticssupporting

confidence: 52%

Endocrine Adverse Events of Nivolumab in Non-Small Cell Lung Cancer Patients—Literature Review

Dudzińska

Szczyrek

Wojas‐Krawczyk

et al. 2020

Cancers

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In recent years, we have observed significant progress in cancer treatment associated with the development of immunotherapy. A programmed cell death 1 molecule (PD-1) on the surface of T lymphocytes may be stimulated via a specific PD-ligand 1 (PD-L1), which inhibits lymphocyte activation and leads to apoptosis. Some malignant cells are characterized by high PD-L1 expression. Nivolumab, an anti-PD-1 antibody, blocks the interaction between PD-1 and its ligands and inhibits the signaling pathway by preventing the tumor-derived PD-L1 from blocking T lymphocytes. In patients with non-small cell lung cancer (NSCLC), it is used either in monotherapy or in combination with other drugs. Immunotherapy is associated with the possibility of immune-related adverse effects (irAE) including endocrinopathies (3–23%). Thyroid disorders are the most common, with severity rarely exceeding grade 2. Hypophysitis, adrenal insufficiency and diabetes are possible complications which require immediate treatment. Individuals with autoimmune diseases diagnosed prior to immunotherapy are at risk of its exacerbation. In the management of patients receiving immunotherapy, evaluation of history of autoimmune diseases, awareness and early diagnosis of irAE are crucial and may affect treatment outcomes.

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“…Therefore, a diagnosis of lymphocytic hypophysitis was suggested based on the clinical course. [10] In the current case, it is possible that we detected the lymphocytic hypophysitis at an advanced stage.…”

Section: Discussionmentioning

confidence: 82%

Severe hypoglycemia and hyponatremia caused by hypopituitarism in a female patient with type 1 diabetes

Zheng

Qiu²,

H³

2019

Medicine

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Rationale: The misdiagnosis of hypopituitarism is common due to its rarity and its nonspecific clinical manifestations. Our case report highlights the importance of critical evaluation regarding hypopituitarism as a cause of recurrent hypoglycemia, hyponatremia, and gastrointestinal symptoms in patients with T1DM, as misdiagnosis might be fatal to the patient. Patient concerns: We herein report the case of 35-year-old female patient who presented with 18 years of history of well-controlled type 1 diabetes mellitus and a 6-month history of recurrent nausea and vomiting, generalized weakness, hyponatremia, and severe hypoglycemia, despite a reduction in the dose of insulin. She was considered as having “type 1 diabetes and gastroparesis.” Four months later, she was diagnosed with hypothyroidism, and 25 μg/d of levothyroxine was prescribed. However, the levothyroxine had to be discontinued 1 week later because of frequent vomiting by the patient. Diagnosis: Further evaluation in our hospital revealed low-normal adrenocorticotropic hormone, low-normal serum cortisol, and low 24-hours urinary cortisol excretion. Secondary hypothyroidism and hypogonadotropic hypogonadism were also demonstrated. Based on the endocrinological findings, she was diagnosed with hypopituitarism possibly due to lymphocytic hypophysitis. Diabetic nephropathy was another diagnosis made after kidney biopsy. Interventions: The patient was treated with 100 mg/d of hydrocortisone intravenously for 2 weeks. After that, she continued on 15 mg/d of prednisone, and then 25 μg/d of levothyroxine was administered. Outcomes: The patient's insulin requirement increased to a premorbid level, the severe hypoglycemia resolved, the physical discomforts were alleviated, and blood electrolytes returned to normal. Lessons: This uncommon case reinforced the significance of a timely diagnosis and appropriate treatment of hypopituitarism. We recommend that physicians focus their awareness on this potentially life-threatening disease, as it is a condition potentially fatal to the patient if not recognized and treated.

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Reversible impairment of the processing of proopiomelanocortin into ACTH in pituitary enlargement suspected of lymphocytic hypophysitis

Cited by 5 publications

References 21 publications

Nivolumab-induced hypophysitis causing secondary adrenal insufficiency after transient ACTH elevation

Nivolumab-induced hypophysitis causing secondary adrenal insufficiency after transient ACTH elevation

Endocrine Adverse Events of Nivolumab in Non-Small Cell Lung Cancer Patients—Literature Review

Severe hypoglycemia and hyponatremia caused by hypopituitarism in a female patient with type 1 diabetes

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